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xN THE UNITED :`STATES DISTRICT COURT

FOR THE EASTERN .DISTRICT OF PENNSYLVANIA


Civ'i1 Action'No . 96CV-5903,

$TEVEN R . . ARCH ; WILLIAM BARNES, ) .:


CIARAN McNALLY,• CATHERINE ;POTTS,°_ )
NORMA RODWELLER, BARBARA 'SALZMAN,
EDWARD J . SLIVAK'and JOHN ;_TEAaLE, )

Plaint`iffe,

) Alan Rodgman,
) Ph .D .
THE . .AMERICAN'TOBACCO''COMPANY, )
INC ., et al ;, ) Volume 4,
) Pages 522 - 739
Defendants . )
)
- ---~ ------~---------
----------- -- _ _)
-

TRANSCRIPT of testimony as taken by and

before LINDA RUSSELL, :a Certified Shorthand

Reporter and Notary . Public of'the State of

North Carolina, at the offices of Womble Carlyle

Sandridge & Rice, :200 West Second Street,

Winston=Salem, North`Carolina, on Monday,

1997, commencing at . 9 :28 in the

forerioon .

(201) 992-4111
Vol . 4, Pg . 52 3

SUPREME -COURT .OF THESTATE OF NEW YORK


COUNTY OF NEW YOR K

------- --- ------- -- --•-----------


PHYLLX,SSMALL and DENISE~FUBINI,
individuaJ.ly, and on behalf of )
others similarly situated, )

Plaintiffs ,

LOkILLARD TOBACCOCOMPANY, INC ., ) Index No .


LORILLARD, .INC .( LOEWS CORPOR .ATION, ') .110949/96
COUNCIL FOR TOBACCORESEARCH-USA, )
INC . (S,uccessor to .Tobacco Industry ~
Research Comma.ttee) ;, AND TOBACCO )
INSTITUTE, INC .-,

Defendants .
----- - --------0 .,-- --~ :. :--------- )

SUPREME COURT OF THE STATE OF NEW YOR K


COUNTY OF NEW YORK

__._- ,.__....___ ..,.. .---------------


MARY ._ANN HOSKINS, Executrix of the )
Estate of Edwin Paul Hoskins, )
WALTINA'BROWN and DANTE AUBAIN, )
individually, and on behalf of )
others similarly eituated,, )

Plaintiffs ,

agains t

R .J .REYNOLDS TOBACCOCOMPANY, ) Index No .


RJR NABISCO, INC ., COUNCIL FOR ) 110951/96
TOBACCO. RESEARCH-USA,, INC . )
(Succeseorto Tobacco Industry )
Research Committee), AND TOBACCO
INSTiTUTE,` INC .,

Defendants .
--~---------------------- )

(201) 992-4111
Vol . 4, Pg . 524

SUPREME COURT OF THE 'STATE OF NEW YORK


COUNTY OF NEW YORK

-- -- ------ ---- -- -•±-------- ----- -- )


SHARLENE HOBERMAN and AUDREY HULSE, )
as Executrix, on behalf' ;of the )
Estate of Lewis Huise,' . .individually, )
and on behalf of othera .similarYy )
situated, )
)
Plaintiffs, )

- against - ) Index No .
) 110953/96
BROWN & WILLIAMSON TOBACCO -- )
CORPORATION, B .A .T . INDUSTRIES )
P .L .C ., BATUS, INC ., BATUS HOLDINGS, )
INC .,•`COUNCIL FOR :~OBACCO'RES ;EARCH- )
USA, INC . (Successor to'Tobacco )
Industry Research Committee), AND )
TOBACCO INSTITUTE, INC . )

Defendants . )
- --- -- - ----- - -- =-------------------- -- )

SUPREME COURT OF THE STATE OF NEW YORK


COUNTY OF NEW YORK

-- - -------------- - -- --------------)
ROSE FROSINA, ELIZABETH-COLAVITO and )
ANILDA ROSS, individually, and on )
behalf of others :similar3 .y situated, )
)
Plaintiffs, )
)
- against - ) Index No .
) 110950/96
PHILIP MORRIS, INC ., PHILIP MORRIS )
COMPANIES, INC ., COUNCIL,FOR TOBACCO )
RESEARCH-USA, .INC . (Successor to ) Ln
~
Tobacco Industry Research Committee) ) J
~
AND TOBACCO INSTITUTE, INC ., ) m
) ~
w
Defendants . )
am
----- ------ - -- - -- _-- - --------- -)

'WAaA &`SPINELLI (201) 992-4111


Vol . Pg . 525

SUPREME COURT OF THE ESTATE OF NEW YORK


COUNTY OF NEW YORK

-----•-- -----------------------------)
CATHERINE ZITO, PETER`HOBERMAN, )
and GEORGE ELISSEOU, individually, )
and .on behalf of othere similarly )
situated, )
)
Plaintiffs, )
)
- against - ) Index No
) 110952/96
THE AMERICAN TOBACCO COMPANY, INC ., )
AMERI:CAN,BRANDS, INC .`, COUNCIL FOR )
TOBACCO RESEARCH-USA,,INC . )
(Succ.esaqr to Tobacco 3ndustry )
Research_Committee), ANO fiOBACCO . )
INSTITUTE, INC ., )
)
Defendants . )
----------- .. ....------- .-----------=------- )

WAdA & SPINELLI (201) 992-4111


Vol . 4, Pg . 526

A P P E A R A N C E S :

J . D . LEE, ESQ .
422 Gay Street
. .Knoxville, Tennessee 37902
For the Plaintiffe°in Pennsylvania case
(423) 544-0101

SHELLER, .LUDWIG & BADEY


3rd Floor
.1528 Walnut Street
Philadelphia, Pennsylvania 19102
8Y : STEPHEN A . SHELLER, ESQ .
SHERRICE A . KNISELY, ESQ .
For the Plaintiffs in Pennsylvania case
(215)_790-7300

`CLIMACO, CLIMACO, LEFKOWITZ &


~GAROFOLI CO ., L .P .A .
Ninth Floor, The Halle Building
Cleveland, Ohio 44115
. BY : JACK D . MAISTROS, ESQ .
For the .Plaintiffa in Pennsylvania case
(216) 621-8484

GOODKIND LABATON,RUDOFF & SUCHAROW L .L .P .


100 Park Avenue
New York, New, York ' 10 017
BY : MARTI S ANN . BRACHTL, ESQ .'_
For the Plaintiffs in New York case
(212) 907-0700

-WOMBLE CARLYLE :-SANDRIDGE & RICE


200 west Second Street
;Post Office Drawer 84
Winston-Salem, North Carolina 27102
BY : MARTIN L .`HOLTON, III, ESQ . ~
For the Defendant R .J . Reynolds Tobacco Corp . ' w
(910) 721-3600, 00

WAGh,' .& SPINELLI (201) 992-4111


Vol . 4, Pg . 527

A P P E A R A N C E S (Continued)

JONES, DAY, REAVIS & POGUE


Metropolitan .Square
1450 G Street N .W .
Waehington, D . C . 20005-2088
BY : :ROBERT-F . McDERMOTT, .JR ., ESQ :
''For the Defendant`R .J . Reynolds Tobacco Corp .
(202) 879~3939

MCCALL DOUGHTON & BLANCATO


633 West Fourth Street
Suite 150
Winston-Salem, North Carolina 27101
BY : WILLIAM A . BLANCATO, .ESQ .
(910) 725-7531
For the witness Dr . Alan Rodgman

MILLER & MARTIN .


Suite 1000 Volunteer Building
832 Georgia `Avenue
Chattanooga, Tennessee 37402
BY : MARCIA MEREDITH EASON, ESQ .
,,(423) 756-6600 .
For the Defendant'Lorillard Tobacco Company

WAG4A' & SPINELLI (201) 992-4111


Vol . 4, Pg . 528

I N D E X

WITNESS REcR,osS REDIRECT RECROSS

ALAN'RODGMAN, Ph :D . .

Maistros'' 532

j X H_ I B I T S

PESCRIPTION IDENTIFICATION
Vol . 4, Pg . 529

VIDEOGRAPHER : We're going on the

2 record . The time is 9 :28 . This is the videotape

deposition of Alan Rodgman, Ph .D ., taken by the

4 plaintiff in the matters'of William P . Perry and

Sandra Perry, Plaintiffs, versus Brown &

Williamson Tobacco Corporation, ;et al .,

7 Defendants . Case number, civil action .2-473-95 .

8 Also the case Phyllis Small, et al .,

Plaintiffs, again .st Lorillard ;Tobacco Company,

10 Incorpora,ted,-et :al ., .Defendants . Index number

11

12 Plus the case of Mary Ann Hoskins,

13 et al . Plaintiffs, .against RJR Tobacco Company,

14 et al ., Defendants . Index number 110951/96 .

15 Plus'the case of Sharlene Hoberman,

16 et al ., Plaintiffs, against Brown & Williamson

17 Tobacco Corporation,>et al ., Defendants . Index

18 number 110953/96 .

19 Plup the case .of Rose Frosina, et al . I

20 Plaintiffs, against Philip Morris, Incorporated,

21 .et al ., Defendants . Index number .110950/96 .

22 Plus the case of Catherine Zito,

23 et al ., Plaintiffs, against the American Tobacco

24 Company, Incorporated,,et al ., Defendants . Index

25 number 110952/96 .

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 530

This deposition is being held at the

2 offices of Womble Carlyle Sandridge & Rice, 200 --

MS : KNISELYs Excuse us . The main

4 caption is Arch .' This is what it --

VIDE04RAPHERa Okay, I have that also .

o.,, y o.u want -me to

. :KNISEL'Y :

8 VIDEOaRAPHER : Also the case of Steven

9 R . Arch, et al,, Plai,ntiffs, versus Brown &

10 Williamson Tobacco -~ excuse me, the American

11 Tobacco Company, Incorporated, et al ., Defendante .

12 This deposition is being held at the

13 offices of Womble Carlyle Sandridge & Rice, 200

14 West-Second,Street, Winston-Salem, North Carolina .

15 M . ItNtSELY : Excuse me . Could you

16 read the full caption in Arch for us .

17 VIDEOGi2APHER : Okay . Do you want me

18 to start over?

19 MS . KNISELY : No .

20 VIDEOORAPHER : Arch, et al ., versus

21 the American Tobacco Company, et al . Case number

22 U,S . .District Court_EDPA 93-5903-CN .

23 This is Monday, August 4th, 1997 . My

24! name is John Girdler ; I'-m the video specialist .

25 The court_reportex is Linda Russell . We are here

(201) 992-4111
Vol . 4, Pg . 531
r

in connection with ;Waga and Spinelli, with offices

located ,at' Four . . Be .cker= Farm Road, Roseland,

New Jersey .

Counsel will now state their

appearances f or"-the record, and'the court reporter

will ewear`in the witness .

MR . MAISTROS : Jack Maistros for the

pla3.ntiff .

MS .'KNISELY : Sherrice Knisely for the

10 plaintiffs in Arch .'

11 MR . LEE :

12

13 Martis Brachtl, here for

14 the plaintiffs in the New York actions Small,

15 Hoekins,' Hoberman, Froeina, and .Zito .

16 MS . :EASON : Marcia Eason for the

17 defendant Lorillard`Tobacco Company in the

18 Tennessee litigation, William and Sandra Perry

19 versus Brown & Will,iamson .

20 MR . BAG4LEY : Rick Bagley, legal

21 assistant for the -defendant .

22 MR . HOLTON : Mark Holton for RJR .

23 MR . MCDERMOTT : Robert McDermott for

24 Reynolds Tobacco Company .

25 MR . BLANCATO : Bill Blancato

(201) 992-4111
Vol . 4, Pg . 532

representing Dr . . Alan Rodgman .

2 ALAN RODGMAN, Ph .D .,

having been first duly sworn, was examined and

4 did testify as follows :

EXAMINATION (Continued)

BY MR . MAISTROSs

8 you?`

10 R

11

12 Q

13 pleasurable experience .

14 My name is :'Jack Maistros and I

15 represent the plaintiffs in an action pending in

16 Pennsylvania . It's the Arch case .

17 I'm going ;to ask you a series of

18 questions today . If you don't understand my

19 questions, stop me . If you, want to confer with

20 your counsel, stop',me- . ',:If 'you want to go to the

21 me, ' okay?

22 A. Yes, sir .

23 Q . We're here,for your schedule as much

24 as`everyone elee's, and more so for yours,

25 probably .

(201) 992-4111
Vol . 4, Pg . 533

1 Who are you represented by .today?

2 Mr . William Blancato .

3 Q Is he your only counsel today?

Could :'you

full name for me .

7 My name is Alan Rodgman, A-L-A-N,

8 R-Or-D-G-M-A-N :

Q . Would you prefer Dr . Rodgman or

10 Rodgman?

11 Whatever you desire .

12 You are a doctor?

13 I m a Ph .D . in organic chemistry .

14 Q. Organic chemistry?

15

16 Q. What is your date of birth?

17 February the 7th, 1924 .

18 Q . Where`do you currently reeide?

19 A . 2828 Birchwbod Drive, Winston-Salem,

20 North Carolina .

21 Q Do you have any intentions, in the

22 of moving, relocating?

23 Not that I'know of .

24 Are you married?

25

(201) 992-4111
Vol . 4, Pg . 534

1 Q . How long have .you been married?

A. F.ifty years on .June the 7th, 1997 .

Q . Is your 'wife' employed?

4 No .

5 Q . Do you have any children?

Yes .

Q . How many?

Three

MS . BRACHTL : Counselor, could you

10 speak up, .pleaee .

11 MR'. MAISTROS : Sure .

12 BY"MR . MAISTROS

13

14 49, 47, and 44 .

15 o any of your children work for

16 . Reynolds, or have they?

17{ All three have°worked for Reynolds in what

18 was .known as Reynolds Summer Program for children

19 of'dmployees,~loading boxcars, and so on and so

20 forth,` My youngest son is'a manager in personnel .

21 What- ' s,

22 Mark Rodgman .

23 manager,of personnel'trainingl

24' o either of your other two children

25 work full time for Reynolds, or have they?

(201) 992-4111
Vol . 4, Pg . 535

Yes .

Q What years?

was in the"-Canadian Navy :£rom 1942 to 1945 .

4
10 was born' in

11

12 Q When did y

13 1954 . . But, before that, I'moved to Canada .

14

15 °'Twenty-six-years :'

16 Where ; clid you attend high school?

17 Toronto, Ontario,' Canada ; Humberside

18

19

20

21 Did you .

221

231 I went i

24 R

25

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 536

A . I entered the-University of Toronto in honors

chemistry .

4 Q

5 University of Toronto?

6 Eight yearsi .

7 Q, And what-degrees did you obtain?

Bachelor of arts in honors chemistry, and

master of arts in organic chemistry, and a Ph .D .

10 in-organic chemistries ; '49, '51, '53,

11 respectively .

12 Q . Up until 1953,` had you done any

13 work'related to or with a tobacco company?

14 A . No, I had not .

15 t2 Had any of your research involved

16 tobacco, in any fashion, up'to 1953?

17

18 Q What was'your first involvement with

19 tobacco?

20 A . When I was hired by R .J . Reynolds in 1954 .

21 Q . What '`month?

22 June the .23rd .~

23 Was that your first full-time

24 employment after 'college?

25

WAGA & SPINEhLI ` (201) 992-4111


Vol . 4, Pg . 537

2 Reynolds?

Well, I had a peculiar circumstance that, in

1941, I obtained a summer position at the

Banting & Best Department of Medical Research .

And for t .he summers, and then during the falls and

7 winters, I worked evenings and weekends, until I

got'my Ph .D .' in 1953 . Then I worked "full time at

9 the'Banting &<Best,Department of Medical Research .

10 Q . Where is the Banting & Best Department

11 f .Medical Research?

12 -Toronto, Ontario, Canada .

13 Q : What did you do there?

14 was involved in the study of

15 carcinogenesis . ;

16 S2 . How ;were you involved?

17 A. was a -- did_research .

18 What is "carcinogenesis?

19 Carcinogenesis is the,process whereby a

20 carcinoma is formed_ .,

21 0. What is a

22 Carcinoma is a tumor .

23 Did you do research on any specific

24 type types of tumors?

25 N

:WAGA' & `SPINELLI (201) 992-4111 .


Vol . 4, Pg . 538

materials that were used in the studies .

Q Did you have a major goal or theme of

your :research during that period of time?

A. The major'goal well,-my .major goal was to

synthesize the compounds that my professor there

material that'would act as a`'vaccine against

cancer .

10 certain compounds?

11 3t e s . That'a=what I was-there-for .

12 Q . Multiple-compounds? How many

13 compounds did you synthe'size?

14 Well, they,were :peculiar compounds in which

15 polycyclic hydrocarbon .`was'--linked to proteins .

16 And .I probably synthesized .-- to'be able to link

17 the,polycyclic to .the protein required a series of

18 reactions, and then the final reaction to do the

19 li:nking . And I probably did 10 or 15, I guess .

20 And, of :course, because the-material

21 wae being used in animal studies, I had to keep

22 making them again and again, because these studies

23 ran . -.f or many yeara .

24 And _what- is the -- what is the purpose

251 of making these synthesized compounds, as opposed

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 539

to using naturally .occurring compounds?

You couldn't find them naturally occurring .

Did you publish'any research?

Wheze was it published?

A . , :Sotrie of it was in the Journal of American --

jimerican''CYiemical Societv,'and some was in the

annual report of the Ontario Treatment and

Research Association, which was =- did the funding

10 of ,the work . Some of .it was published -- or

11 presented before various meetings . Canadian

12 Physiological Society,'I think, was one of them .

13 Q . And that was from '47 to '53?

14 Yes .

15 Q . How did your research progress in

16 terms of coming up with a vaccination?

17 . It wasn't too'succeseful .

18 Q Was`that research continued after you

19 left?

20 Yes .

21 Q•

22 No .

23 Q. . Why did ° :it ,stop?

24 A . Well, .my,professor, Dr . W . R . Franks, who was

25 .a cancer research professor at the University of

WAGA & :SPINELLI (201) 992-4111


Vol . 4, Pg . 540

1 Toronto, he eventually retired, and then, of

2 course, -_a couple of years ago he died .

4 Who was funding that research? Do you

4 know?

5 Ontario Treatment and Research Association,

think it's called . And some of it was funded by

7 the National Cancer Institute of Canada .

Q . Was there any specific type of cancer

that you were focused on, as opposed to just

10 cancer I general or tumors in general?

11 Well, it was the vaccine, if you want to call

12 it that . It was, you know, an attempt to find

13 something that would counteract the -- the effect

14 of polycyclic in -- polycyclice in animals .

15 4 What is a polycyclic?

16 Polycyclic compound is .one with more than one

17~

18 Poly

19' Each ring is

20 Q

21

22"

23 Q How are' .polycyclic compounds formed,

24 or how do they get in the animal's system?

25 A . Well, in the experimental work, they were

WAaA & SPINELLI , (201) 992-4111


Vol . , Pg . 54 1

injected into the animal .

2 Q . What type of animals?

A . Mice .

4 Q . Why did you use mice ?

A . Well, I had no control over what~beast was

used ; Dr . Franks was the one that selected the

7 mouse .

Q . Didyou ever use any other type of

animals ?

10 A . Some of the people in the group were studying

11 what was called Rous sarcoma, which occurs in

12 chickens . So they used chickens .

13 Q Is there some product or proces s

14 whereby the average person would be able to relate

15 what polycyclic compounds come out of or ar e

16 created by? I mean, why -- how -- why do yo u

17 focus on polycyclic compounds ?

18 MR .'MCDERMOTT : Object to the form of

19 the question .

20 THE WITNESS : Well, as I say, I was

21 doing a job for the professor . But, at that point


;Ln
-

22 ,in .time, 1947, polycyclic hydrocarbons were quit e


I m
23 rampant in the gasoline exhaust, the foods yo u
w
Ln
24 -exhaus effluents .from your W

25 coal-fired furnaces,- ;-oi1-fired furnaces, gas-fire d

WAGA & SPINELL I (201) 992-4111


Vol . 4, Pg . 542

furnaces, tires that are being worn out on the

that they were in tobacco or tobacco smoke?

about°°the`--: 1950, after some of the

9 epidemiological s.tudies resu3 .ts were published,

10 there-'was an effort-to f4gure out . And then

11 Dr . :Wynder had his mouse ski .n painting work, to

12 find'out if there was .-,- what was in the cigarette

13 smoke . And of course they concentrated on the

14 po3.ycyclic hydroca,rbons right .away, starting in, I

15 gueds, '51/'52 .

16 Q . "They" ;; w o is they?

17 People in . the scientists around the world

18 were -- looked at it,' an .d'`primarily because of the

19 tremendous background on the polycyclic

20 hydrocarbons that had :begun'in 1931 .

21 By who? .

22

23
i &
24 hydrocarbons?

25 would say,- if you categorize them into

(201) 992-4111
Vol . 4, Pg . 543

different types, there ;;are ::probably about 75

different types of polycyclic hydrocarbons . Of

course,,one of the classifi-catione .,ia whether they

have two rings, three .ringp, four rings, five,

And

Q . Are they`all,carcinogenic?

7 No . In fact, some`of them are

non=carcinogenic, and eome of them will offset the

effect of carcinogenic .hydrocarbone .

10 Q . Are there

11 MS . KNIS.ELY :

12 minute? want to talk with you for a second, if

13 we-can go off the record .

14 MR . MAISTRQS_ :

15 VIDEOQRApHER :

16 record at 9 :48 a .m .

18 a .m .

vIDE00RAPHER :

20 record at 9 :52 a :m .

21 BY`MR . MAISTROS :

22'~ Q

23 talking about .polycyclic hydrocarbons . Let me ask

24 you, first of all, of the 75 different types that

25 you`said existed ; some are cancer-producing ; is

(201) 992-4111
Vol . 4, Pg . 544

that correct?

Yes . In mice -- or animals .

{~ . If I use'the phrase "carcinogenic," do

you equate that ;:with cancer-producing or not?

. Carcinoma-p'ro'ducing .

Q, Of t :he 75 different types, are they

carc,inogenic or carcinbma-producing?

A . It depends on how you'adminiater them . There

are some polycyclic .hydrocarbons which are not

10 tuntorigenic . There are some that, if you

11 administer them one way, they will cause a

12 carcinoma, by skin painting, and another one, if

1. 3 you inject them, it will cause a sarcoma . And

14 some, ;if ;you feed them, they don't cause anything .

15 o the term tumorigenic or

16 carcinogenic is dependent on about 50 factors that

17 have to be,t`aken into account .

18 Q inlhether .it's carcinogenic, tumorigenic

19 or carcinoma-producing, is the end result cancer?

20 Well, if you're"talking tumorigenic, not

21 neceaearily so, be-cause the tumorigenic compound

22 could cause_a papilloma, which is not is a

23 benign .tumor, which is not considered a cancer .

241 `Q . What is the major alleged link between

25 polycyclic hydrocarbone and tobacco smoke?

WAC3A&'BPINELLI (201) 992-4111


Vol . 4, Pg . 545

1 MR . I4CDERMOTT= Object to the form of

the question .

BY MR .'=MAISTROS :

If you .could survey the literature

and .- not holding you to -- from a scientific

standpoint, this opinion . I'm asking you, out of

th,e .literature out there, the major alleged link

-bettaeen polycyclic hydro -- or polycyclic

hydrocarbons,'tobacco'amoke and disease, what is

10 the alleged link?

il MR ._BLANCATOt Object to the form .

12 MR . MCDERMOTT Object to the form .

13 THE WZTN$SSs You're talking now, or

14 1954, or '55?

15 BY MR . MAISTROS t

16 Q Let

17 A . Well, in'view of the evidence that's been

18 cQllected over the last 40 years, the~aasociation

19 between polycyclic h,ydrocarbons and cigarette

20 smoking disease in smokers is very tenuous .

21 s the alleged link between polycyclic


Ln

22 hydrocarbons and smoking a carcinogenic effect, ~


..m
23 tumor-producing effect? What is it? w
Ln
,-J
24 MR . MCDERMOTT : Object to the form .

25 Compound .

(201) 992-4111
Vol . 4, Pg . 546

1 BY MR . :MAISTROSs

Q . I want to just understand, for th .e

next:`couple of days, if I use the word

"tumor-producing' or "carcinogenic" or

"cancer-producing," we re,not missing each other

6 in the night because I'm thinking one thing and

7 you're thinking another . Is`there some agreed

upon format we can use that you're comfortable

9 'w .ith?

10 Yes . If you' .re going,to use the term

11 "carcinogenic" or "tumorigenic" or "sarcogenic," I

12 think you should be aware of what goes into

13 determining'that effect .

14 And, for example, the effect of a

15 compound is species-dependent . Things that happen

16 in mice cannot happen in ra,ts, do not happen in

17 rabbits, guinea pigs, or monkeys, dogs . And you

18 may have eomething_happen in a,rat that doesn't

19 happen in a mouee :

20 Tumorigenici :t,y a.~e also

21

22 animal won! t 'may not happen in a male, and vice ;


i
23 versa . Tumorigenicity is also dependent on the

24 age ;of the animal, .what happens when you've got a i

25 six-week-old mouseland you start the experiment

WAaA` .&,SPINELLI (201) 992-4111


Vol . 4, Pg . 547

versus what happens when you've got a year-old

2 mouse . You can tell -- you may get entirely

3 different reactions .

4 The other thing is the mode of

administration . ;Whether it's skin painting ;

varioue types of irijection, intravenous,

intraperitoneal, .subcutaneous injection --

8 Q . Those are factors that affect --

9 inhalation .

10 Those are factors that affect the

11 tumorigenicity, ;if, you :will,

12 .Right .

13 Q . -- the compound .

14 What_ Y

15 assume, .• . .1

16

17 Well, tumorigenic is an all-encompassing

18 word .

19 That's

20 looking °for the al .l -encompassing word that I can

21 use,,that you're comfortable with, that is an


I
22 alleged adverse health risk related to polycyclic

23 hydrocarbons . What's the broadest word you can


,
24 think of today?

25 A . Well, tumorigeneaie would be one . But I say,

(201) 992-4111
Vol . 4, Pg . 548

even<vin that case,'you've got to take into account

the factors I was trying to tell you about and

Q . ' I , apologize`.

6 -administration .makee_a,great :deal .of difference,

whether it's the substance administered neat or in

solution ; and it depends on the kind of solution,

the .+concentration, and so on .

10 Men are :not,mice type theory?

11 Yes . You,probably read that'I had written

12 that someplace, `but I` plagiarized it . If you want

13 to find-out where it is, look in something Ernest

14 Wynder wrote .

15 Q I like that quote, though .

16 Well, in that case, I'm sorry I wasn't

17 the .inventor .

18 Q. I wi11 t

19 "tumorigenesis .°',And if I ask you a question in

20 the future, that<you think it's not accurate

21 because .•I'm not using the right phrase, I'd like

22 .you to interrupt me and tell me, okay?

23

24 I

25

(201) 992-4111
Vol . 4, Pg . 549

doing from 147 to 153, was there a particular type

f tumorigenesis you were looking at?

We were looking . :at the -- .there ,are four

polycyclic hydrocarbons that,_ .from -- after

1932 -- well, actually 1931, that, when they were

syntheeized,or,isoi .ated .from something identified,

th-en synthesized, there'were four polycyclic

hydrocarbons'that are considered the most potent


.,
available :' Dibenz ia ; h] anthracene

10 Okay .

11 benefit, and`partially mine, if you could do these

12 long words slower, okay?

13 . Okay . Dibenz[a,h]anthracene, and those are

14 square parens, too . ; benzo[a]pyrene ;

15 3-methylcholanthrene ;

16 7, 1,2-dimethylbenz Ta] anthracene . And the "All is in

17 brackets, .

18 What :do you mean by "most potent"?

]. 9 Well, if you were to look at a eeries of

20 hydrocarbons, you get -- polycyclic hydrocarbons,

'21, you .get some .that aren'.-t active at all, some are

22 very slightly active . In other words, you may get,(„

23 o ne : t u m o r i n a t h ous ari d mi ce . B u t , those four , at m

24 thee right concentration in the right beast and I W

25 administered in the right .way, will cause a large

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 550

percent of tumor-bear,ing animals . And they're

used~many times as standards .

6 o that ; even?

-We11, dibenz [a, hlanthracene was ' f irst found

to be`tumorigenic in 1931 . It was synthesized by

9 Dr .•Fieser at Harvard and found to be tumorigenic

10 by Kennaway in England .

11 Q . In what beast?

12 Mouse .

13 0 How about benzo [a] pyrene? .

14 It'was isolated from coal tar in 1932 by

15 W . Cook and his colleagues . He isolated it,

16 proved its-structure by-synthesis and then showed

17 thatt it, was tumorigenic in mice .

18 Q

19 I forget the exact date'about

20 -methylcholanthrene . But the interest in

21 3-methylcholanthrene is that, for years, from 1935

22 to 1950, people : were looking at

23 -methylcholanthrene because, if you heat food

24 stuffs containing cholesterol -- cholesterol is

251 structurally similar to 3-methylcholanthrene

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 551

there-was a likelihood or a theory that you would

get 3-methylcholanthrene in your food stuffs . And

that was the reason :for the high level of cancer

f -the stomach in the United States versus places

like Japan that very`seldom had cooked meat or

things with cholestero,l in it that were cooked .

How about dimethylbenzla]anthracene?

Well, that was .-actually .the -- that was

started about the 1950s . 'it actually was thought

10 to, be just a .straight synthetic compound, until it

11 was found in .a l,ot of things, food stuffs . And,

12 of course, it is found in tobacco smoke ; but it's

13 a very small amount .

14 Q . These four, what .you've described as

15 the most potent polycyclic hydrocarbons, is that

16 still true today, that those are the,four most

17 potent?

18 would sl! y yes

19 of that, becaub+e .there `have been writings that

20 maybe an individual coimpound might be more potent

21 than`those . But .those'four have been used in so

22 many experimental systems that, if you're going to

23 do an experiment in tumorigenesis and you want a

24 control, you might pick, :=one of those four, because

25 you've got something'like 50/60 years of

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 552

background to fall'back o

- And'the object, during an animal

experiment, is .you always have what's`called a

positive control, which`would include maybe one of

these four, And if something went wrong with a

certain concentration and mode of administration,

and .you didn't get .the percent tumor-bearing

animals that you usually got, you knew you were

doing the experiment wrong and you better look at

10 your procedure :' Were your technicians doing the

11 skin painting properly, or was the solution right,

12 or so on and 'so forth .


,. . :
13 Q . Now, when you say that they were --

14 these four .were known to produce tumors back in

151 the '30s,-'31/'32, is that a specific type of

16 1 tumor? The same`for all four?

17 A . Well, here,again, if you skin paint

18 benzpyrene, I'm sure -- we might as well stick

19 with that, because that's the one you're going to

20 rattle on about for the next few days .

21 Benxola]pyrene, if you paint it on the

22 skin, will-cause`a carcinoma of the skin . But if

23 you inject it subcutaneously, it causes a sarcoma .'N


m

24 If you administer it by -inhalation, it doesn't

25 cause anything .

(201) 992-4111
Vol . 4, Pg . 553

1 Q . Are there percentages that have been

attached to these different polycyclic

3 hydrocarbons, such as 80 percent of the mice that

.are, skin painted with particular ones have

developed-tumore, or 90'percent0

6 Well, it depends on the concentration, sir .

could -- D

experiments in 1957 ;-_showed that you could start

with a certain concentration of benzo [a] pyrene

10 solution and paint mice`with a certain

11 coneentration, cut it in half, cut it in half, cut

12 it in half, and paint different groups with the

13 solutions, and .you got to a point where you had a

14 level of benzo[a]pyrene_in solution that didn't

15 cause any tumore : But that level was 300 times

16 what's in a normal cigarette . .

17 That was'out of Dr . Wynder's lab in

18

19 That would' b

20 aseume1 ` y

21 A. In the tar from 300 cigarettes . He has the

22 precise figures in there ; it may be 280, it may be

23 320 but it :'was cloae .to 300 .

24 Q So there's'a certain minimum level

25 that has been discovered of - of at least some o

WAGA& SPINELLI (201) 992-4111


Vol . 4, Pg . 554

these polycyclic hydrocarbons, at which they do

.not, promote --

3 -Every one tested has aminimum thresh -- has

a threshold,limit value .

that you were talking about had about as much

as you need 300 cigarettes to equal?

8 A . Benzo [a7 pyrene :

Q : Why are they referred to as "most

10 potent"? I mean, how would a,layman understand as

11 to why they're the mos`t potent? Do they all cause

12 som'p form of ;tumors at some levels?" Are they just

13 biologically more active?

14 No . As I just finished telling you, they

151 don't, .cause it at al1`levels . It is the fact

161 that, if you were'to-administer a certain number

17 of millimoles of benzpyrene versus a certain

181 number -- the same number of .millimoles of, say,

19 benzoCa]anthracene,'which is a borderline

20 tumorigenic, if it's`a tumorigenic at all . Then,


Ln
~
21 at a .given concentration, say, benzo[a]pyrene ~
m
22 might produce 8fl_percent tumor-bearing animals, ,~
. w
23 and benzo[a]pyrene (aic) may produce 2>percent at ;~

24 the same concentration .

25 And`it was found that those four, at a

(201) 992-4111
Vol . 4, g 555
r

certain concentration, always produced the

2 highers, versus everything else that was tested .

Q• Are all "four of those,polycyclic

hydrocarbons you mentioned in tobacco smoke?

As far as I know, 3-methylcholanthrene has

neve,.r been found in -- well, it's been found in

cigaret-te smoke but never confirmed . A man in

8 Germany called :Krt511er reported it, but there was

some question about the accuracy of his

10 identification . Dietrich Hoffmann and Ernest

11 Wynder disagreed with his identification .

12 Q . Do you know when the other three were

13 discovered to be in tobacco smoke?

14 A . Well, as I mentioned before, there was a big

15 controversy about whether the_polycyclics were in

16 cigarette smoke, and that controversy rattled on

17 between '51, '52, 'S3 . And even as late as 1957,

18 f.or example, for benzo[aJpyxene :, Dr . .Fieser, who

19 was :probably one'of the two great-polycyclic

20 hydrocarbon chemists,in this country, did not

21 agree wit .h the evidence indicating benzopyrene was

22 in cigarette smoke : His own staff could not find

23 it, yet they could find it in coffee .


&

24 Q . Who's the other great polycyclic

25i

(201) 992-4111
Vol . 4, Pg . 556

Melvin Newman`at`Ohio State . I believe he's

Those are -- polycyclic wizards in

almost every_country . : J . W . Cook in England, whom

I have mentioned ; Clar, in Germany, wrote several

big, huge books on polxCyclics . The French had

Lacassagne ; that's L-A-C-A-S-S-A-G-N-E ; and a

Vietnamese called Buu-Hoi, B-U-U, hyphen, H-O-I .

8 So each country had somebody who was doing

p.olycyclic hydrocarbon-~work, from 1931 to probably

10 the war time ; everything was interrupted by the

11 war .

12 Q . And who was America's?

13 `Melvin Newman at Ohio State and Louis Fieser

14 at Harvard . And Louis Fieser, of course, was the

15 chemist who did ;this chapter on cigarette smoke in

16 the :1964' ;Surgeon General's report :' . .

17 The three hydrocarbons that -- is it

18 generally accepted,they're in cigarette smoke, the

19

20 as' I'said, after --`in '57, because

21 Fieser wouldn't accept the evidence, there

22 was -- that was in the literature, there was a big ~

23 push to definitely identify them . And the -- I

24 guess the culminating thing was, in 1959,

251 Dr . Wynder and Hoffmann'published -• gave a


Vol . 4, Pg . 557

presentation and s.aid ; Well, .here's absolute

proof that it's' .from it's in-cigarette smoke .

3 And they showed a pictu,re of some-crystals of

ben,zo [a7 pyrene, which I' m sure they found .

5 So after ;.i67/'58, everybody accepted

th'at it was there` . 8ame as everybody accepts it's

in .your toast this morning .

Q . S forgot my toast . I did get my

oatmeal, but they forgot ~ the toast .

10 The .levels you mentioned, I'm sure

11 there's a minimum threehol .d you have to get to

12 before it .is tumor promoting . As you said, for

13 benzo [a] pyrene ,you need 300 cigarettes?

14 no .

15 With cigarettes ;~he backed off on solutions of

16 pure benzo {a] pyrene ;: And when he got to an

17 equiv;alent that-wae .many"times what was in the

18 cigarette tar that he usually used, he didn't get

19 any .

20

21 sure you may be aware .that Dr . Wynder,

22 Dr . Hof fmann, `-Fred .Bock :, Ben j amin Van Duuren and

23 Alvin Kosak have repeatedly written that, in the

24 skin painting studies with cigarette smoke tar,

25 the polycyclic hydrocarbons, as a class, can

(201) 992-4111
Vol . 4, Pg . 558

explain no more .than,two and :a half percent of the

And J'. W . Cook, Fieser, .everybody, has

.said, for 50 years, .you oannot explain the

observed response by the polycyclid hydrocarbons .

And if you look in the -' 79 .Surgeon General, the

'82 Surgeon General the

all say the same thing .

10 To .add something to this business

11 about the controversy : From '51, that area --

12 that :time period, I ;personally couldn't understand

13 why there was a'controversy . Because, from 1935

14 to 1950, every material that was --'had an organic

15 compound, whether,,iaas chicken` wings, or steak, or

16 isoprene, or methane, or simple organic`compounds,

17 every one that was he`ated at a temperature above

-'18 500 degrees gave :a series .of polycyclics .

19 Q . In the ;'work' you were doing, which is

20 where`we started, from,'47 to ',53, were you

21' focusing on these four polycyclic hydrocarbons?

22 Well, focusing on`thope, plus another one,

23 benzo [a] anthracene, ` which 'ie actually in smoke

24 too . It's`a borderline tumorigenic . In fact,

25 there'are probably as many reports in the

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 559

literature that it's non-tumorigenic than there

are ; that" says , it s very mildly tumorigenic .

I also °some of my work involves

eome,other .things besides'polycyclic hydrocarbons

5 There's nitrogent~mustards that are tumorigenic

6 compounds, and I was involved with those .

Q~

mustards?

9 We want -- there was

10 that,- if you had linked a compound -that was

11 tumorigenic to another one'that was,tumorigenic,

12 would you get addition,'synergism or cancellation?

13 And ;I was interested in the fact that -- of

14 hooking a nitrogen mustard to a polycyclic

15a hydrocarbon and made a,series,of those compounds .

16 And,they really acted like the

17 polycyclic . Nitrogen mustard had very little

18 influence, because nitrogen mustard, as you

19 .probably are aware,' ;_for some years was used to

20 treat leukemia in .children .

21 Q . What other research were you doing '47,


Ln
22 53? ~
~
23 Well, one of the things that did prove useful i m
w
J
24 later was -- other than my experience with

25 polycyclic hydrocarbons, was my -- 'Professor

(201 992-4111
Vol . 4, Pg . 560

Franks had a good frie.nd ;who was head of the

medical department_ot a large U .S . corporation .

They were having some"problems,with -= and asked

us to do f ind `out~ wh'at wae the problem in a

5 tarry-like substance that .was .being emitted from

6 equipment . And I developed a,procedure to look at

7 it .

It_was,obvious, very quickly, that it

contained polycycl#,c'<hydrocarbons .c I developed a

10 procedure, based - I pay :"developed ;" :I combined

11 two procedures that were in the literature : That

12 >f .J . W . Cooky~ and`hie work on the isolation of

13 polycyclics from coa3, tar, with a procedure called

14 column chromatograpliy,''and developed a procedure

15 o .tsolate polycyclic hydrocarbons from a complex

16 mixture .

1 7_: It was a much easier procedure, much

18 si.tnpler than the'one Cook had used .- And, of

19 course, you got to remember, in 1931 there was

20 very little known about -- they' .didn't'know what

21 they .were looking for, for one thing . And they

22 started with two tons of coal tar . .

23 © What 'company was this?

24 The company in the United States?

25 Yes .

WAaA & SPINELLI" (201) 992-4111


Vol . 4, Pg . 561

I m not at liberty to'tell you that .

2 This was -- you signed a

confidentiality agreement?,_

My boss did . Well,_it was one'of those

f;riendship things .

A. Well, as I say,- ;there seemed to be a problem

with=a --`the tar emitted from the equipment they

10 were ueing and the effect on the ekin of some of

11 the workers .

12 Q . Was the problem solved?

13 A . I have no idea . I just gave the results to

14 my boss, and he transmitted them to liis friend,

15 and .I don't know .w.hat wa ;s done with them .

16 Q . And the reeearch you did for that

17 particular projeCt-•was to .identify the polycyclic

18 hydrocarbons

19 Well, to see if they'were there, and it was a

20 .good guess that they were . And I did identify

21 some of them . There we're a_whole series, startin


Ln
~
~
22 with-naphthalene, N-A-P-H-T-H-A-L-E-N-E,
!N
m
23 anthracene, benzpyrene, benzanthracene . . They were ~
w
~
24 all : there . . w

25 4 And what kind . jof `skin problems was the

WAC3A : & SPINELLI


Vol . 4, Pg . 562

1 tar;,causing : for the ' employees?

2 I have no_idea,` sir .

whatever happened to that issue, or -

today?

8 Yes .

Q-

10 work?

11 A . When I came .to Reynolds, I was given a

12 project to do, which I did, and which`ended . Then

13 I was asked what`I :would like to :work on ; which I

14 was-a little surprised, because usually you're

15 told,what you're'to work on . And I said : Well,

16 in view of all the stuff that's .going on in the

17 literature, I think`we should look at cigarette

18 smoke . They said" ; Go ahead ._

19 And, of course, with all this

20 'controversy on polycyclic hydrocarbons and having

21 a method to determine"them or isolate and separate


Ln

22 them, we set up a smoking system that matched, as

23 near as we could, the one that Dr . Wynder

24 described in his 1953 paper on the skin painting

25 work, the Wynder, Graham and Croninger paper .

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 563

1 looked at that .diagram and built a smoking machine

2 as :close to that as we could, from the diagram,

and used .the same smoking regime that'Dr . Wynder

had used, which he had said simulated the human

smoking eyetem ; ."whichy it .,really didn't . He used

three puffs per minute, which nobody used at that

7 time ; but we copied that .

And looking at the -- putting my

procedure through the` the cigarette smoke, we

10 isolated and identified polycyclic hydrocarbons in

11 cigarette smoke .

12 Q . Before we'get to Reynolds, the work

13 you were doing from '47, .to '53 was -- the end goal

14 was to develop a vaccine for cancer-promoting or

15 cancer -- tumor-p`ro .moting-.compounds?

16 . A . Tumor-initiated .

17 Q . And between '47 and '53, you weren't

18 doing research to see if the compounds were

19 tumor-producing,youu were doing research to figure

20 out`a solution to combat the tumor-promoting

21 compounds, correct? Ln
~ 1
~
22 . That's right . . ~
~ m
23 Q . You took it :as a given, between '47 w
J
Ln
24 and ."53, that certain`polycyclic hydrocarbons were

25 cancer or tumor promoting, correct?

(201) 992-4111
Vol . 4, Pg . 56 4

vaccine for animals or_humans ?

Well, I thin k

in hope that, if there was a correlation_between

tumorigenicity in animals and .the tumorigenicit y

8 in humans,,that it would .work in humans .

Q . Did :you do

10 53 ?

11 My work was all chemistry, sir .

12 Q . Did anyone .in your laboratory, eithe r

13 Franks or anyone else, do you'know if they studie d

14 any,polycyclic hydrocarbon effect on humans ?

15 . ' No , they da.dn' t :

16 Q . They did not ?

17 coupl e

18 history, .sir .

19

20 are subjected to polycyclie hydrocarbons and watc h

2 1 them, over a period of °time, to see what happens ?


Ln
22 For e :xample, yo u mentioned that, I ~_A

23 th.i;nk, polycyclic-hydrocarbons are' prevalent i n

24 some fuels . Has a'nyone ever done etudies to look

2 5, at :re.finery workers, over a period of,time, to see

(201) 992-4111
Vol . 4, Pg . 565

if there's_any correlation with .the animal

studies?

~A . Well,"you have a problem with -- in some

instances, of compari'eon . °zf you'r,e .looking at

po],ycyclics and the 'effect on skin ;i if somebody

gets stuff on the skin,` tar or oi1 .'or whatever,

you may get somewhat the sajme` effect : But one of

the problems has been that, on inhalation, the --

it's~been, I,think, .very .rare circumstance has

10 anybody ever beon abie to produce lung tumor in

11 animals with inhalation of a polycyclic

12 hydrocarbon .

13 Q . I'm just asking you if you're aware of

14 any'long-term-or short-term studies that were done

15 on humans that were eubjected to polycyclic

16 hydrocarbons in the'environment .

17 No . But there was a study done in Italy,

18 before the war, 1937/'38, by Cottini,

19 C-O=T-T-I-N-z, .'and Mazzone, M-A-Z-Z-O-N-E,

20 which' they actually painted human -beings with

21 solutions of polycyclic hydrocarbons that had

22 produced tumors in animals . I .think the skin

23 painting went on for four`or`- .five months . I

24 believe it was done .with prisoners . And I believe


,.
25 it`was terminated when -- Labor'Day of 1939, when

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 566

war ..was dec'lared`between Great Britain, Canada,

Germany, Italy, and'the prisoners were shipped

into the Italian Army .

Q . Was this published research?

Q . Do you know if there were any

7 conclusions drawn as to .a,ny analogies that can be

made to the animal skin painting?

I don't think it`ran .long enough . I think it

10 only` ran three o,rr four months .

11 Q . When you'were doing your studies in

12 147 to '53, was it a11 .:-skin painting?

13 No . Well, I didn't do any of the skin

14 painting . I saw a lot of it . I would say there

15 were, :eome injection -- the vaccine thing was

16 tested on skin-painted animals, on

17 inttaperitoneally-injected animals,-on intra --

18 eubcutaneously-injected animals,

19 . .in't•ravenously- :injected animals . And, of course,

20 work going on_there did -- as I said before, there

21 wae one small .,group under Dr . Franks, .working on

22 the ;Rous sarcoma with chickens . Rous sarcoma is a

23 virus-caused tumor .

24 0 Was there a

25,1, period, was there a generally scientifically

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 567

1 accepted method of doing this testing, skin

guessing?

4 A :-, No . If you were

there was a pretty well-set protocol . If you were

doing subcutaneous injection, there was a

defined -- fairly well defined protocol . And that

wasiprobably due to when I was running through all

9 that stuff about-the`factors that influence

10 tumorigenesis . Between "31 and 1941 --- '31 was

11 when .i'-the first polycyclic hydrocarbon tumorigenic

12 for mouse skih`was found, and then '32 was the

13 benzpyrene in coal tar .

14 Between that time, people were

15 -synthesizing polycycliO hydrocarbons in all

16 directions, different structures, ones with methyl

17 groups dangling on them and two methyl groups,

18 three methyl groups .' And they were painting them

19 on mice, and making all sorts of wild claims . And

20 a man who was a very noted cancer .research

21 specialist in polycyclic hydrocarbons and other

22 tumorigens, Dr . . Murray .Shear -- I don't know if he

23 worked for the National Cancer Institute or the

24 predecessor of the National -- but he was asked to

25 write an article to put all this mees in

WAaA & SPINELLI (201) 992-4111


Vol . 4, g 568

And he

Shear and Leiterr are-the authors, in which he went

through-'and described,all the intricacies of

tumorigenesis atudies, : ;`whatl it : all meant, and so

on .and eo forth .'

7 work he had done'came the procedure, for example,

in ekin painting, that=you had various groups of

mice . `One you''called .the cage control, and all

10 you did was put them in a cage, 100 mice or 50,

11 whatever number you wanted to use, put them in six

12 to a-cage or something, and you fed them and gave

13 them water and'cleaned their cage up every day .

14 And,then you had what'was called the

15 solvent control ; you had a group of mice that

16 you -- on the shaved surface of their.a:.back, you

17 painted them with the solvent . Th,en ;you had a

18 positive control, benzpyrene,or whatever,

19 that you_wanted to<use, maybe one of the four that

20 I talked about,

21 pai.nt'ed the back with


Ln
22 Then whatever your test, material was, :I-
N
23 was~'the subsequent ;groupst

24 different materials,you were'testin_g

251 ten groups painted the`same way as you did with

WAGA' &,. SPINEL .L,I (201) 992-4111


Vol . 4, Pg . 569

1 the benzpyrene positive control .

So it was all fairly well set out that

3 way . And of course, one of the interesting things

4 is that when you all -- everybody talks about

carcinogenicity and tumorigenicity . If you look

in"`the government documents that cataloged the

7 compounds that were tested for tumorigenicity,

8 that book was first published in 1947 and the

second edition in '51, and then .another one in

10 '57, and it keeps on going . It's now -- if you

11 had them'all-together_here, they'd be as wide as

12 this-table, all stacked side-by-side . But in the

13 first 25 years,`one of the'compounds that was used

14 as the solvent was benzine .

15 And in the solvent controls, the -- I

16 didn't look at all the books some time ago, when

there was a big fuss=about benzine . But as far as

I know, there are only three-tumors that ever

appeared in something like 11,000 animals painted

with benzine . Now is that tumorigenic or not

21 tumorigenic?

22 Q . Which three tumors? ~


~
J
~
23 Pardon? m
~
Which three tumors? w
24 Q OD
~
251 A . Well they were all the same type, as I

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 570

1 recall . I've forgotten what they called -- it had

a weird name .

3 Q You mean three tumors, or three types

f'tumors, or three :gpecific tumors?

A .. No, three animals had tumors, and I don't

know what the tumor type- ;was, out of thousands of

animals tested that way .

8 0

9 A .

10 What `a-tudy are you referring to?

11 Ve11, I say, in many studies benzine was used

12 as .the solvent . And the solvent control, if

13 benzine had been ag tumorigenic as some people

14 claim, you,certainly :would have found more than

15 three in 20 years out of the thousands and

16 thousands of animals treated .

17 Q Is therea'a :specific paper that I could

18 .identify or go'to that would summarize the

19 majority of the work you did from '47 to '53?

20 A . (Witnese shakes head .) No .


Ln
21 Q. Are :there .specific titles of those r
_J
N
~
22 papers you recall, as you sit here today, that I
~
w
23 could look up? 00
N

24 Well, as I-- ohe of them, I think -- the one

251 that' .s in the Journal gf American Chemical Society

WAGA & SPINELLI- (201) 992-4111


Vol . 4, Pg . 571

is a compound :I prepared with -- linking thyroxine

to .dibenzanthracene .

Thyroxin, of course, is the active

amino .acid that's .in`your thyroid . But I think

someplace you' mua`t have -- in all this stuff I've

given you, you must .have a copy of all my

publications .

Even prior~ .to Reynolds?

You have everything I've ever written that

10 has been,published . Or presented at meetings .

11 Which I'gather you :mustn't have looked at .

12 Q . And, again, up until '53, none of your

13 specific research focused on tobacco or tobacco

14 smoke?

15 None of my`work at the Banting Institute

16 nor :`my work in the chemical department nor my

17 master's or my Ph .D . or -- my bachelor's degree

18 might -- you .might say : Well . . .

19 As it turned out years later, might

20 have had .-- been connected or had an indirect

21 connection .

22 But when I told you I was involved in' ;

23 an honors chemistry course in the University of

24 Toronto, the University of Toronto is different

251 Ontario universita.es are different from those in

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 572

1 the rest of Canada and in the United States, that,

2 when you take what's called an honors course,

particularly in science, the first three years you

take nearly all the-courses that you have to take

to graduate . Your fourth year you may have one or

two courses . And the rest of the time in your

fourth year you were assigned a research project ;

8 it's .sort of a mini master's .

9 And they believe, at the University of

10 Toronto, . that you should not graduate from an

11 .honors chemistry course or honors physics without

12 knowing how to do research . And my project for my

13 bachelor's degree was to develop a procedure to

14 prepare unsymmetrical hydrazines . The Canadian

15 government was interested in unsymmetrical

16 hydrazines because they were very fine -- thought

17 they :would be a very fine rocket fuel .

18 We1l, to get unsymmetrical hydrazines,

19 what you needed to ;do was to make -- first get a

20 nitrosamine, and then reduce it to the hydrazine .

21 So I prepared, the Canadian

22 government, and it_became part of my bachelor's

23 thesis, if you will, pounds of dimethyl

24 nitrosamine, half of'which I converted to dimethyl

25 hydrazine . And of course, at the time I did this

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 573

1 work, 1948/49, dimethyl nitrosamine was not known

2 to be tumorigenic . : It was only discovered in 1956

3 that it was-tumorigenic . But I guess I was lucky,

because I probably made 25 pounds of dimethyl

5 nitrosamine . .> I .'.m still here .

6 Q

And how is that arguably related to

tohacco or tobacco smoke?

10 . In 1963/64 two guys in -- two gentlemen in

11 South Africa said dimethyl nitrosamine was in

12 cigarette smoke .

13 Q Who were those two?

14 . Serfontein, S-E-R-F-O-N-T-E-I-N, and Hurter,

15 H-U-R-T-E-R .

16 Q. The work you were doing when you got

17 your bachelor's degree, at that point in time you

18 didn"t-know it would .have some bearing upon your

19 future work?

20 A. No . In fact, nobody knew until 19 -- well, I

21 had suggested in -'you've probably seen it -

22 something I wrote in the_late '60s -- late

23 'S0a/early '60s that the conditions in a burning

24 cigarette were such that things like dimethyl

25 nitrosamine could possibly be formed . And then

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 574

1 two ;men in Germany, Druckrey, D-R-U-C --

2 D-R-U-C-K-R-E-Y, and Schmahl, S-C-H-M-A-H-L,

proposed the same thing, I think, in 1961 or '62 .

4 And ; subsequently, they were found .

5 Q . What is a nitrosamine?

6 A . It's an amine with a nitrosa group hanging on

it .

Q Is there some alleged health problem

9 with nitrosamines?

10 A .~ Well, in 1956, Magee and Barnes, in England,

11 found that they were tumorigenic .

12 Q . Hae,there been any work published

13 . since 1956_that would suggest that -- was it

14 Magee?

15 .Magee, M-A --

16 Q And .Barnes were wrong?

17 No .

18 . Q Have you ever disputed Magee and

19 . Barnes' work?

20 . Vve never done the kind .of work they did .

21 Q When -- did you ever accept that

22, nitrosamines were .tumorigenic?

23 Were tumorigenic in animals .


G,

24 0 When did you first believe that

25+ nitrosamines were tumorigenic in animals?

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 575

1 Well, when you start reading the literature

after,1956 -- I forget the exact number, but

probably 350 nitrogamines have been synthesized,

used for one thing or another, and I think all but

about ten of them have shown some activity in

animals in some way or another . Mostly on

feeding .

8 Q . Mostly on what?

9 On feeding .

10 Of couree, .some of them are -- some of

11 them .are in cigarette smoke . Some of them are in

12 your ;bacon . Some of them are in your cooked

13 bacon .

14 Have there been similar studies, like

15 the polycyclic hydrocarbons, where you"need a

16 minimum level of'nitrosamines to become .

17 .tumorigenic?

18 A . I'm sure there'have been, but I can't think

19 mean

20 Q Nobody did like Wydner (sic) did,

21 where they kept-reducing the amount in half, until

22 they got to a level that --


Ln
N
23 A . You mean Wynder W-Y-N-D-E-R . ~
~
m
24 Q . Wydner . ~
w
Co
Wynder . W-Y-N-D-E-R . -j
25 A.

WAaA & SPINELLI (201) 992-4111


Vol . 4, Pg . 576

1 Q . W-Y?

2 N-D-E-R .

Q . D-E-R .,

Nobody did any studies like Wydner,

5 that -

A. Wynder .

7 Q Wynder . Nobody did any studies -

A . The'man's`been'in the business for 47 years,

and you don't know his name?

10 Q . 41 .

11 He was the`first published --

12 0 I thought you said me . I'm sorry .

13 Wynder published his first article in

14 1950 .

15 0 If you criticize my age, I want you to

16 get it'right .

17 Nobody"did any studies similar to him?

18 A . I don't know, sir .

19 Q . You didn't do any .

20 No .

21 Q . And,, I'm sorry, what year did you say?

22 It was, '50 -- '63/'64, to be determined to be in

23 tobacco smoke?

24 Yeah . I think it was "63/'64 .

25 Then there was a big controversy of

(201) 992-4111
Vol . 4, Pg . 577

whether it was formed actually there or formed

2 arti•factually du.ring the collection of the smoke .

it seenmed,-every time something came

4 up, .:there was a-c-ontroversy . And eventually

5 procedures were worked out .that it could not be

artifactual . It had .to be -- whatever you found

was the true`bill of .goods .

Q . Have you been deposed before today?

9 Yes .

10 Q . How many_times?

11 A . ` Well, three weeks ago, was it? Would be

12 Minnesota, in the beginning of the Arch

13 deposition . That's the only time I've been

14 deposed for smoking and health-related .

15 Q . What other types of depositions have

16 you given?

17 A . There was a deposition on a procedure that

18 Reynolds .had developed on how to expand tobacco .

19 And'in some of our .work we -- in examining

20 competitive products, we-became very suspicious

21 that :American'was using our process . And there

22 was a case invOlving-that, and I was deposed

23 during .,'-that .

24 Q
25

(201) 992-4111
Vol . 4, Pg . 578

Q . Did that actually go to trial?

No . American paid up .

3 Q. It was :a patent infringement case?

A. Yes .

5 Q . What process?

Expansion off tobacco .

Q . Does that have .a number on it or a

letter, G1'3?

G13 .

101 Q How long were you deposed?

11 think it was two days . Day and

12 a half, something like that .

13

14

15

16

17

18

19 court action?

20 I have no idea .

21 Q . Other than,that deposition, have you


Ln
~-A
22 ever given`any other depositions? -4
N
m
23 A . - There 'was a c`ase of -- about the -- about the 4%

24 tobacco expansion business, with Philip Morris .

25 And",that was probably 15 years ago I've

(201) 992-4111
Vol . 4, Pg . 579

1 forgotten the date . It was done over in

Charlotte .

Q . How long were you deposed in that

4 case7 ~ ~ ~

was guess .

10 N

11 Q . Have you<given any

12 related to,the research you've done at Reynolds?

13 A. I don't understand'"sworn etatement ."

14 Q . . Have you ever signed any documents

15 where somebody aeked, you to swear under oath the

16 truth .of what was'in the document, affidavit or

17 otherwise, notarized?

18 MR . BLANCATOs There is an affidavit

19 dealing with some'doCuments, privileged documents,

20 that has been provided in one of these smoking

21 health cases .

22 MS . KNISELY : Was that in Minnesota?

23 MR . MCDERMOTT I believe that's

24 correct .

25 BY MR .' MAISTROS :

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 580

Q . We'll get into your employment history

at Reynolds, but when was your last year of

full-time employment at Reynolds?

A . Well, in 1987 -- it's a little difficult to

explain . 1987, ,Reynolds offered an incentive

retirement plan . And since -- under the

conditions of the incentive retirement, it took me

past .65 . I accepted it .

So .my last day of work was August the

10 31st, 1987 . But my .fu]1-time employment or pay

11 continued through`March<the lst, 1989 . Because

12 I-- because of my tenure at Reynolds and the

13 conditions of the' :incentive plan, I had 18 months

`14 continued pay, I guess_they called it . So I don't

15 know how you want to fit that i

16 MR . BLANCATO : Are we at a good point

17 or about to take .' a break?

18 MR . MAISTROS : Sure . Any time .

19 MR . BLANCATO : Let's take a break .

20 VIDEOGRAPHER : We're going off the Ln


~
J

21 record at 10 :44 a .m . m
~
22 (Recess taken from 10 :44 a .m . to 11 :00 w
~
N

23 a .m .)

24 VIDEOGRAPHER : We're going back on the

25 record at 11 :00 a .m .

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 581

MR . MAISTROS : The affidavit you

provided, that's in'the'Minneeota litigation, is

that a stipulation? Is`that a -- are we --

MR . BLANCATO : I think --

MR . MAISTROS : I don't want to stop

now, but if~we can, .at the break, just check and

.7 a

or -- I'd just like to see it .

9 MR . BLANCATOs- Sure .

10 BY-MR: MAISTROS

11 Doctor,"have you given any -- whether

12 they were sworn or unsworn statements, any

13 statements to third parties, related to the

14 research you've done -- or you did at RJR, to

15 somebody other than your counsel? Has anyone ever

16 come up to you and eaid, "I'd like to ask you some

17 questions about what .you_did at RJR," just in an

18 informal setting?

19 Yes . I'm trying to think of his name .

20 reporter'in Greensboro, Catanosa, phoned me

21 some four or five years :back, and I refused to

22 talk to him .

23 4. Did he do an article-eventually or

24 Well, he did a whole bunch of articles on

25 some things other people had told him .

(201) 992-4111
Vol . 4, Pg . 582

Q . Was there a particular subject or

theme that he ;was writing about?

It was"about an .incident that happened in

4 1970 .
. :
Q . And 'this was,what newspaper?

6 A . The Greensboro some ;thing or other . I don't

know the name of it .

Q Did anyone at Reynolds tal,k to him in

series, in that'article?

10 I don't know if'they were -- whether they

11 were .at Reynolds at the`time . Some ex-employees

12 talked with him .

13 Q . Was the subject of that article about

14 the animal testing?

15 A . I guess you'd aay that .

16 0 The closing of the mice or the rat

17

18

19 Q Was :it .mice or rats?

20 A . Mostly mice . Did have some cats .

21 Q . Have you ever given any media or

newbpaper interviews'about your work at Reynolds? Ln


22 ~
_J
23 No . Iive given presentations at scientific

24 meetings .

25 Q . Has anyone from the Justice Department

(201) 992-4111
Vol . 4, Pg . 583

attempted to interview you?

2 was trying to think .

4 That would include the FBI, the U .S .

`Attorney .'s .Office .

About my work?

6 Q . Yes .

A. No . I had an FBI guy come and talk to me one

8 time ., many`years agoi because a young lady that

was working for me had applied to go in the Peace

10 Corps, and they wanted some background on her .

11 Q . That's the only time :you've ever

12 been --

13 I think the -- to my recollection .

14 you know of any'current or former

15 employees at Reynolds that have been interviewed

16 Justice Department, including the FBI?

17 No, I don't . I don't know anybody .

18 Have you'been interviewed by anyone

19 from the FDA?

20 A. No .

21 Q Have you ever appeared before any

22 panels of the FDA to give testimony?

23

24 Have you,ever appeared before Congress

25) to}give testimony?

WAdA &-SPINELLI (201) 992-4111


Vol . 4, Pg . 584

A . No .

R• Have you ever appeared before any

legislative ;body to'give testimony?

5 0 Did .you ever prepare any papers that

were presented before any legislative body with

respect to the work you did at Reynolds?

A . No .

Q . Did you ever review any papers that

10 were provided'to any legislative body with respect

11 to research that was :being done at Reynolds?

12 Can we back up a second?

13 Q . Sure .

14 A . What do you call .legislative body?

15 Q Like before a House of Representatives

16 or a Senate panel or congressman or -

17 .(Witness shakes head .) No . No .

18 Q Did you prepare any papers that were

19 presented to any sort of governmental entity?

20 .' Back in the mid '60s I .prepared some stuff

21 for management that was-- much of which was

22 turned over to the FTC, :when they were getting

23 ready to implement .their procedure .-- develop and -j


~
' m
24 implement their,procedure on the FTC tar and ~
w
~
m
251 nicotine .

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 585

Is that the kind of thing you're --

Q. Yes ., something along those lines .

You prepared -- but those were papers

you did for Reynolds't hat, at the time .you

prepared them, you didn't know they were going to

be turned over to the government? Or did you?

No, I ;didn't -- I prepared them for the folks

that asked for them .

Q . And theee papers related to measuring

10 the tar and nicotine'in cigarettes, or the

1.1 labeling?

12 That, plus some of the problems that exist -

13 coexist with that procedure, many of which have

14 resurfaced again now,

15 Q . You mean the procedure for determining

16 levels?

17 Yeah . And what it``meant and so on .

18 Q. Did you .ever review the work of anyone

19 else at Reynolds-that was eubmitting paper or

20 statemente'or li'terature to the government with

21 respect to any iseue ;related .to smoking?

22 A . We -- back in -- around 1980, Reynolds was

23 involved in a-- a problem with one of our

24 competitor's cigarettee ; we did a large amount of

25 work on that . The,.Barclay ; I'm sure you're aware

(201) 992-4111
Vol . 4, Pg . 586
r

of the 'Barclay incident . And we turned over a lot

information that we had generated on the

Barclay -- Barclay being measured on the FTC

proCedure, and the Barclay as it was'being smoked

by people . We-turned all that over to the FTC .

.Q What was'°-your role in that process?

Well, I was :director

And the people-that weree doing the work, worked

for .~m Dr . Jokin Reynolde,

10 David c3ilbert ; >so on . .

11 Q

12

13 Q Have, you ever

14 Pritchard?'

15 . . : a . ... .

16 Any other circumstances-you can recall

17 where you were-invo] .ved in either preparation or

18 review of documents that were submitted to

19 governmental agencies?

20 Well, I'm sure you were aware'of the National

21 Cancer .Institute study on less hazardous

22 cigarettes ; I wae-invo1ved in that . I don't know

23 whether this is pertinent or not . I audited many

. 24 of thoee meetings :and was the representative at

25

WAGF# ~ & SPINELLI` (201) 992-4111


Vol . 4, Pg . 587

were -- drafts of-the reports were put together, I

2 did`a lot of proofreading and correcting, and so

onand so forth, for the '-

reports, which'was `sent'back to the NCI . I don't

5 know whether, tthey r- they included some of the

changes Irecommended,' and some they didn't .

7 Is that the kind of thing-you're

looking for?

Q . Indirectly, ]

10 governmental-related, but

The ``FDA, ii

12 testimony you've never presented any papers or

13 testimony to that'agency? Other than the one

14 you -= well that was FTC . So, FDA,' .you've never

15 presented any papers or teptimony?

16

17 Have you ;prepared anybody that

18 appeared'before any .governmental agency, such as

19 the FDA or the FTC? .

20 No . Not that I

21 Q .< In Ap .ri1. o ;f of Reynolds

22 and some other C :O .'s, testified before Congress . Ln

23 Did you play any role in the preparation of that

24 testimony?

25

(201) 992-4111
Vol . Pg . 588

wasn't an employee, t)ien .

Q . Were you receiving any`money from

Reynolds in 1994?

A . I had two contracted -- consulting things

'One was to write the book on

nitrosamines, and the other was to take part in a

planning s'ession, but I-think both -- both of

those were prior to 1994 .

10 MR . MCDERMOTT : This was reviewed in

11 the~past deposition that you all participated in .

12 MR . :MAIS.TROS : I'm not ;getting into

13 that . Ijust wanted to make certain that none of

14 youx` work involved any preparation for testimony

15 that was-provided to .Congress in April of '94?

16 THE WITNESS : No . No, sir .

17 BY MR . MAISTROS

18 Have you assisted in the preparation

19 any witnesses thathave been deposed in any of

20 the`:tobacco litigation?

21 Just myself .

22 Q. And':how' many times --


m
23 I needed all the help°I could get .

24 many' times

251 Counsel to; prepare",for your deposition?

WAGA & ;SPINELLI ' (201) 992-4111


Vol . 4, Pg . 589

. : . Let's l.t' a

we'last met, about three weeks ago . I guess I

5 probably met with them .Iour or five times, maybe

six . I don't

Q And i f :: you

8 time you spent with your counsel preparing for the

deposition, what would .the number of'hours .be?

10 Well, a lot of -it involved those boxes .

11 The documents?

12 Yes . Carrying them back and forth from my

13 house to Mr . Blancatols office,- and back to my

14 home, and here to get'them copied, and so on and

15 so forth .

16 Were you paid by anyone to do that?

.17 supposedly was paid,by the Arch people .

18 if you iaant to know

19

20 0 Were you paid by Reynolds or anyone

21 affiliated by Reynolde"to prepare for your


N
22 depo,sition today? ~
,m
23

24 Other,-than actually -physically

25 carrying the documenta ; how much time was spent

(201) 992-4111
Vol . 4, Pg . 590

preparing for the depos.ition today?

A . Oh, I don't know . Maybe a dozen hours .

Q . Was there anyone other than

Mr . Brancato`-

,MR . MAIS TitOS

MR .

7 BY MR .`MAISTROS :

Q . -- Blancato present`at those meetings?

Sometimes Mr . McDermott, sometimes

10

11 Counsel :for RJR attended the meetings

12 with your counsel?

13 mean, just these two : Jones Day and

14 Womble Carlyle .

15 4 They're .not your attorneys, though,

16 are they?

17

18 Q, What did you discuss in those

19

20 MR . MCDERMbTT : Object . Privileged .

21 MR . .-,ShANCATO : Objection .

22 MR . MAISTROS : How is it' privileged?

23 MR . MCDERMOTT :_ He's a former

24 employee . We re t'alking about matters that relate

251 to the defense of the caee ; we're entitled to talk

WAGA &'SPINELLI (201) 992-4111


Vol . 4, Pg . 591

to .him on a privileged basis .

2 BY MR. . MAISTROS :

Q Do you have

do you have a written document with Reynolds that

pertains to'the .teetimony that you've given in

Have you entered into any agreements

with Reynolds to not disclose information without

1. 0 advising Reynolds .or their counsel first?

11 No .

12 Q . And the only counsel you've retained

13 in this matter is your own personal counsel?

14 Yes .

15 Q . Reynolds' :'counsel is not your counsel?

16 As far as I kndw, they're not .

17 Q . Who is paying your counsel?

18 -Reynolds .

19 Q . Who selected your counsel?

20 I guess, - i'ndirectly, I, did .

21 Q . How, indirectly?

22 . Well, I needed a .lawyer, and the first one

23 that came to mind was tny. `son . But he works

24 200 -miles away -and' .w.as alreadyd tied up,' and so on

251 and so forth .

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 592
r

1 Q. And :how .did you get to your current

counsel?

3 A . . Well, I guess Mr . Holton .said : There's a

young man that w .ould ;do a'good job for you .

does work for Womble Carlyle, and so on .

Q M Holton, Reynolds' counsel?

Yeah .'

10 preparation for .your,deposition?

11 Well, for the Minnesota case,' they provided

12 us :with a stack of documents, a foot and a half

13 high . . went through those prior to the last time

14 we ;met, what, two or three weeks ago, three weeks

15 ago . But I reaily didn't -- since you folks

16 didn't provide me with :,any, .documents, I didn't go

17 through that many .

18 n the ' preparation for the Minnesota

19 deposition or the Minnesota case deposition, you

20 reviewed°only documents that were,provided .by the

21 person who was questioning you?


Ln
~
22 A~ . I don_'t .know who provided them . They showed ~
6
23 up one day here . . 4%
~
6
24 Q, Did ;you review any documents that were ~

251 provided by your own counsel?

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 593

An affidavit, I`reviewed, before I signed it .

2 Did you review any documents that were

provided by Reynolds' counsel?

4 You mean these two gentlemen?

©'

The reason .`I'm ;heaitating, I've been involved

in this businees" so long and I've reviewed so

much, can't put it in perspective of when I did

what .

10 I guess I did,'but I couldn't tell you

11 There weren't .very many .

12 Did you review'any of the previous

13 that were taken in any -- any tobacco

14

15

16 Which'onee?

17

18 Q. Was :that-a`'deposition or was that

19 court .test-imony?

20

21

22

23 Q . And why did you review that?

24 Well,'I had hired David Townsend in 1977/78,

25' and I just wanted to see how he handled it . I had

WAGA'& SPINELLI (201)' 992-4111


Vol . 4, Pg . 594

seen him, a little bit on television, and I wanted

How"did'you obtain-the transcript?

I got a copy, of it f rom Mr .

Q .' Did you ask M

the'transcript?

Yes .

I :.asked for it .

10 Q Other than Dr . Townsend's court

11 testimony, did you`review any other testimony?

12 'For this case?

13 Q

14

15 did .

16 Who else?

17 I looked at the depo,sition of -- or the trial

18

19 1961 . .

20 Who i Ochsner?

21 Dr .-Ochsner is one of the first two men to

22 remove lungs, either i - whole lung or part of a

23 lung,,back in'the early days . Dr . Evarts Graham

24 .And Dr . Ochsner :had a clinic m

25 New-Orleans . Very famous man .

WAaA~& ;SPINELLI` (201) 992-4111


Vol . 4, Pg . 595
r

Q What prompted you to review his

2 testimony?
>
3 Well, he was a :great proponent of the fact

that cigarette smoking,wae the cause of lung

-canc-er . And some of the testimony in that case

6 showed that there was a fluctuation between his

7 opinion on that and the'data he presented over six

8 °or eight years,-"in half a dozen publications, of

9 his clinical findings . But he kept saying he

10 would write an article at one point, in time,

11 saying : My opinion ia, This is the cause . And

12 his clinical data said ; We can't find any

13 correlation between place of residence, and

14 occupation ; and smoking or diet . And this went

15 So he was .ul

16

17 And course he is quoted in the '64,

18 the '79, the ".82 Surgeon General's report, and the

19 only one they .-- paper they quote is the first

20 time he ever said it in 1939, that cigarette

21 .smoking was probably the cause of lung cancer .

22 A11 the caaes-where<his clinical data didn't prove

23 that, they left out .

24

25 A . They left it out .

(201) 992-4111
Vol . 4, Pg . 59 6

1 Q What prompted .you, though, to read hi s

testimony before your deposition today ?

happened to be looking at something and saw the

I had a copy of his testimonyand I remembere d

What :were`yo u

8 What wae,I looking at

Q . That you saw a

10 hooking at som e

11 some diaries that you folks copied .

12 Is Ochsner strial testimony among th e

13 documents you provided to us ?

14

15

16

17 Nobody .

18

19 Where is . it now ?

20 It's at home .

21
Ln
22 documents at home to :produce, I assume somebody
i 6
23 asked you to look and see what you had at home ?

24 Yeah .

25

(201) 992-411 1
Vol . 4, Pg . 597
1

1 home?

They're here .

Q . So Ochsner

theee boxes?

5 No, it isn't . No .

Q .' Why did you

I didn't .

MR . BLANCATOs-

-tYiat were responsive` to the : subpoena .

10 BY`'MR : MAISTROS3

11 A11'the .~documerits at your home, were

12 they provided to an attorney who went-through them

13 and decided what would be produced .to us?

14

15 Including the Ochsner testimony?

16 o, I didn't .

1? What, ot:her-than the Ochsner

18 testimony, did you not give'`to'Mr . Blancato?

19 got - for example, I've got files

20 on and I think we' ;ve been through' this . I have

21

22

23

24

(201) 992-4111
Vol . 4, Pg . 598

Q . You didn't .pro.duce your index card in

there?

offered to, and'said they didn't want it .

THE WITNESS- ; Right?

MR . MAISTROS : I'll take it . You

still have it?

F MR .'BLANCATO : No, no, no, no .

MR . MAISTROS : We'll discuss it at a

10 BY MR .•`MAISTROS

11 Q . You have-an index file of what?

12 What's on the indexes?

13 Well, there's more work -- references

14 perti-nent to the work I did, from 1947 probably up

15 to 1970-something, :'75, maybe 1980 .

16 MS . RNISELY : If I could clarify the

17 record for just a .second : I believe,

18 Mr . Blancato, we,made t'he agreement and

19 -underetanding, w3,th r{egard :to the index, we would

20 not, at the present time, require Dr . Rodgman to

21 produce that .' We wouZd, however, reserve

22 depending on'the deposition testimony with regard

23 o :the index, reserve the right to request the

24 production thereof . .

251 MR . BLANCATOr And my position would

WAGA & SPINELLI (201) 992-4111


Vol . 4, g 599

1 be!that we objected to : :production of that on the

grounds set forth .in the written objection . I

provided Me .-Knisely>with an example of one or two

or three of these cards,'if you still have a copy

of t.hem .

7 MS . KNISBLYs Right . And we decided

to disagree until ---,until Arch made a

determination, after the deposition, whether they

10 would -- or as the deposition progressed, whether

11 they would require the production of that or not .

12 And4I believe that wae the same with his

13 bibliography .

14 MR . BLANCATO : Correct .

15 MS . :KNISELY : I'm sorry .

16 BY MR .-MAISTROSs

17 4 What else did you not produce to

18 counsel?

19 That's it, as far as I know, sir . I mean, I

20 .didn't give you'copies-,of every issue of Tobacco

21 Science or every=issue of Beitragezur

22

23 T-A'-B-A-K= .S .-F-O,-R-S -C=H-S-U-N- ;G

24

25

(201) 992-4111
Vol . 4, Pg . 600

I don't know about the public library, but

any good science library will have them .

Q . I tried to get in Bowman .aray ; they

wouldn't let .me in . You mean the public library

or Bowman Gray?

know,- ; x .+.ve got

figured you didn't want those . . Books that I refer

10 MR . BLANCATO : For the record, those

11 books are in public domain,

12 THE ;WYTN$SS : Yeah . Oh, yeah .

13 BY MR . MAISTROS s

14 Q . Did_`you have any documents, other than

15 those that were at your home, that related to the

16 work you did while at; Reynolde?

17 A . Would'you say that again, sir . .

18 Q . Other than the documents you had at

19 your home, is there any other location where you

20 had documents related to the work you did at

21

22 A. No . I mean, Reynolds has copies o N


i 0
~
23 everything I ever wrote,' think . r
N
24 Q Between '54 and '87 or '89, did you

25 keep documents on computers?

WAaA' & SPINELLI (201) 992-4111


Vol . 4, g . 601

1 N

2 Q .

3 era? You didn't keep any

or~

5 There waa'computer .otuff at -- computer

6 system at work,,but I didn't --

things on the computer . I`don',t :know where that

stuff is now .

Q . You didn't take any computer discs or

101 keep any computer diece ;after your employment at

11

12

13 Did you "review any of the" documents

14 that you gathered .from your home specifically for

15 preparation of this deposition today?

16

17 Q Did you re other than the

18 Och`ener testimony and Townsand ;testimony, any

19 other testimony?

20 A. No .

21 Q Did`you talk to anyone'that had been


Ln
22 deposed in any of the .' .-- what I'll call "current ~

23 . tobacco litigati, .on, ." to see what was said in their


~
24 depo.sitions? w

25

WAGA & SPINELLI


Vol . 4, Pg . 602

Q Dc you know anyone, other than

yourself, who's been deposed from Reynolds?

. .Murx'ay Senkus, John Reynolds .

know several people that are going to be deposed :

Charles Green, Michael Ogden . I think

6 Dr .'DeBeth .izy has been, but I-- I haven't talked

to him about it .

8 Q. You just-know they were deposed? You

didn't discuss any questions they were asked?

10 No .

11 Q . They didn't tell you what they were

12 asked or how fun it'was or how miserable it was?

13 A. No .

14 Q. How about Dr . Hayes? Do you know

15 Wallace Hayes?

16 haven't`seen Wallace Hayes since

17 1987 .

18 Q Did you .`do any-thing else specif ically

19 in preparation-for your deposition today?

20

21 Q .' Did you meet with any attorneys, other ;


Ln
22 than your personal counsel and Reynolds attorneys? ~
~
m
23 No . ~
~
24 Q . Have you provided any sort of outlines I &

25 or papers to assist your attorneys in this

(201) 992-4111
Vol . 4, Pg . 603

Q Are,`you being paid'in any fashion to

assist Reynolds i this specific litigation?

I'm not being paid for anything to do with

6 this deposition .`'

0 How about in --~are you being paid in

any,fashion for tobacco litigation?

. I have been, in the past, but not for this

10

11

12 any compensation from Reynolds?

13 most of my

14

15 mentioned of specific contracts, which Reynolds

16

17

18

19

20 .

21 specifics that were .previously :,gotten into at the

22 other deposition the~ ;~other day, but I'm just

23 looking'gene'rally for time framea . From '87 or

24 '89 to the present, ;have you, on and off, been a

25 paid consultant to Reynolds?

WAaA & SPINELLI 201) 992-4111


Vol . 4, Pg . 604

1 Twice .

of the incentive'retixement was that -- one of the

5 conditions was that you could`not serve as a

consultant for Rey)iold,s through five"yeare after

.-' after the en'd,of ;your ; employment .

0 Okay . -you-are a

9 Womble'Carlyle,'t .hough? .

10 . Right .

11 And`'d

12- for•any tobacco companies, other than Reynolds?

13

14

15 confuse these two projects . You're .;not suggesting

16 that the only consulting you've done since '89 for

17 Reynolds is on those two projects . .`When .I say

18 °coneulting for Reynol :de," .`I don't care who pays

19 you . If the end benefit is going to be to

20 Reynolds, I just want to know if you're still --

21 I!ve`done things for Womble Carlyle that I

22 presume that t he money comes through Reynolds, to

23 Womble Carlyle, to me . But those were the two

24 specific things where -- in which I had a contract

251 with R .J . Reynolds, which was -- been spelled out

WAGA .& SPINELLI (201) 992-4111


Vol . 4, Pg . 605

1 before .

Q The work that you do for Womble

Carlyle is 100 percent Reynolds?

4 Yes . Yes .

5 And have ; you provided documents to

7 A .

©'

those documents?"

10

11 Q

12 you're going to be an expert or fact witness in

13 the .Arch litigation?

14 was told I would be a fact witness .

15 Have you .been told you're going to be

16 an .expert or fact witness :in any other litigation?

17 understand I'may ..be -- supposed to be an

18 expert witness with Texas .

19 o you know what areas of expertise

20 you're going to .testify .on?

21 A . Tobacco smoke composition and control .

22 0 Would that include the concept of

23 addiction or habituation?

24 We11, I didn't do much anything on those

25 areas, sir .

WAGA & SPINELLI• (201) 992-4111


Vol . 4, Pg . 606
r

0 What's the time period - I'm looking

generally for .inonths, if :you can give me months ;

have you been a

conau.1:tant to ;Womble :Carlyle?

Are we talking about .specifiC ;cases or total?

Q. No .

That would go •back to 1984 .

Okay . So you were a

Wombl,e Carlyle while you were still a full-time

10

11 Yeah . was helping them with'a couple of

12 projects at that time .

13 Were you also paid by Womble Carlyle

14 from 184 to 87 or '89?

15 No . . Up till

16 after ; that .

17 .Q .

18 9 you were still-on .;the payroll at Reynolds --

19

20 Q

21 You were also receiving compensation


cn
22 fro.m .Womble Carlyle?' ~
; 1-4

23 A .` Setween September-the lst, and March the ~ ~


~
~
~
24 1et,, . .,' 89, yes .

25 Could you ;tell` me how much you were

(201) 992-4111
Vol . , Pg . 607

be,ing paid by Womble Carlyle .

2 $12 0 an hour .

Yes .
,$140 an hour .

4 8

10 The ;two incidents that I had two projects

11 through -- with>R .J`. Reynolds R& D .

12 Other than : :those two . is it all

13 Womble Carlyle .or Reynolds?

14 A .

15

16 Arch?

17

18

19
m
20 s Ochsner,still .alive?- ~~
~
%D
21 think so,

22 What prompted .you'to,be at that trial,

in New Orleans?

24 Soon after i came to ReYnolds,> in 1954, I had

25 wri .t'ten a --, a report, which really,wae an update,

WAaA & .SPINELLI


Vol . 4, Pg . 608
I

1 I guess .. I'm'sure you've seen it, a report

written by Dr . Claude E . Teague in February 1953 .

And : -

than mine .'

Because of the ;things that had happened

between February '53_and when I came in June, and

8 work at the-Banting & Best

Department of -Medical-Research, they`asked me to

10 update Claude's'thing -- report .

11 And, 'o

12 there was still the ongoing controversy of, you

13 know, the polycyclic°'hydrocarbong in smoke and so

14 on, in some of the work that had been published .

15 And'then, of course, in'late '53, Dr . Wynder and

16 his ;colleagues published the-`ekin tnouse -- mouse

17 skin painting :study .

18 I updated it .- And somehow or other

19 it got .from the research department into -- it was

20 shown to' .management, including Mr . #ienry H . Ramm,

21 the head lawyer, vice president of legal counsel .

22 And he-asked if I would help do something for the

23 law department and outside counsel, to collect and

24 critique publications dealing with the smoking and

25 health situation .

WAGA'.' . & S P I NE L L I .' (201) 992-4111


Vol . 4, Pg . 609

2 make a- comment here . D

number of years ., a scientific assistant, a

paralegal, assisting :I.,awyers, both in-house and

outeide ; in preparing for and defending

6 litigation .

general-terms the nature of his activities, we

regard all of that as .privileged .and off limits .

10 And ;_other than giving,you a bit of background,

11 should you choose to make any sort of a challenge,

12 we're going to claim .privilege .

13 Rodgman, I would caution you

14 to be very general in your description of your

15 activities . And

16

17 yeare for that?

18 .{ MR . MCD$RMQTT

19

20 number of ;y:ears ."

21 MR . MCDBRMOTT .
Ln
22 approximately, to 1966''or I-A

%4

23 inte'rmittent-dutiee`thereafter . But on a regular

24 basis, for approximately a 12-year period .

251BY MR . MAISTROS :

WAGA & SPINELi,I . (201) 992-4111


Vol . 4, Pg . 610

1 Q . Is .that_'correct,

. Yes .

What :was ;the question about 1960?

5 ;The original question was why you were

in New Orleans in`1960 with Dr . Ochener .

7 Well I had

161,' whenever that tri,al was, I had been

collecting the literature and had hard copies of

161 all the .pertinent pa,pers,-and so on and so forth .

11 And with,the trial in"New Orleans, the lawyer

12 said -- both in-houee`and external said : We want

13 al1 that stuff .in New Orleans . .- You .come with it,

14 and it we need something, you find'it for us .

15 So I was there for that purpose, sort

16 gopher, I guepe, with regard to scientific

17 literature . And course I

18 the courtroom .and watched all the goings-on, and

19

20 I,d d run and get ; a.

21 VIDEOQRAPHER : : M

22

23

24

25

WAaA & SPINELLT_ (201) 992-4111


A . June the 23rd, ;1954 .

2 Q And when did you start providing sort

f legal assistance to :Reynolds?

The end of october 1955 .

5 Who hired ;you? Who ;interviewed you?

Well,,the person I was .;in most contact with

7 was' Dr . Murray Senltus, The interview involved

it-wag a very nice .'interview system : You met

every manager and,-of course, director, . .which was

10 Dr . Kenneth H .°Hoover . And you .met Dr . Colby in

11 the library ; Dr . Markunas, head of analytical

12 chemistry ; Mr . Sprinkle was agricultural research ;

13 and "so on and . eo forth . >

14

15 title at'that point?

16 He was manager . .of'the chemical research

17 division .

18 Q Did 'they, have a health or -- health

19 type~department at 'that point in time?

20

21 Smoking .,and health?

22

23 Are you aware of D

24

(201) 992-4111
Vol . 4, Pg . 612

Yes . Dr . Simmons didn't come till 1965 or

2 I think it was .in there .

3 Q .` And his department was referred to as

what?

5 Smoking ;and health?

I think it ;was called biochemistry and

biological I've f orgotten the exact name of it .

8 0 Okay .

MR . MAISTROS : Let's take a short

10 break while they'exchange the videotape, okay?

11 VIDEOaRAPHER : We're going off the

12 record at 11 :41 :a .m .

13 (Recess taken from 11 :41 a .m . to 11 :47

14 a .m .)

15 VIDEOGRAPHER : This is tape 2 of the

16 videotape deposition of Alan Rodgman, Ph .D . We're

17 going back on the'recor .d at .11 :47 a .m .

18 BY MR . MAISTROS :

19 Q. Doctor, how did you hear about the

20 opening at .Reynolds? :;

21 It was an advertisement in the -- one of the

22 issues -- it's a weekly publication of the

23 American Chemical .Society called Chemical and

24 ,ar}g4ineerinq Newe . And they had an ad in there

25 looki.ng for chemists skilled in isolation work,

(201) 992-4111
Vol . 4, Pg . 613

Q •; Had you

companies?

advertised?

Research chemist .

10 Here . April -t,

©' When you say you met every -- was it

12 manager in the company?

13 . In the research department .

14 Q . Was that all on April the lst or --

15 A . April the lst and 2nd .

16 Q What was the research department in

17 April,of 1990 -- 1954?

18 What do you mean, "What was it"?

19 Q . What did it :consist of?

20 Well, it was .in'a new'building that had been

211 opened in 1953 . believe the whole procedure of


~
22 the-opening was on .national television with John , N
~
~
23 Cameron, Swayze . It had a chemical research m
~
~
24 division under Dr . Se'nkus ; biochemical division N
(J1

251 under M.r . Jerry Snyder ; the analytical research

WAGA" & SPINELLI . (201) 992-4111


Vol . 4, Pg . 614

1 division under Peter Markunas ; the agriculture

.regearch under Dr . Charles Sprinkle ; the flavoring

3 and product department work under Dr . Samuel

Jones ; the .science information division was

managed by Dr . Frank'G .,eColby . I don't know

6 whether`there_was .anybody else I met .

Q. And they did not have a specific

8 division devoted to health at t'hat point in time?

10

11 particular division?

12 Chemical research division .

13

14

15 Oh, three or four months ago, on the phone .

16 a -in New 'York .

17 How was hishealth? : Do you know?

18 s not well . Hi e wife died a .little while

19 well, he wasn't too well anyway, and

20

21 old

22 What 'did you

23 A . Periodically, he'll call and-aak how things

24 are going, and we-chat : We've known each other,

25 as I say, since 1954 .

WAGA &'SPINELLI (201) 992-4111


Vol . 4, Pg . 615
,

you joined?

of ; ;years .

somewhere around there .

Do you know when he left?

was thinking'_-- probably -- someplace

thingg situation-in New York City .

Who was he consulting to? Do you

10 know?

11 guess, the: tobacco industry .

12 Q What did the science information

131 division do in 1954?

14 got - kept tabs of all the

15 publications on to bacco`and smoke and smoke

16 components, and anything to_do with smoking and

17, health and,so on, and .cataioged them and, in many

18 instances, had hard copies .. And of course they

19 subscribed to a great number of journals, and

20 those .were scanned for pertinent articles . And

21 there .was a pub -- not a publication, I guess, an

22 inter - in-house document that signaled to the

23 research employees :,that here's some articles that

24 have just come out,, whether they be biochemistry,


N
J

25 or whatever chemistry, analytical chemistry . And

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 616

that was ci.r"culat,ed, I think, twice a month,

something like that .

And then, of course, periodically they

would take the journals :that came in, you know,

once a month or twice a month, get them bound .

And there they are,` they're all up in the library .

Q . How`many,;people were in the science

information division in ' 54?_'

10 Q . Did that-divieion continue to exist

11

12 It sti11 exists .

13 Q. And what :,would you describe as the

14 overall purpose of that .division?

15 . It's to provide .the -- collect and-provide

16 the staff with information pertinent to the

17 research pro j ectss_' going on .

18 Outside of RJR? Or inside? Or both?

19 Everything : .

20 When you say "provide the staff,"

21 woul they provide research scientiets, such as


~
~
22 yourself, and management, both, or one or the ~
m
23 o the r ? ~
~
I N
~ OD
24 A . Well, I think, .in"the case of management, ~

25 they'd probably provide-summaries or -- more

WAaA & SPINELLI (201) 992-4111


Vol . 4, Pg . 617

1 .general articles rather than ., you know, detailed

analysis . You know, :the -- for example, Reynolds

3 people published articles on the composition of

smoke and .decide the isolation identification of

5 700'compounds, 400,of which`are new and have names

that inost people,cou .l_dn 't even read, let alone

pronounce . Well,,is .management interested in

8 that? So we sent them the abstract and said 700

compounds identified, 450 for the first time, or

10 . whatever number it was,

11 Q . This newsiet,ter or`memo you referred

12 o that went out twice a month, . .was that a -- like

13 an internal newsletter? Did i,t'have a title?

14 Well, it .wae a document that -- probably half

15 an .inch thick, and it would have the't'itle,

16 jouxnal -- couple of .lines .about what .was in thee

17 article . You know, 4eolation of -so-and-so from

18 tobacco, or isolation of so-and-so,from tobacco

19 smoke, or new and analytical procedure for

20 whatever in smoker tobacco, things like that .

21 Q. Would .it -- would it have listings of

22 publications on anything that had to do with

23 bad?

24 I used-to kid D.r .`' Colby about it, because, if

251 it had anything do ;with tobacco, or cigarettes,

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 618

or cigars, or something, it was in there . And I

called him one day and'said : Frank, what are you

doing?

And they :had

5 zealous, they had picked up_ an entry from a

journal~that said,`so=-and-so company - .I forget

was now - has Pur,chased a new ;cigar shaped

for viewing-sports events, and that was

10 aoodyear .?

11

12 Frank,',that's stretching it, cigar-shaped balloon

13

14 4 The articles he would gather and

15 summarize or circulate t o the rest of the staff at'

16 Reynolds, it would be --'<there would be health

17 issues involved, as well?

18 Oh, yeah .

19

20 differentiate,between favorable and,unfavorable

21 articles to tobacco?

22 All you would have .to do, sir',

23 D

24 Q That's what' I'm asking . If the

25 articles is good, bad, or indifferent,

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 619

whatever is there, they're in this publication?

They're in this publication .

So if there was a tobacco-related

articl$ that appeared in any journal between 1954

and .the present ;' there's a 99 to 100 percent

chance it appeared 4n a circular that was

d3stributed to the RJR staff?

8 Yeah, I would say so .

9 When you`eaid management -- I used

10 thatword . I don't -khow what I meant by it . What

11 did .:you mean by it? .-Who's management?

12 A . - Well, I'm talking about people out - - you

13 .know, the business manager, outside the R & D

14 management . Every department has a management

15 I guess, has a management situation .

16 4 Were th,e business managers copied on

17 thie circular that updated the periodicals?

18 No . I , don

19 Colby 'was

20
Ln
21

22 manager, as opposed

23 A . He had, a Ph .D . in :organic chemistry from

24 Univereity in Switzerland .

251 Q . When you were hired in June of --

WAaA :& SPINELLI (201) 992-4111


Vol . 4, Pg . 620

©'

chemical research department, approximately?

A .

5 20 .

7 departments, biochemical? Did it vary or .

Yeah . For example,, the agriculture research

division, I think, ended up with six people . They

10 didn't do any extra agriculture research, but what

11 they did was, . to attend to the funding of

12 agriculture research projects by various -- North

13 Carolina'State University'or University of

14 • Kentucky, or whatever, t .hat,g wae ',being done on

15 tobacco growing and agronomy and all that stuff .

16 And,`they monitored the :progress of the projects

17 that'Reynolds was funding in the agronomy area and

18 .-so on .

19 Now, .th.e staff in the science

20 in'formation were :a-couple of staff people ; but

21 most ., ;o£ the work was done by clerical people . Of

22 course, there .were a lot of typing, and so on and

23 so forth, that was required for keeping track .

24 -those days they had,everything on-cards .

25) Q. Like your index card, index system?

WAGA & 'SPINELLI


Vol . 4, Pg . 621

Q. The five groups you mentioned that

were in existence in '54, would,there,,be one that

would look at .health'issues, even though it wasn't

designated as a, health divisiori or health

department?

Well, as I-- .a~s : .I said, when starting out at

Reynolds, the ;big controversy in terms of the

health issue, if ~you will, was, okay : Were the

10 polycyclice~there? If•._t'hey were, involved in

11 anything, should we know it .? And if they're

12 there, should''we lower them :and get rid of them?

13 o most of that work was done in the

14 chemical division .

15 Q . What,did the', biochemical ` division d

16 that was different than what the chemical research

17

18 . A'lot of their work involved what happened to

19 tobacco I don't know whether you know the

20 procedure of with tobacco, is,`when you buy

211 tobacco at auction,"you'get it so ;many pounds on


! cn
f..
22 pallet . And it's'brought in ~

23 and .then it's stemmed and it's stored for anywhere ~


w
24 between 12 months and 24 months . And as it ages, W

25 cert :ain things happen to it that improve the


Vol . 4, g . 622

flavor of the smoke .

They did,a lot of work -- what was

3 going on : When ;tobacco aged, and did you have to

age it as long as that, and so on . A l,ot of the

work involved the composition of tobacco as it

aged, and the'effect'on the flavor and consumer

7 acceptability_, and how,=it blended in with other

things in the tobacco .

Q That biochemical division, did that

10 etay•in'existence, in one f orm or another, u

11 until you left?

12 Well, in the mid '60s, roughly, it was

13 called

14 Dr .-Aldon Nielson came, it was expanded to

15 include, not oniy biochemistry, but some

16 biological work .

17 Q. Did you ;;ever cross over .from chemical

18 research to one of .these other divisions?

19 Yes', in

20 seventy let'p see .`

21 was promoted to~manager of the analytical

22

23

24

251

WAGA" & SPINELLI'' (201) 992-4111


Vol . 4, Pg . 623

research chemist, or the section head in charge of

the emoke work .

Q . I want to just focus on the period of

time-you were exclusively in the chemistry

5 department, !54 to '75 . When you were hired, were

6 you'tolds We''re,going to have you be w'orking on

7 this project o"r that project'=

or was it

10

11 Nothing specific .

12 4 Chemical research .

13

14 Were they ;aware of your seven-odd

15 yeare working wit h`polycyclic hydrocarbons?

16 it~was .in my resume .

17 Did they tell`you : You're going to

18 have the opportunity t

19 . No .

20

21 when : you started in '54, that had the type of

22 background you had in polycyclic hydrocarbons?

23

24

25I f rame ; you were the most knowledgeable person at

WAaA & SPINELLI (201) 992-4111


Vol . 4, Pg . 62 4

Reynolds in terms of polyoyclic hydrocarbons ?

3 Didthat ever change, during the whol e

period of time you~were at Reynolds ?

I doubt if it did . . Because what eventuall y

happened -- or what happened wasthat, after I

finished,my firs.t project and was'asked what I

8 wanted to work on and saidemoke, over the nex t

few,years_we did ourthing on the polycycli c

10

11 history of what_happened and what we -I guess I

12 shouldn't say "jokingly" defined as "what's th e

13 compound of .the month things ` went fro m

14 polycyclichydrocarbona ., and the next group o f

15 compounds that were considered to be a -- a

16 problem or might be a''problem, were a group o f

17 compounds called aza-arenes . Then it came to a

18 group of,compounda that -- called the phenols, an d

19

20 ciliaetats, and then came the'-nitrosamines, and

2 1 polonium, and so on and so forth . So, by th e

22 early '60s , most of the work on polycyclics wa s

23 finished .

24

25

(201) 992-4111
Vol . , Pg . 625

Can we get

the'record to show

3 MR . LEEs

M Steve Sheller came in, from Arch litigation,

fr-om"Philadelphia .!

0 Did you have' to -gign an employment

8 agreement in .1954 when wyou joined Reynolds?

10 What was .=the'nature of that agreement?

11 It`'s been produced . It -- it was sort of a

12 : standard thing . Primarily, I think, protecting

13' t .he company -- if'•you were to leave and had been

14 involved in certain ._manufacturing functions, that

15 you°weren't to tell .anybody about it till so many

16 I've forgotten

17j

18 it like a .Confidentiality

19 agreement,

20 .Yeah . But it :-- it was, primarily, I guess

21 for proprietary things to do with`manufacturing,

22 more than anything . I`don't think it ever

23 m6ntioned research and,development in it . But

24 it's been so long ago since I read it .

25 ' You never, then, had to execute any

WAGA & SPINELL`l . (201) 992-4111


Vol . 4, Pg . 626

confidenti.ality.agreement :with respect to

was thinking :I-signed a document sometime

' . .80s

about the Premier--cigarette . Which I wasn't

involved with,that•much anyway .

Q . Whatever you knew, you weren't allowed


,
to disclose without getting somebody's permission

first?

10 Thatl s

11 Whether-i't's Exxori°or Pittsburgh

12 St6el or whoever .

13 Did you'ever actually sign a contract

14 for a specific length or- term of employment

15 Reynolds?

16 No .

17 Q . And the consulting -- two consulting

18 jobe-.you mentioned sPecifically for Reynolds were

19 not written documents?

201 Yeah, they were written -- they're written

21 contracts . They've already been provided .

22 MR .=MAISTROS : Have those been

23 provided?

24 THE WITNESS : Someplace

25 MR . MCDERMOTT : They were'produced in

(201) 992-4111
Vol . 4, Pg . 627

1 the`- :last deposition .

2 BY MR . .MAISTROS

Q• Were the agreements_with Womble

Carlyle produced?- Are .there written agreements

with Womble Oarlyle? .~,

we :didn't have them anymore . When .they ran out,

; .they,never renewed them and neither did I .

Q . Do you have some sort of letter

10 agreement, just confirming what your hourly rate

11 is 'or

12 No . Well --` yea

13 the f irst ' ;coupl,e,-oi' years . You' know, I do

14

15a

16

17 ;_anything .

18 Q. . From 154 '' to '75

19 w Orleans case in the '60s tli$t you assisted on .

20 How many such cases -did you assist on when you

21 were' .in the chemistry department in that 21-year

22 period?

23 There was one in-New Orleans - - one in


I 0.

24 New Orleans, which .I, was there several times . w

25 There was 'one in St . Louis . I don't even remember

(201) 992-4111
Vol . 4, Pg . 628

1 who .t:hat wae,, 'Then I was asked to provide some

2 information on occasion with -- was it Green case,

which wasn' t"agains't • Reynolds, and a Pritchard

case against somebody else . It wasn't Reynolds .

And that, as far ae '1 . :know, was it .

have no I

.,g . A tobacco manufacturer?

Oh, yeah . It was I don' t-`know whether it

3. 0 waa''American or . :who` it waa .

11 W ho :asked you to assist American in

12 that case?

13 Reynolda' lawyers . They wanted a summary of

14 something or other ; I've even forgotten_ what it

15 was .

16 Q . Did you attend any portion of the

17 trial?

18

19

20

2i

22 Did you

23

25 No : Provided the stuff to_Reynolde' lawyers,

WA,GA :& SPINELLI ,


Vol . 4, Pg . 629

and then I guesg it wen:t on its way .

n the .Pritchard case, you weren't

helping Reynolds? What company were you helping?

I've forgotten . .

Another

were'.1ike the Lartigue .-caae, which was the case in

8 New Orleane .

9 a . I

10 Lartigue, L-~A-12-T-I-G-U .-E, That was the case

11 in .:New -0rleans :

12 Q . How .' .were they similar?


.
~
13 -They're :all smoking and lung cancer cases,

14 bel,ieve .

15

16 asking you .to assist=other tobacco manufacturers

17 in their lung cancer'litigat'ion?

18 A . '-No, not really . I guess z,figured they


,
19 wanted this information . I think it was pretty

20 well to do with'smoke composition and so on . I

21 had published a lot,on smoke . .

22 Did you assist in the defense of any

23 other cases'fox any other tobacco manufacturers?

24

25 Do you know whether you received any

WAGA & SP.INELLI


Vol . 4, Pg . 630

,extra :income for assisting those other tobacco

Just my rbgu ;lar .pay ;f rom' Reynolde .

Q . Where was' the Pritchard case? Is that

Louis?

No . St . Louis was against Reynolds . I don' t

know-what it --'the name "Lowell" rings -- comes

o mind, but I'm not sure about the name of

the

10 4
11

12 . They were in the '60s, early '60s, I think .

13 : MR . MAISTROS : What do you gentlemen

14 want to do about lunch?

15 THE WITNESS : It's a good time to

16 quit•

17 MR . MCDERMOTT : I guesa .the witness

18 Why don't we accommodate

19 him . .

20 MR : MAISTROS : It.' .s his party .

21 VIDEOORAPH$.R : We're going off the

22 re off the record .

23 .

24 .m , . to . 1 :26 : p .m . )

25 VID'SOGRAPHER :' We' re going back on the

WAa,A & SPINELLI (201) 992-4111


r

record .at 1 :26 p .

Q Dr . Rodgman, what was the first

project you worked .on at Reynolds?

5 The first project I worked on was the

synthesis of a series of compounds that might have

7 potential use .as flavorants,. These were a series

of'phenols . And what they were .looking for was

10 And -went about synthesizing, I don't

11 know, maybe 20,- .-22•of them . However, I knew, from

12 my previous work at .the literature surveying at

13 the .Banting, that some"phenols, at high

14 temperature, convert`to quinones, another class of

15 compounds . And the Japanese had done some work on

16 quinones, mouse painting experiments and so on,

17 ~and found them to be tumorigenic .

18 So-putting that together with a new

19 article : that came out while 'I wae inthe midst of

20 this, that a'man called Boutwell and his

21 colleagues,, ``thatls B~ .-0-U-T-W-E-L-'L,-reported that


Ln
~
22 some phenols were classified as`promoters because ~
~
m
23 they . enhance the activity of polycyclic ~~
~
w
24 hydrocarbons that show ' some tumorigenicity .

25
Vol . 4, Pg . 632
f

said ; Hey, you know ;` I,'ve nearly finished these

the grumbling~about polycyclics . Do you want to

put something that might .contribute quinones to

the "'smoke and have'another problem?

And the.y, ilooked at what I had there

They never used the

8 23 .or 22 compounda I,synthesized .,

Q. How long did that proj ect last?

10, A . About four months ., from June till November,

something like that ..;

12 Q.
13 being tumorigenic promoters, are there different

14 kinds of phenols?

15 V3.tamin E °

16 one of the great anti-carcinogens known .

17 . Everybody's t'aking .it nowadays, aren't they, to

18 divert cancer :=

19 Q . Vitamin E?'

20 MR . SHELLER : I knew it .

21 THE WITNESS3

22 are phenols that are -- that are in all our food ~


a
~
23 stuffs .- Cloves and cinnamon are loaded with m

24 various phen,ols .

25 BY MR . MAISTROSi

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 633

1 Q . Was there-a lot of literature, a

2 minimal literature?' . Describe the course or the

amount of literature there- ;was on phenols in '54 .

No, it ~- the literature on phenols escalated

when they couldn't expl .a.in~the mouse-contained

data', the number of tumors they were getting with

polycyclic hydrocarbons, either benzpyrene itself

or the'total polycyclic hydrocarbon fraction of

cigarette smoke ;-thie was Dr .- .Wynder, Hoffmann .

10 Dr . ."Wright, .who was`actually my major professor at

11 the :'University of Tdronto'did the chemistry for

12 Dr . Wynder for four or five years, until

13 Dr . Hoffmann came on the scene .

14 They --'when they couldn't explain the

15 pol'ycyclic hydrocarbon results, they said :

16 There's not enough there ; that only accounts for

17 two, three percent . Said : Oh, we've got

18 promoters .

19 they lit on'the phenols, because of

20 this article by Boutwell . And then from about

21 1960, perhaps, to .1962/'b3, everything was phenol

22 promotion, plus polycyclic hydrocarbons . Except ~

23 there was only one problem with it . That Wynder ~


~
~
24 himself and Hoffmann ehowed, .what we had already I&
; L

251 shown : That, if you take the phenol-out of smoke,

WAGA ..& SPINELLI`


Vol . 4, Pg . 634
I

1 it°doesn't affect-the biological activity of the

smoke . So how can°you have a promoter that

doesn't promote? E

dropped after that .

Q .: Forever?

No, it's still around . But -- you know,

there are people who°never drop anything .

8 Q
It .was then . It i

101 man :'called,Aivin Kosak published an article

11 describing all the components in cigarette smoke

12 that ;had been,reported in ,the literaturee

13 throughout the world . There are about 90 ; of

14 which about .30 were<wrong,`by :the way . And phenol

15

16 it's been known for a long time . I

17 think it was identified in smoke someplace in

18 probably the 1930

19 Q . Have phe,nols been blamed as anything

20 else other than•a promo"ter?

21 We11, yeah, I guess some -- there has been Ln


H

22 gome work done`that phenol some-of the low


m
23 molecular weight .phenols are cocarcinogens, rather,,,

24 than promoters .

25 Do you know if Reynolds has done any

(201) 992-4111
Vol . 4, Pg . 635

such work?

A. On the biological work?

5 Q
or verify or dispute whether`phenols were

promoters?` :

0 , we'didn't do any work . We did do work on

the fact that they were present ; we determined

10 their levels,'which agreed :with some of the work

11 in the .litexatur$ . And we also demonstrated that

12 the filter tip that we-used, which has a substance

13 called a plaeticizer!1n .it, took out about

141 85 percent of the phenols from the smoke . That

15' was'subsequently confirmed by four or five groups,

16 both `pro- and -anti-tobacco`.

17 Q Has°'there been any more recent or

18 modern .work relate.d'to .phenols and their potential

19 as,'promoters? . .

20 No . Once the -

21 Hoffmann ;showedathat if you took out the phenol

22` from smoke that°it didn't change the biological J ~


m
2 .3 ;activity of the smoke . I'd say : Hey, you had a
~

24 promoter that-wasn't promoting . And they sort o J

25

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 636

1 Now, at one time they considered

2 phenol as an indicator of that class of compounds

and :its .promoting effect, but they subsequently

dropped that argument .when it was proven to be

wro~'lg .

Q . What's an'indicator?

7 Yeah . It'was like a,marker, that phenol

itself gave a clue tp the series,of-low molecular

9 weight phenola, which .usual].y,is considered about

10 five or six or eight--compounds~that are present .

11 The same thing it .eai,d about benzpyrene : It's an

12 indicator'of tumorigenic -pol .ycyclic hydrocarbons,

13 b t~Wynder and Hoffmann_'s own data show that's the

14 wrong,conceptg

it,your opinion ; as you sit here


W 5
7 7

16 today, that phenols then play no role in the

17 biological activity that is caused by cigarette

18 smoke?

19

20 been' ; done in animals, there has been some work

21 that ahows it' :doe's promote, there's some work that


Ln
22 shows .it doesn't promote, there's some work that ~
m
23 shows it's a cocarc .inogen, and some that shows it,,,
- ~
24 ien't-a c?ocarcinogen : And all that work has beea OD

25

WAGA & SPINELLT (201) 992-4111


g 637

1 Well, isn't,it true that most of the

work related to cancer,research has been done in

re3ied upon animal studies to make, certain

conclusions with respect to compounds involved in

smoke?

9 A. Yes . ; And of course,,one of the things is

10 about that is ;that you may, as I do, disagree with

11 trying to extrapolate from a mouse skin painting

12 experiment to inhaling smoke as an aerosol . One,

13 you've got a eolution of a thick gummy substance,

14 the`other is an aerosol .- `You can't extrapolate

15 That has been .a',,-- a no-no since 1941 .

16 4 How'did you know that -- that phenols

17 were potentially`,promoters?

18 A . This man Boutwell had this article .in the -

19 Q And` `what method did he use to

20 determine they were po"ntial promoters?

21
Ln
N
22 with a level'of polycyclice that normally wouldn't

23 give a very .`high percent tumor bearing animals .

24 And if he painted t .hem .at the same time -- or

25 . . sequentially with solution of phenol, following

(201) 992-4111
Vol . , Pg . 638

the :poiycyclic painting, then the polycyclic

seemed to behave like there was a lot more of it

3 there, or it_promoted the effect .

4 Well,'if -- and I :think your testimony

or Reynolds did not do any

6 testing on ita'own of the phenols, correct?

,Right .

Q . And if you were just reviewing

, test

10 ,painting of mice, why wouldn't you tell Reynolds

11 not=to be concerned about it, because you can't

12 extrapolate`thoee results to the human experience?

13 Well, I think,`if .you read some of the things

14 wrote, that's what-I'implied in a lot of it .

15 But, then again, I also pushed, as you probablyy

16 are-aware, that I thought we should be doing some

17 biological work ourselves, because some of it was

18 actually very poorly done .

19 Wee had developed or, ;:if you wil.l,

20 acquired, a fairly good reputation`from our work

21 in chemistry of smoke ;and tobacco -- smoke


Ln
H
~
22 analysis/tobacco analyeis, and I felt-we could do ~
m

23 1 t he same thing in the biological area .

24 Q .Why ;was the why were the test

251 results, in and of themselves, the test results

WAC3A & SPINELLI (201) 992-4111


Vol . 4, Pg . 639

1 'arising from :the'moude akin painting of the

phenols,'enough : :to-Convince you to advise Reynolds

rrot, to exp3 .ore using phenols as flavorants?

,_ Well, here again,

things that happened :in-'54, or '52, '53, '54,

'56. . Benzpyr,ene,` :for example, got to be a term

that was altnost, ;ae aCary to people as the word

cancer . And I felt : Wel1, gee, we got enough

9 problem .with thia,term .' Let's not start

10 introducing something that could go to a quinone

11 and-have another problem that would be our doing .

12 as I eay, .I was frankly surprised,

13 wher;i here' s a man'that' ;s been there three or four

14 months, walks into .research management and says :

15 Hey, . .here's some,_articles ; .I don't think we should

16 use 'these . ''And they say :

17 won't use them .

18 Q. Who did :you specifically talk to?

19 Dr . Senkus'and Mr . Hoover, my manager and the

20

21 0 Was your, -- was your opinion that

22 those shouldn't`be explored based upon your

23 your scientific belief that there were

24 health risks related to those compounds, or was it

25 . based upon your belief :that it wasn't worth

(201) 992-4111
Vol . 4, Pg . 640

1 getting into because the public thought there were

2 health risks related'to .itd

3 Well, I thought why stir up another mess that

we were -- like the-one,we're already into with

-the'polycyclics :

mean, I ;was convinced the

had discovered benzpyrene and saya there isn't

a'problem . The American

10 Association for Canoer_Research said the same

11

12 When?

13 t i '84 . I've

14

15 What 'did 'they say?

16 That there'a no compound`in cigarette smoke

17 that :can be attributed_as a cause of cancer . .

18 Something in those words . J . W . Cook said the

19 same` thing, Do11- .and Hill and' -- Doll and Peto

20 said the same thing . Doll is the guru of

21 statistical standings :`
Ln
22 And ; as
. ..
I. say, Wynder and Hoffmann, '~
. . . ~. .. ~ ~ - . ~ . '~. F..

23 and Fred Bock, and Benjamin Van- .Duuren pr o ba bl y ~~


; ,r,
[ IN
Ln
24 have said that 30 times in thee last 30 years . N

25 You're`saying that'they :said that


Vol . 4, Pg . 641

there cannot be a compound that is the cause of

cancer?

3 A . What they say is you cannot explain the

animal experiments on .skin painting with the

5 .composition of smoke as dictated by polycyclic

hydrocarbons or benzo[alpyrene .

Q That group,was not'suggesting, were

they, and they did_not suggest,'that there was not

a'statisticalj.link .be;tween smoking and certain

10 forms of cancer?

11 Oh, no . Nc

12 Q . You agree that--there was definitely,

13 even by '56, a statistical link between smoking

14 and cancer?

15 A . A statistical association .

16 Q Isn't it-,more fair to say that what

17, that'group was, .e'aying was that"th.ere was no

18 specific compound that could be identified as the

19 specific cause of,the cancer?

20 guess you might_,say that,

21 after this four-month period

22 where you were working on phenols as a flavorant,

23

24 it surprised me .

25 was told to'drop the phenol

(201) 992-4111
Vol . 4, Pg . 642

pxoject, that they said : What do you want to

work on?' And I said, well -- you know, I think

it's in something I wrQte someplace : I said :

What .we're selling is smoke . I would like to do

5 work ; on amoke_ composition .

,And because so little was known, as

I told you,'about the :article by Alvin Kosak and

8 the 90-something compounds .

So I set upFa whole . system of

10 examining smoke ;' the'smoking machine was patterned

11 after :that of :Dr . Wynder's And we set out t

12 look at tobacco .smoke,And between examining the

13 composition of tobacco .~'s°moke and finding ways to

14 modify it, it t-ook 'the'next ten years .

15 Q What was your beginning goal in

16 '-looking at smoke composition?

17 Well, I've already told you that I had worked

18 out a-p ;rocedure for ;,isolating and identifying

19 polycyclic aromatic hydrocarbons from my work at

20 the' `Banting- and Best : And I was so f irmly

21 convinced that all this controversy was a bunch

22 nonsense, that the first thing I did was go after

23 the polycyclic hydrocarbons --

24 Q Were-you --

25 -- and settle the issue once and for all, in

(201) 992-4111
Vol . 4, Pg . 643

my mind, that,they"were there in very low levels .

2 We actually`isolated the benzopyrene in

crystalline form . : First time that had"ever been

done .

Q . You were convinced that the

controversy ;was nonsense . Was that before or

after you began-at Reynolds?

Well, I really had nothing to do with medical

emok~e until I-got to Reynolds . And, as I say,

10 when I started reada .ng -a little more about it and

11 suddenly realized some people were saying no, they

12 can't there and, yes ;'they can be there . And I

13 thought, the background of everything that had


..
14 been done since the mid '30s, there was no way

15 they could not be'there .

16 Q . I'm talking specifically about the

17 polycyclic

18 }That's what I'm talking about .

19 0 Carbo -- polycyclic hydrocarbons . Did

20 you, before you began at Reynolds, ever express in

21 writing that you-believed that t he polycyclic

22 carbohydron hydrocarbon controversy was

23 nonsense?

24 A. Ln

251 MR . SLANCATO ; I'm going to object to

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 644

the form .

2 BY MR . MAISTROS :

3 Q . Did you ever express, before you began

at Reynolds, orally that you believed that the

polycyclic hydrocarbon .controversy was nonsense?

Well, in my-work at the Banting, as I said, I

did :a lot of work in polycyclic hydrocarbons, and

would have "occasiori :, .to talk with my boss there,

9 Dr . .Franks . And of'° .course he was very

1, 0 knowledgeable in''polycyclics . And there were

11 papers that were~appearing,in some of the chemical


.,
12 j ournale and talkxng _about the presence of

13 polycyclics in their .;,'-- in cigarette smoke . And

14 then,there were papere .saying, well', they couldn't

15 fa.nd it .

16 And in our•

17 We11, the curves tha't'these people have, spectral

18 curves, .really don't tell you that they claim to

19 be polycyclics, really don't show that it is, they

20 were so poor, and this was Dr .'Fieser's criticism

21 in 1957 . And between us, I said : Hell -- pardon

22 my language . Heck, there's no way they can't be

23 there, from all we knew about how-they were formed

24 0c)

25 0

(201) 992-4111
Vol . 4, Pg . 645

.controversy was . Was the controversy --

2 The controversy was whether they were there

6 controversy as to whether

or not they were tumor-promoting or tumorigenic?

Well, if there was a controversy about

9 whether they were there or not there, you have to

10 prove that-they were there,to find out which ones

11 were there before you'could say : Well, if you had

12 a dozen polycyclics, which ones had ever been

13 tested?

14 Q . So your -- when you say this ten-year

15 project, you -- at the end of this ten years, were

16 you'convinced one way or-the other as to the,

17 quote, controversy, unquote?

18 A. was convinced that there was no

19 controversy in 1956 .when we isolated them .

20 Q . So the controversy you're referring to

21 that was resolved in your own mind -- or resolved

22 earlier but confirmed ten years later, was that cn

M
23 they are there? m
~
24 I knew that in '56 . . 1 said -- I think you're ~
cn
-1

251 misinterpreting my talking about --

WAGA & SPINELLI . (201) 992-4111


Vol . 4, Pg . 646

1 I think I-did .

2 A. about the ten-year period . What we did,

once we :were there, we .did a great deal of work on

4 how .could we diminish'them . And as -- one of the

things"that a lot of people were doing in labs all

over the place, was trying,to reduce polycyclics

7 specifically . And -l'_m sure we 'll get into the

fact that, when you .zry,that'with any class of

compounds in cigarett .e'smtike, you'run into a

10 problem .

11 4 Why were you trying to reduce them?

12 Well, here again, you had everybody saying

13 these things about polycyclics and they were

14 tumorigenic to mouse skin or on subcutaneous

15 injection, and the best way to shut up the people

16 complaining was to say, okay, let's get them out

17 of there or diminish them . They're not flavorful,

18 or at least most of them aren't . . Some of the

19 lower molecular rate :polycyclics are flavorful .

20 One of'~`them used to be ;ueed in mothballs :


,

21 Naphthalene .
,
22 Q . Was your'research to reduce the

23 polycyclic hydrocarbons related to your personal

24 Oesire•to make cigarettes-safer or to reduce the

25 controversy around polycyclic hydrocarbons?


Vol . 4, Pg . 647

A . Probably part .;and parcel of both . When we

2 started the first,study on ways to reduce

polycyclic .hydrocarbons, we -- the polycyclic

hydrocarbons have to come from something in the

5 tobacco . Now, tkiere .had been a big controversy

whether they got there by"atmospheric pollution,

'by stuff settling on .the leaves in the fields

the big contr:oversy, well, all the

polycycl .ice came'from the cigarette paper and this

10 type of thing . 'But those

11 another group that thought,the :polycyclics came

12 rettee with a match, the burning

13 of 'tY}e wood "in '`the mat-ch, or the hexane in the

14 .cigarette`ligh"ter .

15 Well, ` it
16 well, it come from something in the tobacco . And

17 i't was determined there were things in tobacco

18 that-'would give more polycyclics than cigarette

19 paper and so on . So,`if we got rid of those, the

20 polycyclic levels'wou1d go down . And the way we

21 did that was .toI extract what is called precursors .

22 Well, unbeknownst to us, for some


J
23 . time, Dr . Wynder was'working on the same project .im

24 And ' the way I found out that waa,because, as I

25 said, my major professor did all the chemistry

NELLI
Vol . 4, Pg . 648

with Dr . -- for Dr . Wynder, until he got

2 Dr . Hoffmann . And .I .found out that they're

working on extraction the same as we .are .

And in ..1960

Dr . Wynder, at a meeting in Atlantic City, said :

6 We'+ve given up on extraction ; it's economically

7 and :practically unfeasible .

8 Well, we had given -- we gave it up

too, for the :same -- for part of the same reason .

10 But- .the second part of the reason was that, when

11 you take out the precursors, you end up raising

12 .the :level of the non-soluble parts of tobacco,

13 like cellulose"and lignin ; they get to be a larger

14 percentage of the filler .- And one of the main

15 source of phenols Is`lignin, which is non-soluble

16 in'the`solvents that we .used . So did you want to

17 lower polycyclics and raise the .-phenols when there

18 was still a13l thie chatter abo'ut,phenols being a

19 problem?

20 The .other

21 soluble in t he solvents used for the extraction .

22 And, as we suepected, if 'you' left the nitrates

23 there, their`ratio in the residue -- : extracted

24 residue would increase, so you'd effectively

25 increase the nitrosamines in smoke . So do you

(201) 992-4111
Vol . 4, Pg . 649
r

want to lower one thing and raise two?

So we said, "To heck with it," and

3 went on to something .else .

4 Q . At what point in time in your ten

years of your research`did you say'"to heck with

it," or was that after ten .years?

No . We did that about 1960, somewhere around

there . We looked, at .extraction for about three

years, and was actually so serious about it, we

10 had A major engineering company design a plant to

it, when we thought it was a good way to go .

12 But when we figured out that there were more -- it

13 would raise more problems than .it would solve, we

14 ended that .

15 Was there any -- you referred to a

16 ten-year period and`I just want to be clear in my

17 mind . What were you talking about,' .that ten-year

18 period?

19 Well, the ten=year period was from '54 to

20 '64', early '65, somewhere in there . . We were under

21 Hoover was the director

22 of D ,Senkus was a manager and then he u,


N
~
23 was`aseistant director of, research . And we did a ~..~
m

24 lot~ of t-hings on_smoke-composition, polycyclics,

251 , phenols, ciliastate, nitrosamines, and we looked

WAGA & SPINELLI . (201) 992-4111


Vol . 4, Pg . 650

at,'different ways to ;-- ;we concentrated, mostly,

on`the polycyclic business . And everything we

3 came,up with,~where we tried to look at --

reduce things specifically, selectively, in other

5 words, only the polycyclics, only the phenols, we

ran ;into a trouble that we'-- if you lower one

thing, you were raising something else .

SO we went•to a philosophy : If you're

going-to make a safer cigarette, less hazardous

10 cigarette, lower everything as near, :in proportion

11 as you can . And the""work on, if you will, the

12 less hazardous cigarettes, everybody was looking

13 at it . And the interesting thing -- it may not be

14 interesting to you . But in 1960 D . Wynder came

I 15 out with an article and said the --`at this point

16 in time, the four cigarette design technologies

17 significant in making a less haza,rdous cigarette

18 are°the blend, the-'filter tip, paper porosity, and

19 reconstituted tobacco sheet .

20 Now, . if you look historically at those

21 four, the first blended cigarette, called the


1i
22 "American blend, was introduced in 1913 by R .J .
m
23 Reynolds Tobacco Company . And, subsequently,

24 after 1957/58,' it .was shown that a blended

251 cigarette was less -- smoke was less tumorigenic

WAGA & SPINELLI ` (201) 992-4111


Vol . 4, Pg . 651

1 to mouse skin, its .benzpyrene content was less,

2 its phenols were less, .so on and so forth . The

-second, on filtration --

4 Q . Less carcinogenic than what?

A . . Pardon?

R Did you say .less carcinogenic?

7 Less :tumorigenic to mouee skin .

The second one, filtration, the first

success .really .succes.sful cigarette acceptable

10 o the consumer was the Wineton, 1953, introduced

11 by`R . . .J . Reynolds Tobacco Company . There had been

12 filter .cigarettes,, but'they were 1-ess than one

13 percent of the market .

14 When the'Winston came out, the filter

15 tip cigarette took off like a skyrocket .

16 Well, the-other thing that the Winston

17 cigarette had, and wnich was also'incorporated

18 into t he other Reynolds brands, was reconstituted

19 tobacco sheet . Reconstituted tobacco :,sheet had

20 been used as a wrapper for cigars . But no

21 successful one .'had e,ver_been made that was

22 t for
r
23 did'it . Dr . Samuel Jones invented it .

24 The third ' one was paper porosity, that

25 you lowered the tar'and nicotine and everything

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 652

1 else by having paper that let the air flow through

it fast .

So .the ;first four things that were

ever introduced, that Wynder and Hoffmann said

5 were signif .icant, all came out of R .J . Reynolds

6 Tobacco Company .

7 Q . Of those four items -

8 A. And they were a1l copied by everybody else,

within three years of~their introduction .

10 Q . Those four items that you mentioned,

11 were they originally"developed as health ideas?

12 they weren't . But, you know, it is, if

13 you will, serendipity, good fortune, that they all

14 worked out to be that way .

15 Q, Have,you seen any documents in your

16 employment or consulting relationship with RJR

]. 7 that would . ;suggest that- any of those four things

18 e,-further developed as a potential -- let me

19 start over .

20 The .'

21 you said`they did not start out with the

22 concept that 'they would be health-related benefits

23 to 'smoking?

24 Well, obv .iously the blend one in 1913

25

(201) 992-4111
Vol . 4, Pg . 653

Q . . Did you ever see any,documents at RJR,

during your employment or during your consulting

period, that'suggested that there wouid be health

benefits to theae :four._items that ..should be

exptored?
y. ;
A ." `"Not "that- I .recall . It may have been

;merit'ioned, after•~the`-whole concept of -- when

Dr . Wynder .talked :about'lowering the tar he did

soaie''work in 1957, and at the same time he did the

10 benzpyrene work . And his conclusions were : If --

it tar is the problem in smokers, then lowering

12 the tar by 40_percent would almost do away with

13 any respiratory tra'ct,problems . And that was in

14 hist testimony before the Blatnik Committee in

15 1957 .

16 there was a"look .at, you know,

17 if you increase the reconstituted

18 tob.acco sheet, that would lower the tar, which was

19 in agreement with what -- at least -- not i

20 agreement with, but complied with the things that

21 Dr ., Wynder was sayin.g .


~
22 Do you )Criow of any promotional ~
~
Im
23 campaigns that touted-either'blendg,~filter ti Pf

24 paper porosity, reconstituted tobacco°with

25 providing health benefits?

(201) 992-4111
Vol . 4, g . 654

No . As

anything . The fact that well, let's look at

reconstituted-tobacco .

4 . Now, ;ahat wae .introduce by 1953 . By

1958, everybody ;in the industry had copied, not

6 our .specific reconstituted tobacco sheet, but one

7 similar to it, that they either designed

themselves or`had,p.omebody`deeign for them, like

the"American Machine and Foundry .• Well, if you

10 look .at the curve of ;tar versus sales-weighted

11 average tar, it becomes obvious that that tar is

12 dropping, dropping, dropping ; and it's still

13 dropping : So, you know, if what Wynder says is

14 right, then we've done something in accord with

15 his wishes .

16 Q . Can you tell me any specific research


. , ,
17 that you were assigned to in that ten-year period

18 that the goal was to~-.develop a'safer cigarette?

19 1962, one`of the people that worked for

20 me,' 'Dr . Fredricks:on, wrote a memo about tobacco

21 and how to, perhaps, generate a less hazardous Ln


~
~
22 cigarette . And his philosophy or proposal was : m

23 Put less tobacco in the cigarette . m


rn
24 And how do you do that .when you've go,

25 a certain dimension, you've got a thing that's

('201) 992-4111
Vol . 4, Pg . 655

1 about the size of a pencil and it's so long, that

-you don't want toy drastically change the shape of

the,cigarette, but,how do you put less tobacco,

and'that .taking into account the filter? And he

said: Well,'make the tobacco lighter, y

expanding it .

And in his memorandum he points out

that, not only would .this generate considerable

9 revenue, but it would also lower the tar and

10 whatever`elae you were interested in and want

11 lowered, that were -- that 'people were possibly

12 saying that was responsible for this or that .

13 And he worked on it, got the patents

14 on it . We put it in ;the cigarettes, we licensed

15 it, everybody else copied ; those that weren't

16 licensing developed one'of their own . And that's

17 one of the eight_significant technologies listed

18 by the Surgeon General as contributing to a safer

19 cigarette . That, came out of R .J . Reynolds,

20 because we had the first' patents on it .

21 Q . And it's considered safer because each

22 cigarette has less tobacco in it?

23 No . Because ,the smoke has -- the smoke

24 generated by the cigarette ; according to the -

25 you've got to go back, I think, sir, to who

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 65 6

defined the safer cigarette . And it was a

cigarette -- the cigarette with expanded tobacc o

in it,fitted the definition of those who define d

safer cigarette . . Tar was less tumorigenic to

5 mouse skin ; tar was lowered . And the ratio of

certain ingredients to tar per milligram of tar

werelowered, and that included benzopyrene and

8 phenol and whatever else you wanted .

9 nd, as I. .eay, all you got to do i s

10 look at the Surgeon :4eneral's report for 1979 ,

11 1981, and thereit gives you a list of eigh t

12 technologies, seven of which came out o f

13

14 Which isthe only one that didn't ?

15 not the first who incorporate d

16 ventilated filter tips into a cigarette ; I thin k

17 American Tobacco Company was . But we utilized i t

18

19

20 tip, paper`porosity, reconstituted tobacco . Wha t

21 .are the other four ?

22 in ;sequence ,

2 3

24 phenols, which, by the way, also take out volatil e

251 nitroeamines : The othex was paper additive, th e

WAC3A & SPINELLI (201) 992-4111


Vol . 4, Pg . 657

1 seventh was .expanded .tobacco, and the last one

introduced was venti,lated filter tipe .

Q . Is it your suggestion that RJR did

research and used these areas to develop a safer

cigarette?

A .- Well, we -- we fitted it into the same type

of_program, if you-will~` that the National --

National Cancer'Inst,itute called .their less

hazardous --'~its lees .~hazardous cigarette program .

10 Q . Did'RJR act,ually ._have a less hazardous

11 cigarette program?

12 Well, we incorporated all these things -- I

13 mean, there was :a great deal of research that went

14 into expanded tobacco, for example . We did the

15 chemistry of the smoke, very detailed chemistry .

16 We,.did the biology~ "of -the smoke on skin painting

17 study . Our .results on the biology -- biology of

18 the smoke -- ;bioa`ssay of the . smoke were checked

19 and confirmed in the NCI study . They,were also

20 checked and,confirmed in Germany by a man called

21 Dontenville . And if you look at the definition

22 that` came out in the`late '50s of what a safer


F"
m
23

24

25 Q

(201) 992-4111
Vol . 4, Pg . 658

cigarette"?

A . I don't have . a definition, sir .

Q . Do you believe there is a safer

cigarette?

. We .used the definition that Dr . Wynder and

Hoffmann and Bock came-- :up with in,the '60s

early ',60s, late 50s .

Q . I'm talking about you, individually .

Do-you be3 .iede there"is a safer cigarette?

10 well, - as I say, I'm not too sure

11 cigarettes are that ;unsafe . But

12 Q. Okay .~ guess that's a good starting

13 point . Do you believe cigarettes are unsafe?

14 , Cigarettes are .unsafe? No, I don't believe

15 ciga'rettes' are unsafe .

16 Q . : Do you believe that there are no

17 health risks related,to,smoking?

18 A. . Well, there is t .he association between

19 smoking and :certain diseases .

20 Q. Do you .believe that's a valid

21 association?

22 MR . BLANCATO : . Object to the form .

23 THE WITNESS : I'm not that much of

24 expert, sir, on statistics . But the -- I'm

251 aseuming that the - - most of the incidences, the

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 659

methodology and :so .on, .,would indicate an

association .

BY MR . MAISTROSt

4 Q The association you're referring to is

5 just a statistical one?


6 On the samples that were done, yes .

And the fact that you-recognize

8 there's a statistical association between smoking

and certain diseases does not convince you in

10 any way that cigarettes are unsafe or smoking is

11 unsafe?

12 I'm not sure . I won't -- I will not equate

13 association with cause and effect, if that's what

14 you're looking for .

15 Q . You don't think there's enough

16 biological, chemical, analytical research out

17 there to establish a link between smoking and

18 certain forms of cancer?

19 . Well, you talk about biology . According to

20 the what you should look for in bioassays ia .

21 Can : you induce thee aame kind of tumor by the same

22 route that you get in humans? And you can't do

23 that with inhalation of cigarette smoke . Yet you

24 can`do the .same thing_with the exposed mice, for

25 example, by inhalation to .the same level of diesel

(201) 992-4111
Vol . 4, Pg . 660

exhaust fumes, at the same level as you do with

cigarette smoke, and you will get squamous cell

carcinoma in the mice that you don't .get with

4 cigarette smoke .

Q When you were in Canada for those

6 seven years, you did :mice and rat and some chicken

7 studies?

8 A . Well, as I

Q You were involved in them?

10 A . I was involved with them at -- I did the

11 chemistry of'the things they wanted to use in the

12 animal work .

13 Q If during the course of those studies,

14 you were, I asoume,youu were doing those for some

15 purpose . In other words, if you saw .that

16 certain compound would cause cancer in a mouse,

17

18 MR .'MCDERMOTT :

19

20 I mean,

21 .relevant information to know that a .compound

22 promotes tumors .in a mouse?

23 Weli, here again, tumor promotion is an

24 entirely different thing, sir, than tumor

251 initiation .

WAGA & SPINELLI, (201) 992-4111


Vol . 4, Pg . 661

But beyond that point is -- we already

knew ;that the compounds that we were working with

were either very potent in the way they caused

tumors, either on skin :'painting or subcutaneous

injection or intraperitoneal injection .

Q . You were doing animal testing, were

you,not, back in '47 to °'53, so that you can draw

sonte,conclusions upon the biological activity of

c,ertain compounds? .

10 A . Well, we were interested in the fact that the

11 serum' we were ge:n.erating, the vaccine we were

12 generating, would it stop the production of tumors

13 in :the animals that, we knew we were going to cause

14 tumors in .

15 Q, Let's take>4t another way . Why did

.16 you want RJR, in '54 ., to develop it's own in-house

17 animal research laboratories?

18 A . I didn't say`that in 154 .

19 Q. Okay ; when'did you say that?

20 A . . . I don't know . Late '50s, early '60s .


~
21 Q. Why did .you want R .J . Reynolds to
~
~
22 develop its own in-house animal testing in the w

23 late 'S4s, earYy ;'60s? :

24 . Well, one of the`reasons, as I said, was, if

251 you look at what Reynolds did from 1952, when they

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 662

1 began to augment their research capability, we had

2 developed -- Reynolds had developed quite a

3 reputation in the field of tobacco composition,

tobacco and smoke a,nalysis . And then, when we got

into the smoke :composition work, where -- when I

started it in '54, by_1960, we had quite a

reputation for our skills in these .areas . And if

8 you looked at some of the stuff in the literature

9 on biology,-some of it was very poorly done . And

10 I felt : Let's do i`t, develop the expertise to do

11 it properly, and it may be more meaningful .

12 And one of the things -- you may not

13 realize this either,' that if you go to a meeting

14 and somebody's giving a talk on animal studies,

15 and!it doesn't necessarily have to be on tobacco

16 smoke, but usually we were interested in what

17 pe ople were saying in that area, and you asked a

18 question of,Dr . Wynder or Dr . Bock from Roswell

19 Park in`Buffalo, t he first thing they would look

20 and'say : Gee, there's~:Alan Rodgman from Reynolds

21 or Joe Smith from someplace else :, And they would

22 ask'the question : Was your question an outgrowth

23 ot fiomething you noticed .in your work? And of

24 course you were stuck . If you hadn't done any

25 biological work, you could .say : Well, I haven't

(201) 992-4111
Vol . 4, Pg . 663

1 done any ; and'they'd i ust ignore your question .

Q . Up to this .,_point in time, had Reynolds

contracted with .outside laboratories to do such

4 work?

5 A . -No, I-don't think,so . I was trying to think .

6 That'didn't happen,until the '60s, I guess .

7 Q : Which companies -~ in the '60s, when

8 you decided to recommend that Reynolds develop

more biological in-house research, which companies

10 were doing biological in-house research?

11 A . . Well, when I first recommended -- or

12 recommended the acquisition of a biological

13 capability through bioassays and so on, nothing

14 happened for a while . But, then, I guess it was

15 about the mid '60s, we actually formed a group,

16 you know, that did some biological work . Not

17 necessarily all on tobacco smoke either, because

18 of some other ongoing things at Reynolds .

19 And`in addition to some in-house work,

20 we had some work done at'various -- Bio-Research

21 in Chi,cago,

22 Do you know which tobacco companies

23 were ;doing in-house biological research when

24 Reynolds was not? w

25 . At that time I didn'

WAGA'& SPINELLI (201) 992-4111


Vol . g . 664

Q . When`did you first recommend that

Reynolds develop biological research in-house?

MR . MCDERMOTT :

THE WITNESSs I-guess it was late '62,

really, in May_;

6 BY MR . MAISTROS :

Q . And when did they develop in-house

biological research?

In '65 . They started to acquire the staff .

10 And one of the problems, you know, you say -- you

11 don't jump into doing biological work overnight,

12 sir . You've got to get the staff, you've got to

13 get .a facility . A biological facility is -- is

14 not just like putting your kitchen together . ; it's

15 quite an elaborate setup . And it took time to get

16 that all done, and get the appropriate staff, and

17 get things started .' And, as I say, all of the

18 biological work that was done, underway, was not

19 all on cigarette smoke .

20 Q . Who was in charge of the efforts to

21 put_together sophisticated biological research Ln


~
22 capabilities within RJR in 1965? ~
m

23 A. A man called Dr . Eldon Nielson, E-L-D-O-N,

24 N-I+E-L-S-O-.N ., I ;guess .it is .

25 What role did you play in that

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 665

project?

A . None . I was just glad to see they were

getting a move on .

Q . And the primary benefit you saw, at

least, was so that'you could be more knowledgeable

when'you attended these seminars?

Well, that would have been a help . But

the~-- one of our problems had been, we do all the

chemistry of ways to control smoke and lower this

10 and that, and we sort of had to rely on people

11 doing the same thing outside and then seeing what

12 they did with the animal work, their animal work,

13 because they could do both . This way, if we were

14 .doing them both in-house, we could probably speed

15 up our knowledge reserve, and so on and so forth .

16 Q . And is it your testimony, that prior

17 to the development of this biological laboratory

18 in 1965, that Reynolds did not have'any in-house

19 capabilities to either confirm or deny the

20 biological work that'was being done by third

21 parties?

22 MR . MCDERMOTT : Object to the form of

23 the question .

24 THE WITNESS : I don't think they did .

25 BY MR . MAISTROS :

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 666

0 When I say Reynolds, I mean either

in-house or by contracting it out .

m really -- I don't remember them going

outeide . I think they may .have for some things,

but I don't'remember them going outside .

Q . When, if,you could put the year -- if

you could put a year to it ; if it's an unfair

question, tell me . When do you think Reynolds

first had the capabilities to personally examine

10 the biological activity of smoke?

11 Probably -- oh, ;I'11 say '60s . Let's say it

12 took them a year and a half to get everything

13 staffed and so on . Probably late '66 or early

14 167, somewhere in there .

15 Q . And the in-house biological research

16 that was developed in`'66/'67, did that continue

17 through the time you left RJR?

18 . No . The -- some of the biological work was

19 terminated in 1970 .

20 Q, What "some" of it?

21 Pardon?

22 Q . What "some" of it?

23 Well, I'm sure you're referring to all the

24 fuss about the 1970 supposed closing of a Mouse

25 House . But there were several things going on in

WAaA .& SPINELLI (201) 992-4111


Vol . 4, Pg . 667

the biologica] . areatthat -- for example, we were

in the proc'ess of considering a liaison with a

,pharmaceutical .Gompany ; Warner Lambert, I think it

was . We also were doing biological work -- and

with that regard ; we were -- had looked at some

6 compounds I forget whether they came from

7 tobacco or smoke, ._ We were looking at the

8 biology -- bioaseay of them as

9 cho.lesterol-reducing compounds . And so there were

10 several people working-on that .

11 The`n, .there was another group who were

12 working on what was called the isomerase project,

13 Which actually wa`s`a bacteriological project of

14 way to convert'glucose to a mixture of glucose and

i5 fructose . And,~ nowa;days, if you look at Coke or

16 Pepsi or soft drinks or ice cream, you'll notice

17 that t hey all .contain what's called liquid sugar,

18 which is a mixture of glucose and fructose,

19 produced by a similar system . Reynolds has its

20 own developed'its own system for a company

21 called Penick `& 'Ford .

22 Now,` Penick & Ford was also a seller

23 'starch compounds, and`some of them, of course,

24 were> used in `foods,' ,some' were used as coatings on

25 paper, so on .' So they were a group testing the

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 668

compounds that were used -- that would have been

2 taken in by people .

3 And then . .t here were, of course, people

4 working on the effects of cigarette smoke . And

5 then there was another group -- the Council for

6 Tobacco Research was'looking for a smoking machine

to use, to expose'animals to inhalation . It's

8 called the "nose only exposure method," where the

beast gets the smoke"`right at his nose and mouth .

10 And `Reynolds designed one .

11 So there were people -- biological

12 people working on the design of that machine with

13 people from the electronic -- electrical

14 department . And'all the companies, I think, made

15 one . I think Lorillard had one, we had one -- I

16 don't know if Philip Morris had one or not . But

17 it`ended up the Council for Tobacco Research

18 didn't pick any of ours, they picked a machine

19 called the Walton smoking machine .

20 So, contrary to what has been said

21 about what went on in the -- all these articles in

22 the newspaper that the whole biological group was


I cn
23 terminated, ' it was terminated because they were ~
N
m
24 all'' .working on cigarette smoke, their notebooks
~
OD
251 were taken and''`dest"royed ; it was a bunch of m

WAGA'& SPINELLI (201) 992-4111


Vol . 4, Pg . 669

nonsense . And if you want to take :the time, I

2 think I could go .through and demonstrate to you

3 how-much nonsense it`really was . If I haven't

already .

For example,` they said the only people

terminated were biological . There were at least

eight people who were not biologically oriented .

Some of them were analytical chemists, some of

9 them were organic chemists, working on a flavorant

10 synthesis, analytical chemists, wasn't terminated .

11 And ; :the other thing abnut it was .there were about

12 12 people, including Dr . Nielson, who stayed on

13 after that, all biologi .cally oriented, except one .

14 Q . Who's that?

15 A man called Fred Wendelboe . He was doing

16 some analytical .chemistry for the biological

17 people .and went to the -- back to the

18 biological -- went back to the analytical group .

19 But the interesting thing is that some

20 f .the .people in :the biological area, they were --

21 according to people,who said everybody was gone,

22 a`re still there . In .fact, one of them is giving

23 two papers at the Tobacco Chemists Conference next

24 week .

25 Who is=that?

(201) 992-4111
Vol . 4, Pg . 670

1 Riley Davis . Riley, R-I-L-E-Y, Davis . Fred,

2 Wendelboe is still there .

The-other interesting thing, the same

4 people who were saying Reynolds was so nasty in

5 getting rid of all this stuff about smoking and

health, three of,them came back : Dr . Bruce,

Dr . Colucci, and Dr . Simmons . And Dr . Simmons is

still there . And"why would you come back if

9 ~things were so ;ugly? :

10 MR .`BLANCATO : Would this be a good

11 time for a break?

12 MR . MAI9TROS : Just a couple of

13 minutes .

14 BY MR . MAISTROS :

15 Q . What` was so"uglyo

16 mean, one-of those three

17 peo, ple said that~_th .ey destroyed his notebooks,

18 which he had to admit wasn't true' . He was the one

19 that gave the_ .interviews that said everybody in

20

21 R . Who'e that?
Ln
Colucci . ~
22 J
F-+
I
m
23 MR . MAIS .TROSs Do you want to take a ;
, ~
~
CO
24 break? N

25 MR . BLANCATO : Yes .

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 671

VIDEOGRAPHER : We're going off the

record at 2 :23 p .m .

(Recess taken from 2 :23 p .m . to 2 :40

p .m,)

VIDEOGRAPHER : We're going back on the

record at 2 :40 p .m .

7 BY MR . MAISTROS :

Q. Dr,; Rodgman, in 1970, the biological

research laboratory, if you will, at RJR was

10 shut down, was it not?

11 Yes .

12 Q . Where was it located?

13 A . It was located across the street from the -

14 the main research building .

15 Q . What was the building called where

16 biological research was done?

17 . People called it "the Mouse House," but it

18 probably had a more sophisticated name .

19 Q. Was there anything else in the

20 building, other than biological research?

21 Not that I know of .

22 Q Were there any employees in the

23 .building, other .than biological research

24 employees?

25 A . Well, now,'it depends on when you were there .

WAGA & SPINELLI (201) 992-4111


Vol . Pg . 672

For example, the people that were working on the

2 design of the inhalation smoking machine would go

over there and they'd pop animals in and they

wouid adjust things in :the computer, and so on and

But I was never really that much

7 involved, so -- other than that one thing, I don't

know who who wae in another building .

Q . Who made t he decision to close the

10 biological research laboratory referred to as the

11 "Mouse Houee

12 A . `` I have no idea

13 Q Who .was,in charge of biological

14 research in 1970 at Reynolds?

15 A .` Dr . `Eldon,Nielson . ;

16 Q What happened with the animals that

17 were being biologically researched at the Mouse

18 House?

19 I have no idea .

20 Q . Never heard any stories?

21 No .

22 Q• Not even rumors, hearsay, cocktail

23 party conversation?

24 I don't,even remember reading it in the

25 articles in the Greensboro newspaper, when there

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 673

were five articles, I think, spread over a week, a

page and a half each .

3 Q :, Did you`ever see any memos that

4 described why the Mouse House was shut down?

5 N

6 Q Do you`know if they did any research

in the Mouse House that would establish a link

n between cigarette smoke and any form of tumors or

9 cancer?

10 No .

11 Q . Do you know what kind of biological

12 research they were doing in the Mouse House?

13 . Would you rephrase that, please?

14 Q . Do you know what kind of biological

15 research they were"doing in the Mouse House?

16 A . Well, as I,mentioned before, they were doing

17 some things on cholesterol reducing drugs, on

18 inability or toxicity of starch derivatives that

19 would be in food .' And of course this isomerase

20 thing, they had,to make sure that the liquid sugar

21 you ended up with was -- didn't have bacteria in

22 it, the one that was causing the isomerization . , Ln


~ ~-4
~
~
23 And I'believe they did some work on ciliastasis,

24 cigarette smoke and ciliastasis . , ,0p.


OD
' Ln
25 Q . What is ciliastasis?

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 674

Well, the cilia are small, little hair-like

things that are in your lung . And I guess the

3 best :-way to describe them is they move in the --

synchronously,` like a wave, you know . On the

surface of -- the tips of these things is -- is a

layer of fluid . And if you get anything in your

lung, particles, smoke particles, .dugt, these

8 little cilia wiggle in a rhythmic motion and move

that : fluid with,the . particles` in it up -- and you

10 end`up swallowing them . It brings them out of

11 your lung and you swallow them .

12 Well, it had been this -- after the

13 demise, if you wi11, .-,of the polycyclics, the

14 aza-arenes, the phenols, the next group were the

15 ciliastats, which were ;primarily in the vapor

16 phase of smoke, not in-the particles . And there

17 was some work .on that .

18 The exposure to these ciliastats, done

19 in vitro with clam cilia or a piece of lung tissue

20 extirpated out of a ;rabb .it, exposure to these

21 vapor phase parts of smoke slowed these down ;

22 sufficient concentration ended stopping

23 their little waving motion . In other words, you

24 were -- the claim was that the ciliastats in smoke

25 hindered the clearance mechanism of the lung .

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 675

1 And, as a result of that, one of the -- it was

2 written up a great deal in the Readers Digest and

3 so' .on, as the same time as the Lark cigarette came

out,'which had a,carbon filter which was supposed

;o take the ciliastats out of the smoke .

Well -- I think they were doing some

work :'on that . I'm not sure of that, but I believe

they were .

9 Unfortunately, by 19 .-- the end of,

10 1968 -- well, let,me,back up a little .

11 1965, Lawrence Cook-and I did some

12 experiments that showed that the compounds that

13 are supposedly responsible for ciliastasis or this

14 impairment,never reached the lung, or-very little

15 of them . They're all dissolved out of the mouth

16 the saliva, and then the laryngeal, and the

17 fluids coating the larynx .

18 We reported that, wrote it up ; it's in

19 some reports . But some other workers in Europe,

20 Da].hamn,' Edfords and Rylander, did it very

21 sophisticated ; very fancy equipment . Got

22 : essentially the same numbers that we did for the v+~


~
23 compounds that are considered ciliastats . And, as '0

24 a result, by the 1969,,1970, the whole carbon

25 filter cigarette'thing fell apart . It ended up

(201) 992-4111
Vol . 4, Pg . 676

1 with -- I don't know, 13 brands going down to two,

2 the Reynolds' brand and the L & M brand, Lark and

3 Tempo .

And what-they were doing over in

the -- I think one of the things they may have

been doing, we had also found, Lawrence Cook and

that if you pass the smoke through a moist

8 system, that the water would take out the

9 ciliastats . In fact, there was a commercial

10 cigarette made with :that principle, that

11 encapsulated water .was included in the filter tip,

12 and before you smoked the cigarette, you crushed

13 the filter . The water came out of the capsule,

14 and when you smoked it through -- smoked the

15 cigarette, all the ciliastats were taken out .

16 But thatl all fell apart when it was

171 shown that the ciliastats, or very little of them,

18 ever got to the lung .

19 Q Now, did RJR do research to establish

20 that ciliastats : nevex'.' got to the" lung?

21 just told you .

22 Where is that published?

23 It's not published .

24 Q. Why not?

25 Well, shortly thereafter, Edfords and

(201) 992-4111
Vol . , Pg . 677

Rylander-came out with their publication, and

there it was .

3 R So'is it like medically not subject to

debate that ci3iastats -don't get to the lung?

I didn't say they didn't get to the lung . I

said the level that :>gets to.the lung is very much

reduced . Only about--a querter of them get there .

Q. How'many .cigarettes do you have to

smoke befor,e you .get`a level that gets to the lung

10 .that matters?

11 I have no'' idea .

12

13 A . No . The thing is, the effect disappears

14 between cigarettes .

15 Q . Pardon me?

16 The effect disappears between cigarettes .

17 Q . Is there any health d :isease that you

18 would feel comfortable, sitting here today,

19 acknowledging as related to smoking?

20 MR . MCDSRMQTTs . "Related"?

21 MR . MAISTROS : Related .

22 THE WITNESS : I still didn't hear you?

23

24

25

WAaA ;& SPINELLI (201) 992-4111


Vol . 4, Pg . 678

it .

s there any .adverse health

3 consequence, that you feel comfortable discussing

today, ;that is related or associated with smoking?

MR .' BLANCATO : Object to the form .

MR . MCDERMOTT : Object to the form of

the question .

around so much

10

11 4. Let me

12

13 There are certai•n people out there

14 that you've referred to as zealots or

15 I never used that word .

16 I forget what word you used,

17 opponents, proponents of theories, or anti-smoking

18 people, that would suggest that there are certain

19 diseases related to emoking . Are you aware of

20

21 Well,`I've already said that there were


m
22 epidemiological-studies that indicated an

23 association .

24 Is there any health disease or adverse

251 health consequence that you, sitting here today,

WAdA`& SPINELLI (201) 992-4111


Vol . 4, Pg . 679

1 feel comfortable stating that you believe, you

personally, not RJR, you personally believe is

caused by smoking?

4 o, I can't -think of anything .

5 Q . So as far as you' .re concerned, there

6 are .no adverse health consequences-that are caused

7 by smoking?

MR . MCDE,RMOTT : Object to the form of

9 the question .

10 THE WITNESS : Here, you come back to

11 .thie business of association and cause . It's been

12 my training that you cannot prove cause and effect

13 with statistics . You can prove association, but

14 not cause and effect . .

15 BY MR . MAISTROS

16 Q. Okay . So if I paint a million mice

17 with compounds that's contained in tobacco smoke,

18 and one million get cancer, you can draw no

19 conclusions from that, related to the human

20 experience?

21 . Only if you were to paint the human the same

22 way and get the same-response . And by the way,

23 there has been a akin painting study done with

24 humans and cigarette .smoke .

25 Q . The`prisoners you•talked about?

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 680

1 no . No .' That was with benzpyrene .

2 Who did the .human skin painting study?

There was a mari'here in the United States, in

1956 . .,: It's in Wyndev's boo•k ; he's got it

described . He did it for three or four months,

and then they'quit, : because they didn't see

anything .

I was surprised at reading that,

because I had~never realized that reference was in

10 existence .

11 Q Give me something that the average,

12 common :person can relate to that would establish

13 the distinction that you see'between association

14 and cause .

15 A . : Well, I think part ;of my problem, sir, is

16 that -- as I mentioned, I was collecting and

17 critiquing literature for the law department, and

18 whether it's`a fortunate`position or an

19 unfortunate position, by the time of the trial in

20 New Orleans, the Lartigue case, I had read

21 something like 20-something thousand articles on

22 all aspects, pro and con,`of smoking and health .

23 By the time I got out of that job and it was

24' actually turned over to Dr . Frank Colby,

25 probably had read 40,000 articles .

(201) 992-4111
Vol . 4, Pg . 681

1 Now, whether I am right or wrong --

the average person gets his knowledge from a front

page of the newspaper, a magazine, Time magazine

or whatever . If he`reads 52 issues of Time a

ye.ar, maybe three or five of them will have

smoking articles in . So z,think it's very

. ..difficult to pin down and say : Well, the average

8 ,person should know :what Alan Rodgman knows, or

9 vice ::verea . So I'm•not in a position to say what

10 the ` average person would f eel about it . I don' t

11 know if'that answers your question .

12 4•

13 The other thing`about it, if you -- to jump

14 from aesociation'to cause and effect, maybe I'm

15 being the ultimate scientist, but there are

16 inconsistencies, even in the_epidemiological

17 studies considered taboo, to even say there's

18 something wrong with them .

19~ I've mentioned the Ochsner case . Why

20 is not Ochsner ever mentioned in the Surgeon

21 General's report, other than his first paper that

22 says cigarette smoking is associated or caused

23 by -- is a cause of lung cancer? All his

24 contradictory clinical data is omitted . Why does

25 Dr . Doll and Hill, in their first study, say they

(201) 992-4111
Vol . 4, Pg . 682

can't explain why "the incidence of lung cancer

among people who said they did not inhale is

3 greater than,that in the people who say they

4 inhale .

5 Now, the American Cancer Society

6 sloughed that off and said : Well, the people

7 didn't understand the difference .between inhaling

8 and .not inhaling . B t Doll and Hill then went

on to do a study that,was a prospective study, in


. . . . . . 3 . , . .

10 which they started out with people, 57,000 to be

11 precise, that'they were going to get their smoking

12 habits and see what happens to them . They never

13 asked the question about`inhaling .

14 Now, you .may say, well, people might

15 not understand again ; but this was 57,000

16 physicians . You can't tell me'that you got 57,000

17 physicians that do not know the difference between

18 inhaling and not .inhaling .

19 And, of-course, if you want to look at

20 the chemistry, which I'm much more familiar with,

21 if you want to take the ;time, I can give you at Ln


F-A
a
22 m
~
23 Dr . . Bock, Van Duuren made an ~

24 on-t e front page -of the

25 newspapers that axe"wrong, some of which we showed

(201) 992-4111
Vol . 4, Pg . 683

1 were wrong, some of`which they showed were wrong,

2 but they, to this day, have never retracted a one .

3 Q . Why is your former employer agreeing

4 to FDA regulation of nicotine?

MR . MCDERMOTT : Objection . No

foundation .

7 THE WITNESSs I don't know whether is

or not .

BY MR . MAISTROS :

10 Q . Let's°assume that the newspaper's

11 correct and they've agreed to be regulated by the

12 FDA as a drug . Why would they do that?

13 MR . MCDERMOTT : Objection . No

14 foundation .

15 THE WITNESS : I'm not an expert in the

16 nicotine . All I would say, that I think it's a

17 mistake .

18 BY MR . MAISTROS :

19 Q .' Which is a mistake? You think they

20 should be settling these cases?

21 MR . BLANCATOs Object to the form .

22 MR . MCDERMOTT : Objection . No

23 foundation .

24 THE WITNESS : You want a personal

25 1 opinion?

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 68 4

1 MR . :MAISTROS : Yes .

THE WITNESS : No .

3 BY MR . MAISTROS :

4 You think the settlement's foolish?

5 MR . BLANCATO : Objection to form .

6 THE WITNESS : I think it' s

inappropriate .

BY MR ;MAISTROS s

9 Why do you think its's inappropriate ?

10 A. just think it'sinappropriate .

11 Q . You don't think there's any reaso n

12 that the tobacco-companies should ever agree to

13 any regulation of its product by the FDA ?

14 MR . MCDERMOTT : . Objection :

15 foundation .

16 THE WITNESS : If you go.back in time,

17 at one time there was"a serious consideration of

18 the FDA handling tobacco products the way they do

19 other things, and some people had proposed that .

20 AndI don't know -- I don't think the tobacco

21 companies really had said much either way . But

22 the FDA said : We-don't want to do it . We don't

23 have the time ; we don't have the facilities ; w e

24 don''t have the knowledge .

25+ And that's history, sir . Bac k

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 685

1 sometime -- look up sometime in the '70s .

2 Q . Do you think that t he defense that's

3 asserted by the tobacco company's Freedom of

Choice -- first .of all, are you aware of the

defense, Freedom of Choice?

6 A. No . I'm not'that familiar with what's been

all this

Q Do you know what the defense of the

9 tobacco companies is in the Arch litigation?

10 No, I do not .

11 Q . You've not served in any capacity as a

12 consultant in the Arch litigation?

13 Only by being here .

14 Q . Have you assisted Womble Carlyle in

15 the :defense of the Arch case?

16 A . . By being,here ; I don't'know if this is

17 -helping them or hindering them . I don't know what

18 the -- what's involved in the Arch case, frankly .

19 Q. Have :you ever :written any memorandum

20 to`your managers, supervisors, higher-ups at

21 Reynolds, where you espouse the opinion that there

22 were health risks rel,ated to smoking?

23 . I have written things to them pointing out

24 that these views are held otherwise, and we should

25 be paying attention to them .

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 686

1 Q . But have you written anything

2 forget what other people have espoused . Have you

3 written anything where .you said I, Dr . Rodgman,

believe that the following health risks are

5 related to smoking?

6 A . Not that I remember .

7 Q . So, I just<want to understand the

playing field we're on'. You start from the

proposition that you don't personally believe

10 there'are health risks related to smoking?

11 MR .-MCDERMOTTs Object to the form of

12 the question . You're misstating or not accurately

13 summarizing his prior testimony . It speaks for

14 itself .

15 MR . MAISTROS : Tell me if I'm

16 misstating --

17 THE WITNESS : I think I've already

18 spoken to that .-

19 BY MR . MAISTROSs

20 Q . Do you have grandchildren?

21 A . Yes .

22 Q . Any of them smoke?

23 No .

24 Q . Do you have any concerns if they

251 started to smoke?

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 687

My sons - don' t smoke .

2 Q Wou1d yo:u have any ;concerns if your

g I randchildren smoked?

I believe that's their parents' problem, not

Q It wouldn't`concern you one way or

another if your grandchildren .smoked?

. Well, at their :present age ; .some of them are

three years old .

10 Q . The ones that are old enough to smoke,

11 would it concern you if they started to smoke?

12 Not particularly .

13 Q Did you ever do any research to

14 determine why people smoke?

151 That was outside my expertise, sir .

16 Most of my work'has been on composition of smoke,

17 control of it .

18 Q . What do you mean by "control"?

19 Just what we've'been talking about : Lowering

20 the composition delivery from'a cigarette,

21 compounds in the tar, and so on and`so forth .

22 Q . Any of the papers that you did on the

23 composition of amoke, did you turn those in to the

24 legal department for review?

25 A . Did I?

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 688

Yes .

2 A .. No .

Q. Anyone ever .review your work before it

was`published?

5 Oh, there was a set routine, that you

6 prepared the manuscript, submitted it to your

7 manager, manager took it to the director of

research, and then the-director of research either

9 approved-it there or, if he had some concern, he

10 might take it on .

-11 0 Did you ever submit any documents that

12 were returned, edited by anyone in the legal

13 department?

14 Edited?

15 Yes .

16 0

17 Q . Did you ever .have any manuscripts

18 returned, where suggestions were made that, when

19 you expressed certain views by anti-smoking

20 advocates, that you would highlight they were the

21 views of anti-smoking advocates as opposed to just

22 the views of a third person? Ln


F-A
~
23 No . N
m
Ob
24 MR . MCDERMOTT : Would you read back Ln
m
251 the question . There was a noise here . I didn't

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 689

quite hear the middle part of it .

MR . MAISTROS : He said, "No," but she

can do it again .

(Record read)

5 BY MR . MAISTROS :

Q Now, have you heard of the Gentleman's

7 Agreement?

8 A . . .~Yee .

Q . What is the Gentleman's Agreement?

10 A. We talked about it at the last part of this

11 deposition . It was .:-- I heard about it in a round

12 about way . But no in-house animal work was part

13 of it, I think .

14 Did Reynolds abide by the Gentleman's

15 Agreement?

16 MR . MCDERMOTTs Objection .

171 foundation .

18 THE WITNESS : As far as I know .

19 BY MR . MAISTROS :

20 Q. What was the reason for the

21 Gentleman's Agreement?
Ln
22 I have no idea . ~
~
~
23 MR . MCDERMOTT : Objection . m
~
24 Foundation .

25 BY MR . MAISTROS :

(201) 992-4111
Vol . 4, g 690

Q . Did you hear of a gentleman's

agrefement with respect to a safer cigarette?

A . I don't quite know what you mean .

Q . Was there ever a gentleman's

agreement, to your knowledge, with respect to, if

one tobacco company developed~a safer cigarette,

they'd share that-knowledge with other tobacco

companies?

. Oh . I was ~-,trying to think if -- Dr . Colby

10 and I gave a talk . That may have been in that --

11 so,me parts Frank put'in .

12 Q . Some parts what? I'm sorry .

13 .A . Some parts of the talk D Colby put in . And

14 th'at 'may have, been in there .

15 Q . Talk to who?

16 Management .

17 What year?

18

19 Did` -- I

20

21 into -- back into the biological work . That's

22 when Dr' . Hayes showed,, ., up .

23 Q . You espoused more in-house biological

24 research in '62 . And then there was no biological

25 research, for whatever reason, in '70 . And then

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 691

1 when did°Reynolds get'back into biological

research in-house?

It was about '83 ; I guess . There again, I

got. - Dr . Hayes was hired, and he had to acquire

5 a staff, and was . set up to,do all this stuff,

Q- Why was there no in-house biological

research from 1970 to '83?

9 A . Whenever we needed it, we contracted it .

10

11 Industrial :Bio-.Test, in Chicago, and

12 Bio-.Reeearch .'in Montreal, and I don't know where

13 else, if there was anywhere else .

14 Q Did Reynolds have facilities in other

15 countries that did .biological research?

16

17 Q. Did Reynolds contract with university

18 or outside hospital medical personnel to do

19 biological research,'from 170 to '83?

20 A. No . The only ones I know about are the one

21 done in Industrial Bio-Test, and then the one done

22 at Bio-Research -- well, there were several done


~
~
~
23 at .Bio-Research in Montreal . One was a -- ~_A
m
24 Industrial Bio-Test was a tobacco'substitute -- ,P.
cn
im
w
25 well, both of them were tobacco substitute . Then

(201) 992-4111
Vol . 4, Pg . 692

1 there was the . .expanded tobacco biological work .

2 Q . Have those reports been published and

3 provided, to your knowledge?

4 A . I don't know . I don't have them .

Q. Industrial .Bio-Test, did they do

and -

10

11 and it include the chemistry of the smoke of the

12 eubstitute .

13 Well, unfortunately, just at that

14 time, Industrial°Bio-Test got into all sorts of

15 trouble with -- I don't know who it was, FDA or

16 somebody, because of something,they had done with

17 some agricultural chemicals they_had_approved or

18 not approved or should°have been'approved or

19 whatever . And most of,. the people that were

20 involved got fired, so it was never .finished .

21 'Q Did you .ever see any published reports

22 of Industrial"Bio-Test?

23 A, Did I ever<see'any?

24 Yes . Ln
0
14
on our work?

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 693

Yes .

3 0 Do you know .if Industrial Bio-Test did

any testing to determine if any of the compounds

5 in cigarette smoke promoted tumors, caused cancer,

were tumorigenic?

7 N They did a lot of work on ciliastasis .

8 Q . But they didn't publish any reports?

Well, they sent the reports to Reynolds .

10 Q Do you~know where those are?

11 A . They're in the boxes I gave you . Some of

12 them . I think they"confirmed what Lawrence Cook

13 and I had found, that :ciliastats were taken out in

14 the oral cavity .

15 Q Why di`d Reynolds get back into

16 in-house biological research in 1983?

17 Well, here again, it was a management

18 change upper management change in R & D . First

19 one was 1980, then it was 1982/83 . And I -- so

20 D Colby and I - I<did., actually, the

21 presentation - said we ; .should get into

22 bio-behavioral type things about smoking, and why

23 people smoked and how they smoked, and so on and m


~
w
24 so forth . And it was approved . m

25+ VIDEOdRAPHERs M Maistros, we have

WAGA &`SPZNELLI (201) 992-4111


Vol . 4, Pg . 694

five minutes left on the videotape .

2 BY MR . MAISTROSs'

3 Q . Did you ever hear any reasons or

explanations as to why_ ;Reynolds did not have

in-house biological,research from '70 to '83?

Well, not - nobody ;came up and said : Alan,

here=-are the reason.s . But what happened was, if

8 you thought about it,'that -- to set up a

biological system for various -- for a great

10 number of things is`very expensive .' And you could

11 contract it to a,,univergity lab or a commercial

12 lab and they have everything in place ; they have

13 staff, all expert in certain things, whatever

14 you're looking for . And it ended up being much

15 less expensive to do some things like that than to

16 set up a whole system -in your in-house, and

17 maybe use it tw-ice, and then have to go on to

18 something else .

19 So, you know, in the -- for example,

20 as I mentioned, we did,some of the tobacco

21 substitute work by a contract lab . And, by the

22 way, all of that wae confirmed in the NCI study,

23 the puffed tobacco work, and so on .

24 Q ." In 1970, Reynolds had'in-house

251 biological research .already in existence, did they

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 695

not? So we're not talking about startup costs .'

A . Well, they did -- they weren't set up to

do -- if you did do mouse .skin painting, for

example, you need a tremendous amount of space .

For example, if you have, as I said, cage

controls, solvent controls, positive controls,

test things, you usually do it with 100 or so, 150

mice a piece, and you put six to a cage, and

you're talking an awful lot of space and room, and

10 so on and so forth .

11 Q . In all`the papers that you did in the

12 boxeis-over there, did you ever do a memo to anyone

13 suggesting the reason that there shouldn't be

14 in-house biological testing is the economics?

15 A. No .

16 Q. Did you .ever see a memo, in those six

17 boxes sitting over there, where economics was the

18 reason there was-no`in-house biological research?

19 Well, one of the reasons, for example,

20 that -- here, X had nothing to do with that .

21 That -- the situation aroee in 1970 with the -- Ln


m
~j

22 doing away with the -- if you will, the Mouse

23 House . It actually started in late 1968, when, if

24 you're aware, there was sort of an austerity

25 program ; things weren't going quite as well as

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 696

1 they could have . We were told, for example, in

2 late 1968 : in your`planning for 1969 and '70, do

not budget any new staff acquisitions or

4 replacement of etaff'who are leaving because of

5 retirement or whatever :

Well that budget was prepared for '69 .

And then, of course, it was again -- started to

prepare,it in late '69 for '70 -- well, several

9 things happened . I had mentioned Penick & Ford in

10 the starch work that was biological work .

11 Well, Reynolds was getting rid of

12 Penick & Ford . The deal with Warner Lambert, the

13 company that was sort of interested in our

14 anti-cholesterol business, fell through . And so,

15 with the austerity thing and the collapse of the

16 Penick & Ford starch business -- now,

17 Penick & Ford also had some interest in our

18 isomerase business, and the agreement ended up

19~ there that Penick & Ford would have the rights to

20' the isomerase patent in the United States and we

21 wouid-have it in the rest of the world . I don't

22 know whether they ever'did license it, but we did .!

23 MR . MA 'ISTROS : We're going to have to :

24 change tapes, okay?

251 THE WITNESS : Okay .

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 697

VIDEOGRAPHER : We're going off the

record at 3 :16 p .m` . We're off the record .

(Recess taken from 3 :16 p .m . to 3 :37

5 VIDEOGRAPHER : ; This is tape 3 of the

6 videotape d,eposition of„'A] .an Rodgman, Ph .D . We're

going back on_the ;record at 3 :37 p .m .

BY MR . MAISTROS ;`

D, Rodgman, let me see if I can

10 expedite_today and the rest of tomorrow in some

11 fashion . Maybe ao .

12 There are six boxes sitting over

13 here with documents'`in them . Are you familiar

14 with-those documents?

15 I think so .

16 Q Were all those documents produced by

17 you in'response to document requests in this

181 litigation?

19 A. .' Yes .

20 Q . And all those documents were kept by

21 you in,the regular and .ordinary course of your

22 business at Reynolds? .

23 Well, as I remember, some of them are some

24 things I wrote since I left Reynolds .

25 Q Okay .

(201) 992-4111
Vol . 4, Pg . 698

MR . BLANCATOa Did you testify

earlier, some are from before?

THE WITNESS : That's right . Some of

them are from my work in -- for example, reprints

of some of my publications, prior to coming to

Reynolds in 1954 . And then there's some work --

publications that I actually published on my Ph .D .

thesis, and I actually .wrote them -- or wrote my

part of it as late, ;as 1959 when I was at Reynolds,

10 with my professor Dr . George F . Wright at the

11 University of Toronto .

12 BY MR . MAISTROSs

13 Q . Is it fair to say that . the vast

14 majority of documents 'in° those six boxes,

15 including the ones that .would be dated between

16 1954 and 1989, are related to your work at

17 Reynolds?

18 Yes .

19 Q. And :that,the vast-majority of such

20 documents were created and kept in the ordinary

21 course of business at Reynolds?

22

23 Q . And are copies of original documents

24 that were . kept 'at Reynol `de?

25 A . Yes .

WAGA .& SPINELLI (201) 992-4111


Vol . 4, Pg . 699

And you have no reason to believe that

2 any of those documents in there are other than

3 what they appear to be in terms of copies? None

4 are fabricated, in other words?

No . Why would I do that?

6 Q . I wouldn't suggest you would, but

7 silly questions, lawyers have to ask .

You wouldn't object, then, to the

introduction of any of those six documents, (sic)

10 in terms of either being authentic copies or kept

11 in`the ordinary course of business --- six boxes of

12 documents?

13

14 MR . MAISTROS : Can we have a

15 stipulation to that, other than hearsay and

16 relevancy?

17 MR . MCDERMOTT : We're going -- I mean,

18 I haven't looked through every document in those

19 boxes, and so .I can',t stipulate, in gross, that

20 they're all business'records or that they're --

21 that t hey're properly authenticated : But we're

22 not going to be unreasonable . We're going to --

23 we're going to take a sensible and civilized view N


m
IN
24 of the contents of,those boxes . If they're Ln

25 business records, I'm sure we can work out an

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 700

1 accommodation . If`you"ve got some stuff that you

2 want to examine overnight and you ask me about it

3 or ask Dr . Rodgman about it specifically, that's

fine . I'm not going to stipulate that six boxes,

5 in gross, are :business records, however .

THE WITNESS : For example, along that

7 line, my -- I`believe ; someplace .in that mess, is

a copy of my application for employment at

Reynolds . Now, is that a-~ ;where .does that fit?

10 MR . MAISTROS : Historically

11 interesting, but probably irrelevant .

12 MR . MCDERMOTT : You've also got some

13 calendars that I think .are largely personal and so

14 "fort'h . Again, we're'-not going to be -- we're not

15 going'to be obstructionists, but --

16 MR . MAISTROS s Let me` ask you this,

17 and 'the reason I' m' doing it ° on the record is to

18 : hopefully -- it,was toaexpedite, not to prolong

19 .this . Rather than have me take the witness

20 through all those documents and say, yes, this a

21 copy that -- while I produced at Reynolds . If we

22 can,at least have the agreement, if it's sent to

23 him, :`eent by him or he,'s copied on it and it's got ~


r
m
24 something that says it wae Reynolds-affiliated,

25 then we won't be getting a business record

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 701

objection or hearsay objection .

MR .,'MCDERMOTT : Let me suggest this .

We're going -- we're going to be back tomorrow

morning ;with'this"witness . I m : not involved in

the case directly ; : .I'm not sure what .the history

6 has been between the parties at ;this point . Let's

get'Mr . Belasic'on-the phone at 4 :30, after we let

8 the witness go, and we'can take a look at the

boxes ourselves, and make, maybe, a more sensible

10 determination w,ithout wasting the witness' time or

11 the court reporter's time on this, and we can put

12 stuff on,the record in-the morning . All right?

13 MR . MAISTROS : Okay . Or possibly at

14 4 :30 .

15 BY MR . MAISTR,OSt

16 Q. Now -

17 MR . MCDERHOTT : Possibly 4 :30 .

18 BY MR . MAISTROS :

19 Q . -- you mentioned two studies or two

20 projects you were-involved in at Reynolds,

21 separate and apart from the consulting work you've


Ln
22 done for Womble, right? r
V

23 A.
Ln
24 4 Was one of those in 1994?

25 Well, here again, can remember things in

(201) 992-4111
Vol . 4, Pg . 702

1 1954 that I can't remember from yesterday . But

one of them was a book on nitrosamines I wrote .

The .other is a-- there was a gentleman called

Dr . ;;,Dennis .Regan, who . ;wanted a planning meeting --

research planning meeting, and he invited several

retirees to it : . And there was some small amount

of preparation for,the meeting and some things I

wrote for the meeting and presented at the

9 meeting, and I got paid for that, and so on and so

10 forth . So those are the two things --

11 When was that latter meeting?

12 Well, both'.of them have-to have been after

13 I guess . Because I had that five-year

14 restriction on being able to do work for Reynolds

15 until the five years up was after my'retirement .

16 So -'- I mean, the information -- the contracts

17 have been provided, and how much I was paid, and

18 all this -- and the books are in there .

19 Q . So all the results of those two

20 projects are in .those six boxes?

21 Someplace, yeah .

22 0 •You were reviewing Dr . Townsend's

23 trial testimony from the Florida case earlier ; do

24 you remember that? .

25 A . Yeah .

WAaA & SPINELLI (201) 992-4111


Vol . 4, Pg . 703

Was there anything in there that -- as

2 you .were reviewing it, that you agreed with or

disagreed with, that you remember as you sit here

today?

5 Well, I agreed with a lot of what he said .

6 Q. Was there anything that you can recall

that you disagreed with?

Not really . I didn't read it that closely,

9 Mr . ;Maistros . I just want'ed to see how -- I had

10 seen him on television . And, of course, I hired

11 Dr . Townaend . And -- he's a very brilliant young

12 knew ;he would do .a good job, anyway .

13 You were not aware he was going to

14 te .stity in that case, before he did so?

15 I knew he wae`getting ready for something,

16 but I didn't know which one it was until, all of a

17 sudden, I looked at the television and there he

is, being asked questions .

In '54 to 165 you've already testified

what you were primarily involved in . Were there

other projects you were working on, that you

22 haven't testified .about, in that time period?

23 Well, as I<say, we were doing the smoke

24 composition -- if I may, let me run through .

25 Polycyclic,,-- discounting the phenol

WAGA & SPINELhI (201) 992-4111


Vol . 4 , Pg . 704

synthesis thing, it was polycyclic work ; we did

some work on the aza=arenes ; which are nitrogen

compounds that are structurally similar to the

polycyclic hydrocarbons ; then we did the phenol

work ; we did the ciliastat work ; and we started to

do some work on nitroeamines in the '63/'64 era .

And then -- and, here, I've forgotten

8 the date, we had a shift in management .

Mr . Hoover retired ;`Dr . Senkus became director of

10 ~research ; and a new man, the vice president of

11 R& D, Dr . Willard Bright became vice president of

12 R& D . And he had a bit different attitude about

13 what we should be doing and what we shouldn't be

14 doing . He was very interested in acquisitions,

15 and he was the one that triggered the

16 Penick & Ford thing and the Warner Lambert thing .

17 And he also got :us involved in a tobacco

18 substitute study'for a material called Sutton

19

20 4 -Sutton?

21 A .' Sutton, S-t7-T-.T-O-N .

22 So the tobacco work -- or tobacco

23 smoke work and our tobacco composition studies

24 were, sort of dropped in favor of some of the new

25 things he wanted done . And for the next several

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 705

ye'ars, my group, which I wasn't familiar with, you

know, studied, not only the Button .smoking

3 material, but,a smoking material manufactured by

Celanese, and that's called Cytrel, C-Y-T-R-E-L,

5 and emoking materiai manufactured in England

called_New Smoking Material, by Imperial Chemical

and Imperial Tobacco Company .'

8 And we looked at these, and we had

9 problems with all of them . And over the next --

10 between 1965 and maybe 1970, early '70's, a young

11 man called Jack'White,•developed a smoking tobacco

12 substitute that was better than any one we could

13 buy or license or whatever . And we did all the

14 smoke work on it and so on, the animal work .

15 And we never used it, because there

16 were thirteen brands introduced in the United

17 Kingdom with NSM 3mperial smoking material and the

18 Cytrel, and within nine months every one of them

19 hadn't sold enough to make a penny . So we never

20 did`market and put it in our cigarettes .

21 R. Do you k~ow°if ff there was nicotine in Ln


~
V
22 those materials? ~.A
m.
~
23 Not per se, no . And, of course, nobody ever Ln
N
J

24 marketed a cigarette made of 100 percent smoking

251 material .' It was always blended with 80 percent

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 706

1 tobacco or 70 percent tobacco or 90 percent

tobacco .

3 Q . When you say "not per se," you mean

4 what nicotine there was, was from the natural .

5 tobacco that appeared in the product?

A. .Right . These things are all cellulose

derivatives, mixed with a bunch of inorganic clays

and .whatnot, or salt .

Q. Was the .primary interest of your

10 supervisor the fact that it would be a tobacco

11 substitute and reducee the cost of the product, or

12 it .would reduce the biological activity of the

13 product?

14 A . Well, actually'the cost of most of the

15 tobacco substitutes, the -- except for the one we

16 developed in-house, the cost of the'three we could

17 have bought cost more than the tobacco .

18 Q . So what was the primary goal, then, of

19 developing

20 Well the primary goal was to -- would this be

21 an`additional_way that -- to add to the eight

22 technologies that would be acceptable in the

23 generation of a less hazardous cigarette . And,

24 well, the Cytrel, for example, was tested in the

25 NCI study that ran from '68 to '78 and, despite

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 707
I

their claims,'it was-worse than tobacco, in terms

of producing tumors on mice and so on .

Q. Has anyone when you say that there

4 were thirteen brands .that -

They were introduced in England .

Commercially?

Commercially .

And how "long were they .on the market?

Oh, some`of them were out there -- most of

10 them were gone within nine months . I happened to

11 when --

12 nine-month, ten month after they had been first

13 introduced, and I finally found a,pack ; but I had

14 to go into eleven-tobacco~stores in London to find

15 a pack . And the'fel,low said : Here, take it . He

16 didn't even :~harge me ., He'said : It's the last

`17 one-I've got, and it's~been sitting here for five

18 months .

19 Q . And how long did you work on a

20 potential tobacco substitute?

21 Well, I said, we worked on the Sutton one, we

22 worked on the° .NSM, we worked on the Cytrel .

23 didn t do an awful lot ;of work on the NSM ; most of

24 that work was some really fundamental .smoke work,

25 tar and nicotine - _well, not nicotine . Tar,

(201) 992-4111
Vol . 4, Pg . 708

carbon monoxide and .so on .

2 That one we did quite a bit of work on

panel evaluation' . That was one of the problems

with all those three,that -- whether`they were

alone-or mixed with tobacco at various levels, the

parieaists just didn't cotton to them, smoking a

cigarette, per se . But`t he,other thing that they

8 didn't like was, if somebody was in the room, side

9 stream smoke was very obnoxious, in terms of an

10 .of flodor, that it smelt ,like, 'burning paper .

11 Nobody liked to have .that .

12 Now, the one we developed in-house,

13 and we panel-tested it,'and the people didn't

14 know, of course, that it was ours . It didn't have

15 a taete'problem, and it did all the things that we

16 had hoped it would do . And so`it would have been

17 a W y to' make money .. And of' course we had it

18 patented . And I' :mFaaure, if you look at the

19 patents, you'll see .what it is ; it's a puffed

20 _ so

21 0 Did :'you'personally believe that these

22 potential tobacco eubet'itutes :would result in a

23 safer cigarette?

24 ~Well, we were hoping, that when we looked at

251 the!Sutton material and the Cytrel material, that

WAaA & SPINELLI (201) 992-4111


Vol . 4, Pg . 709

it_ would be another way to do things that were in

the definition that had been laid out in the '60s

by W.ynder, Hoffmann, Bock and all that bunch .

Q . But you personally didn't believe, in

your heart of hearts, that it mattered anyway, did

you?

Well, what Is was looking for is, if that's

f course,

10 t

11 sales-weighted average, we kept dropping it,

12 the industry kept dropping that

13 in -- the requfrement that Dr . Wynder and others

14 had said : Drop it 40 percent and the effect will

15 go :"_away . Well we dropped it 40 and then they said

16 not'enough . We dropped it another 40 ; not enough .

17 You, know, where do you stop?

18 Q . Are you talking about the FTC testing

19 method or -

20 Right .

21 Q. When`you say that the -- you kept

22 dropping the tar content, that's -- and you've L,


~
;_j
23 testified about that on a couple occasions today . m

24 You!re talking about the FTC testing method?

25 Right .

WAaA & SPINELLI (201) 992-4111


Vol . 4, Pg . 710

1 Q . Had you done, in fact, research that

2 would indicate that the FTC testing method was ann

inaccurate method to test tar content of

c,igarettes?

MR . MCDERMOTTs Object .t o the form of

THE WiTNESS : "it -- the way it's done,

what you get is,what you get .

BY MR . MAISTROSs

10 But nobody smokes that way .

11 A. .Nobody smokes that way . We told them that in

12

13 They don't

14 And, now,

15 everybody's complaining that the FTC doesn't do -

16 the people don't smoke the way the machine smokes,

17 eo, ;therefore, there's something wrong with it .

18 And we had told ;them that in 1963, '64, '65 . And

19 they came out in`1966 and said : You will do the

20 analysis this way, period . And that was that .

21 Q Has there ever been any discussion at

22 Reynolds about whether or not Reynolds has an

23 .obligation .to advise the_public on its cigarettes,

24 or otherwiae, that the FTC yields published on the

25 ciga.rettes, don't mean a .whole lot?

WAGA & SPINELLI' (201) 992-4111


Vol . 4 g . 711

MR . BLANCATO : Object to the form .

MR . MCDERMOTT : Object to the form of

the question .

THE WITNESS :, You know, what

management wants to`do about that is their

business . You know, you usually don't tell the

FTC too much .

8 BY MR . MAISTROSs

Q . Did yo'u ever tell management that

10 perhaps RJR should consider"publishing what it

11 believed to be more realistic tar and nicotine

12 yield numbers on its cigarettes?

13 A . Well --

14 MR . MCDERMOTT : Object to the .form of

15 the :question . No foundation . .

16 THE`WITNESS : The number that .you get

17 is all right, except people don't smoke that way .

18 Now, there may be one person in ten that smokes

19 exactly the same as the smoking machine . But, you

20 know, if you were to,smoke a cigarette in Alaska

21 at 20 below zero

22 BY MR .`MAISTROS :

23 Q, I would hope you would be doing

24 e'omething other than -

25 A .' -- and compared it to smoking one at Key West

WAGA .& SPINELLI (201) 992-4111


Vol . 4, Pg . 712

at 90 degrees and 100 percent humidity, that's

2 going to be entirely different than smoking a

3 cigarette at the FTC parameters .

And the other thing, that if you, say,

have three cigarettes, just take an example, at

20 milligrams delivery of tar, depending how those

cigarettes`were made,j those tars could be entirely

different . And`they know that ; it's all in the

NCI'report of -- on the less hazardous cigarettes .

10 Q . Again, though -- and you can say you

11 disagree if it's the case with the premise of my

12 question . But did you ever suggest to anyone at

13 RJR that the results that you determined at age --

14 not you, but that RJR determined, the tar and

15 nicotine content of cigarettes and how it differed

16 from the FTC, that those results should be

17 published?

18 Well, which smoker would you pick?

19 Q . Well, didn't you do tests that

20 indicated that the average smoker took in more tar

21 and nicotine than would be established by the FTC

22 testing method?

23 A . I don't -- I don't know about -- that might

24 have been done after'I left . I don't know .

25 Q . Did you''view or did you ever express

WAGA & SPINELLI (201) 992-4111


Vol . 4, g . 713

the-opinion, while-you were at RJR, that the

2 FTC-published reductions in tar and nicotine

3 indicated that RJR was producing a safer

4 cigarette?

Well, the FTC never .said that .

Q Is the fact that a cigarette is lower

9 in tar and nicotine indicative that it's a safer

10 ciga,rette,, An your''opinion?

11 Well, that's one part of the -- well, the

12 nicotine was :never mentioned in the original

13 definition . But that is one part of the overall

14 definition that,came oLtt .in the late '59 --

15 '50s/early '60s . 0ne of the parts is that the tar

16 is re'duced, the tumorigenicity -- specific

17 tumorigenicity of the,tar'is reduced and the level

18 of certain. components relative to tar are reduced .

19 Q . Do you concur in the assessment that,

20 if you have lower tars, you're going to have a

21 safer cigarette?

cn
22 ; I don't know . You know, you'd have to say :
J
F-A

231 What kind of tar? And .there again -- for example m


Sch
Ln
24 if,,you looked at the F-- the NCI work, which nJ
M

25 involves a hundred and-something experimental

(201) 992-4111
Vol . 4, Pg . 714

cigarettes, you would make your choice -- for

2 example, you could have a 20-milligram cigarette,

take one of their-samples -- and here I'm just

giving you an example, and I'm sure the numbers

5 aren't going to be the same as in those four

reports .

But .you could take a 20-milligram

8 cigarette that had -- and let's just pick a

figure, ten nanograms of benzpyrene per cigarette .

10 Now,-if you had any health concerns, would you

11 pick that cigarette,_20 versus 10, versus another

12 c.igarette that, say, had 15 milligrams of tar but

13 20 .mi1 -- 20 nanograms of benzpyrene? Which would

14 you pick? Would you ;pick the -- it depends on

15 whether you're concerned about tar per se or the

16 polycyclics per se .

17 But the number you get ,from the FTC

18 does not tell you what the'composition of that tar

19 And when we tried to tell the FTC that in the

20 mid '60s, they'said all you're trying to do i

21 make your produCt tsound good . And that's the lastj


Ln
- ~
22 we heard of it until'people, in the last five or ~
_ Im
23 six years,, have started to say : Well, you know, !Ln
N
~
24 there's a problem here . And actually, the problem

25 came up in 1980, with the Berkley cigarette --

(201) 992-4111
Vol . 4, Pg . 715

Barclay cigarette .

Q What' prob],em?

A . Well, the .Barclay cigarette, when you smoked

4 it on the -- in the FTC method, you got a certain

tar yield . But when ;the smoker smoked it, and was

forced to smoke exactly the same as'the smoking

machine'- that can be done by appropriate

mechanics - because of the way the lips press down

on the filter tip, which had some grooves in it,

10 theJsmoker was`taking in twice as much'as the FTC

11 method :ehowed on the Phipps & Bird smoking

12 machine'. And

13 the FTC .'

14

15 things you'were doing between 1954,and '65 .

16 Well, as'I say, in -- well, we got to the

17 substitute thing, which actually ran from the late

18 '64s -- .,- I guess '65 Is when we got into the

19 substitutes .

20 There was a time there, and I'm sure,

21 if you look at some of the reports I wrote, I know

22 there was a question- :that came up in the - - f rom

23 M O'Fallon about publishing/not publishing

24 things we had done . Well, I think, at one time,

25 we ."'looked to perhaps fifteen different kinds of

WAGA `& SPINELLI (201) 992-4111


Vol . 4, Pg . 716

filters that had been proposed for their effect on

certain smoke components . And every one did not

perform like the patent said it would .

4 Well, there's a report on each one of

those, or maybe some that are combined, the

two-in-one reports, but how can you publish

something that shows -- ends up being a failure?

_ The,`journal won't take it .

Then if you look, for example -- I

10 went to a lot of meetings in conjunction with my

11 research work and in connection with my providing

12 infbrmation to the law department . I guess, over

13 the_years, I went to .a dozen AACR meetings, and

14 half a dozen American Cancer Society meetings, the

15 Heart Association meetings and so on . And these

16 are reports to management of what things I had

17 picked up there,•what people had said, and so on

18 and"so forth . Well, you don't publish those .

19 So when,you back off on the, oh, I

20 don't know, hundred or so reports I wrote, you can

21 find'out, about half of them wouldn't be Ln


~
1 1-4
22 publishable anyway .` And the ones we did -- many

23 of the ones .we did publish, of course, are in the

24 literature or presented at meetings .

251 Q. Do you recall any titles, off the top

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 717

your head, that -

published, that indicated that there was health

3 hazards 're,lated to smoking?

4 No, I didn' t .

Q . Are there any, out of the six boxes

over there, published reports that you authored,

that indicate health ;consequences re,lated to

smok'ing?,

Not in so many words . Now, we did publish

10 some components in smoke that subsequently were

11 shoivn to have a problem .

12 Q . I'm specifically talking about papers,

13 where the topic or theme or conclusion was that

14 there was a health_risk related to amoking . Do

15 you recall publishing any such papers?'

16 No . No " I did not .

17 Q . You reviewed a lot of papers, did you

18 not,-that reported links between smoking and

19

20 .

21

22

23

24

25 lot of the chemical stuff .

(201) 992-4111
Vol . 4, Pg . 71 8

Q . Any>of the -- specifically there was

research, was therenot, biological testing, that

established a purported link between cigarette

smoke and its compoundsor components and advers e

health consequences .

literature ?

Yeah . Bu t I was in the chemistrybusiness .

Now, as I say, the people in the bio bunch, they

looked at ciliastasia, and so on . At one time --

10 I mentionedthe work Lawrence Cook and I had don e

11 about the ciliastasis and finding it -- most of i t

12 wasabsorbed in the mouth, the ciliastats . Now ,

13 guess that's biological, because we did it with

14 people .

15 Q . What chemical research did you try to

16 duplicate ?

17 A . . Well, we weren't duplicating any ; we were th e

18 first to find out that the ciliastats were

19 absorbed in the mouth .

20 Q . Separate'and apart, from the

21 .ciliastats,, did you attempt to duplicate any of

22 the chemical studiesthat were done and then

23 publi.shed in the literature, that showed a link

24 between cigarette smoking or the compounds i n

251 cigarette smoke and adverse health consequences ?

WAGA &SPINELLI (201) 992-4111


Vol . 4, Pg . 719

MR . MCDERMOTT : Object to the form of

the question .

THE WITNESS : Well, it was a long

question . But,_for example, there were claims of

e'o,-much volatile nitrosamines or tobacco specific

nitrosamines in cigarette smoke .- We looked at it,

and the work published_in the collection procedure

8 0 avoid-artifactual formation of

nitrosamines during the analysis, used ascorbic

10 the collection system, which

11 was supposed to :prevent artifactual .formation of

12 the`nitrosamines ; and which it did .

13 ° Well, the ;people at Reynolds -- we got

14 wondering about some of the values they were

15 getting for the nitrosamines, so they looked at

16 it . And in the .collection of cigarette smoke you

17 hav.e a epecial kind of filter that the smoke

18 impinges on and :is collected, 99 .9 .percent . And

19 the people at Reynolds decided to put ascorbic

20 acid on the pad . Well, when they did that -- the

21 levels of nitrosamines reported by everybody else,

22 prior to that, was about 25, 30 percent less,

23 depending on which one,you were looking at . And

24 w
what was happening, you were preventing the 1~

25 artifactual formation right on the~pad before you


I

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 720

ever took it,to the ;analysis . And that's been

2 confirmed in a lot of laborat-ories .

3 o, there's a great deal made of how

much the nitrosamines are in smoke, and -- but,

you know, is it relevant when most of the numbers

6 in the literature, except the ones published since

that`article by=Rey,nolds,,are wrong ; they're not

8' only wrong for cigarette smoke, they're wrong for

9 bac:on and anything .else you see with nitrosamines .

10 If it .would make you feel any better, your bacon

11 has about 30 percent less than what everybody has

12 been telling you .

13 Q . What were your official titles between

14 154 and ' .65?

15 I was a senior research chemist from 1954

. 16 until 1965 . When Dr Bright came -- well, let me

17 back up a littI le . .

18 Mr . Hoover had a peculiar philosophy .

19 There was director of_research, there were the

20 -managers, and ;there . ;were-the troops . The troops

21 were divided into eenior research chemists, or

22 biologists or`b,io-chemists, research chemists, ~

2 asbociate research chemists, .technicians . There


Ln
24 was .no administrative people below manager, ~

251 supervi.sors .

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 721

Dr :'Bright came, and he didn't like

that . Well, also, :another thing, the place was

.getting larger, .more : ;p.eople . And he set up a

system where you had a manager, section head, a

group leader', -and then the :-troops . And when he

came, I was made a sect-ion head in charge of the

What year?

A . 1965, 1 guess, is when he came . He did it

10 soon after he came :

11 Q . And how long were you section head?

12 . Well, in 19 --'I got to get this straight .

13 the spring of 1973, my

14 boss, who was, at that time, the manager of the

151 chemical research, was Dr . Anders Laurene . He was

16 sent off to take a,management course at the

17 University of North Carolina over at Chapel Hill

18 for six months . And then`he was assigned to do an

19 orientation through the -- the development

20 department . And while he was gone, .I was acting

21 manager of the chemical research division .

22 When`he came back, I went back to

23 being section head . And then, the next spring and

24 75,

251 analytical divieion, which, at the time, I thought

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 722

1 was an odd choice, not knowing that they already

had plans . And then, the spring of '76, I was

3 made :director of research .

Q : Director` of research for all of

Reynolds?

6 Tobacco .

And then, in 1980, when we had the

massive organization -- reorganization, our R & D

9 was split into six divisions, instead of just

10 being research and development . I got the task of

11 being director of-fundamental research .

12 Q . As opposed to what other type of

13 research?

14 . Well, there was fundamental research

15 director, applied research director, analytical

16 research director, process engineering,

17 administration -- what was t he other one? There

18 were six•

19 Q . New products?

20 Oh, yeah .. It wasn't new products, it was

21 products . .Just products . So you had fundamental,

22 applied, and products .

23 0 And you were in charge of which one?

24 A. Fundamental .

25 Q Unt il when?

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 723

Until I retired .

2 Q o are we`using the '87 date, then?

3 Right .

Q . From '80 to '87, was there one group

that looked at health aspects, as opposed to

6 another group?

Well, in '83, sometime in there was when we

got Dr . Hayes on board, and I set up the whole

biobehavioral/biological system there . So from

10 then till, I guess, now, that's what they're

11 doing .

12 Q. '83 till now, ;biobehavioral/biological

13 looking at health issues?

14 assume they're related, to some -- I don't

15 knOw`what their projecte are, actually .

16 Q What division under research was

17 biobehavioral/biological?' I mean, was that under

18 one of these six research groups?

19 . No . Actually, when they formed the

20 biobehavioral division, which was in '82, some

21 it was actually put in fundamental ; I had John


Ln
22 Reynolds and John Robinson and those people ~
~
N
23 wo .rking` for me .' Then, when Wally Hayes came, they ', m

24 moved it from fundamental into the more


Ln

25 biologically-oriented part .

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 724

Q,. During .this period of time, were you

familiar with the creation of key issues?

3 MR . MCD.ERMOTTs Object to the form of

thel .queetion .

BY MR . MAYSTROSs

Do you know what a key issue is?

What's an RJR key issue?

If they sell cigarettes .

10 s that one of the key issues?

11 A . ' I've -- I was trying to think- that I' had seen

12 something on that, but I really can't spell it out

13 in .the language I think you're looking for .

14 Q . - Did you ever participate in a project

15 or .* process whereby key issues were identified by

16 RJR~

17

18 Some of the reports in those six boxes

19 over there,have "key issues" written on them and

20 the langua,ge "varies, '' and we' re going

21 to-get into them tomorrow . But I want to ask you,

22 generally, 'if you- know . :how that came about, the

23 development of the key issue concept .

241 May I ask a question?

25 Q Sure .

(201) 992-4111
Vol . 4 g . 725

A . Is this a document where the issues are what

happens in the world and how Reynolds would

respond?

Q . Yes, thatts some of them .

Okay . Well, that was -- they started, I

guess, in the early '70s, as I remember . And

everybody pitched in and gave suggestions of, you

know, what would happen -- what would Reynolds do

if something happened in another tobacco company,

10 or happened in North America, or happened in the

11 world, and so on and'so forth . How would we

12 respond? And for some ;years Dr . Teague put --

13 assembled everything and put them together, and

14 they`were distributed to upper management, to get

15 • their .views . And -

16 Q . You did not participate in that

17 process?

18 A . _ Oh, I-~ I chipped in with some suggestions

19 here .and there . . And then, .of course, when

20 Dr .'Teague left R& D, I ended up, I think, doing

21 the last one or two, assembling them myself . If

22 that's the paper you're talking about .

23 Q . For example, and we'll get into

24 specific
. ones tomorrow, but there's -- there's

25 specific research projects that are set up, and

WAGA & SPINELLI (201) 992-4111


Vol . 4, g . 726

1 then there's a goal or a key issue identified as

2 the basis for that project that it relates to .

And there's been some testimony in the past that

4 every research project had to have a key issue

assigned to it . Are you familiar with that

6 concept at all?

7 I guess I never thought about it in that

8 terms, but it sounds'logical . As I remember, some

things in those key issue things were never done .

10 Q. Were you -- during the period of time

11 that you were at Reynolds, were you ever demoted?

12

13 Q Were you ever written up for any

14 incidents that you view as an infraction or a

15 demotion?

16 No . I was fired .

17 Q . ; By Reynolds?

18 By Mr . Hoover .

19 Q . What year was that?

201 Oh, about 1963 .

211 Q How long were you fired?


m
22 Fifteen mihutes .

23 0 What was that over?

24 There had been an unpleasant incident in the

251 research department that we usually don't like to

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 727

talk about . And when Mr . Hoover went to the

weekly meeting over at the head office, main

office, somebody said : Hey, what about so-and-so?

And he was furious .

And he came back and called me into

his office, and I didn't know what he was talking

7 You

contact with anybody on the board because of your

contact with,Mr : Ramm . Get your stuff out of


.
10 here .

11 Q You disclosed something that happened

12 in re .eearch that he thought .

13 I didn't .

14 e thought you .dieclosu

15 thought .I did . . So I asked him, I said :

16 Why don't you phone Mr . Ramm and ask him the last

17 time I talked to him, and I can tell you exactly

18 when it was .

19 Q . What did he think you disclosed?


I
20 Well, as Z say, it was this unpleasant

21

22 R Well,,what was the unpleasant

23 incident?

24 . Well, somebody was supposed to have done some

251 analysis and just wrote down numbers .

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 728

Q. On .what`research project?

Well, it wasn't . It was -- when you buy

tobacco, we used to get a sample of all the

pallets of tobacco and_,analyze .them for tar -- for

nicotine and sugar . So that, if :nicotine was

6 high, we could remove it and if -- so we could do

the .blending . And'this fellow was -- rather than

run them, he just wrote down numbers, and it

happened to be one set of tobacco was from an area

10 in the south here where it had been very hot, very

11 little rain . And when that happens, the tobacco,

12 ina_tead of being `two 'and' a half percent nicotine

13 will - it may jump'to six .

14 And the-person who had turned in the

15 samples to .him knew that we had a whole bunch of

16 samples, five or six or eight, I forget the

17 number, that probably were going to be around four

18 or five, and they had to be cataloged for nicotine

19 removal . And when he got the usual numbers, two,

20 two and a half percent, he put in some -- we have

21 -to have -- we happened to have some low

22 experimental tobaccos from NC State and you put in

23 some more high, and they all came back 2 .2, 2 .3 .

24 Of course he was fired, right then and there,

25 but -- you don't get that very often .

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 729
i

1 And so Mr . Hoover phoned Mr . Ramm, and

M . Ramm confirmed`the :exact time I had spoken to

3 him, which had been three months before, and said :

A1l-right forget about"leaving .

{~ . The -- who was the gentleman that was

6 tired?

Oh, he was a technician . I've forgotten his

name .

Q . Now, we''11_ ;get into this tomorrow, I'm

10 certain, but you mentioned that, if the nicotine

11 is too high, you`have to remove it . Are you

12 familiar with that`process?

13 A . Yes .

14 Q . How's the nicotine,removed?

i5 Exposure to steam and ammonia . And you can

16 take it down to any value you want .

17 Q .` By adjusting the amount or the timing

18 f the steam and'ammonia?

19 Well, it's the way it rolls through the

20 conveyor belt, timing on the conveyor belt --

21 Q . How long,has RJR treated its tobacco

22 with` "ateam and" ammonia?

23 I think the first report on it is someplace

24 around 1958 .

25 Q . Were they still doing that when you

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 730

le'ft in ' 87?

assume so, if they -- if you had high

nicotine tobacco from a hot, dry summer or

something .

Q . The only occasion that RJR would treat

nic -- or tobacco with 'steam .and'ammonia was when

they had high nicotine•content?,

A . Well, only that'part of the`tobacco . Now,

they'did have a reconstituted tobacco sheet they

10 treated with ammonia .

11 Q . That's a different process though,

12 correct?

13 A . Right .' It also reduces the nicotine .

14 Q . The process of applying steam and

15 ammonia to the tobacco to reduce the nicotine, you

6 said you could get the nicotine to 'whatever level

17 you wanted . -Within_what degree of error?

18 A . I really =- I'm -- you know,•I never was

19 involved in the engineering of, that . But the

20 objeot was that`, if, you'had -- here again, you

21 have to have some understanding .of how you blend

22 tobaccos . You .don't go out and buy .a year's

23 tobacco . And of cou,r.se it's,always aged for -- in

24 storage` :sheds for maybe 12 months to two years, to

251 let all' .the things go on that goes on when tobacco

WAGA & :: SPINELLI (201) 992-4111


Vol . 4, Pg . 731

a ged . You .don't take all that tobacco two

years .later, say, .and use it .

What you do is you combine tobaccos

from three .consecutive years and you juggle it so

that the nicotine change is a minimum . And if you

have -- well, just say you have flue-cured tobacco

from Georgia that's two and a half percent

nicotine, and flue-cured tobacco from someplace in

North Carolina where it's five, you remove the

10 nicotine f rom the five percent nicotine tobacco

11 and bring it down to the two and a half, or a

12 little less, depending on whether you, over the

13 years, want t o keep reducing it . Because,

14 usually, what happens is, as things go by, the

15 ni`cotine sort of para11e1s .the tar .

16 But,the'-- I've been interested in

17 some of the things I've heard about nicotine on

18 the news and so on . And what some people should

19 find'out is that, when you bring tobacco in from

20 the market, the first thing you do is stem it .

21 And when you stem 'it, you keep it at -- keep it

22 moist so it doesn't shatter . And when it goes

23 down the conveyor belt, the stems go in one

24 direction, the cut lamina go in the other . But if

25 you measure the nicotine from the time you put it

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 732

on',that conveyor belt to the time it comes off the

2 other end, you've lost two percent of your

3 nicotine .

Then when you store it and age it for

5 12 monthe, .two years, you've got to bring it out .

6 And to take it out of the containers so it doesn't

7 fragment, you again moisten it, warm it, run it

8 through the conveyor belt for a certain period of

9 time, and you lose another couple of percent

10 nicotine -- a percent of the percent you've got

11 there .

12 So when you puff tobacco -- all you

13 got to do is look at the'NCI study where they used

14 our puffed tobacco, Philip Morrie' puffed tobacco,

15 North Carolina State . Every state where puffed

16 tobacco was used, the nicotine is down 40 percent .

17 So when you take tobacco that has been

18 losing nicotine because of the way you process it,

19 then you put in a tobacco that's been expanded and

20 has lost nicotine, the nicotine in that cigarette j Ln


.
~
21 is going to be less'than the tobaccos that you ;~

22 bought to put in it . Ln

23 And I can -- might tell you one other

24 thing, if you're interested . Is that, if Reynolds

25 or anybody else want to increase the nicotine to

WAGA & SPINELLI (201) 992-4111


Vol . 4, g . 733

the'consumer, there are two ways to do it . And

they could make afortune .

Q . How° is that?

Don't put cellophane around the pack .

Because, as a cigarette dries out, the nicotine in

the smoke increases . The only reason the

cellophane'or the protective material around the

pack is to ;prevent moisture loss . As the moisture

goes'down, the nicotine in the smoke goes up .

10 Now, why would you --

11 Q . What's the second way?

12 Is to leave out half the humectants . If you

13 drop the humectants`from, say, five percent to two

14 and a half percent, the nicotine in smoke will go

15 up . And glycerine is expensive . Propylene glycol

16 is expensive .

17 Q . Why .is Reynolds, then, concerned in '(n


_
.i
18 the initial process -- I assume youfre talking im
i
19 about the initial process whereby they have to ~
L"

20 remove nicotine of high nicotine yield tobacco?

21 Well, the object is to keep the product, from

22 year to year, from-quarter to quarter, fairly

23 uniform so the consumer does not all of a sudden

24 see a big'change . Now, you might say : Well, they

25 could .increase it gradually . But all .you have to

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 734

is look at the sales-weighted average data and

it's obvious that from -- well, from 1954 to the

current time, the nicotine has been,dropping

gradually in every` :cigarette marketed in this

5 country .

6 Q . Is there a process you're familiar

with that Reynolds employs when the-nicotine

8 content is too low in .the tobacco?

can't think-of one, but T ; ;could think

10 of a .solution .to it .

11 What's that?

12 s mix low'tobacco -- low nicotine tobacco

13 with one that's'slightly above average, and

14 average it .out . . I don't know whether they do

15 that .

16 Q •-

17 manufacturing process?

18

19

20

21 Weren't you,identified as an expert ir

22 the .manufacturing process in the Texas case? L,


t,,

23

24 You weren't?

25

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 735

1 Did you ever read what your expert

designation was,in that case?

Yeah . I don't believe I am .

4 t2 . You're. not an expert in,the production

process?

Q . Do you know what methods, if any, have

8 been employed'by Reynolds to attempt to control

9 the nicotine level _in the tobacco, other than the

10 one you've testified to about the steam and

11 ammonia,

12 here again ;,I come'back to the eight

13 significant technologies . Foz .example, you can

14 control the nicotine .-in the smoke by controlling

15 the blend . You can control the nicotine in the

16 smoke by controlling'the efficiency of the filter,

17 which removes the total particulate matter which

18 contains the nicotine .

19 You can control it by increasing or

20 juggling the amount of reconstituted tobacco which

21 is ).ow in nicotine . The more you put in, the


Lq
H
22 lower your nicotine . You can reduce it by the _j
r

23 degree of air .dilution you use, by perforated

24 filters or by porous cigarette paper .

25 Q . Doesn't Reynolds -- doesn't Reynolds,

WAGA & SPINELLI (201) 992-4111


Vol . 4, Pg . 736

1 at the beginning of the process, have a specific

2 nicotine content that it's striving to achieve at

the end of the process for every particular type

4 of cigarette they're selling?

I don't really know that .

0 I mean, I look in the supermarket and

7 see all these different brands of cigarettes,

from Reynolds, for example, and they .all have

different t-ar and nicotine yields . I assume

10 that"s not by accident-that they end up that way

11 in those particular packages .

12 would imagine :that the big thing they try

13 to do ie'control the tar, and ;the nicotine falls

14 where it may .

15 You know, talking about nicotine

16 well, maybe I won't say that .

17 Q ao'ahead . This is the end of the day ;

18 it~'-s~'your opportunity to say --

19 Do you ever wonder why the FTC equation is as

20

21 Why?

22 Wet TPM,equals tar, plus water, plus

23 nicotine?

24 MS . BRACHTL : Would you repeat that?

25 I couldn't hear you back here .

(201) 992-4111
Vol . 4 g . 737

THE WITNESS : The FTC equation for

calculating tar is wet TPM equals tar, plus water,

plus nicotine . In other words, tar is water-free,

nicotine-free, wet TPM . And the reason it's that

wa-y is 'cause, if you read the 1964 Surgeon

aene-raY's report, nicotine essentially is given a

clean .bill of health . So the two ingredients in

wet,TPM, that was obvious to everybody at that

tinie had no concern :with health, was wa,ter and

10 .nicotine : And that equation is still the same to

11 this day .

12 MR . MAISTROS : Okay . We're going to

13 b.reak .until tomorrow morning . Nine o'clock?

14 MR .-MCDERMOTT : Yeah .

15 VIDEOaRAPHER : We're_going off the

16 record at 4 :30-p .m .

17 (Deposition adjourned at 4 :30 p .m .)

18

19

20
Ln
21
~
22

23

24

25

(201) 992-4111
Vol . 4, Pg . 738
I

1 U~T RAT

2 Alan Rodgman, Ph .D ., do hereby

3 certify that I have'read the foregoing transcript

of my testimony, taken on Monday, August 4, 1997,

and have signed it subject to the following

changes :

PAGE' LINE CORRECTION

10

11

12

13

14

15

16

17

18

19

20

211 DATE :'

22 Sworn and subscribed to before me on this

23 d a y o f -------~------------

24 NOTARY PUBLIC ------------------------------ m

25

WAGA & SPINELLI - (201) 992-4111


Vol . 4, Pg . 739

1 STATE OF NORTH CAROLINA


COUNTY OF YADKIN

REPORTER'S CERTIFICATE

I, Linda N . Russell, a'Notary Public in and

5 for the State of North Carolina, do hereby certify

6 that-there came before me on Monday, August 4, 1997,

7 the person hereinbefore named, who was by me duly

sworn to testify to the truth and nothing but the

9 truth of his knowledge .concerning the matters in

10 controversy in this cause ; that the witness was

11 thereupon examined under,oath, the examination

12 reduced to typewriting under my direction, and the

13 deposition is a true record of the testimony given

14 by the witness .

15 I further certify that I am neither

16 attorney or counsel for, nor related to or employed

17 by, any attorney or counsel employed by the parties

18 hereto or financially interested in the action .


~
~
19 IN WITNESS WHEREOF, I have hereto set my ~

L_ a E~~ "a ""~F „"4 ~ I 1 1- hi ..+


a
2V LlanGiaanCx ZlLL17Ce~d 'illy ~LLl~:iai aava.a+.~.vL i vv~+, .+. .+tha . ii~

21 12th day of August .1997 .

22

23 North t~tpia i VWkin


UNDA N. RUSSEL ~
-N~wPiei;,, ~'Li da N . Russ 11, Notary Public
24 #ly Oommfssbri EzDiros a-2S•qt„~,~,, , j Commission Expires 8/25/97

25

WAGA & SPINELLI (201) 992-4111


LAWYER'S NOTES
Pwo6 LINB

I*
LAWYER'S NOTES
LIN6

0
LAWYER'S NOTES
Pwoe LIN6

O
LAWYER'S, NOTES
PAGE LIN6

0
IN THE UNITED STATES DISTRICT COURT
FOR THE EASTERN DISTRICT OF PENNSYLVANIA
Civil Action No . 96CV-5903

STEVEN R . ARCH, WILLIAM BARNES, )


CIARAN McNALLY, CATHERINE POTTS, )
NORMA RODWELLER, BARBARA SALZMAN, ) CERTIFIED COPY
EDWARD J . SLIVAK and JOHN TEAGLE, )
)
Plaintiffs, )
Deposition of :
)
vs . ) Alan Rodgman,
) Ph .D .
THE AMERICAN TOBACCO COMPANY, )
INC ., et al ., ) Volume 5,
) Pages 740 - 1024
Defendants . )
)
----------------------------------)

(Caption continues . . .)

CONFIDENTIAL
TRANSCRIPT of testimony as taken by and

before LINDA RUSSELL, a Certified Shorthand

Reporter and Notary Public of the State of

North Carolina, at the offices of Womble Carlyle

Sandridge & Rice, 200 West Second Street,

Winston-Salem, North Carolina, on Tuesday, August 5,

1997, commencing at 9 :50 in the forenoon .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 741

SUPREME COURT OF THE STATE OF NEW YORK


COUNTY OF NEW YORK

------------------------------------)
PHYLLIS SMALL and DENISE FUBINI, )
individually, and on behalf of )
others similarly situated, )
)
Plaintiffs, )
)
- against - )
)
LORILLARD TOBACCO COMPANY, INC ., ) Index No .
LORILLARD, INC ., LOEWS CORPORATION, ) 110949/96
COUNCIL FOR TOBACCO RESEARCH-USA, )
INC . (Successor to Tobacco Industry )
Research Committee), AND TOBACCO )
INSTITUTE, INC ., )
)
Defendants . )
------------------------------------)

SUPREME COURT OF THE STATE OF NEW YORK


COUNTY OF NEW YORK

------------------------------------)
MARY ANN HOSKINS, Executrix of the )
Estate of Edwin Paul Hoskins, )
WALTINA BROWN and DANTE AUBAIN, )
individually, and on behalf of )
others similarly situated, )
)
Plaintiffs, )
)
- against - )
)
R .J . REYNOLDS TOBACCO COMPANY, ) Index No .
RJR NABISCO, INC ., COUNCIL FOR ) 110951/96
TOBACCO RESEARCH-USA, INC . )
(Successor to Tobacco Industry )
Research Committee), AND TOBACCO )
INSTITUTE, INC ., )
)
Defendants . )
------------------------------------)

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 742

SUPREME COURT OF THE STATE OF NEW YORK


COUNTY OF NEW YORK

-------------------------------------)
SHARLENE HOBERMAN and AUDREY HULSE, )
as Executrix, on behalf of the )
Estate of Lewis Hulse, individually, )
and on behalf of others similarly )
situated, )
)
Plaintiffs, )
)
- against - ) Index No .
) 110953/96
BROWN & WILLIAMSON TOBACCO )
CORPORATION, B .A .T . INDUSTRIES )
P .L .C ., BATUS, INC ., BATUS HOLDINGS, )
INC ., COUNCIL FOR TOBACCO RESEARCH- )
USA, INC . (Successor to Tobacco )
Industry Research Committee), AND )
TOBACCO INSTITUTE, INC . )
)
Defendants . )
-------------------------------------)


SUPREME COURT OF THE STATE OF NEW YORK
COUNTY OF NEW YORK

-------------------------------------)
ROSE FROSINA, ELIZABETH COLAVITO and )
ANILDA ROSS, individually, and on )
behalf of others similarly situated, )
)
Plaintiffs, )
)
- against - ) Index No .
) 110950/96
PHILIP MORRIS, INC ., PHILIP MORRIS )
COMPANIES, INC ., COUNCIL FOR TOBACCO )
RESEARCH-USA, INC . (Successor to )
Tobacco Industry Research Committee) )
AND TOBACCO INSTITUTE, INC ., )
)
Defendants . )
-------------------------------------)


WAGA & SPINELLI (201) 992-4111
Vol . 5, Pg . 743

SUPREME COURT OF THE ESTATE OF NEW YORK


COUNTY OF NEW YORK

--------------------------------------)
CATHERINE ZITO, PETER HOBERMAN, )
and GEORGE ELISSEOU, individually, )
and on behalf of others similarly )
situated, )
)
Plaintiffs, )
)
- against - ) Index No .
) 110952/96
THE AMERICAN TOBACCO COMPANY, INC ., )
AMERICAN BRANDS, INC ., COUNCIL FOR )
TOBACCO RESEARCH-USA, INC . )
(Successor to Tobacco Industry )
Research Committee), AND TOBACCO )
INSTITUTE, INC ., )
)
Defendants . )
-------------------------------------)


WAGA & SPINELLI (201) 992-4111
Vol . 5, Pg . 744

A P P E A R A N C E S :

J . D . LEE, ESQ .
422 Gay Street
Knoxville, Tennessee 37902
For the Plaintiffs in Pennsylvania case
(423) 544-0101

SHELLER, LUDWIG & BADEY


3rd Floor
1528 Walnut Street
Philadelphia, Pennsylvania 19102
BY : STEPHEN A . SHELLER, ESQ .
SHERRICE A . KNISELY, ESQ .
For the Plaintiffs in Pennsylvania case
(215) 790-7300

CLIMACO, CLIMACO, LEFKOWITZ &


GAROFOLI CO ., L .P .A .
Ninth Floor, The Halle Building
Cleveland, Ohio 44115

• BY : JACK D . MAISTROS, ESQ .


For the Plaintiffs in Pennsylvania case
(216) 621-8484

GOODKIND LABATON RUDOFF & SUCHAROW L .L .P .


100 Park Avenue
New York, New York 10017
BY : MARTIS ANN BRACHTL, ESQ .
For the Plaintiffs in New York case
(212) 907-0700

WOMBLE CARLYLE SANDRIDGE & RICE


200 west Second Street
Post Office Drawer 84
Winston-Salem, North Carolina 27102
BY : MARTIN L . HOLTON, III, ESQ .
For the Defendant R .J . Reynolds Tobacco Corp .
(910) 721-3600


WAGA & SPINELLI (201) 992-4111
Vol . 5, Pg . 745

A P P E A R A N C E S ( Cont inued )

• JONES, DAY, REAVIS & POGUE


Metropolitan Square
1450 G Street N .W .
Washington, D . C . 20005-2088
BY : ROBERT F . McDERMOTT, JR ., ESQ .
For the Defendant R .J . Reynolds Tobacco Corp .
(202) 8 7 9 - 3 9 3 9

MCCALL DOUGHTON & BLANCATO


633 West Fourth Street
Suite 150
Winston-Salem, North Carolina 27101
BY : WILLIAM A . BLANCATO, ESQ .
(910) 725-7531
For the witness Dr . Alan Rodgman

MILLER & MARTIN

• Suite 1000 Volunteer Building


832 Georgia Avenue
Chattanooga, Tennessee 37402
BY : MARCIA MEREDITH EASON, ESQ .
(423) 756-6600
For the Defendant Lorillard Tobacco Company


WAGA & SPINELLI (201) 992-4111
Vol . 5, Pg . 746

I N D E X

WITNESS DIRECT CROSS REDIRECT RECROSS

ALAN RODGMAN, Ph .D .

Mr . Maistros 747
Mr . Sheller 806
Mr . Maistros 990

E X H I B I T S

EXHIBIT MARKED
Exhibit 1 . 761

847

. . . . . . . . . . . . . . . . . 859

. . . . . . . . . . . . . . . . . 859

. . . . . . . . . . . . . . . . . 871

. . . . . . . . . . . . . . . . . 898

• Exhibit 7 .
7A .
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901
903
7B . . . . . . . . . . . . . . . . . . 903

910

928

937

. . . . . . . . . . . . . . . . . 940

Exhibit 12A . 951


12B . . . . . . . . . . . . . . . . . . 951

. . . . . . . . . . . . . . 954

972

. . . . . . . . . . . . . . . . . 996

996


WAGA & SPINELLI (201) 992-4111
Vol . 5, Pg . 747
r

1 ALAN RODGMAN, Ph .D .,

• 2 having been previously sworn, was examined and

3 testified further as follows :

4 VIDEOGRAPHER : This is day two of the

5 videotape deposition of Alan Rodgman, Ph .D . We're

6 going on the record, Tuesday, August 5th, 1997, at

7 9 :50 a .m .

8 EXAMINATION (Continued)

9 BY MR . MAISTROS :

10 Q . Good morning, Dr . Rodgman . How are

11 you?

12 A . Fine . And before we start, I'd like to

• 13

14
correct one thing from yesterday .

Q . Okay .

15 A . I had mentioned that in those boxes, wherever

16 they are, there were two notebook -- or material

17 from two notebooks about my publications . And

18 last night I was -- remembered that there is one

19 publication that is not in there . It's a paper

20 that Dr . Charles Green and I prepared for last

21 year's Tobacco Chemist Conference symposium . And

22 the symposium papers are published in a journal

23 called Recent Advances in Tobacco Science . And

24 our paper is in volume 22 .

• 25 The reason the copy isn't in there,

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 748

1 this is not a very well bound book . And if you

• 2 were to open it to copy it, the article is

3 170-something pages long, you would have to do

4 that for every double page to go on an

5 eight-and-a-half by eleven sheet . That book will

6 fall apart .

7 Now, if you want a copy, you can get

8 it from the North Carolina State University

9 library ; they have all the back available copies

10 of that journal, probably back to volume 9 or 10 .

11 Before that, they run out of them .

12 And, of course, the authors are given

13 five copies each, but I've given four of mine

14 away . So I only have the one left .

15 Q . That's pretty good, if that's the only

16 thing you want to correct from six hours .

17 A . Pardon?

18 Q . That's pretty good if that's the only

19 thing you want to correct from six hours .

20 A . Well I thought somebody would say : He did

21 something last year and it's not in there, and

22 picky, picky, picky . So I thought I'd correct it

23 right here and now .

24 Q . Not me .

• 25 Let me ask you about the six boxes of

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 749

1 documents . Where did they originally come from?

• 2 Were all these at your house, originally?

3 A . Yes .

4 Q . How did it come to be that you had

5 documents -- six boxes of documents at your house?

6 A . Well, some of them, I think, if you look at

7 them, were prepared since I retired, and some are

8 copies of the formal reports I wrote while I was

9 at Reynolds . And because of the peculiar way I

10 worked, during the daytime -- or normal working

11 hours -- for many years at Reynolds I was a lab

12 man . I did my research at the bench from 7 :30 in

13 the morning till five o'clock at night . And I did


• 14 a lot of my writing at home in the evenings ; much

15 to my wife's regret, I sometimes would write until

16 two o'clock in the morning . And in order to do

17 that, I would have pre -- previous reports I had

18 written so I could refer to the references, and so

19 on and so forth .

20 Q• And who did you turn these documents

21 over to?

22 A . When?

23 MR . McDERMOTT : Asked and answered .

24 BY MR . MAISTROS :

• 25 Q . Originally . Your attorney or RJR's

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 750

1 attorney?

2 A . Mr . Blancato .

3 MR . McDERMOTT : I believe we went into

4 this yesterday .

5 MR . MAISTROS : I'm trying to

6 establish -- yesterday we had some objections to

7 conversations with you and attorney/client

8 privilege, and I'm just trying to establish how

9 there's an attorney/client privilege there . And

10 I'll get to that very shortly .

11 MR . McDERMOTT : Well, the providence

12 of these documents was reviewed yesterday . And,

13 again, if there is concern about using time

• 14 efficiently, I suggest we get into new areas .

15 MR . MAISTROS : Well . . .

16 BY MR . MAISTROS :

17 Q . What is the attorney/client

18 relationship, if any, that you have with

19 Mr . McDermott? Do you have any attorney/client

20 relationship with Mr . McDermott?

21 A . Well he, I guess, represents Reynolds .


Ln
22 Q . And you are not currently an employee ~
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m
23 of Reynolds, are you?
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o.
24 A. No .

• 25 Q . So I want to know -- take me through

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 751

1 the conversations you've had with Mr . McDermott

2 concerning this case .

3 MR . McDERMOTT : Objection . Counsel is

4 well aware of the fact that attorneys for

5 corporate entities are allowed to consult former

6 employees under an umbrella privilege, in order to

7 determine facts and prepare a defense . We are

8 invoking privilege .

9 If you've got something you want to do

10 that doesn't deal with my conversations relating

11 to litigation, you can pursue that . If you want

12 to deal with other conversations Dr . Rodgman has,

13 that's fine . But it is absolutely specious to

14 suggest that I cannot communicate with Dr . Rodgman

15 about events that occurred while he was an

16 employee that are not covered by privilege .

17 That's nonsense .

18 BY MR . MAISTROS :

19 Q• And you -- do you consider yourself a

20 private person in this litigation?

21 A . I consider myself a private person, I guess .

22 I'm here because I was deposed .

23 Q . Do you consider yourself as working

24 for Reynolds in this litigation?

A . No, not really . No .


,

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 75 2

1 Q . And you're not being paid in any

• 2 fashion in the Arch litigation ?

3 A . I was not paid for Minnesota ; I'm not being

4 paid in Arch . In fact, I'm probably the only one

5 around this table that's not getting paid .

6 Q. The documents were not provided to -

7 from you to Mr . McDermott or any other RJR

8 attorney, they were provided to your personal

9 counsel, correct ?

10 A . That's right .

11 Q. Do you know what he did after he go t

12 them?

13 MR . BLANCATO : Well, he doesn't have

14 to disclose any priv -- that would be privileged .

15 BY MR . MAISTROS :

16 Q . Do you know what he did after he go t

17 the documents ?

18 A . He arranged for them to be copied .

19 Q . Do you know what he did after that ?

20 MR . BLANCATO : Well, wait a minute .

2 1 You know -

22 MR . MAISTROS : How is that privileged?


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23 I'm trying to establish how the documents got from N
m
24 the garage to this room . If you can tell me ho w Ln

• m
CO
25 they got from the garage to this room, do that .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 753

1 THE WITNESS : From the garage --

• 2

3
MR . MAISTROS : I don't know how that's

privileged .

4 THE WITNESS : What garage are you

5 talking about?

6 BY MR . MAISTROS :

7 Q . Your house, whatever . Where did you

8 store them?

9 A . There --

10 MR . McDERMOTT : Object . Asked and

11 answered .

12 MR . MAISTROS : Let's speed this up .

13 BY MR . MAISTROS :

• 14 t2 • Can you tell me how the documents got

15 from your possession to this room?

16 MR . BLANCATO : Can I answer it?

17 MR . MAISTROS : If you know .

18 MR . BLANCATO : They were given to me .

19 We had them photocopied . A set was made for the

20 Reynolds attorneys, and the set that was here

21 yesterday was Mark Holton's extra set of those

22 photocopies . It should be the same -- a duplicate

23 set of what was sent to Ms . Knisely .

24 MS . KNISELY : Actually, I might be

• 25 able to shed some light on that, if I might .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 754

1 From what I understand in my

2 conversations with McDermott and Mr . Holton, as

3 well as Mr . Blancato, and please correct me if I'm

4 wrong, those documents -- those documents were

5 originally provided to Mr . Blancato ; but I also

6 understand Mr . Blancato then provided them, prior

7 to the first deposition of Dr . Rodgman, to Womble

8 Carlyle, and most particularly, Mr . Holton went

9 through them originally to review for privilege,

10 as well as work product .

11 The two -- possibly one to two boxes

12 were provided at the last deposition . Our office

13 was advised that there were three to four other

• 14 boxes that had -- were being withheld for the

15 purpose of reviewing them again for privilege by

16 Reynolds' counsel . We were provided a subsequent

17 list of those withheld documents, minus any

18 privileged and a privilege log .

19 We've also been supplied a

20 supplemental privilege log, because I understand

21 Dr . Rodgman has reviewed his documents at home and

22 provided, I don't know who first, with copies of

23 two additional documents . And we received last

24 Fri -- Thursday or Friday, from Mr . Belasic, an

• 25 additional supplemental privileged log for two

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 755

1 additional documents .

• 2 Now, we were not advised of that by

3 Mr . Blancato . The privilege log did not come from

4 Mr . Blancato . I also understand that the copies

5 of the documents were made here at Womble Carlyle .

6 Now, I also understand that perhaps

7 Dr . Rodgman may or may not have been present

8 during various review processes of the documents .

9 Is that all accurate?

10 MR . BLANCATO : No .

11 MR . McDERMOTT : I don't know the

12 extent to which it's accurate or not . But let me

13 suggest, to the extent you all are concerned about

• 14 time, this does not concern Dr . Rodgman, as such .

15 The lawyers can spar among themselves over breaks

16 and after Dr . Rodgman goes . If this is how you

17 want to use your time with the witness in the

18 chair, we can have lawyers talking all day long .

19 I suggest it is not a particularly fruitful

20 expenditure of time, however .

21 MS . KNISELY : I believe Mr . Maistros

22 was trying to go into the questioning of the chain

23 of custody of the documents and Dr . Rodgman's

24 knowledge of that .

• 25 MR . McDERMOTT : And I --

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 756

1 MS . KNISELY : And I think that's

• 2 perfectly appropriate .

3 MR . MCDERMOTT : And I believe you will

4 find that Dr . Rodgman doesn't know that the

5 documents passed from his hands, as indicated, and

6 it was Mr . Blancato who was providing further

7 information . Use your time as you wish .

8 MR . MAISTROS : I will offer -- I will

9 offer, once again, to a stipulation that the --

10 insofar as authenticity is concerned, that we have

11 a stipulation on those six boxes of documents . I

12 don't think we've put that in the record . You've

• 13

14
declined that, just so the record is clear .

So I will go through, and you can take

15 a break if you want to do this . I want you to go

16 through the six boxes today and tell me which ones

17 you have problems that aren't authentic, aren't

18 original -- or copies of originals, and you would

19 dispute are not of business records of Reynolds .

20 You can do that at lunch, you can do it tonight, I

21 don't care when you do it . I'm not going to take

22 the time up today . But unless we get a

23 stipulation, I want you to go through those six

24 boxes .

0 25 1 THE WITNESS : Sir, I've been through

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 757

1 those six boxes .

2 BY MR . MAISTROS :

3 Q . And you believe they're all business

4 records of Reynolds?

5 MR . BLANCATO : Object to the form .

6 BY MR . MAISTROS :

7 Q . Other than the ones that you did

8 before you joined Reynolds and the ones that you

9 did after you joined Reynolds?

10 MR . McDERMOTT : Object to the form .

11 THE WITNESS : Well, I wasn't sure what

12 you folks really wanted . And I think you'll find,

0 13 for example, obituaries of my two mentors at the

14 University of Toronto . You'll find an award I was

15 given for -- the testimony I was -- for an award I

16 was given for my participation in Little League

17 programs, and things like that . I just put it all

18 in there and you've got it .

19 MR . McDERMOTT : And, again, we're not

20 claiming any of those documents are fraudulent .

21 So as to authenticity, what you said is not

22 correct .

23 We spoke last night, outside, after

24 the deposition, about breaking the documents down

25 into categories . Those documents which are

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 758

1 clearly copies of Reynolds' materials and

2 Reynolds' records we're not going to be picayune

3 about .

4 There are materials in those boxes,

5 however, which are not business records of

6 Reynolds . We talked about segregating them into

7 categories ; we can do that now or later . But to

8 suggest that we are responsible for your not

9 having examined the documents and been a little

10 bit more systematic about how we treat these

11 documents is again nonsense . I suggest that we

12 use this witness' time more efficiently than we

• 13

14
are doing now .

MR . SHELLER : I just want to put

15 something on the record that -- I would note that,

16 when we had the conversation with the judge's law

17 clerk, Judge Newcomer's law clerk, Mr . Blancato

18 was agreeable to allow me to question the witness,

19 rather than bother Judge Newcomer on vacation or

20 have the other law clerk intervene, when

21 Mr . McDermott interfered and told Mr . Blancato to

22 wait for the second law clerk's call at 11 :00 a .m .

23 to see what he said . I would also note that I

24 watch Mr . McDermott constantly coaching

• 25 Mr . Blancato .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 759

1 Mr . McDermott, if you want to

2 represent Mr . Rodgman, why don't you change seats

3 with Mr . Blancato . Otherwise, I suggest that

4 Mr . Blancato, if he really is Mr . Rodgman's

5 counsel, that you leave him alone and stop

6 interfering with his decision processes .

7 MR . McDERMOTT : I will respond to this

8 nonsense after Dr . Rodgman is gone . If you keep

9 giving speeches, Mr . Sheller, I will not look

10 kindly on your petition for more time . I think

11 you've burned that bridge already .

12 BY MR . MAISTROS :

13 Dr . Rodgman, I would like to take you


• 14
Q .

through the manufacturing process and your

15 knowledge of the same at Reynolds during the years

16 you were there, okay?

17 You have been -- I'll show you --

18 we'll mark it later . I only have one copy . It's

19 a designation of yourself that was provided in the

20 Texas litigation . And I'd ask you, before I have

21 it marked, have you seen that document before?

22 (Witness reviews document)


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23 A . I saw this a couple of minutes before we met ~
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24 here this morning . ,P.
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• 25 Q . Who showed you that? "'


J

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 760

A . The gentleman here .

Q . Which gentleman?

A . Mr . McDermott .

Q . And what was his purpose of showing

you that?

A . Well, because yesterday it was -- you had

mentioned that I was supposed to be an expert in

manu -- things about manufacturing . And I said

something to the effect that I was not an expert .

10 Now, this business about manufacture,

11 the one that was -- the opinion list that was sent

12 to Texas does not have that in there .

13 I did not write this . I didn't --

14 I've never seen it till this morning .

15 Q . Are you suggesting, then, that the

16 designation that's in this exhibit, which we'll

17 mark Rodgman Exhibit 1 for purposes of this

18 deposition, is accurate? You are going to testify

19 concerning the design, construction, manufacture

20 of cigarettes?

21 A . Well, I think, someplace down later on in

22 there, it says familiarity with manufacturing

23 processes in general . And I would agree that I

24 know a little bit about it, but I am not an expert

• 25 in the manufacture of cigarettes .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 761

1 (Plaintiff's Exhibit Number 1 was

• 2 marked for identification)

3 BY MR . MAISTROS :

4 Did you know you were going to testify

5 in Texas with respect to the design, construction

6 and manufacture of cigarettes?

7 A . As I say, this -- I saw this, this morning .

8 It's different from the one that I had seen

9 earlier, which is three pages long .

10 MR . McDERMOTT : For the record,

11 counsel, this is a preliminary disclosure which

12 was produced some weeks ago in accordance with the

• 13

14
case management order where the final list of

Dr . Rodgman's opinions was filed, or at least

15 provided to opposing counsel last week .

16 BY MR . MAISTROS :

17 Q . Do you have knowledge concerning the

18 design, construction and manufacture of cigarettes

19 at Reynolds?

20 A . Well, that's an all-sweeping statement, sir .

21 I know -- as I say, I know a little bit about the

22 manufacturing . I know a little bit more about the

23 design . As you know, most of my work has been

24 involved in the smoke composition, it's con -- and

• 25 its control .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 762
r

1 Q . And what do you know about the

2 manufacturing process?

3 A . Well, as I mentioned in my testimony

4 yesterday, when you buy tobacco on the auction

5 market, the first thing you do, you bring the

6 tobacco in to the facility, stemery . You

7 moistened it ; you warm it so it doesn't fragment ;

8 you cut out the stems . You store the lamina

9 separately from the stems, and they're stored in

10 sheds for various periods of time, usually from 12

11 to 15 months, up to two years . And while they're

12 in the storage shed, the tobacco slowly changes in

13 certain ways .

14 And when it's withdrawn from the shed

15 at the appropriate time for manufacture, it's

16 taken out of the containers, it's moistened,

17 warmed ; it's called "reordering ." And if you're

18 talking flue-cured tobacco or burley, then you

19 start your blending process . It's done in --

20 usually in two lines : Part of the blend is done

21 in one line, part in another . Because you also

22 have to bring in Oriental tobacco and Maryland

23 tobacco . Oriental tobacco comes from abroad and

24 has to go through customs, and so on and so forth .

0 25 And at that point, the stems, of

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 763

1 course, can be used to make reconstituted tobacco .

2 That is incorporated in part of the blend . And

3 part of the tobacco, the flue-cured burley part,

4 is expanded . And that whole thing comes together

5 and mixed, and it's cut . And there you have the

6 blend for the -- what goes into the cigarettes .

7 And that -- the last thing that's done

8 on the cigarette is called -- the cutting and

9 casing operation is when the casing materials and

10 flavorants are added and the cigarette blend is

11 all ready to be run through the cigarette-making

12 machine .

13 And at that point it's put in hoppers


S 14 to feed the cigarette-making machine . It runs

15 through the cigarette-making machine ; the paper's

16 wrapped around it and stuck together . The filters

17 are inserted into the cigarettes in pairs .

18 Cigarettes are cut -- the tobacco rod

19 part is two units long and it's cut in the middle,

20 and the double filter is dropped in between and

21 they're attached . And at that point the thing is

22 cut in half and -- through a very neat, little Ln


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23 device that Reynolds invented . The one set of ~

24 cigarettes is flipped over so they're all facing Ln


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• 25 the same way, and then they're inserted in


to

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 764

packages . The packages are sealed . The packages

• are incorporated into the cartons, and the cartons

are incorporated into big cartons, and they're

shipped out the door .

Q . At what point in the manufacturing

process does Reynolds know that a certain tobacco

is going to end up in a certain brand of its

cigarettes?

MR . McDERMOTT : Object to the form of

10 the question .

11 THE WITNESS : Sir, I have very little

12 knowledge about the precise nature of blends and

13 how they're put together .

• 14 BY MR . MAISTROS :

15 Q . Do you know what's added to the

16 cigarettes in the manufacturing process?

17 MR . MCDERMOTT : Object to the form of

18 the question .

19 MS . EASON : Object to the form of the

20 question .

21 BY MR . MAISTROS :

22 Q . What compounds?

23 A . I know something of the -- what goes into the

24 casing material .

• 25 Q . Do you know if there's a compound

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 765

1 that's applied to the tobacco itself during any

2 portion in the manufacturing process?

3 A . Would you say that again, sir .

4 Q . Is there a compound that's applied to

5 the tobacco itself during the manufacturing

6 process?

7 A . Yes .

8 Q . What compounds?

9 A . Well, glycerin, propylene glycol, licorice,

10 sugar, cocoa, and then the flavor formulation .

11 Q . Anything else?

12 A . Well, during the expansion of the tobacco

there is an agent used in the expansion -- or was


• 13

14 used ; it's no longer used at Reynolds .

15 Q . What's that?

16 A . It's Freon 11 .

17 Q . And what years was Freon 11 used?

18 A . 1969 to sometime after I left Reynolds . I

19 don't know when they quit using it .

20 Q . What is Freon 11?

21 A . Freon 11 is similar to the material that's in

22 your air conditioner -- car air conditioner and

23 your refrigerator . It's called a

24 chlorofluorocarbon .

• 25 Q . Who developed the process to use

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 766

Freon 11 during the manufacturing process?

A . The original work was done by Dr . James D .

Fredrickson in the laboratory . And then two other

gentlemen developed the engineering aspects of the

process --

Q . What was the original --

A . -- Moser and Stewart .

Q . I'm sorry . What was the first one?

A . Moser, M-O-S-E-R ; and Stewart, S-T-E-W-A-R-T .

10 Q . What was --

11 A . And there were two patents issued to these

12 gentlemen ; one the theory part and one the

13 engineering part . They were issued the same day

• 14 and are sequential in the patent list .

15 Q . This process went till sometime after

16 1987?

17 A . I don't know when they quit using Freon 11 .

18 Q . Do you know why they quit using it?

19 A . Because of the ozone question .

20 Q . What was the ozone question? Ln


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21 A . Well, freon is a very -- well, extremely m


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22 inert substance . That's, you know, why it's N

23 used -- how it became used as a refrigerant .

24 However, when freon vaporizes -- it's a liquid ; it

25 boils at a very low temperature . When it

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 767

1 vaporizes, it rises through the atmosphere and is

• 2 so inert that very little happens to it until it

3 gets into the stratosphere . And then it comes

4 apart on the effect of intense sunlight . And,

5 supposedly, part of the degradation products

6 combined with oxygen -- combined with ozone in the

7 stratosphere and -- convert ozone, which is a

8 trimolec -- triatomic form of oxygen, breaks it

9 down into regular oxygen . And when that layer

10 thins, the ozone layer thins, more types of

11 sunlight can get through to the earth's surface .

12 And that's supposed to cause all sorts of

• 13

14
problems .

So, some years back, I forget the

15 exact year, there was a move to diminish --

16 decrease the use of ozone freon -- Freon 11 and

17 Freon 12, which were the two main compounds used

18 in refrigeration .

19 Q . Was there -- prior to '69, was there

20 expansion of tobacco at Reynolds?

21 A. No . That's -- well, experimentally there

22 was . Dr . Fredrickson did the work in -- I believe

23 it was '63 that he actually did the lab work,

24 looking at a whole variety of solvents that could

• 25 be used in the expansion process .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 768

1 And from then till 1968/'69, we were

2 looking at -- Reynolds was looking at the

3 incorporation of expanded tobacco into blends and

4 whether the consumers would accept this . And they

5 did, on test panels and market testing and so on .

6 And it was, I believe, introduced into Reynolds'

7 products -- it was either late '68 or early '69 .

8 Q . And do you know if there were other

9 expansion processes being used, other than the use

10 of Freon 11?

11 A . Well, when we came up with the expanded

12 tobacco, it was -- I don't know whether you're

13 familiar with how competitors look at each other' s

14 products, but when somebody has a -- products are

15 monitored frequently by competitors . And of

16 course it did not take long for some of our

17 competitors -- what they do is you take a bunch of

18 cigarettes, and you cut the paper off, and you

19 have a pile of tobacco . And you have some

20 technicians, who are usually very skilled at it,

21 and they pick out the burley tobacco, the


Ln
22 flue-cured tobacco, the oriental tobacco, the ~
~
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m
23 reconstituted tobacco sheet, and say : Look, you
~
Ln
OD
24 know, what's Reynolds got in this blend? Or we 4~1

0 25 look and say : What's Philip Morris got?

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 769

1 Well, it's obvious, when they picked

2 apart the Winston in 1968 or '69, whenever it was

3 issued, they got a fifth pile . You know, what's

4 this tobacco that's all fluffy? And so everybody

5 knew that we had expanded tobacco .

6 Now, people had been trying to expand

7 tobacco for years . They could succeed in

8 expanding stems, but no one had been able to

9 expand the lamina of tobacco - that's the leaf

10 part - until Dr . Fredrickson discovered how to do

11 it .

12 And, of course, soon after that, some

13 other people -- Philip Morris came up with an

14 expansion process of its own . Prior to that, we

15 elected to -- if anybody wanted our process, we

16 would license our expansion process to anybody who

17 was willing to pay the licensing fee . And the

18 Japanese tobacco company, which is an immense

19 company, licensed it ; Lorillard licensed it, L & M

20 licensed it . Eventually our process was licensed

21 in probably 25, 30 countries around the world .

22 But Philip Morris elected not to

23 license it, our process . And that's because they

24 had been responsible, primarily, for all the

patents on expansion of stems, and I think they

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 770

1 were a little miffed that they had worked so long

2 trying to expand tobacco, had been successful in

3 stems and unsuccessful with lamina . And I think

4 there's a bit of pride there .

5 So they had developed a process of

6 their own - it involved the use of different

7 expansion agent - and used that in their own

8 c i garettes .

9 Q. Which agent?

10 A . It was -- it was called ammonium carbonate .

11 Q . Back to my original question ; maybe

12 you misunderstood it .

• 13

14 process,
Did RJR use any other expansion

other than Freon 11?

15 MR . McDERMOTT : During what time

16 f rame ?

17 MR . MAISTROS : '69 to when you ceased

18 working, consulting or advising RJR, whatever it

19 is .

20 THE WITNESS : Well, when I left they

21 were still using Freon 11 .

22 BY MR . MAISTROS : Ln
~
J
N
23 Q. Was that the only expansion process m
~
Ln
24 RJR use d? CO
m

• 25 A . Well, we kept looking at different things .


i

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 771

1 For example -- as I say, Dr . Fredrickson looked

2 at -- and I think if -- you probably have it

3 someplace, his report in 1963 ; he must have looked

4 at 15 different solvents . And there was a problem

5 with them, and primarily in manufacturing, that

6 some of the solvents -- for example, ethyl alcohol

7 will work ; hexane will work ; pentane will work .

8 But one of the problems is, here you

9 have this facility to expand tobacco with pentane

10 or hexane, and I'm sure you know that they are

11 components of gasoline . And they're -- hexane --

12 gaseous hexane and air is a very explosive

13 mixture .

14 And -- but Freon 11 was designed in

15 edict by Boss Kettering at General Motors to be

16 inert, non-flammable and usable in a car engine

17 for air conditioning of the car . So it does not

18 burn ; it's not explosive ; it has very little -- in

19 fact, it was so inert it has very little

20 biological effect on anything . And so we -- of

21 the 15 or 20, I forget the exact number that

22 Dr . Fredrickson looked at, we ended up using

23 Freon 11 .

24 Q . Did Reynolds test the biological

0 25 effects of Freon 11 before it incorporated it in

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 772

1 the manufacturing process?

2 A . Well, we didn't need -- we did . But we

3 didn't really need to, because Freon 11 is the --

4 was a patented or copyright, whatever -- a product

5 owned by DuPont . And they had done so much work

6 on the biological properties of Freon 11, Freon

7 12, that acceptance of their data -- but we did do

8 some things to see how it affected tobacco smoke .

9 4• Were studies done to determine

10 biological effect of taking Freon 11 through the

11 respiratory system?

12 A . Not by us . But Philip Morris -- not Philip

13 Morris, DuPont had done that .

14 In fact, the FDA had approved -- I

15 don't know whether any of you have had -- have

16 asthma, but for many years there were little

17 propellant gadgets with medication in them that

18 you placed against your nostrils and pressed the

19 button and, psst, psst, you got shots of the

20 medication plus the propellant .

21 Well the propellant, in most

22 instances, was either Freon 11 or a mixture of

23 Freon 11 and 12 . And that had all been checked

24 out by the FDA and so on . And in using those

inhalers, the amount you got on one squirt was

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 773

1 something between 25 and 35 milligrams, which

• 2

3
would -- say, 25 milligrams is 25 million

nanograms, which was the equivalent of what was in

4 the smoke of many, many cigarettes, but less than

5 a nanogram of Freon 11 in the smoke of one

6 cigarette after we made it .

7 Q . Did -- to your knowledge, did DuPont

8 test Freon 11 in a state after it had been burned,

9 such as in a smoking process?

10 A . No . But over at Triangle -- Research

11 Triangle, there was a group that was doing work on

12 various things . And I don't know whether you

13 remember that, at one time, there was a big

14 problem with -- in Philadelphia, with what turned

15 out to be called the Legionnaire's disease . And

16 the cause of Legionnaire's disease was -- the

17 first cause was that an air conditioner or

18 refrigerator had malfunctioned and there had been

19 a fire, that the Freon 11 or 12, what was ever

20 used in the refrigerator, had decomposed or

21 something during this fire, generating phosgene,

22 which was a World War I gas used by the Germans to

23 kill Allied troops . And that was supposed to be

24 the cause of Legionnaire's disease .

• 25 Well, this group over at Research

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 774

1 Triangle took Freon 11 and studied its effect on

• 2 combustion, studied its effect on -- in cigarette

3 smoke, and the formation of cigarette smoke, and

4 so on and so forth, and found that it does not

5 generate phosgene . But -- and then, of course,

6 Legionnaire's disease was found to be an entire -

7 caused by a bacteria of some type, which -- whose

8 name escapes me .

9 Q . What year was that research done?

10 A . Over at the Triangle? Oh, early '70s, I

11 would say . I forget .

12 But we did in-house -- one of the

13 things we worried about was the effect of -- would

14 Freon 11, during the com -- smoking process, form

15 phosgene . Because, if you look at the structure

16 of phosgene, the structure of Freon 11, it's

17 obvious that, given the right circumstance, it was

18 possible .

19 So we did a study, great detail ; we

20 had to develop all the analytical procedures for

21 it, to determine nanograms of phosgene, and so on

22 and so forth, in smoke . And we conducted it --

23 could find no phosgene in the smoke of a cigarette

24 made with expanded tobacco, with a lot more freon

• 25 than would be in a commercial product . We had

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 775

1 that checked by a contract lab, Industrial

• 2 Bio-Test . They came up -- they couldn't find it .

3 And as I say, the group over in Research Triangle

4 couldn't find anything wrong with -- at least

5 phosgene generation .

6 Then a man in Germany, because we were

7 going to license our process in Germany, he looked

8 at the question, because I had given presentation

9 to several companies in Germany on our process as

10 part of the licensing ploy . And he was intrigued

11 by it all . And -- and he was a physical chemist .

12 And he took -- looked at the thing

13 from phosgene and the conditions in a burning


• 14 cigarette and said : You folks didn't need to do

15 the experiments . That if you just looked at the

16 thermodynamic calculation, it's impossible to

17 generate freon -- phosgene from freon in a burning

18 cigarette .

19 Q . Let me just cut you off for a second,

20 because I know time is a concern .

21 The question was that, prior to using

22 Freon 11 in the tobacco manufacturing process, Ln


N
~
23 first, did Reynolds do any testing to determine m
4~-
24 the effect of burning of the Freon 11? ~
N

• 25 A . I just told you .


1

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 776

1 Q . I don't think you answered my

2 question .

3 Prior to the use of Freon 11 in the

4 manufacturing process, did RJR do any testing to

5 determine the effect of burning the freon?

6 A . Between 1963 and 1970, sir, we did the

7 phosgene work ; we did what's called a material

8 balance study .

9 If you end up with a cigarette blend

10 that's got so much -- a certain percentage of

11 expanded tobacco and that expanded tobacco has so

12 much freon on it - and here we're talking

• 13

14
nanograms, parts per million - that we examine

what happened to that freon during smoking ; where

15 did it end up? Obviously, if it didn't form

16 phosgene, it exits the smoke -- exits in the smoke

17 as Freon 11 itself . And we determined what was in

18 the mainstream smoke, the sidestream smoke, how

19 much was retained in the cigarette filter, so on

20 and so forth, and could account for everything in

21 the Freon 11 business of where it ended up in the

22 smoke . That was all done before it ever went into

23 the cigarette .

24 Q• Did you determine if there were any

• 25 other compounds that were created during the

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 777

1 burning process as a result of the addition of

2 Freon 11?

3 A . I just finished telling you . Freon 11 is so

4 inert that -- if it won't form phosgene, it won't

5 form anything else . Now, we could account for, in

6 our material balance study, if you had -- and here

7 I'll just pick a figure, because I'm sure you have

the document that I wrote -- put together on the

9 T13 process, and I've forgotten the numbers . But

10 say you had ten nanograms of Freon 11 on a

11 cigarette . You get so much in the mainstream

12 smoke, so much in the sidestream smoke, so much in

• 13

14
the -- the tobacco part of the butt, so much in

the filter tip . And then, in the way you

15 determine this, there was some Freon 11 on the

16 walls of the gadgetry where you collect the smoke,

17 which is a very small amount . So if you had ten

18 nanograms to start with, we could account for all

19 of it .

20 MR . McDERMOTT : Let me point out,

21 counsel, that the report Dr . Rodgman just referred

22 to is, in fact, attached as an exhibit to the

23 first part of this deposition, and a lot of this

24 was covered in detail in the initial part of the

• 25 deposition . But you may use your time as you w

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 778

1 choose .

• 2 BY MR . MAISTROS :

3 Q . Did you do any tests to determine the

4 effect of Freon 11 -- or the burning of Freon 11

5 on nicotine content or yield of the tobacco?

6 A . No . The -- part of the -- well, indirectly .

7 You -- you asked about freon itself . But,

8 obviously, if you have expanded tobacco in a

9 cigarette, you have less tobacco in the cigarette .

10 Correct? Then, when you smoke that cigarette,

11 you're going to get less nicotine in the smoke .

12 And if you look at the Surgeon

• 13

14
General -- not the Surgeon General, I'm sorry, the

National Cancer Institute study, they repeated and

15 confirmed the effect of our expansion process,

16 Philip Morris' expansion process, and the one

17 developed at North Carolina State, which was

18 actually a freeze-dried tobacco that was expanded .

19 All of them were significant in their

20 contribution, if you will, to a less hazardous

21 cigarette, but all of them dropped the nicotine in

22 the smoke . And that's in the data and -- by our

23 National Cancer Institute .

24 Again, though, the primary motivation

S 251 behind expanded tobacco was not to drop nicotine,

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 779

1 was it?

2 A . Well, I think I mentioned yesterday, when we

3 talked about the technologies, if you read

4 Dr . Fredrickson's proposal --

5 Q . I'm going to cut you off because I

6 want a specific answer to this specific question .

7 Did RJR develop the expansion process to reduce

8 nicotine or did they do it so that they could --

9 A . If you let me answer the question, sir .

10 There's one -- two purposes for

11 expanded tobacco . One, money . The second was to

12 design a cigarette that would have reduced total

• 13

14
particulate matter in the smoke . And if you

reduce the total particulate matter in the smoke,

15 you would reduce the nicotine .

16 Q . What was the first purpose of

17 expansion of tobacco? Out of the two .

18 MR . McDERMOTT : Objection . Asked and

19 answered .

20 BY MR . MAISTROS :

21 Q . It was money, wasn't it? The primary

22 purpose was money?

23 A . Well, he had two things in his report .

24 Q. Wasn't the primary purpose of the

0 25+ expanded tobacco process -

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 780
I

1 A . No, it wasn't .

2 Q . It wasn't money? It was to reduce the

3 particulate matter?

4 A . No, it -- I will say that -- make -- make

5 them equal, if you want .

6 Q . I invite you on a break to go over the

7 six boxes of documents and show me one where

8 reduction of particulate matter was mentioned

9 above money .

10 MR . MCDERMOTT : Objection .

11 MR . BLANCATO : Objection to form .

12 BY MR . MAISTROS :

Q . The very first document that ever was

created that discussed Freon 11 and the expansion

15 of tobacco, do you know if it ever mentioned the

16 goal of reducing the particulate matter in the

17 smoke?

18 A . Well, as I say, Dr . Fredrickson's first memo

19 didn't mention any specific solvents, because he

20 didn't know which ones would work, if any .

21 Q . Didn't his first memo say that the

22 primary advantage of expansion of tobacco was to 1-n


~
~
23 use less tobacco in the cigarettes and thereby m
~
24 increase the profits to Reynolds? Ln
m

25 A . I don't know whether he had it that -- you

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 781

1 probably read it more recently than I have, but I

• 2 don't remember him saying it that way .

3 Q . Did you examine the other tobacco

4 manufacturers' processes that they used to expand

5 tobacco?

6 A . Yes . We looked at ammonium carbonate .

7 Q . How did -- I'm sorry .

8 A . We looked at carbon dioxide puffing, which

9 actually other people looked at . Nitrogen was

10 used by some people . And of course -- we did not

11 spend much time looking at the process North

12 Carolina State University had, the freeze drying

13 procedure .

• 14 Q . The ammonia process, what's the full

15 name, do you know, that you mentioned?

16 A . Pardon?

17 Q . The ammonia process that you

18 mentioned, what's the full name?

19 A . Well, it's -- ammonium carbonate is the

20 expansion agent, mixture of ammonium carbonate and

21 ammonium bicarbonate .

22 Q . And which companies were using that

23 process?

24 A . Philip Morris ended up with the U .S . patent

• 25 for it .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 782

1 S2 • Did you study how the ammonium

2 carbonated -- carbonate affected nicotine content?

3 A . We -- we looked at the ammonium carbonate as

4 an ex -- expansion means . I don't know whether --

5 a man called Charles D . Mays did the work on the

6 ammonium carbonate expansion . I don't know what

7 he looked at in terms of nicotine .

8 But the chances are that, if you --

9 looking at the ammonium carbonate puffed tobacco

10 that was involved in the National Cancer Institute

11 study, that the nicotine level in the tobacco was

12 reduced . And I have -- I would take a guess that

13 Charles Mays found the same thing when he did --

14 checked it at Reynolds . But I -- I can't say that

15 for sure .

16 Q . Did you explore the possibility of

17 Reynolds using the ammonium carbonate method of

18 expansion?

19 A . No -- well, let me back up on that .

20 At -- at -- when we were looking at

21 various expansion methods, of course we were very

22 pleased with the Freon 11 exercise .

23 Dr . Fredrickson looked at other things, and one of

24 them happened to be ammonium carbonate .

• 25 In fact, if you look at the patents

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 783

1 issued in the -- I think it's Belgium, Reynolds

2 has the first patent on -- was issued a patent on

3 ammonium carbonate before Philip Morris . We did

4 make a mistake, I guess you would consider it a

5 mistake, that we decided not to file a patent in

6 the United States, and Philip Morris -- I think

7 the rule is you have to file -- if you have a

8 foreign patent, you've got to do it within a year .

9 Philip Morris filed the patent in the

10 United States, so they had the patent on ammonium

11 carbonate puffing . And -- even though ours, in

12 Europe, preceded theirs .

13 But we had looked at it ; we looked at


• 14 many things . We looked at carbon dioxide as a

15 puffing agent and --

16 Q . And you said you looked at nitrogen?

17 A . Now, somebody else had reported nitrogen . We

18 checked to see how that would work . It's a little

19 difficult to handle, because, to get it to work,

20 you have to have liquid nitrogen, and liquid

21 nitrogen is -- requires a temperature of, I don't

22 know, minus 270-something degrees .

23 Q . Do you know who was using nitrogen

24 process?

• 25 A . I don't know whether anybody was using it .


i

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 78 4

1 It was reported that it would expand tobacco . I

2 don't know if it was in a patent or what .

3 Q . Did you -- are you saying that

4 Reynolds didn't seriously explore the use of

5 nitrogen to expand tobacco ?

6 A . Well, we looked at it . As I say, from

7 1970 -- '68, '69, till I left, they were still

8 using Freon 11 . And so were all the people that

9 licensed it from us .

1 0 Q . Was Reynolds using any other expansio n

11 processes for tobacco that was sold and markete d

12 overseas?

• 13

14
A . No .

Q. To your knowledge, then, the onl y

15 expansion process Reynolds has ever used is th e

16 Freon 11?

17 MR . McDERMOTT : Objection ; misstates

18 prior testimony .

19 THE WITNESS : Until I left . I think

20 I've said that about five times, sir .

21 When I left Reynolds in 1987, they

22 were using Freon 11 . And if they're using

23 anything else since then, I have no idea what it

24 would be .

• 25 BY MR . MAISTROS :
1

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 785

Q . Do you know who was using carbon

dioxide expansion?

A . A company called Airco was the one that

pioneered the use -- or at least pushed the C02

expansion of tobacco . And that was another case

where Reynolds had actually been the first to look

at C02 expansion and decided not to proceed with

it because it took rather bulky machinery, and so

on and so forth, and was no less effective

10 than was -- than our process . And, of course,

11 subsequently, Airco got the patent on it, I

12 believe --

• 13

14
Q . Do you know if Reynolds ever used

ammonia or any compound related to ammonia in the

15 manufacturing process, other than -- let's

16 back up .

17 In any fashion, were you aware that

18 Reynolds used ammonia in the manufacturing

19 process?

20 A . Well, I think I said yesterday, they used

21 ammonia to denicotinize high nicotine tobaccos

22 down to whatever level they wanted . And I can't

23 think of the date, but at one time they were

24 using -- ammoniating their reconstituted tobacco

• 25 sheet .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 786

1 Q• Why did they use ammonia on their

• 2 reconstituted tobacco sheet?

3 A . Well, they were trying to -- in the Philip

4 Morris products, the -- their reconstituted

5 tobacco sheet is made by an ammoniate -- ammonia

6 process . And when Marlboro be -- began to look

7 like such a winner, we wondered, well, should we

8 do something to our sheet to -- to imitate the

9 ammoniated effect of the Philip Morris sheet, and

10 we obviously couldn't use -- without royalties and

11 so on, the procedure used by Philip Morris, which

12 involved treatment of the sheet material with an

• 13

14
ammonium salt .

Q . Do you know why Philip Morris did

15 that?

16 A . I guess they wanted a sheet of their own .

17 Q . No . What is the chemical effect of

18 adding ammonia salt to the reconstituted tobacco?

19 A . Well, the addition of the ammonium salts to

20 the -- you're not adding them to the reconstituted

21 tobacco . What happens is that stems -- stemmed

22 material have some compounds in it that are

23 calcium salts of pectic acid, P-E-C-T-I-C . And

24 you want to get that calcium away from the pectic

• 25 acid . So if you treat it with a compound, one of

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 787

1 the ammonium phosphate salts, the ammonia replaces

2 the calcium as the pectic acid -- to make an

3 ammonium salt of pectic acid, instead of the

4 calcium salt . And the calcium combines with the

5 phosphate part of the ammonium phosphate that you

6 added, and calcium phosphate is very insoluble in

7 water . So the ammonium pectate, now, can be made

8 into a sheet much easier and a much nicer sheet

9 than the calcium pectate material .

10 That's what I got out of the patent

11 they had .

12 Q . Well, how did that affect the

• 13

14
popularity of Marlboros?

MR . McDERMOTT : Object to the form of

15 the question ; no foundation .

16 THE WITNESS : I have no idea why it

17 affected the popularity .

18 BY MR . MAISTROS :

19 Q . Why did you mention Marlboros?

20 A . Well it's their main -- major product . And

21 as I say, we did the same kind of thing that

22 everybody does : We looked at their product, and

23 all of a sudden they had a reconstituted tobacco

24 that was different . About 1968, I guess, it was,

• 25 '69 .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 788

1 Q . And did you find or did you discover

2 any effect that the ammonia -- ammonia process

3 that Philip Morris used had an effect on the

4 nicotine yields of the tobacco?

5 A . I don't know what they looked at, sir .

6 Q . You didn't look at that?

7 A . I didn't look at that .

8 Q . Did Reynolds look at that?

9 A . I don't know what they looked at . I think

10 they were interested in the sheet, per se . And,

11 of course, the one thing about -- when you make a

12 sheet, like reconstituted tobacco, you're actually

13 starting something that's rather low in nicotine

14 anyway . Stems have much less nicotine than the -

15 the lamina .

16 Q . Do you know if Reynolds did any

17 studies to determine if Philip Morris was

18 controlling the amount of nicotine yields of its

19 reconstituted tobacco?

20 A . I don't know whether we did or not .

21 Q . Did Reynolds do any independent work

22 on the effect that ammonia had on nicotine yields? cn


N
-j

23 Separate and apart from looking at Philip Morris . m


OPb

24 A . If it did, I don't recall . m


to.

• 25 Q . Do you know if Reynolds did any work

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 789

to determine the effect that any compound had on

the nicotine yields of cigarettes?

A . There was a study, I believe it was done by

Miss Janet Wheeler, putting various additives in a

filter tip to see the effect on -- how it would

affect the nicotine level in smoke . Like acetic

materials put in the filter tip, would that --

nicotine is a basic compound . And'my vague

recollection is that, when you use some of these

10 additives, you got to -- have a problem with

11 acceptability on test panels . But it's been years

12 since I even thought about that .

13 Q . Do you know if Philip Morris did any

14 research to determine the effect that its

15 additives had on the nicotine yields of these

16 cigarettes and the end product nicotine yields?

17 MR . McDERMOTT : Excuse me . Your

18 question was Philip Morris?

19 MR . MAISTROS : I'm sorry . RJR .

20 THE WITNESS : Would you say that

21 again, sir .

22 BY MR . MAISTROS :

23 Q . Do you know if RJR did research to

24 determine the effect that any of its additives had

25 on the nicotine yields of the tobacco, other than

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 790

1 the filter one you just mentioned?

2 A . Well, in an indirect way . For example, we

3 did a study on use of humectants, glycerol and

4 propylene glycol, part of the casing material for

cigarettes . And of course'your main concern with

6 the humectants is that they help the cigarette

7 retain its moisture level at manufacturing . And

8 of course, being here in the south, when you

9 manufacture cigarettes in Winston-Salem and then

10 you ship them to California or wherever, you have

11 problem sometimes that there they're locked in a

12 truck and they're driving through areas that are a

13 hundred degrees Fahrenheit . So you -- you don't

14 want to lose moisture from your product .

15 So we were looking at the advisability

16 of raising or lowering, or doing whatever, with

17 the humectants . And, of course, one of the things

18 .that happens, if you increase the humectants

19 level, and more of humectant gets into the smoke

20 and the humectant turns out as part of the -- what

21 you weigh as total particulate matter and ends up

22 as being in the calculation, the FTC tar -- part

23 of the FTC tar number, then what happens is, as

24 you increase the humectants from, say, three to

• 25 four to five to six percent, the nicotine level in

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 791

1 the smoke goes down . That was just an observation

2 we made, that you could control nicotine by the

3 use of various levels of humectants .

4 But the primary purpose of -- oh, I

5 think at one time we increased the level of

6 humectants . It was not to lower the nicotine, but

7 it was primarily to make sure our products retain

8 their moisture for a longer period of time .

9 Because what happens, if you lose moisture from

10 the cigarette and the moisture loss is -- gets --

11 gets over a percent or two, that is it drops, say,

12 from 12 to 11 to 10, the tar level goes up and the

13 nicotine level in smoke goes up . And it gets to a

14 point where the smoke is very irritating .

15 Q. Did RJR do studies to determine

16 whether or not the tar levels could be reduced,

17 independent of reduction of the nicotine levels?

18 A . Well, here -- let me go back, 1980 . In 1980

19 there was a conference on less hazardous

20 cigarettes, called the Banbury Conference, and

21 Dr . Russell from England gave a presentation

22 there . And one of his theses, which he had

23 proposed sometime in the '70s, I forget the exact

24 date -- M .A .H . Russell is his name . He, in

25 England, and a man called, I believe, Jarvik,

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 792

1 J-A-R-V-I-K, in this country, proposed that the

2 safer cigarette should encompass lowering the tar

3 and leaving the nicotine alone, or lowering the

4 tar and raising the nicotine . And we looked at

5 that, and there was problems with it about -- when

6 you got an imbalance in the tar to nicotine ratio,

7 the cigarette became very harsh and the consumer

8 said no, no, no .

9 VIDEOGRAPHER : Mr . Maistros, we have

10 five minutes left on the videotape .

11 THE WITNESS : Well, if you gentlemen

12 don't mind, I'd like a break .

13 VIDEOGRAPHER : We're going off the

14 record at 10 :51 a .m .

15 (Recess taken from 10 :51 a .m . to 11 :07

16 a .m . )

17 VIDEOGRAPHER : This is tape 4 of the

18 videotape deposition of Alan Rodgman, Ph .D . We're

19 going back on the record at 11 :07 a .m .

20 BY MR . MAISTROS :

21 Q. Dr . Rodgman, so I'm clear on this,

22 when you were talking about Philip Morris'

23 addition of ammonia to the reconstituted tobacco

24 sheet, was it your understanding, or is it your

25 understanding, that the only purpose in doing that

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg 793

1 was to make the sheet easier to work with?

2 A . That was in the patent .

3 Q . Did you ever have any information that

4 there was another purpose behind adding ammonia to

5 the tobacco?

6 A . I didn't .

7 Q . Did anyone at Reynolds?

8 A . Not that I know of .

9 Q . And when you left, was Reynolds adding

10 tobacco to its sheets -- I'm sorry, adding ammonia

11 to its reconstituted tobacco sheets?

12 A . Not all of it . They had two variations of

13 reconstituted tobacco sheet, and I'm sure you've

14 heard of them . One's G7, the one that was

15 invented in nineteen fifty -- first used in '54 ;

16 and G7A, which was the ammoniated one . And I

17 don't know how much they used of either .

18 Q . Do you know what years G7A was used?

19 A . No, I don't .

20 Q . And do you know what the purpose of

21 Reynolds adding ammonia to the reconstituted

22 tobacco process was?


Ln
23 A . I believe they were thinking, well does this ~
~
m
24 have anything to do with the acceptability and ,p
m
m
25 sudden surge in the sales of Marlboro? Was it W

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 794

something that the consumer liked? And they were

seeing, I guess, if they could match it .

That's a speculation on my part .

Q . You don't know of any research that

was done to determine if the ammonia being added

to the reconstituted tobacco sheet affected the

amount of nicotine yield of the tobacco?

A. No . The only thing I know, sir, is that --

and, here, I'm not an expert on nicotine ; I think

10 you're quite aware of that .

11 With every case I've seen that --

12 where you add ammonia or ammonium salt or ammonia

13 solution to a tobacco, you end up with less

14 nicotine in that tobacco than you started with .

15 Q . How about free nicotine? Do you know

16 what the concept of free nicotine is?

17 A . Yes . And I think, if you read the deposition

18 that went on here two weeks ago, three weeks ago,

19 you'll get a good idea of my view on free

20 nicotine .

21 Q . Does anyone share your view in the

22 chemical world?

23 A. Yes .

24 Q. Who?

. 25 A . That the free nicotine is a calculated

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 795

1 number?

2 Q . Okay, we can start there . Who shares

3 your view that the free nicotine is a calculated

4 number?

5 A . I think everybody realizes it's a calculated

6 number . As far as I know, there's no chemist that

7 has ever isolated -- identified free nicotine in

8 mainstream cigarette smoke .

9 Q . Was the -- to your knowledge, the

10 primary purpose Reynolds added ammonia to the

11 reconstituted tobacco was to attempt to duplicate

12 Marlboro?

13 A . That was my understanding .

14 Q . Is it your understanding that the

15 only -- only manner in which ammonia is added in

16 the manufacturing process is in this reconstituted

17 tobacco process?

18 A . I have no idea if it's added any other way .

19 And you've got to remember, too, up until 1980,

20 the R & D part of Reynolds was R & D . And there

21 were a lot of things went on in development

22 that -- where I was in research, that I had very

23 peripheral knowledge of . I was aware of some

24 things going on, but had no basis of knowledge of

25 the reasons for it or the reasons not to do things


i

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 796

1 or to do things .

2 And then, as I said before, in 1980,

3 research and development was split into six parts,

4 and the process engineering and applied work was

5 entirely separate from my work in fundamental .

6 And I had enough to do with fund -- directing

7 fundamental research, that -- to be worried about

8 what other people were doing . And --

9 Q. Between 1953 and 1980, did R -- R & D

10 do any research on nicotine?

11 A . I wasn't there in '53 .

12 Q . I'm sorry . What year did you join?

13 A. 1954 .

14 Q . Between 1954 and 1980, did R & D do

15 any research in nicotine?

16 MR . MaDERMOTT : Object to the form of

17 the question .

18 THE WITNESS : Yes .

19 BY MR . MAISTROS :

20 Q . What research?

21 A . In the late 'SOs, two men at Reynolds -- well

22 one was actually a manager, the other was a lab


Ln
f-~
23 chemist, Dr . Markunas and Mr . Robert H . Cundiff ~
~
~
24 developed a -- an improved analysis of nicotine in',P .
rn
N
N
25 tobacco and cigarette smoke that became used by

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 797
1

1 almost every tobacco company in the world . It

2 took several years' research to develop that

3 process .

4 In fact, it was one of the reasons

5 that his development of a variety of analytical

6 methods for tobacco and tobacco smoke, which

7 included nicotine, nornicotine, and so on, that

8 Mr . Cundiff was awarded the -- a very prestigious

9 prize for his work in analytical chemistry .

10 Q . What other research?

11 A . In 1960, Benjamin Van Duuren and his

12 colleagues reported the identification of three

13 polycyclic aza-arenes, A-Z-A, hyphen, A-R-E-N-E-S,

14 in cigarette smoke . And these are -- have been

15 reported to be tumorigenic to mouse skin . And

16 Dr . Van Duuren studied nicotine pyrolysis to see

17 if these compounds arose from nicotine during

18 heating . And he said that they were, the three of

19 them .

20 However, we looked at the pyrolysis of

21 nicotine and couldn't find these three compounds .

22 And subsequent to 1960, from 1963 to 1992,

23 seven -- eight different studies had been

24 conducted and published, including some by

25 Dietrich Hoffmann and some from the U .S .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 798

1 Government . But nobody can reproduce those

2 findings of Benjamin Van Duuren, either with

3 respect to those compounds in smoke or the

4 pyrolysis of nicotine .

5 And the reason I mention it is these

6 compounds are listed by EPA and Wynder and

Hoffmann as being three significant tumorigens in

8 cigarette smoke ; and for '63 to '92, in eight

9 different studies, in three different countries,

10 nobody can find them .

11 Q . And what -- what work were you doing

12 that would have piqued your interest to look,

13 after '87, at whether nicotine promotes tumors?

14 A . After '87? I wasn't there in '87 .

15 Q . What -- why are you still researching

16 what reports are out there on nicotine and its

17 potential tumor causing effects between '87 and

18 '92? Just as a --

19 A . Who?

20 Q . You .

21 A . I was reading the literature, see .

22 Q . After '87, when you left Reynolds, you

23 still kept up on the scientific literature of

24 tobacco?

25 A . Tobacco smoke .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 799

1 Q. Were there any cases, litigation or

S 2 legal matters that you were consulting on, between

3 '87 and the present, that you haven't testified

4 about?

5 A . Not that I -- not that I know of .

6 Q• And going back to my original

7 question . Were you aware that Reynolds was doing

8 studies subsequent to Van Buren's (sic) study to

9 determine --

10 A . Van Duuren .

11 Q . Van Duuren's study, to determine if

12 his results could be duplicated?

• 13

14
A . No . When we couldn't find it in the nicotine

pyrolysis, we went on to other things .

15 Q . Did, to your knowledge, Reynolds ever

16 do any research to determine if nicotine promoted

17 tumors, caused tumors, was tumorigenic?

18 A. No .

19 Q . Are you aware of any other research

20 that was done at -- in R & D between '54 and '87

21 with respect to nicotine?


Ln
22 A . Well, I'm not really aware of any research . ~
~
a
23 When I came to Reynolds in 1954, I was shown a
~
m
24 facility that was not too far from here - it's w

25 gone now - where Reynolds recovered nicotine from

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 800

scrap tobacco and stems, and this was before the

days when -- in the manufacture -- preparation of

reconstituted tobacco sheet, Reynolds didn't use

all its stems . And they used part of the stems in

this facility ; they would treat it with alkali and

distill off the nicotine and sell the nicotine to

the company that made -- I'm thinking Black Leaf

40, which people use it on their rose bushes .

Q . A bug killer?

10 A . Bug killer .

11 Q . Do you know during what period of time

12 Reynolds continued to sell nicotine to that

13 company?

14 A . I -- I don't know when it quit or -- or it

15 was probably before -- maybe 1960 they quit . It

16 was probably earlier . Because, as their increased

17 use of the stems occurred, there was less and less

18 stems to process .

19 Q . If R & D wasn't doing nicotine

20 research, what entity within Reynolds would have

21 been? vn
N
v
22 A . If it wasn't done in R & D, I don't know m
bN

23 where it would have been done . rn


N
rn
24 Q . But when --

25 A . There was some work done -- now that I think

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 801

about it, it wasn't done at Reynolds, it was done

• at Bowman Gray School of Medicine . And it was the

first use of the radial-labeled nicotine to see

what happened to nicotine in a mammalian body .

I'm not too familiar with the work,

but it was done by a man called Dr . Wolff,

W-O-L-F-F . And the results were presented at

several of the earlier Tobacco Chemists

Conference, and which the first one, I believe,

10 was 1947 . And he presented several papers over

11 the years, between '47 and early '50s . I've seen

12 abstracts, but I didn't hear the papers .

13 Q . What is the largest particulate

14 compound that's contained in the cigarette smoke?

15 A . Largest particulate?

16 Q . Yes .

17 A . How do you mean "large"?

18 Q . Greatest quantity .

19 A. Water .

20 Q . And what about after water?

21 A . Nicotine .

22 Q . And between 1954 and 1987, is it your

23 testimony that there were no studies, other than

24 those you've testified about, with respect to how

25 nicotine interacts with the human body?

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 802

1 MR . McDERMOTT : Objection ; no

2 foundation .

3 THE WITNESS : Well we didn't have any

4 biological facilities, you know, '65, '66, '67, in

5 there . So as far as I know, no .

6 BY MR . MAISTROS :

7 Q . And Reynolds, to your knowledge, other

8 than the Bowman Gray study you just mentioned, did

9 not contract with any outside agencies to

10 determine how nicotine interacted with the human

11 body?

12 MR . McDERMOTT : Objection ; no

13 foundation .

14 THE WITNESS : I don't know .

15 BY MR . MAISTROS :

16 Q . Are you aware of any work that

17 Reynolds did to determine if nicotine had an

18 effect on the central nervous system of humans?

19 A . No .

20 Q . Did you prepare any literature,

21 reports, memorandum, that addressed the role

22 nicotine plays in tobacco smoke?

23 A . Not specifically on nicotine . I may have

24 mentioned nicotine . But not a report devoted to

25 the effect of nicotine during smoking, that I can

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 803

1 recall .

2 Q . As you sit here today, do you know

3 what role nicotine plays on the smoking process?

4 MR . McDERMOTT : Object to the form of

5 the question . Vague .

6 THE WITNESS : Say that again, sir .

7 BY MR . MAISTROS :

8 Q . Do you know what effect or what role

9 nicotine plays on the smoking process?

10 MR . McDERMOTT : Same objection .

11 THE WITNESS : On the smoking process?

12 BY MR . MAISTROS :

13 Q . I don't want to limit it to tobacco,

14 smoke, smoking process ; so I use "the smoking

15 process" as a catchall phrase .

16 A . Well, the smoking process is the process

17 whereby tobacco is converted to smoke and

18 nicotine -- some nicotine is transferred to --

19 from the cigarette to the mainstream smoke, and

20 some is transferred to the sidestream smoke, and

21 some is decomposed . That's the role of nicotine

22 in the smoking process .

23 Q . Do you know what role nicotine plays

24 insofar as interaction with the human body is

25 concerned?

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 804

1 A . I have no idea how nicotine works in the

2 human body . You're way outside my area of

3 expertise, sir .

4 Q . Who was the most knowledgeable person

5 at Reynolds between '54 and '87, with respect to

6 the role nicotine plays in the smoking process?

7 A. John H . Robinson .

8 Q . Was he within research and

9 development?

10 A . He came to research and development -- the

11 research department about 1978, '77, somewhere in

12 there .

13 Q . And you eventually were director of

14 research and development?

15 A . I hired John Robinson . I was director of

16 research, sir . I heard somebody saying something

17 on the phone that I was the grand guru of all

18 R & D, and I wish you'd get it straight .

19 Q . When you were director of research,

20 you were John Robinson's supervisor?

21 A . I was -- well, I was director of research,

22 and John Robinson's manager was John Reynolds, who

23 reported to me .

24 Q . And were you copied on the reports

25 that Robinson was preparing, insofar as he was

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 805

1 doing research on nicotine?

2 A . Yes . Well, his first work in -- first couple

3 of years he was there, he wasn't particularly

4 working on nicotine per se . The -- one of the

5 large projects he was working on was the Barclay

6 problem, which lasted for a year and a half .

7 Someplace in 1981 it was all finished ; they turned

8 over the information to the Federal Trade

9 Commission .

10 Q . Did you review Dr . Robinson's work on

11 nicotine?

12 A . I can't remember whether he did very much

• 13

14
nicotine work while I was director of research .

Q. Did Dr . Robinson have to obtain your

15 approval before commencing any research projects,

16 when you were director of research?

17 A . Well, it was usually done through the

18 manager, from Dr . Reynolds .

19 Q . Have you written any papers,

20 memorandums, research reports that address the

21 contentions made by some people out there that

22 Reynolds and other tobacco companies manipulate or

23 control the level of nicotine?

24 MS . EASON : Object to the form .

• 25 THE WITNESS : Would you say that

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 806

1 again, sir .

2 BY MR . MAISTROS :

3 Q . Are you aware there's allegations

4 floating out there that tobacco companies,

5 including Reynolds, manipulates and controls the

6 level of nicotine in its tobacco products?

7 A . I'm aware there -- that's been said .

8 Q . Have you ever written any papers,

9 documents, memorandum that address that issue?

10 A. No . I think most of the manipulation thing

11 came up after I retired .

12 MS . KNISELY : May we go off the

13 record, please?

14 VIDEOGRAPHER : We're going off the

15 record at 11 :28 a .m . We're off the record .

16 (Recess taken from 11 :28 a .m . to 11 :44

17 a .m . )

18 VIDEOGRAPHER : We're going back on the

19 record at 11 :44 a .m .

20 EXAMINATION

21 BY MR . SHELLER :

22 Q. Dr . Rodgman, my name is Steve Sheller

23 and I'm one of the counsel for the plaintiffs, and ~


J
H

24 I ' m go i ng to ask you some additional questions . ~


4~-

• 25 Mr . Maistros will be back asking you questions N


m

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 807

1 when I'm done with my portion of the deposition .

2 And hopefully it won't be too long .

3 In terms of the compounds that are in

4 tobacco smoke, the Cambridge filter system, which

5 is used by the Federal Trade Commission to measure

6 particulate matter in tobacco, you're familiar

7 with that?

8 A . Yes, I am .

9 Q . Okay . And that -- what does that

10 measure in terms of tobacco smoke? Just

11 particulate matter?

12 A . It -- the Cambridge filter pad was designed

13 that, when smoke impinges on it, it takes out

14 99 .9-something percent of the particulate matter

15 that strikes at the vapor phase gas components go

16 through .

17 Q . Now, you say, the vapor phase gas

18 components . Can you explain what the vapor phase

19 gas components are in generality? What -- what is

20 that, as distinguished from particulate?

21 A . Well --

22 Q . I-- I know we know, but this is for

23 the jury .

24 A . Okay . Cigarette smoke is, of course, an

0 25 aerosol . It's little liquid droplets, balls,

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 808

1 little liquid balls, spheres, whatever you want to

2 call them, suspended in a vapor . And when you

3 pull smoke through the cigarette, it goes through

4 the cigarette, tobacco rod, and the filter . And

5 then, if you're collecting the smoke on a

6 Cambridge filter pad, like in the FTC procedure,

7 the particulate matter impinges on the Cambridge

8 filter pad and it stays there . The vapor phase

9 components continue on through and are expelled,

10 unless you're specifically studying those .

11 And if you look at the particulate

12 phase of cigarette smoke versus vapor phase, what

13 happens is, obviously, when you're smoking -- take

14 a puff on the cigarette, you're pulling air

15 through the lit end . So what goes through the

16 Cambridge filter pad, the vapor phase components

17 of course is : The nitrogen that was in the air,

18 it doesn't burn, or very little of it does ; the

19 unconsumed oxygen ; plus carbon monoxide, carbon

20 dioxide, helium that was in the air, acetaldehyde,

21 formaldehyde .
Ln
~
22 There are probably four or five J
F-+
m
23 hundred components in the vapor phase that go ~
ON
N
24 through the -- ~

i 25 Q . That go through the filter?

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 809

1 A . Right . And, fortunately, every -- almost

2 everything in the vapor phase is known .

3 Now, if you look at the vapor phase

4 versus the particulate phase, in a normal

5 cigarette, with nine-tenths of a gram of tobacco

6 or so, the vapor phase -- well, the total smoke,

7 counting what impinges on the -- stays on the

8 Cambridge filter pad and what goes through it, is

9 roughly 500 milligrams . And if the particulate

10 matter is a 20-milligram -- well, say,

11 20-milligram TPM cigarette --

12 Q . Tar per --

0 13 A . Four hundred -- 480 is gas phase, of which

14 probably -- nearly 400 milligrams is unused air .

15 Q . Okay . So -- let -- let me understand .

16 The -- there's 500 milligrams --

17 A . Uh-huh .

18 Q . -- approximately, that goes through

19 the Cambridge filter .

20 A . Well, no . The total smoke generated from a

21 cigarette in ten puffs or eight puffs, whatever it

22 takes, would be about 500 milligrams . Twenty

23 milligrams of total particulate matter,

24 480 milligrams of vapor phase components, of which

25 about 400 is air .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 810

1 Q . So there's about 80 milligrams of

2 something in the vapor?

3 A . Yeah . Well, if you have a TPM of 20, you

4 could take a rough guess that your carbon monoxide

5 will be 20, plus or minus one milligram .

6 Q. Okay . But let -- let me kind of get

7 these numbers straight . And I was not good in

8 chemistry . I want you to understand that .

9 A . Uh-huh . I'm just giving you approximations .

10 Q . No . No, I understand . So, I'm going

11 to go very --

12 A . Let's say, take a 20-milligram TPM cigarette .

13 Q . That's a tar per milligram .

14 A . No .

15 Q . What does TPM stand for?

16 A . Total particulate matter .

17 Q. Matter . Total particulate matter .

18 A . Okay .

19 S2 • So 20 milligram total particulate

20 matter .

21 A . Right . Okay .

22 And -- and then, if you're speaking

23 about the non-air components that go through the

24 filter pad, like acetaldehyde, and so on and so

25 forth, then the ones that are the most plentiful

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 811
)

1 are carbon monoxide ; which, as a rule of thumb, if

2 you know the TPM, the carbon monoxide will

3 probably -- that number, plus or minus one or two

4 milligrams, so you're looking 18 to 22 . The

5 carbon dioxide, as a rule of thumb, will be about

6 twice that, two and a half times that . And those

7 are the most plentiful components in the vapor

8 phase .

9 And of course you have acetaldehyde,

10 and so on and so forth . And then you --

11 Q . Okay . Let me -- let me -- so the

12 vapor phase consists of -- let me get this

13 straight . You've got 500 --

14 A . Total smoke matter .

15 Q . Total smoke matter .

16 A . Right .

17 Q . TSM I'm going to call that .

18 A . Okay .

19 Q . Then of that 520 --

20 A . Say -- let's say 20 .

21 Q . Approximately 20 .

22 A . Twenty would be TPM .

23 Q . That's what gets onto the filter?

24 A . The Cambridge filter, right .

25 Q . Then there's 480 left .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 812
(

1 A . Right .

2 Q . Approximately .

3 A. Ri g ht .

4 Q . And of that 480, 400 is air?

5 A. Roughly .

6 Q . Roughly four --

7 A. Nitrogen, and oxygen, and helium, and

8 whatever, krypton .

9 Q . I thought that's Superman .

10 So 80, I'll say, is stuff?

11 A. Right . And of that 80, probably half of it

12 is C02, carbon dioxide .

13 Q . Right . So let me write this down .

14 Forty equals -- of 80, 40 equals C02 --

15 A . Two --

16 Q . Which is carbon -

17 A . Dioxide .

18 Q. -- dioxide .

19 A. Carbon monoxide would be the same as the TPM,

20 about 20 .

21 Q . Twenty . And what's the other 20?

22 A. Well, you've got -- probably the next highest


Ln
F-
23 component in the vapor phase is acetaldehyde, ~
m
24 which is about one milligram . Then everything 4~*
rn
N
CO
! 251 after that goes down, milligrams -

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 813

Q . Is that where they talk about benzines

and all those other things that --

A . Yeah, they're way down there, in micrograms

and nanograms, and so on and so forth .

Q . Okay . Now --

A . And in that 80, it -- rough -- roughly 80

that we said were non-air components, there are

about four or 500 compounds -- 400 compounds that

have been identified .

10 Q. Now, if I wanted to make a cigarette

11 to reduce the tar per milligram at that 20 that's

12 collected on the Cambridge pad --

13 A . Right . Right .

14 Q . -- could I vaporize some of those

15 things and get them out of there?

16 MR . McDERMOTT : Object to the form of

17 the question .

18 MS . EASON : Object to the form of the

19 question .

20 MR . BLANCATO : Object to the form of

21 the question . ~
~
-3
22 THE WITNESS : I don't quite ~
m

23 understand -- you mean -- ~


N
0
24 BY MR . SHELLER :

9 25 Q . Well, I want to turn it -- I want to

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 814

1 lower -- I want to have less gook . I want to get

2 it out of the gook stage and turn it into the air

3 stage, the vapor stage .

4 MR . BLANCATO : Object to the form .

5 MR . McDERMOTT : Object to the form of

6 the question .

7 BY MR . SHELLER :

8 Q . How would I do that? Could I vaporize

9 it, could I do something to it to -- to do that?

10 A . Well the best way is to have the cigarette

11 burn differently .

12 Q. Okay .

13 A . And you could do that by air diluting filter .

14 And if you -- there's a mathematical correlation

15 between percentage air dilution as imposed by

16 filter tip ventilation and the particulate matter .

17 Because, what you're doing is -- normally, with a

18 normal cigarette, you would pull 35 milliliters of

19 air into it, according to the FTC procedure . If

20 you air dilute it ten percent through the little

21 holes in the filter, then ten percent of the air,

22 which would be three and a half milliliters of

23 air, would come through the little holes ; and then

24 the remainder, 31 and a half milligrams, would

25 come through the cigarette . Which means that you

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 815

1 would form less material that would impinge on the

2 Cambridge filter pad .

3 Now, if you went to 20 percent,

4 then - -

5 Q . Well, would that material go into the

6 air? Where would it go?

7 A. What?

8 Q . The less -- material that didn't get

9 on the Cambridge filter .

10 A . It's because -- no . It's because you didn't

11 generate it .

12 Q . You didn't -- it didn't get generated .

13 A . Right .

14 Q . Okay . Now, is there any way to

15 generate it, but turn it into vapor?

16 A . Uh --

17 MR . McDERMOTT : Object to the form of

18 the question .

19 Generate what?

20 BY MR . SHELLER :

21 Q . In the four -- the 500 --

22 A . Well, you see, sir, the -- the --

23 Q . The 400 air stuff that you take

24 through the filter, that the filter doesn't

_ 25 pick up, which includes the 80 --

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 816

1 A . Right .

2 Q . -- 80 milligrams that we talked

3 about .

4 A . No, what would -- you would have to do

5 MR . MoDERMOTT : Let me just --

6 I object -

7 MR . SHELLER : Please let me ask a

8 question .

9 MR . McDERMOTT : Yes -- I object to the

10 form of the question . It is vapor already . So

11 your question is : How do you turn the vapor into

12 vapor?

13 MR . SHELLER : No . No, we're talking

• 14 about the 20 part TPM .

15 THE WITNESS : Okay . Okay .

16 MR . MCDERMOTT : Well, then, will

17 you --

18 BY MR . SHELLER :

19 Q . I'm -- I'm -- I'm designing a

20 cigarette that I want'to know -- you're -- you're

21 a cigarette engineer, right? Design --

22 A . No . I'm an organic chemist .

23 Q . An organic chemist . All right .

24 So you -- well, I'm asking you, as an

25 organic chemist -- and I did take organic

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 817

1 chemistry ; that was one of the few chemistry

2 courses I took . But if I wanted a --

3 A . You've got to -- let -- let me back up, if

4 you want to learn about what's on the Cambridge

5 filter pad .

6 What's on the Cambridge filter pad are

7 things that are relatively non-volatile when they

8 hit that Cambridge filter pad .

9 Q . All right .

10 A . Now, things like acetaldehyde, formaldehyde,

11 air, components, nitrog -- they are gaseous or

12 vaporous ; they go through .

13 Now, because the particles, these

14 little balls, are whizzing down the cigarette,

15 they hit the Cambridge filter pad, and the

16 Cambridge filter pad is designed to stop

17 everything above a certain size . Well, above a

18 certain size is almost everything that is-not

19 little molecules like the air . So they hit the

20 Cambridge filter pad and are impinged there .

21 Now, what's in that 20 milligrams is

22 all the things that are non-volatile at the ~


_j
23 temperature that they impinge, which usually is 30 m
~
24 or 40 degrees, a little above room temperature -- W
w
251 all right . I mean, let's get to the point .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 818

1 Benzpyrene does not vaporize at room

2 temperature or 40 degrees . You -- to vaporize

3 benzpyrene, you got to get it to 350 degrees

4 centigrade . So, theirs stick there now . You

5 cannot -- there's no way you can vaporize

6 benzpyrene, for example, or -- to get it to go

7 through as a vapor at 30, 40 degrees . So it's

8 going to impinge .

9 What you do, you control the design of

10 the cigarette so what comes through and hits that

11 pad is less . And you can do that by what you put

12 it -- how you design your filter tip, how you

13 design the -- use expanded tobacco or

14 reconstituted sheet . And -- and, of course, if

15 you look at the FTC -- well not FTC, the

16 sales-weighted average for tar, from 1955 to the

17 present time, it's been dropping .

18 Q . Well, I understand that . But what I'm

19 trying to understand is -- let's -- let's talk

20 about benzpyrene, for example . Is that in the

21 TPM?

22 A . Uh-huh .

23 Q . That -- that never gets vaporized .

24 A . No .

25 Q . The cigarette doesn't burn at a high

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 81 9

1 enough -

2 A . And by the way, I'm sure you may b e

3 heading for -- because you cannot find nicotine in

4 the vapor phase of a cigarette ; it's on the pad .

5 Q . Right .

6 A . So, therefore, it's not --

7 Q- Your view -- now, benzpyrene -- wha t

8 deg -- can only vaporize at how many degree s

9 temperature?

10 A . What --

11 Q . 350 degrees ?

12 A . Yeah . You have to get it above its melting

13 point . And it melts --

14 Q . Right . And cigarettes never burn at

15 350 degrees ?

16 A . Well, yeah, the burning temperature of a

17 cigarette, out of the fire cone, is 850 degrees

18 centigrade .

19 Q . 850 . Well, wouldn't some of that

20 benzpyrene then be vaporized ?

21 A . Well, it's not formed at the 850 degree

22 temperature . It's formed back in the cigarette,

23 where the temperature is lower . And the thing is,

24 the benzpyrene, because of its nature, gets into

25 the particle .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 820

1 Q . Well -- well I understand that . But

2 suppose, now -- I'm being very simple here . I'm

3 at the end of my cigarette butt and it's -- the

4 burn is down at the bottom near the filter . Are

5 you -- you telling me that none of that benzpyrene

6 is vaporized?

7 A . It's probably vaporized during the

8 formation -- during its formation . Benzpyrene

9 isn't in tobacco .

10 Q . I know, during the formation . And

11 you're saying none of that benzpyrene is going to

12 get through that filter, according to you?

13 A . No .

14 Q . Okay .

15 And you're saying, you don't know

16 any way to vaporize that tar per milligram, that

17 20 that the pad gets, that -- now, I want to make

18 a cigarette that I want -- what -- what's in that

19 tar per milligram? You got benzpyrene --

20 MS . EASON : Objection .

21 MR . McDERMOTT : Objection . Total


Ln

22 particulate matter .

23 BY MR . SHELLER :

24 Q . Total particulate matter .

25 A . Total particulate matter --

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 821

1 Q . I'm sorry . I used TPM before .

2 A . -- there are 4400 known components --

Q . What are the major ones? Nicotine?

4 A . Nicotine, water .

5 Q . Which -- is nicotine, the ma -- that's

6 the most --

7 A . Water . Water .

8 Q . Water is the main thing? So --

9 A . Nicotine .

10 Q . Then after that? What's the next big

11 ones?

12 A . The saturated aliphatic hydrocarbons ; which

13 is a series of about 80 compounds, but they act as

14 if they were one .

15 Q . I see .

16 A . And they probably represent a fair -- let me

17 correct one thing .

18 Well, the third one I would put down

19 would be the humectants, glycerin and propylene

20 glycol .

21 Q. Okay . Now, let me ask you something .

22 The water -- how much of the 20 TPM is water?

23 A . About eight percent .

24 Q . And how much is nicotine?

25 A . Six or seven, depending on the cigarette .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 822

1 Q . I see . And how much is whatever that

2 word was?

3 A . Humectants?

4 Q . No, the one be -- poly --

5 A . Oh, the saturated aliphatic hydrocarbons?

6 Q . Yes .

7 A . Probably three or four percent .

8 Q . And then humectants?

9 A . And, see, that will be dependent on the

10 tobacco, because those are in tobacco .

11 Q. Uh-huh . What are humectants?

12 A . The glycerin and propylene glycol are used to

13 help the cigarette retain its moisture during its

14 transport from manufacture to the consumer, and

15 across the country, and so on .

16 Q . What's the usual amount, approximate?

17 A . In smoke? Probably a couple of a percent .

18 Two percent .

19 Q . All right .

20 Now, is there any way, that you know

21 of, that nicotine can get vaporized so it doesn't

22 get counted on that pad?

23 MR . McDERMOTT : Object to the form of Ln

24 the question .

25 BY MR . SHELLER :

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 823

Q . As TPM .

2 A . No, I do not know .

3 Q . Do you know whether ammonia vaporizes?

4 A . Ammonia is in the gas phase of smoke .

5 Q. Right . But does ammonia free the

6 nicotine from the salt? The TPM?

7 A . As far as I know, no .

8 MR . McDERMOTT : Object to form .

BY MR . SHELLER :

10 Q . What is that calculated amount of

11 nicotine you were talking about in the prior

12 deposition in Ju -- I think it was in July or

13 June? What is that? Is that an amount that

14 people calculate as in the vapor?

15 A. No . They -- as I say, it's a funny

16 calculation . It's based on the pH of the smoke .

17 And I say, as far as I know, nobody has ever found

18 free nicotine that went through that filter --

19 Cambridge filter pad .

20 Q . But they -- but they calculate that --

21 that there is some amount going through there,

22 right, because of the ammonia ; isn't that true?

23 MR . McDERMOTT : Object to the form of

24 the question .

25 THE WITNESS : No . They calculate

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 824
)

1 that -- in the smoke that you take in there may be

• 2 free nicotine, according to that calculation .

3 BY MR . SHELLER :

4 Q. Right . That's not on -- that doesn't

5 get picked up on the pad, right?

6 A . Well, it gets picked up on the pad 'cause

7 none goes through, sir .

8 Q. Well --

9 A . You don't smoke a cigarette through a

10 Cambridge filter pad .

11 Q . I understand .

12 A . Personally .

13 Q . Are you saying that the Cambridge

14 filter pad picks up all the nicotine that's in the

15 smoke?

16 A . Yes .

17 Q. Okay . And you're positive of that?

18 A . I have never seen a report where somebody has

19 reported nicotine, per se, in the vapor phase of

20 the mainstream smoke .

21 Q . But people believe that nicotine is in

22 the vapor phase because of ammonia, don't they? Ln

23 Many scientists .

24 A . No, they don't .

25 Q . They don't . Where do they believe it

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 825

1 is? They believe it's not in the vapor phase?

2 A . No, they don't believe it -- I think you're

3 missing the point about this calculation with free

4 nicotine and nicotine in the vapor phase .

5 Q. Uh-huh . Right .

6 A . If nicotine is free and in the vapor phase,

7 it will go through the Cambridge filter pad .

8 Q. Right .

9 A . But none does, so it can't be in the -- can't

10 be f ree .

11 Q . So you're saying, if nicotine is free,

12 it will be in the --

13 A . Vapor phase .

14 Q . -- vapor phase and not counted in the

15 filter . But you're saying, to your knowledge,

16 none is in that vapor phase, right?

17 A . Right .

18 Q . So you don't agree with those who

19 believe that a substantial amount of nicotine is

20 in the vapor phase . You disagree with that view .

21 A . I keep telling you, sir, that nobody has been

22 able to measure it .

23 Q . I understand that . But that's --

24 because no one has measured it, you're saying it's

25 not there . Right?

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 826

1 A . It's not in the vapor phase that goes through

0 21 the filter pad .

3 Q . Now, has Reynolds ever tried to

4 measure it?

5 A . Yes .

6 Q . When?

7 A . Oh, I forget when .

8 Q . When you were there?

9 A . Yeah . When I was there . I wasn't involved

10 in it .

11 Q . Who was?

12 A . Somebody in analytical .

13 Q . Who was that?

14 A . Probably somebody like Patrick Cooper,

15 who .

16 Q . And did you ever see a report from

17 Patrick Cooper, saying : I tried to measure the


,
18 nicotine and -- to see if it's in the vapor phase,

19 and I tried and tried and tried and couldn't do

20 it?

21 A. No . There are reports in the literature by

22 other people that have done it and have tried it

23 and tried it .

24 Q . Now, you do use ammonia to free the

25 nicotine from the tobacco stems . You did that

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 827

1 back in the '60s . Remember, you said that? How

2 does that work?

3 A . I didn't say I used ammonia to --

4 MR . McDERMOTT : Object to the form of

5 the question .

6 THE WITNESS : -- free tobacco from the

7 stems .

8 BY MR . SHELLER :

9 Q . Not tobacco, nicotine .

10 A . Nicotine from the stems .

11 Q. Well, remember, you were talking about

12 selling the nicotine

13 A . I didn't say I used ammon -- they used

14 ammonia . They didn't use ammonia .

15 Q . They didn't . What did they use?

16 A . Sodium hydroxide .

17 Q . Sodium hydroxide . Well, I thought you

18 said somewheres that they used ammonia, before, to

19 free -- to get nicotine out .

20 A . That was the denicotinization process .

21 Q. Okay . And how did ammonia take out

22 the nicotine in the denicotinization process?

23 A . Well, ammonia is more basic than nicotine,

24 and nicotine is present in tobacco as a salt . And

25 it --

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 828

Q . But --

A . -- frees the nicotine, which temperature

drives off, and it's burned or collected or

whatever .

Q . It frees the nicotine into a

collectible air which is then -- what -- how does

it get back into a fluid or a salt?

MR . BLANCATO : Object to the form .

9 BY MR . SHELLER :

10 Q . Once it's freed by the ammonia .

11 A . Well, in that case, it's -- there's enough

12 ammonia there to keep it going, to keep it as free

13 nicotine .
• 14 Q . I see .

15 A . There's nothing else there, like the smoke

16 particles, to get the nicotine --

17 Q . What does it look like? Have you ever

18 seen it?

19 A . What?

20 Q . The free nicotine in --

21 A . Nicotine -- yeah, I've seen free nicotine .

22 Q . What does it look like?

23 A . Water .

24 Q . Water . Is it wet?

25 A . I wouldn't advise putting your finger in it .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 829

Okay .

Now, if that -- and you've never done

any -- to your knowledge, no one's ever tried to

heat that water to see if it vaporizes?

A . Heat what water?

MR . MCDERMOTT : Excuse me . What

water?

8 BY MR . SHELLER :

Q . The nicotine water, that looks like

10 water .

11 A . Nicotine vaporizes .

12 Q . Hmmm?

13 A . Nicotine will vap -- you can boil nicotine -

14 Q . It will vapor --

15 A . -- and it boils like water, and it gives off

16 an equivalent of steam .

17 Q . Right . So you don't know whether

18 Reynolds has ever tested the product to see if

19 in the cigarettes the vapor that -- the nicotine

20 that's freed is vaporized?

21 MR . MaDERMOTT : Object to the form .

22 BY MR . SHELLER :

23 Q . And gets through that Cambridge

24 filter?

251 MR . McDERMOTT : Objection, asked and

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 830

1 answered .

2 BY MR . SHELLER :

3 Q . You don't know .

4 To your knowledge, that's been tried

5 and they never found anything?

6 A . As I have said repeatedly, sir, no one has

7 found, either at Reynolds or elsewhere, free

8 nicotine passing through that Cambridge filter

9 pads from the mainstream smoke of the cigarette .

10 Q. Okay . Now, we talked about ammonia,

11 in terms of vapor -- can vaporize things,

12 nicotine, right? You agree it can vaporize it --

13 MR . BLANCATO : Object to the form .

14 BY MR . SHELLERt

15 Q . -- if it's boiled?

16 A . You're wandering around . I can't follow you .

17 Q. Okay . Well, let me try another

18 question .

19 Is there anything else in the tar that

20 is freed by any additives --

21 MR . BLANCATO : Objection --
Ln
22 BY MR . SHELLER : ~
~
~
m
23 Q . -- similar to, for example, the way
~
m
~
24 nicotine is freed? m

25 MR . BLANCATO : Object to the form .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 831

MR . McDERMOTT : Object to the

question .

3 BY MR . SHELLER :

Q• The TPM -- the total particulate

matter? I'm sorry about the tar .

A . Well, as far as I know -- you're talking

about freeing nicotine in the TPM . As far as I

know, there's no free nicotine been found in TPM .

Q . Well, how about in the cigarette? Is

10 there any -- it frees it from the salt?

11 A . As far as I know, there's no free nicotine in

12 tobacco .

13 Q . I see . So the ammonia does nothing to

14 the nicotine . It doesn't free it in the tobacco

15 in the cigarette, but it will free it in the

16 tobacco that you're going to sell for bug killer .

17 A . Pardon?

18 MS . EASON : Objection .

19 BY MR . SHELLER :
~
~
20 Q . It will free it in the tobacco that J
N
m

21 you're going to sell for bug killer? ~


m
~
J
22 MR . BLANCATO : Object to form .

23 MR . McDERMOTT : Object to form .

24 THE WITNESS : As I said, we didn't use

25 ammonia to make the -- free the nicotine for sale .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 832

1 BY MR . SHELLER :

2 Q . Well, what did you do with the free

3 nicotine that you freed with the ammonia?

MR . BLANCATO : Object to the form .

5 THE WITNESS : We burned it .

MR . MCDERMOTT : Ditto .

7 BY MR . SHELLER :

Q . You burned it?

9 Yeah .

10 Q . Why did you burn it?

11 A . What would we use it for?

12 Q . Bug killer .

13 A . Well, you got to remember, in one case you

14 had a controlled or contained system . It looked

15 like a large liquor still, where you cook the

16 stems with the alkali and the nicotine distilled

17 over, and you caught it in suitable vessels . But

18 this is being done in a huge belt . Nic -- tobacco

19 is going along a belt . And you're dealing with

20 great volumes of air and ammonia and nicotine .

21 it's either collected and disposed of, or actually

22 burnt at an outlet . Ln
N
23 Q . And has that always been the case, ~
S)
24 they were burning it, at Reynolds?
~
~
25 A . I don't -- I don't know whether they still do0D

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 833

it or not . There are probably rules against it

now .

Okay . When did -- when you'were

there, up to, what, 1987, did they always burn all

that nicotine?

A . Sir, I saw it done once on an orientation

tour, back in the early '60s, and that's the only

time I ever saw them do it .

Q . So you really don't know what happens

10 to that free nicotine --

11 MR . McDERMOTT : Objection to the form

12 of the question .

13 BY MR . SHELLER :

14 Q . -- after that . You have no personal

15 knowledge of what happened .

16 A . I have no personal knowledge what they did

17 after that one time I saw it ; I didn't know what

18 happened before that .

19 Q . Is there anything else that -- in the

20 processes you're familiar with, in the chemistry c„


N
~
21 that goes into cigarettes, that frees anything ~
m
0.
22 else besides the nicotine from tobacco? m
10.
ko

23 A . Well --

24 MR . McDERMOTT : Object to the form of

251 the question .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 834

MR . BLANCATO : Object to the form .

THE WITNESS : I think you may be

confused about something . You sound as if we

ammoniated every pound of tobacco we bought .

5 BY MR . SHELLER :

Q . I didn't say that .

A . We only ammoniated the tobaccos -- we removed

the nicotine from tobaccos when the nicotine was

very high . Which, in some years, if the normal

10 crop or the crop that was going to be used were in

11 the range that we normally used, there was no

12 denicotinization . It was only those crops that

13 arose out of a situation where it was very hot,

14 very dry, and you ended up with a tobacco that was

15 six percent nicotine and you didn't want that .

16 Q. Right . There were two times ammonia

17 was used ; I think you already pointed that out .

18 One with -- is that G7A --

19 A . Right .

20 Q . -- product, which is actually put into

21 the cigarette, and then the other is the

22 denicotinization process you talked about .

23 A . Right .

24 Q . No, I understand that .

25 I'm talking about, is there anything

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 835

1 else, similar to ammonia, or does ammonia also

2 free any other salt-type thing like nicotine or

3 any other product in this tobacco?

4 MR . MoDERMOTT : Object to the form of

5 the question .

6 BY MR . SHELLER :

7 Q . To your knowledge .

8 A . You know, the -- tobacco contains several

9 compounds similar to nicotine, and there --

10 Q . What are they?

11 A . Nornicotine .

12 Q . Does it free that?

13 MR . McDERMOTT : Object to the form of

14 the question .

15 THE WITNESS : Well, I think you're

16 trying to trap me into this "free" business . it

17 will, if you're denicotinizing tobacco with

18 ammonia to reduce the nicotine, it will also

19 reduce the nornicotine, in the same way .

20 BY MR . SHELLER :

21 Q . Well, I want to know : I've got that


~
22 tar . And I'm trying to get out of the tar, free ~~
~
23 stuff from it, for whatever purpose . Is there ~
m
~
24 anything else that you know of, in the chemistry ~

251 that's used in Reynolds' products, that frees

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 836

1 anything other than the nicotine and the

2 nornicotine?

3 MR . McDERMOTT : Objection to the form

4 of the question .

5 MR . BLANCATO : Objection .

6 MS . EASON : Objection to the form .

7 BY MR . SHELLER :

8 Q . From that tar .

9 I don't follow the question, sir .

10 Q . Well, let me -- what's . -- give me --

11 in the tar itself, what -- the main thing in the

12 tar, you said, is water, 80 percent . Let's take

13 the saturated, what do you call them, alo --

14 A . Aliphatic hydrocarbons?

15 Q . Yeah . Is there anything that can free

16 them?

17 A . They are free .

18 Q . They are free?

19 A . They are free .

20 Q . I see . So they're in the partic -- is

21 there anything that vaporizes them?


Ln
22 A . That's -- ~
~
~
m
23 Q . Hmmm? Is there anything that can
~
24 vaporize them? ~
N

25 A . Yeah .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 837

Q. What?

A . That's how they get in the smoke .

Q. I see . Are all of them picked up by

the filter?

A . Yes -- well, I shouldn't say "all" of them .

There are saturated aliphatic -- aliphatic

hydrocarbons that are very low molecular weight,

like methane or ethane, and they go through in the

vapor phase . It's only when you get up to about

10 eight or ten carbons that they stick on the

11 filter . And it's a matter of molecular weight and

12 size .

13 Q . Well, if I wanted to design a

14 cigarette to reduce the amount of particulate

15 matter that gets on that filter and yet get the

16 smoker to take it in -- the smoke, get it into

17 that 480 milligrams of stuff that goes in the

18 smoke -- is that it, milligrams?

19 A . Uh-huh .

20 Q. How could I do it?

21 A . I don't understand --

22 MR . McDERMOTT : Object to the form of

23 the question .

24 THE WITNESS : I don't understand what

251 you mean .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 838

1 BY MR . SHELLER :

Q . I want to get around that filter .

Get what around the filter?

Q . I don't want the Cambridge filter

counting everything that I got in my cigarette .

How would I do it? You don't know how to do that?

MS . EASON : Objection to the form .

MR . McDERMOTT : Object to the form of

the question .

10 THE WITNESS : I -- I still don't get

11 what you mean .

12 BY MR . SHELLER :

13 Q . Well, let me make it a little simpler

14 for you .

15 If I turned ammonia into my cigarettes

16 and I had -- 6 to 7 percent of it was particulate

17 matter, but I was able to vaporize it, still get

18 it in -- in the body of a human being, and reduce

19 that 6 to 7 percent to 2 percent, wouldn't that

20 fool the .Cambridge filter? I'm being very clear

21 with you, not hiding anything, throwing it right

22 to you . Wouldn't it fool the Cambridge filter?

23 MS . EASON : Objection .

24 THE WITNESS : Which 6 or 7 percent are

25 you talking about, sir?

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 839

1 BY MR . SHELLER :

2 S2 • You told me a few minutes ago that 6

3 to 7 percent of the total particulate matter

4 picked up on the filter, the Cambridge filter, is

5 nicotine .

6 Right .

7 Q You said 3 to 4 percent is this other

8 thing I can never pronounce, and you said

9 8 percent is water . And then -- and isn't it true

10 that, if I'm able to vaporize a good portion of

11 that nicotine into -- it's not going to get on

12 that filter, right?

13 A . Right . But I say --

14 Q . Well, you're saying that you never

15 counted it .

16 MR . BLANCATO : Objection . Objection

17 let him answer .

18 THE WITNESS : No . I said that nobody

19 has been able to measure it .

20 BY MR . SHELLER :

21 Q. I see . Is there anything else that

22 can vaporize things that nobody's been able to

23 measure that was in that tar -- that particulate

24 matter?

251 MR . McDERMOTT : Object to the form of

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 840

the question .

THE WITNESS : Nornicotine .

3 BY MR . SHELLER :

Q . Nornicotine . How about anything else?

MR . MCDERMOTT : Object to the form of

the question .

THE WITNESS : I can't think of

anything .

9 BY MR . SHELLER :

10 Q . You're a chemist, now . You mean you

11 can't tell me anything that you could do to that

12 particulate matter that could vaporize --

A . I've told you -- I've told you how you

14 control the particulate matter . It doesn't --

15 Q . I understand what you told me . But

16 now --

17 MR . BLANCATO : Objection .

18 BY MR . SHELLER :

19 Q . -- I want to design a cigarette that's

20 going to trick that filter .

21 A . Well, if you can design it, we'll be glad to

22 hear from you .

23 Q . I know you would . That's been

24 Reynolds' business, hasn't it?

25 MR . MCDERMOTT : Object to the form of

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 841

1 the question .

2 MR . BLANCATO : Objection .

MR . SHELLER : Does he have the

4 materials now that I asked to be copied?

5 MR . HOLTON : We have the first batch .

6 THE WITNESS : I think it's time for

7 lunch, isn't it?

8 MR . SHELLER : What time is it? Do you

9 want to take a break?

10 MS . EASON : It's after 12 :00 .

11 THE WITNESS : 12 :21 .

12 MR . SHELLER : Do you want to take a

13 break?

14 MR . BLANCATO : Sure .

15 VIDEOGRAPHER : We're going off the

16 record at 12 :19 p .m .

17 MR . McDERMOTT : I'd like to respond to

18 Mr . Sheller .

19 VIDEOGRAPHER : Do you want to stay on

20 the record?

21 MR . SHELLER : I don't want to let him

22 respond .

23 MR . McDERMOTT : Or we can do it when

24 we get back from lunch, either way .

• 25 VIDEOGRAPHER : We're going off the


1
WAGA & SPINELLI (201) 992-4111
Vol . 5, Pg . 842

1 video record at 12 :19 p .m .

2 MR . SHELLER : Do it now . Get it done

3 with .

4 VIDEOGRAPHER : Do you want this on the

5 record?

6 MR . McDERMOTT : Yeah, I did want to

respond on the record . I just didn't want --

8 MR . SHELLER : Well, it doesn't have to

9 be on the -- does it have to be on the video?

10 MR . McDERMOTT : No, it doesn't have to

11 be on the video record, like we do it here .

12 VIDEOGRAPHER : So we're going off the

• 13

14
video record at 12 :19 p .m .

MR . McDERMOTT : And you can leave,

15 Alan . I wanted to respond very briefly to two

16 charges which were leveled at the beginning of the

17 deposition today . See if I can get my notes here

18 to make sure I copied them down .

19 Oh, first, that I was coaching

20 Mr . Blancato . I believe that was a reference to

21 my touching Mr . Blancato's arm at a point where


Ln
22 there were questions that first dealt with ~
~
~
23 Reynolds' attorney/client privilege, and I was m
~
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24 anticipating questions dealing with Mr . Rodgman's Ln
CO

• 25 personal attorney/client privilege .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 843

I view it as the obligation of every

lawyer to protect and preserve attorney/client

privilege . And to do otherwise is to bring the

profession into disrepute, which, I regret to say,

it, more and more, seems to deserve, in the

public's eye . I do not regard that as

interfering .

Which brings me to the second charge

that was hurled, and that is that I was somehow

10 interfering with the conduct of the deposition .

11 I invite Mr . Sheller to review the

12 transcript at his leisure and come up with any

13 instances in which I was interfering with this

14 deposition . As to the proposition that I was

15 interfering with the progress of the case in some

16 fashion by indicating my preference to

17 Mr . Blancato with respect to review by another law

18 clerk, we are parties to the proceeding, and

19 Mr . Blancato is not .

20 That protective order or case


Ln
~
21 management order was negotiated between the ~
m

22 parties . I regard what t h e p l a i n tiff' s '~

23 attempted to do there as a breach of the order .

24 We will abide by the -- I won't call it "ruling,"

25 but the "suggestion" of the law clerk . But I do

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 844

not regard what I have been engaged in here as

anything like interference . I regard the

statements on the record, with the witness

present, as specious, frivolous interference and a

waste of time . I hope we can avoid this in the

future . I don't think it's necessary, the conduct

of this deposition, or to the practice of law in

general .

MR . SHELLER : I will not comment

10 further .

11 (Lunch recess taken from 12 :21 P .M . TO 1 :24 P .M .)

12 VIDEOGRAPHER : We are going back on

13 the record at 1 :24 p .m .

14 BY MR . SHELLER :

15 Q . Doctor, where we left off before, I

16 was asking you a couple of questions about ammonia

17 and particle size and that sort of thing .

18 What's the smallest particle that the

19 Cambridge filter system will pick up? If you

20 know .

21 A . I don't know . It's -- it's very small . I

22 know where to find the answer ; it's in an article

23 by Bradley Ingredthsen from R .J . Reynolds --

24 COURT REPORTER : I'm sorry, Doctor . I

25 didn't hear you .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 845

THE WITNESS : Bradley Ingredthsen,

I-N-G-R-E-D-T-H-S-E-N, from R .J . Reynolds .

3 BY MR . SHELLER :

Q . When was that written -- or published?

I'm sorry .

A . Oh, about eight or ten years ago .

Q . So somebody at Reynolds, Bradley --

A . Ingredthsen .

Q . -- actually measured or knows how

10 to --

11 A . Yes . He got a very prestigious prize for his

12 work on the aerosol nature of cigarette smoke .

13 Q . Where is that published?

14 A . Recent Advances In Tobacco Science, and I've

15 forgotten the-year . I don't know whether it's in

16 here or not .

17 Q . Now, Reynolds, when they ammoniate

18 tobacco, there's a couple of processes, one is

19 process gaseous and the other -- another is

20 aqueous? You've heard about that?

21 A . Well, there was some experimental work done

22 on various ways to ammoniate tobacco .

23 Q . And which Reynolds -- which process --

24 does Reynolds --

25 A . I have no idea .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 846

1 Q . You say you have no idea? I see .

You've never said in a memorandum that

3 they ammoniate their process using a specific

4 process, in a 1994 or subsequent memo? Did you --

5 or am I mistaken?

6 A . I'm not sure whether I did or not . I -- I

don't know what they're using now, if anything .

8 MR . MCDERMOTT : Is your question

9 directed to today or at any point in time?

10 MR . SHELLER : At any point in time .

11 BY MR . SHELLER :

12 Q In 1994, did you believe they were

13 using an aqueous process?

14 A . I don't know what they were using . I know -

15 I say they -- they had been experimenting, when I

16 was there, with various ammonia salts, ammonia

17 gas, ammonia solutions, and so on . But .

18 BY MR . SHELLER :

19 Q. I see .

20 All right, Doctor, at this point I'm

21 going to refer you to a document that was produced

22 by you a few weeks ago called "FTC Smoking Method

23 Used For 'Tar' And Nicotine Data," dated

24 August 30th, 1994 .

25 MR . SHELLER : And we're going to call

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 84 7

1 this -- what exhibit are we up to? Exhibit 2?

2 COURT REPORTER : Yes, it is .

3 MR . SHELLER : For today .

4 (Plaintiff's Exhibit Number 2 was

5 marked for identification )

6 BY MR . SHELLER :

7 t2• And, Doctor, what was this documen t

8 authored by you for ?

9 A . Well, there was some questions about the FTC

10 procedure had come up, about what did the FTC tar

11 number mean and so on . And there were criticisms

12 of the FTC tar number, that it wasn' t

13 representative -- representative of what many

14 smokers would take in, because all smokers smoke

15 differently and the machine smokes rigidly .

1 6 And I got intrigued by this because I

17 was involved, back in the '60s, in this stuff .

1 8 And some of the criticisms that kept appearing in

19 the newspaper and then some of the Time magazine

20 and all this stuff about the validity and whatnot

21 of -- or what the meaning was in terms of the

22 smoker . And I thought, well, these people are

23 complaining about things that we told the FTC in

24 1964, 1965, and they just said we don't want to

• 25 listen to .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 848
I

1 Q . Who did you prepare this document for?

2 A . For myself .

3 Q . So this has never been distributed or

disseminated anywhere?

5 A . Well, one of the gentlemen at R & D, I found

6 out, is a good friend of mine . And I heard he was

7 going to participate in a -- some meeting on the

8 FTC thing . And I said to him : Do you want to

9 look at this? And he did . And I gave him a copy .

10 Q . Was that Dr . Townsend?

11 A . That's Dr . Townsend .

12 Q . Did you give him this to use for his

13 preparation as an expert witness in the Connors

14 case in Jacksonville, Florida?

15 A . I didn't know he was ever involved -- well, I

16 do know that he was involved in Florida ; I

17 wouldn't know it was the Connors case .

18 No . This was actually because there

19 was a meeting in -- outside Washington,

20 Gaithersburg or someplace .

21 Q . Who was participating in this meeting?

22 Did he tell you?


Ln
23 A . Well, it was a -- an NCI or FTC meeting . it ~
~
m
24 was open to the public . I don't know who went .

25 wasn't there .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 849

Q . Was he going to testify?

A . He was supposed to give some presentation at

it . Whether he did or not, I'm not sure .

Q . So he may or may not have used this

paper for his presentation?

A . I don't know whether he gave a presentation .

I just finished telling you that, sir .

Q. I see .

Did anybody at Reynolds pay you for --

10 A . For this?

11 Q. -- for the time you spent doing this

12 paper?

` 13 A . No .

14 Q. So this was not part of your hourly --

15 A. No . I say, I was just intrigued by the fact

16 that, 30 years after all of this stuff came out

17 and we had told them, item after item after item,

18 all of these things became : Gee, we've never

19 heard of this before . And the FTC knew all about

20 it, back in 1964, '65 . Ln


N
~
~
21 Q. I see . m
~
m
22 Now, Doctor, in your -- on the first orn
Ln

23 page of the document, on page 1 . Not the roman

24 numeral page, it's -- I'm referring you to . You

25 say the "Statement of Purpose ." And it starts out

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 850

roman numeral one, "Intended Use of Smoking Method

Results, A Statement of Purpose" . And then you

say : (Reading)

The results from the FTC

analysis of the "tar" and

nicotine yields in the

mainstream smoke from

cigarettes marketed in the

U .S . was intended to

10 accomplish the following :

11 To permit the catalog --

12 cataloging of sequential

13 listing of the cigarettes for

14 their MS, mainstream, yields

15 of these two smoke entities

16 [and in parentheses there's

17 some dates] generated under

18 standard and reproducible

19 conditions . Subsequently a

20 third MS entity, CO, was

21 added to the FTC listing

22 (FTC, 1981) .

23 And then the second purpose, you say,

24 was : (Reading)

251 To permit the consumer

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 851

who wished to continue

smoking to select a cigarette

whose MS 11 tar --

Is that what that stands for?

A . No, it was my lousy typing . It's supposed to

be a quote -- quote mark .

Q . I see . (Reading)

MS tar --

A . If you use a typewriter, the quote mark is

10 right next to the "1" .

11 Q. I see . (Reading)

12 -- and/or nicotine yield

13 was compatible with his/her

14 concerns about the effects of

15 cigarette smoking on his/her

16 health .

17 It was never anticipated

18 by the FTC or by the

19 cigarette manufacturers that

20 the FTC lists could serve as

21 a means to catalog or rate

22 cigarette smokers .

23 "Smokers"?

24 A . "Smokers," right .

251 Q . So those were the two basic purposes,

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 852

1 right?

2 A . Well --

3 Q And --

4 A . That's what the FTC said .

5 Q . Right . Where did the FTC say that

6 were the two purposes? Is that in -- you quote

7 from a notification from the FTC that appears on

8 page 9 . Is that where you believe that

9 information is reproduced? Referring to the

10 March 25th, 1966 --

11 A . Yeah . That's it . Mr . O'Shea's letter?

12 (Discussion off the record)

13 BY MR . SHELLER :

14 Doctor, your -- your testimony, and

15 Dr . Townsend's, I believe, at the Connors case,

16 was that the FTC, in 1966, required the cigarette

17 manufacturers to list the FTC Cambridge filter

18 figures for tar and nicotine ; is that correct? Is

19 that your understanding?

20 A. No . I think the FTC rule was that the

21 analysis was to be done according to the way they

22 said it should be done . I don't know whether the

23 cigarette -- as a matter of fact, I think the FTC

24 does the listing, doesn't it?

25 Q . Well, so -- is the -- did the FTC,

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 853

Federal Trade Commission, require the cigarette

manufacturers, in 1966, to anywheres list the tar

and nicotine levels according to the Cambridge

filter system on anything?

A . I think it --

MR . McDERMOTT : Objection . No

foundation .

THE WITNESS : I think it ended up on

some packs .

10 BY MR . SHELLER :

11 Q• Did the FTC require that it appear on

12 the packs of cigarettes?

13 A . I don't know what the FTC required or didn't

14 require, sir . All I know is that the analytical

15 method was to be thus and so . No argument .

16 Q . Did they require that?

17 A . What?

18 MR . McDERMOTT : What?

19 BY MR . SHELLER :

20 Q . That it had to be by that analytical

21 method .

22 A . That's what the letter says, doesn't it?

23 Q . I see . I see .

24 And is there anywheres in the letter

25 where they -- well, in looking at your page 9 .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 854

And let's read what you say on page 9 . (Reading)

The Cigarette

Advertising Guides

promulgated by the

Commission --

MR . McDERMOTT : Excuse me . Let me

raise a point of order . There looks like may be

an elliptical period . I don't know whether that

indicates some matter has been omitted or not .

10 Maybe, before you read this in and represent it to

11 be the entire letter, we can clarify that .

12 MR . SHELLER : What, the three dots?

13 MR . McDERMOTT : Yeah .

14 MS . KNISELY : Actually, the three

15 dots -- the elliptical is in the actual letter

16 itself .

17 MR . McDERMOTT : Okay . Thank you .

18 BY MR . SHELLER :

19 Q. Okay . (Reading)

20 The Cigarette

21 Advertising Guides

22 promulgated by the Commission

23 in September 1955 provided

24 that no representation should

25 be made that [in quotes] "any

WAGA & SPINELLI (201) 992-4111


Vol . g. 855

brand of cigarette or the

smoke therefrom is low in

nicotine or tars . . . when .it

has not been established by

competent scientific proof

applicable at the time of

dissemination that the claim

is true, and if true, that

such a difference or

10 differences are significant ."

11 On the basis of the facts now

12 available to it, the

13 Commission has determined

14 that a factual statement of

15 the tar and nicotine content

16 (expressed in milligrams) of

17 the mainstream smoke from a

18 cigarette would not be in

19 violation of such Guides, or

20 of any of the provisions of

21 law administered by the

22 Commission, so long as they

23 -- in -- (1) [according to

24 your page nine] no collateral

• 25 representations (other than

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 856

1 factual statements of tar and

2 nicotine contents of

3 cigarettes offered for sale

4 to the public) are made, and

5 (2) the statement of tar and

6 nicotine content is supported

7 by adequate records of tests

8 conducted with the Cambridge

9 Filter Method, as described

10 in an article entitled

11 "Determination of Particulate

12 Matter and Alkaloids (as

13 nicotine) in Cigarette

14 Smoke," by C .L . Ogg, which

15 appeared in the Journal of

16 the Association of Official

17 Agricultural Chemists, 47,

18 No . 2, 1964 . It is the

19 Commission's position that it

20 is in the public interest to

21 promote the dissemination of

22 truthful information

23 concerning cigarettes which

24 may be material and desired

25 by the consuming public .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 857

Did that letter require -- is that

what you base your view, that this letter, issued

by the FTC in 1966, was the commission directing

the tobacco industry that the only way they could

list tar and nicotine levels was by the Cambridge

method?

A . Yes, that's right . That's the way it was . I

mean, this is an edict from the FTC .

Q . I see .

10 A . And you kept saying "you have written" . I

11 haven't done -- I didn't write that --

12 Q . No, no, I'm reading it .

13 Now, this letter doesn't require you

14 to list anything on your packs does it?

15 MR . McDERMOTT : Object to the form of

16 the question . Dr . Rodgman .

17 BY MR . SHELLER :

18 Q. Dr . -- Reynolds, does it? It doesn't

19 require Reynolds to list anything, does it? Read

20 it, please .

21 MR . BLANCATO : Well, objection .

22 BY MR . SHELLER :

23 Q . Doesn't the letter say that, if the

24 Commission has no problem, no objections to you

25 doing that, if it's supported by the Cambridge

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 858

1 method?

2 A . That's right .

3 Q. Okay . Did the tobacco -- you say the

tobacco industry objected to that?

5 MR . McDERMOTT : Objection to the form

6 of the question .

7 THE WITNESS : No, I didn't say that .

8 BY MR . SHELLER :

9 Q . I thought you said they did object to

10 that .

11 A. No . I said they objected -- and if you read

12 the rest of the article, that we pointed out to

13 the FTC that the method they were offering did do

14 what they asked about ranking cigarettes, but it

15 was very incomplete in what else it --

16 Q. Well, Dr . Rodgman, I believe you had

17 written a memo, and it was entitled -- it appears

18 as appendix B in your FT -- in your article here

19 that you gave to Mr . -- Dr . Townsend . And you

20 say -- it's entitled "A Short Explanation and

21 Analysis of Methods for Measuring Tar and Nicotine

22 in Cigarette Smoke," right?

23 A . Yes .

24 You're familiar with that one?

251 A . Yes, I'm familiar with that .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 859

Q . Now, you give -- you wrote that in

1965, in January . And who did you give that to at

that time?

A . 1965? Where did you get that date?

Q . It says January/February 1965 . You

say .

MS . BRACHTL : Where are you in the

document?

MS . KNISELY : Page 37 .

10 MS . BRACHTL : Thank you .

11 BY MR . SHELLER :

12 Page 37, Doctor . In fact, I'll give

13 you a draft of the agreement and the original that

14 was produced for us in your boxes . The draft will

15 be 4, and the actual article 5 .

16 MR . McDERMOTT : What's 3?

17 MR . SHELLER : Oh, we don't have 3? We

18 didn't mark that yet . It's 3 and 4 .

19 (Plaintiff's Exhibit Numbers 3 and 4

20 were marked for identification)

21 MS . EASON : Just for clarification,

22 could you please read into the record the Bates

23 numbers that are stamped .

24 MR . SHELLER : There is a Bates number

251 on it .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 860

1 MS . KNISELY : On one of them, I

2 believe .

3 MR . SHELLER : No, on both of them .

4 The draft is 501013245 . And the -- I assume the

5 final, because it's undated, 501013225 .

6 (Discussion off the record)

7 BY MR . SHELLER :

8 Q . Now, Documents 3 and 4, Exhibits 3 and

9 4, those are your documents . You prepared them,

10 right? They were given to us in the boxes that

11 you produced a few weeks ago .

12 MR . McDERMOTT : Object to the form of

13 the question .

14 BY MR . SHELLER :

15 Q . Did you prepare those?

16 A . Yeah . Yes, I did .

17 Q . Now, who did you give these

18 documents -- this document to at Reynolds?

19 MR . BLANCATO : Which one?

20 BY MR . SHELLER :

21 Q . Exhibit 4, or 3, whichever you gave .


Ln
22 Did you give one or both? One is listed as a N
~
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23 draft with a date and the other is undated .
~
m
24 MR . McDERMOTT : Do you have a time ~
m

251 frame?

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 861

1 MR . SHELLER : 1965, I presume .

2 THE WITNESS : I don't know whether I

3 gave them to Dr . Senkus or Mr . Ramm, Henry Ramm .

4 BY MR . SHELLER :

5 Q• Do you know if those documents were

6 ever given to anybody at the Federal Trade

7 Commission?

8 A . I don't know whether they were given in

9 exactly this form, but I -- my understanding was

10 that some of the information in them were provided

11 to the FTC .

12 Q . Do you know which information?

13 A . No, I don't, sir .

14 Q . I see . Well on page -- how do you

15 know what was given -- something was given to the

16 Federal Trade Commission?

17 A . There were some documents about the

18 collaborative submission to the Federal Trade

19 Commission that had some of this stuff in it .

20 And -- which, you know, you don't ask the vice

21 president of legal counsel : Did you submit what I

22 gave you?

23 MR . SHELLER : Have the documents that

24 were submitted to the Federal Trade Commission

25 been produced in the -- any discovery materials?


1

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 862

1 MR . McDERMOTT : Sitting here, I have

2 no idea .

3 MR . SHELLER : Could you find out?

4 Because we've searched and we cannot find them .

5 MR . McDERMOTT : All right . Well, why

6 don't you put the inquiry in writing to Mark

7 Belasic, since I'm -- because I'm not continuously

8 involved in this case .

9 BY MR . SHELLER :

10 Q. Dr . Rodgman, in page 3 of the --

11 MR . McDERMOTT : Let me also suggest,

12 however, that the information, I'm sure, is

13 available through the records of the FTC, as well,

14 as another way of obtaining this information .

15 MR . SHELLER : They may be . They may

16 be .

17 BY MR . SHELLER :

18 Q . On page 3 of the documents, do you

19 know which one you gave to Mr . -- Dr . Senkus? Was

20 it that -- was it the draft or the one that has no

21 date on it?

22 MR . MCDERMOTT : Object to the form of

23 the question .

24 BY MR . SHELLER :

25 Q . They both say the same thing ; there's

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 863

1 no difference .

2 A . Yeah . I assume that the one had no -- not

3 the draft on it . In fact, I didn't think they

4 were the same .

5 Q . Well, if there is a difference, I

6 didn't pick it up . You can tell --

7 A . Well, if you didn't pick it up, you missed

8 11 -- 8 pages of it .

9 Q . Oh, I'm sorry . Oh, you're talking

10 about the appendix . No, I wasn't --

11 A . Well, that's part of the memorandum, isn't

12 it?

13 Q . No, you're right . I meant the body of

14 the document itself, not the appendix .

15 A . Well, that's part of the body of the

16 document .

17 Q. Yeah, you're right . You're right .

18 You got me .

19 Now, Doctor, on page 3, you say :

20 (Reading)

21 The conclusion is

22 therefore inescapable, that

23 labeling the amount of "tar

24 and nicotine" on a cigarette

25 package cannot give to the

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 864

1 smoker meaningful information

2 as to the amount or

3 composition of the total

4 solids and nicotine he

5 receives from the cigarettes

6 he smokes . He is more likely

7 to be misled than informed .

8 That was your opinion then, Doctor?

9 A . Yeah . Not mine -- not only mine, but it's --

10 but expressed by other people since then .

11 Q . And your opinion today is the same ; is

12 that correct?

13 A . That's right .

14 Q . And it hasn't changed through all

15 these years?

16 A . No . It -- you cannot compare three different

17 smokers who smoke in a different way to what's

18 smoked in a machine .- In fact, the machine does

19 not inhale -- exhale, I'm sorry . But people do .

20 Q . Now, Doctor

21 A . I might recommend that, if you want more

22 information on this, you read the report of the

23 Froggatt Committee, which is in -- sometime in the

24 1980s, when Dr . Froggatt says exactly the same

25 thing as we said in 1965 .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 865

1 Q . And this has always been Reynolds'

2 view also since you've been there?

3 A . Well, I haven't heard anybody come out and

4 say that they went along with doing the analysis

5 the way we were told to do it .

6 Q . Now, did Reynolds ever -- now, you say

7 that the -- this letter of March of 1966 from the

FTC required you to do it -- the -- the tar and

9 milligram system the way you des -- the Cambridge

10 system, correct?

11 A . That's what the FTC said to do .

12 Q. Right .

13 Did Reynolds ever submit another

14 procedure recommendation as to how to get

15 information on tar and nicotine levels? Did they

16 make a recommendation of any type?

17 A . Well, we had provided some information before

18 that letter came out . And I don't know whether

19 anybody did after that . I -- you know, you're

20 fighting the FTC . We had a little bit of a

21 problem that -- for example, if you read Ogg's


Ln
N
22 method, for that -- at that time it was a very ~
m
23 good analysis for nicotine . &b

24 Q . That was 1964?

251 A . Right . But, eventually, you know, when

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 866

1 people are testing cigarettes that are on the

• 2 market, our competitors or experimental cigarettes

3 or cigarettes designed in-house, that was a very

4 slow procedure . And as you know, the FTC equation

5 is wet TPM is tar, plus water, plus nicotine .

6 And people like analytical chemists at

7 Reynolds and other places determined that you

8 could get as accurate nicotine values and water

9 values by doing it with -- it's called gas

10 chromatography . And the beauty of a gas

11 chromatography system is that you can do it

12 automatically . You can do -- load up a carousel

13 with 50/60 things to be measured and just turn it

14 on and let it run .

15 Q . Did the FTC ever tell you, you

16 couldn't use that method?

17 A. No . We persuaded them, and they ended up

18 using it .

19 Q . They did .

20 A . Yeah .

21 Q . So when did -- is that what you now


u,
~
22 use to label your packs? Reynolds packs? ~
m
23 A . I don't know what they use . I don't know ~
CO
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24 whether they label packs or not . But they do use

25 the analytical procedure of gas chromatograph .


~ --- ---- --- - _ - _ -

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 867

1 Q . When did that come into effect?

2 A . Oh, I don't know .

3 Q . When you were there?

4 A . Well, I was there -- excuse me . I can't put

5 a year on it . It was probably -- well, let me

6 look . I might be able to get it for you . Let's

7 see here .

'8 (Witness reviews document)

9 Okay . Well, I thought it was in here

10 on the -- on page 21 . Oh, okay . Okay . Okay . C .

11 Page 24, there's a footnote "Gas Chromatographic

12 Method ." And if we run back in time, I believe

13 you'll see that the 1973, under "Nicotine

14 Determination," a man called Randolph, that is

15 1973/1974, has a little "C," which indicates that

16 was a gas chromatographic method that was

17 described -- well, in fact -- well, there's

18 actually some before that . Put i believe that was

19 the one that may have been presented, written up

20 and --

21 Q . So that was of a -- known about since

22 1973?

23 A . I think so . I may be wrong about that .

24 Q . Give or take a little bit .

• 25 A . But the people in Europe and what -- the


i

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 868

1 CORESTA method and so on, eventually everybody

2 went to gas chromatographic method . If you've

3 ever done a water and smoke by the old fashioned

4 method, I won't say it -- I guess I wouldn't say

5 it the way I would think it . It's very difficult .

6 Q . And that's more accurate than the

7 Cambridge method, right?

8 MR . McDERMOTT : Object to the form of

9 the question . Misstates prior testimony .

10 THE WITNESS : It's not -- the

11 determination of the water, sir, has nothing to do

12 with the Cambridge method .

13 BY MR . SHELLER :

14 Q . I see .

15 A . The Cambridge method is the collection . And

16 when you get -- the old days, you took the

17 Cambridge pad, you got rid of the particulate

18 matter from the Cambridge pad, and you used one

19 part of it to determine the nicotine by the

20 Griffith/Still method and you did the water in the

21 other part by what's called the Karl Fischer

22 titration .

23 The way we did it with the modified

24 method, you took the stuff off the Cambridge

25 filter pad, the same way, and you put it in the -

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 869
I

1 and did it by gas chromatography and calculate the

2 water and nicotine .

3 In fact, the old method really didn't

4 do nicotine . It expressed alkaloids as a lump .

5 And, of course, nicotine was 90 percent of the

6 alkaloids, so they just assumed it -- or called it

7 nicotine . But the new method gave it -- the

8 nicotine its value, and actually you could get the

9 nornicotine value, if you wanted it .

10 t2 • Did the new method also take into

11 account the variations among smokers?

12 A . Sir, the new method involved the same smoking

13 procedure outlined by the FTC method, which says

14 you will collect the cigarettes, you will

15 condition them at such-and-such temperature for

16 such-and-such a humidity, you will smoke them on

17 the machine in the laboratory designed . It had

18 nothing to do with the -- relating them to the

19 smoking ; it was just as wrong then as it was

20 before .

21 Q . Well, can you tell me, if the FTC was

22 so wrong, why were they asked to give you

23 permission to use that method?

24 MR . McDERMOTT : Object to the form of

25 the question .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 870
r

1 BY MR . SHELLER :

• 2 Q Isn't that what that letter does?

3 A . What letter?

4 MS . EASON : Objection to the form .

5 BY MR . SHELLER :

6 Q . That March 1966 letter . Isn't that

7 giving the tobacco industry the right to use that

method if they want to use it?

9 MR . BLANCATO : Object to the form .

10 MR . McDERMOTT : Object to the form .

11 MR . SHELLER : You want to read it?

12 THE WITNESS : The letter says you will

13 use it that way .

14 BY MR . SHELLER :

15 Q• The letter doesn't say you will use

16 it . Where does the letter say -- point --

17 MR . McDERMOTT : The letter requires

18 every public statement, with respect to tar and

19 nicotine, to employ that method, and it encourages

20 the use of the method and the information . But

21 the record and the letter speak for itself . Let's


Ln
22 move on .

23 MR . SHELLER : No . Your representation

24 of the letter is not correct . Would you -- does

25 the witness -- we're going to mark a copy of the

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 871

letter . We'll have the letter read .

MR . McDERMOTT : You've already read

it -

MR . SHELLER : Exhibit 5 . No, the

letter is a little different .

MS . EASON : You have a representation

that the letter was identical .

MS . KNISELY : No, no . I said that the

stars -- Mr . McDermott had raised the issue of

10 whether that star pattern was in the original or

11 whether it was an ellipsis that they had removed

12 words .

13 MR . McDERMOTT : Well, let's use the

14 letter, then . Do we have copies?

15 MS . KNISELY : There were copies made,

16 and I assumed everybody took their copy .

17 MR . SHELLER : Where are the copies for

18 the witness, please? Here's one for you .

19 (Plaintiff's Exhibit Number 5 was

20 marked for identification)

21 (Discussion off the record)

22 BY MR . SHELLER :

23 Q . Now, Doctor, would you tell me -- and

24 you read me the words that the Commission used in

25 its letter that said you must use the Cambridge

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 872

method at all times to list tar and nicotine on

cigarettes . Would you read the words that say

that?

A . Well, I think it's implicit in the way that

they said this is the method .

Q . Implicit? Can you point to me any

words in the letter that say you have to use this

method, and you must list the tar and nicotine

levels on the cigarettes?

10 MR . McDERMOTT : Object . Compound .

11 BY MR . SHELLER :

12 Q . Does the letter require you to list

• 13

14
the tar and nicotine levels on the cigarettes?

A . No, it doesn't .

15 Q . It doesn't .

16 A . No .

17 Q . What does it say? if it --

18 MR . McDERMOTT : Object to the form of

19 the question .

20 BY MR . SHELLER :

21 Q . Does it say, if you want to use the

22 tar and nicotine levels on the cigarettes, that

23 you can, using the Cambridge method, without

24 objection of the FTC?

• 25 A . Yeah . It says here : (Reading)

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 873

1 The statement has to be

2 supported by adequate records

3 of tests conducted by the

4 Cambridge filter method .

5 Q. Right . So they say they won't do

6 anything to you about false advertising if you do

7 it that way?

8 A . Well, I don't know about advertising, sir . I

9 don't --

10 Q . Well, that's what this is all about,

11 isn't it, false advertising, sir?

12 MR . McDERMOTT : Let the witness finish

13 his answer, please .

14 MR . SHELLER : I'm letting him finish

15 his answer .

16 THE WITNESS : I'm not in the

17 advertising business .

18 BY MR . SHELLER :

19 Q . The tobacco industry had -- isn't

20 it -- do you remember that history about there

21 being a -- a tar and nicotine derby in the '50s

22 and '60s? And the FTC was getting concerned about

23 false advertising, right?

24 MR . McDERMOTT : Objection to the form

25 of the question .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 874

1 MS . EASON : Objection to the form of

2 the question .

3 BY MR . SHELLER :

4 Q . So didn't the tobacco -- do you

5 remember that?

6 A. Yes .

7 Q . And didn't the FTC say they were going

8 to look into false advertising?

9 A . They did, in 1957 .

10 Q. Right . And didn't the tobacco

11 industry want to have the ability to put tar and

12 nicotine levels on cigarettes and not be

13 threatened with false advertising claims?

14 A . I don't know that, air .

15 MR . McDERMOTT : Objection ; no

16 foundation .

17 BY MR . SHELLER :

18 Q . Didn't the tobacco industry seek

19 permission from the FTC to do it this way, with

20 the Cambridge system?

21 A . Not that I know of .

22 Q . You don't remember . You don't know or

23 you don't remember?

24 A . I don't know .

25 Q . You don't know .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 875

1 Now, Doctor, in looking at your quote

S 2 in the memo on page 9, would you please look at

3 number -- the letter . And you quote in the middle

4 of the body of the letter "no collateral

5 representations" . And would you read that from

6 your page 9 . it says number one . Just that one

7 number one part .

8 A . Yeah, I've read it .

9 Q . Could you read it for the camera, out

10 loud .

11 A . I've already read it, sir .

12 Q . I know, but I'd like you to do it

13 again .

14 A . Why in --

15 Q . I'll tell you why .

16 A . (Reading)

17 No collateral

18 representations (other than

19 factual statements of tar and

20 nicotine contents of

21 cigarettes offered for sale

22 to the public) are made .

23 Q . Now, would you read Exhibit 5, which

24 is the actual copy of the letter . To the camera,

25 please .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 876

1 A . (Reading)

2 No collateral

3 representations, other than

4 factual statements of tar and

5 nicotine contents of

6 cigarettes offered for sale,

7 are made, expressly or by

8 implication, as to reduction

9 or elimination of health

10 hazards .

11 Q . Could you read it again . I think you

12 left out a couple of words .

13 A . (Reading)

14 No collateral

15 representation, other than

16 factual statements of tar and

17 nicotine contents of

18 cigarettes offered for sale

19 to the public, are made,

20 expressly or by implication,

21 as to reduction or

22 elimination of health

23 hazards .

24 Q . Why did you leave out --

251 MR . McDERMOTT : I move to strike the

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 877

1 last question and answer .

2 BY MR . SHELLER :

3 Q . Why did you leave out the part

4 "expressly or" -- in your article that you gave to

5 Dr . Townsend --

6 MR . McDERMOTT : Object to the form .

7 BY MR . SHELLER :

Q . -- "expressly or by implication, as to

9 reduction or elimination of health hazards"? Why

10 was that left out?

11 MR . McDERMOTT : I object to the form

12 of the question . You're misstating prior

13 testimony .

14 MR . SHELLER : I'm not misstating

15 anything . You can answer it .

16 BY MR . SHELLER :

17 Q . Why was that not in your

18 A . I probably just goofed, sir .

19 Q . You goofed .

20 A . Umm .

21 Q . Well, isn't it true that the FTC

22 didn't want any representations, expressly or by

23 implication, as to the reduction of elimination of

24 health hazards by reason of the -- this late

25 information about tar and nicotine?

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 878

A . That's what they said in the letter .

Q . That's what they said .

Now, would you look back at page 1 of

your article .

A . Uh-huh .

Q• And the second point that you made at

the top is : (Reading)

To permit the consumer

who wished to continue

10 smoking to select a cigarette

11 whose MS tar [mainstream tar]

12 and/or nicotine yield was

13 compatible with his/her

14 concerns about the effects of

15 cigarette smoking on his/her

16 health .

17 That wasn't what the FTC was saying could

18 be done, isn't that correct, according to this

19 letter? There could be no implication of that

20 drawn permitted .

21 A . Well not in the advertising .

22 MR . McDERMOTT : Object to the form of

23 the question .

24 BY MR . SHELLER :

25 Q . Oh, not in the advertising .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 879

1 A . That was what the whole list was put together

2 for .

3 Q . So the implication then, from the

4 tobacco industry's point, was that -- that's why

5 the list was put together?

6 MR . McDERMOTT : Object to the form of

7 the question .

8 MR . BLANCATO : Object to the form .

9 MR . McDERMOTT : No foundation .

10 THE WITNESS : You've lost me with your

11 question .

12 BY MR . SHELLER :

13 Q . Well, wasn't the intent of Reynolds to

14 have the public draw the implication that there

15 was, by lowering tar and nicotine levels, a

16 reduction or elimination of health hazards?

17 MR . McDERMOTT : Object to the form of

18 the question . No foundation .

19 MS . EASON : Object to the form of the

20 question .

21 THE WITNESS : If you look back at why

22 this was done, why the FTC got into the act, it Ln
~
-J
23 started in 1957 with Dr . Wynder, who said, from r

Ob
24 his animal work, that if you kept backing off on m
W
cn
25 treating the mouse skin with cigarette smoke

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 880

1 condensate, you got to a point where you didn't

2 get any tumors on the mice . And he said, if this

3 is translatable to the smoker, if -- then,

4 reduction of the tar from cigarettes by 40 percent

5 would significantly lessen the possibility of

6 respiratory tract cancer .

7 BY MR . SHELLER :

Q . I see .

9 A . And that was the reason the FTC got into the

10 business of : All right, if you lower it, and if

11 people are concerned one way or another --

12 Q . Well do you know why the FTC got into

13 it? Were you there at a meeting?

14 A . Well, I read what they were talking about,

15 back then . it was all over .

16 Q . Weren't they talking about false

17 advertising from the tar and nicotine derby that

18 was going on --

19 MR . McDERMOTT : Object to the form of

20 the question .

21 BY MR . SHELLER :

22 Q . -- in the '60s?

23 A . I don't know that, sir .

24 MR . BLANCATO : Object .

• 25 BY MR . SHELLER :
1

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 881

1 Q . You don't know .

2 Now, isn't it true that in 1964 the

3 Surgeon General, for the first time, came out with

4 a report that said cigarettes cause cancer?

5 A . Well, it's -

6 S2 • Was that the first report?

7 A . Well, t hat was the first Surgeon General's

8 report . And that really spurred the FTC to get

into the act, putting -- in fact, the government

10 agency had said this, and with the work of

11 Dr . Wynder, they put it altogether and said :

12 Let's have a list .

13 Q . So -- and the tobacco industry would

14 benefit from that list because the public, who

15 might have stopped smoking, was led to believe

16 that, because the tar and nicotine levels were

17 being lowered, the cigarettes were now safe or

18 safer?

19 MR . McDERMOTT : Objection to the form

20 of the question . No foundation .

21 MR . BLANCATO : Objection .

22 MS . EASON : Objection to the form of

23 the question .

24 BY MR . SHELLER :

251 Q . Isn't that correct?

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 882
J

1 A . I don't know that, sir .

Q . Isn't that what the tobacco industry

contended?

MR . McDERMOTT : Object to the form of

the question .

6 MS . EASON : Object to the form of the

7 question .

8 MR . BLANCATO : Objection to the form .

9 MR . McDERMOTT : No foundation .

10 THE WITNESS : Not that I know of .

11 BY MR . SHELLER :

12 Q• Isn't it true that the tobacco

13 industry wanted to keep the public smoking, and

14 not stopping as a result of the Surgeon General's

15 report about cancer?

16 MR . McDERMOTT : Object to the form of

17 the question .

18 BY MR . SHELLER :

19 Q . Isn't that correct?

20 MR . McDERMOTT : No foundation .

21 THE WITNESS : I don't know that, sir .

22 BY MR . SHELLER :

23 Q . You didn't know that, the tobacco

24 industry didn't want to do that?

25 MR . McDERMOTT : Object to the form --


1

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 883

1 THE WITNESS : You got to remember, in

2 1964 I was a bench chemist .

3 MR . McDERMOTT : Dr . Rodgman --

4 BY MR . SHELLER :

5 Q . You were a bench chemist . How about

6 in 1970?

7 MR . McDERMOTT : Excuse me . Just a

8 minute . Gentleman, Dr . Rodgman, when I interpose

9 an objection, please wait until I finish my

10 objection . It will be easier on everybody here,

11 including the court reporter . And please give me

12 a chance to object, because your questions are

13 getting outrageous .

14 MR . SHELLER : My questions are not

15 outrageous ; they are very true . You know, you

16 always object when things start sticking you in

17 the chest . Why don't you just say "objection" and

18 allow the witness to testify . I understand your

19 problem and I would be troubled too, if I was

20 Reynolds' counsel . Don't laugh, it's true .

21 BY MR . SHELLER :

22 Q . Now, Doctor, if you look at your

23 report, Dr . Townsend, on page 27 --

24 A . This report wasn't to Dr . Townsend .

0 25 Q . Well, the one you gave Dr . Townsend .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 884

1 A . What page?

• 2 Q . Twenty-seven . Now, do you see the

3 chart that you prepared at the bottom of the

4 report, "Table 9" you call it?

5 A . Uh-huh .

6 Q . And in Table 9 -- and we're going to

7 mark this table at a separate exhibit .

8 MR . SHELLER : Call it -- what number

9 am I up to?

10 COURT REPORTER : Six .

11 MR . SHELLER : Six .

12 BY MR . SHELLER :

13 Q . In Exhibit 6, Table 9, you define it

14 as : (Reading)

15 85-millimeter Winston

16 and Marlboro : Comparison of

17 FTC carbon monoxide,

18 nicotine, and 'tar' yields at

19 standard and more 'realistic'

20 smoking parameters .

21 What were the "more realistic smoking

22 parameters" that you figured out to use here?

23 A . This was from a report written by somebody at

24 Reynolds, I believe .

25 Q . What are realistic smoking conditions?

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 885
r

1 According to Reynolds . .

2 MR . McDERMOTT : Object to the form of

3 the question .

4 THE WITNESS : Sir, this was just a

5 table that, when you change the smoking regime,

6 you got the higher numbers .

7 BY MR . SHELLER :

8 Q . Well, is this a report by a Dr . Rix

9 that you're referring to, at Reynolds?

10 A . It may be .

11 Q . You cite that in the body of your

12 report?

13 A . Right .

14 Q . And what does he describe as more

15 realistic smoking conditions?

16 A . It has those -- the parameters are listed

17 there .

18 Q . What are they?

19 A . Sixty-five-milliliter puff, two-second puff,

20 one puff every 45 seconds .

21 Q . And what was the FTC standard?


Ln
FA
~
22 A . Thirty-five, two, and once a minute . ~
m
23 Q . I see . ~
~
m
~
24 And now you took that material

25 prepared -- done by Dr . Rix and converted it into

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 88 6

1 a table? Or is that table right from his article ?

2 A . I've forgotten . It may be -- probably

taken -- he may have had it in a little different

4 format .

5 Q . And what he did is he -- or you -- I'm

6 not sure who did the table, now . But the table

7 you used from Reynolds says "FTC smoking

8 conditions for Winston and Marlboro comparisons,"

9 right? That's -- Marlboro is made by Philip

10 Morris ?

11 A . That's right .

12 Q. And Winston by Reynolds, right ?

13 A . Right .

14 S2 Q . And the -- and according to the FT C

15 tar levels from the FTC standard, the Winston was

16 20 .6 tar, and there's a parenthesis there, 20 .9 in

17 parenthesis, and it refers to a note A . Do you

18 know what that refers to ?

19 A . It was the percent difference between the

2 0 Winston and Marlboro .

2 1 Q. And the Marlboro was at 16 .3 . And th e

22 FTC nicotine level for Winston was 1 .43 milligrams

23 and for Marlboro it was 1 .08 . And the carbon Ln

24 monoxide for the Winston was 19 .1 and for Marlboro m

25 16 .2 ; is that correct ?

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 887

1 A . Right .

Q . But when it was done according to

3 realistic conditions, smoking conditions -- and

4 that's the title in the chart, right?

5 A . Right .

6 Q . The Winston was actually

7 35 .7 milligrams in tar and 2 .35 milligrams

8 nicotine ; is that correct?

9 A. Yes .

10 Q . Can I ask you a question? Is that

11 exactly pretty much the same as the 1955

12 16 milligrams of tar and nicotine for the

13 cigarettes in those days?

14 MR . McDERMOTT : Object to the form of

15 the question .

16 THE WITNESS : Well -- no . The --

17 well, they're comparable, but done under

18 different -- under --

19 BY MR . SHELLER :

20 Q . Pretty close, though?

21 MR . BLANCATO : Objection . Let him

22 finish his answer, please .

23 MR . McDERMOTT : Let him complete his

24 answer .

251 THE WITNESS : In 1955, of course, the

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 888

1 numbers that were -- are in the graph, I'm sorry,

2 were done with the top figures .

3 BY MR . SHELLER :

4 Q . With the "top figures" . What do you

5 mean? The 35 .

6 A . Close to that .

7 Q . The realistic ones, right?

8 A . Right .

9 MR . McDERMOTT : No, no, no, no . Just

10 the opposite .

11 MR . SHELLER : No . I think he --

12 would -- would you --

13 BY MR . SHELLER :
• 14 Q . As I understand it, in 1955 the

15 Winstons were approximately 35 milligrams of tar,

16 weren't they?

17 A . Yeah . But they were determined by a

18 35-milliliter puff .

19 Q . They were?

20 (Witness nods head .) Yeah .

21 Q . I see .

22 A . I mean, if you look back historically at the

23 smoking parameters, which were set in 1936 by some

24 people at American Tobacco and everybody used it

25 worldwide, more or less, it was 35-milliliter


i

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 889

1 puff, one puff a minute, two-second duration . And

2 the numbers -- say, Winston, Camel, whatever

3 cigarette you're talking about in '55, were

4 determined with that .

5 Q . How do you know that? Is that -- the

6 1955 numbers that Reynolds had was based on a

7 35-milliliter puff?

8 A . Yes . There was some slight difference in the

analytical procedure for nicotine .

10 Q . What was the difference?

11 A . Well, I had just gotten at Reynolds at that

12 time . But I believe they were using a

13 modification of the Griffith/Still thing that

14 Mr . Cundiff had incorporated . After all, there

15 was no really set method by that -- at that time .

16 Q . So, then --

17 A . And --

18 Q . -- your -- your point that the --

19 you're responding to Dr . Wynder and Dr . Hoffmann .

20 If you use realistic figures, are you able to tell

21 the jury that there -- that you can actually

22 conclude that there's a lowering of tar and

23 nicotine in the realistic conditions of smoking

24 today?

25 A . Well, what -- you don't compare apples and

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 890

1 oranges . If you're going to make a comparison,

2 let's be fair . If you're going to say these are

3 the conditions we will use in the smoking machine,

4 let's compare the '55 cigarette done the same way .

5 Q . But you're not doing that .

6 A . Pardon?

Q . You said it wasn't -- you don't know

8 how it was --

9 MR . McDERMOTT : Object to the form of

10 the question .

11 BY MR . SHELLER :

12 Q . It wasn't -- if you're going to

13 compare, how do you know what the realistic

14 conditions would have shown in 1955?

15 A . Well, if you use these numbers, if you use

16 those numbers on a'55 cigarette, presumably you

17 would have got higher numbers than are in the

18 graph .

19 Q . Presumably . I thought you don't use

20 calculated, you like to be realistic, you want to

21 know what they are . Remember, we went through

22 this with nicotine? You don't like using

23 calculated numbers?

24 MR . BLANCATO : Let's not harass the

25 witness, please .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 891

1 MR . SHELLER : I'm not harassing him .

2 He's the one who talks about calculated numbers .

3 MR . McDERMOTT : You're asking the

4 witness to apply a different regimen, to

5 hypothesize an answer, and then you're criticizing

6 him for trying to respond to your question?

7 MR . SHELLER : Well, he's the one who

8 criticizes the people who wanted to figure out the

9 nicotine levels by calculating them .

10 MR . McDERMOTT : This is nonsense .

11 Let's -

12 MR . SHELLER : Well, I understand . I

13 understand nonsense to you, maybe .

14 BY MR . SHELLER :

15 Q . Now, Doctor, so what you're really

16 saying today, that if you use realistic conditions

17 for determining tar and nicotine levels, you have

18 to make an estimate of what those conditions would

19 have been in 1955 to determine whether or not the

20 tar and nicotine levels were actually lower

21 today --

22 A . Well, you'd use -- you'd use the same

23 conditions . Wouldn't you?

24 Q . Well, you would ; but you didn't .

25 You're saying you don't know what the realistic

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 892

1 conditions of smoking would have shown in 1955 .

2 Unless these aren't the realistic conditions in

3 1955 .

4 MR . BLANCATO : Objection . Are you

5 talking about the values they got here for tar and

6 nicotine --

7 MR . SHELLER : Uh-huh .

8 MR . BLANCATO : -- or are you talking

9 about 35-milliliter puffs? Or --

10 MR . SHELLER : I'm only trying to

11 figure out what realistic conditions existed for

12 smoking in 1955 .

13 THE WITNESS : Well, I said, if you're

14 going to make a comparison, you would use these

15 realistic conditions that are listed here by

16 Dr . Rix for the 1955 cigarette .

17 BY MR . SHELLER :

18 Q . Why would you assume those are the

19 realistic conditions for smoking a cigarette in

20 1955?

21 A . Well, I think, if you notice, they're in

22 quotation marks . N
N
23 Q. Right . But why would -- wouldn't m

24 somebody who got their adequate dose of nicotine -J


m
Co
25 in 1955 with the higher, quote, tar and nicotine
J

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 893

1 levels you talk about, have a different realistic

2 smoking level?

3 A . They may or may not .

4 MS . EASON : Object to the form of the

5 question .

6 MR . McDERMOTT : Object to the form of

7 the question .

8 BY MR . SHELLER :

9 Q . You don't know the answer to that, do

10 you?

11 A . Well, as I have said repeatedly, sir,

12 everybody smokes differently .

13 Q . Right . And you don't -- do you know

14 what the realistic smoking conditions were, as

15 you -- in 1955?

16 A. No . And I don't know what they are now .

17 Q. Well, apparently Dr . Rix and you

18 reached the conclusion in this 1994 article as to

19 what they were .

20 A . I was summarizing some of the work --

21 Q . For now .

22 MR . BLANCATO : Objection . Please let

23 the witness finish his question .

24 BY MR . SHELLER :

25 Q . Isn't it true, Doctor --

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 894
I

1 MR . McDERMOTT : You cut the witness

2 off . Let him finish his answer, counselor .

MR . SHELLER : Fine .

4 BY MR . SHELLER :

5 Q . Do you have something to finish, sir?

6 A . As you notice, I'm just reporting what

7 Dr . Rix reported .

8 Q. I see . You don't agree with him?

9 A . I was reporting what Dr . Rix reported .

10 Q . Do you agree with him or disagree with

11 him?

12 A . I assume he found what he found .

13 Q . Do you agree with him?

14 MR . BLANCATO : Objection .

15 THE WITNESS : I don't know how you

16 mean, "agree" .

17 BY MR . SHELLER :

18 Q . Do you think he was right?

19 A . Well, I said, he -- I assume that what -- the

20 experimental data he found, he found .

21 Q. Do you think he was right? That's a

22 simple yes or no . Can you answer --

23 MR . McDERMOTT : In what respect?

24 BY MR . SHELLER :

25 Q . Do you think these are realistic

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 895
r

1 conditions? Do you think -- do you have any

2 reason to disagree with Dr . Rix?

3 A . I don't know -- I don't know why he picked

4 the realistic conditions that way . I have no

5 idea .

6 Q . Did you ask him?

7 A . No .

8 Q . He worked for you, right?

9 A . At one time .

10 Q. Yeah . And, in fact, this report was

11 done when you were director of --

12 A . Research .

13 Q . -- research, right? And so he worked

14 under you?

15 A . Right .

16 Q . Did you tell him then : There's

17 something wrong with your report?

18 A. No .

19 Q . I see .

20 Doctor, just to make it clear, you

21 have testified today, several times, that you kept

22 meeting Wynder and Hoffmann's conditions of

23 dropping nicotine and tar levels - when I say

24 "you," I mean Reynolds - over the years . Yet,

25 this document, that you have, would indicate that

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 896

1 the tar and nicotine levels for realistic smoking

2 are con -- are at the same level, at least of

3 whatever the measurement was in 1955, as they were

4 then ; isn't that true?

5 MR . McDERMOTT : Objection to the form

6 of the question . Misstates prior testimony .

7 MR . BLANCATO : Objection to the form .

8 THE WITNESS : Well, here again, this

9 is -- this is -- if you ran the '55 cigarette by

10 what Dr . Rix called realistic conditions, you

11 probably would have got numbers much higher . And

12 if you plotted them over the years, the curve

13 would still drop the way it is . All you'd have

14 done is move your baseline .

15 BY MR . SHELLER :

16 Q . Doctor, how can you say that? There's

17 different smoking compensation factors involved .

18 You talked about it in your report, why smokers

19 compensate and how they smoke differently .

20 You have no basis, do you, for making

21 a claim that realistic smoking conditions for the

22 same cigarettes in nineteen-fifty -- the

23 cigarettes that were in effect in 1955 were, in

24 fact, the number that Dr . Rix used in his report

based on the cigarette smoke in 1979 .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 897

1 A . No, I don't .

MR . McDERMOTT : Object to the form of

the question .

THE WITNESS : The --

MR . SHELLER : Did you get the answer?

6 COURT REPORTER : Uh-huh . "No, I

7 don't ."

8 VIDEOGRAPHER : Mr . Sheller, we have

9 five minutes left on the videotape .

10 MR . SHELLER : What we'll do at this

11 point is let's -- let's mark the next document

12 we're going to refer to, which is the -- where's

13 that one?

14 MR . McDERMOTT : Just a point of order .

15 Have you now made arrangements to make this Table

16 exhibit?

17 MR . SHELLER : Yes .

18 MR . McDERMOTT : So it's going to be

19

20 MR . SHELLER : Yes .

21 MR . McDERMOTT : All right . Has that

22

23 MR . SHELLER : Not yet . All right .

24 (Discussion off the record)

25 1

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 898

1 (Plaintiff's Exhibit Number 6 was

2 marked for identification)

3 VIDEOGRAPHER : We're going off the

4 record at 2 :22 p .m .

5 (Recess taken from 2 :22 p .m . to 2 :42

6 p .m .)

7 VIDEOGRAPHER : This is tape 5 of the

8 videotape deposition of Alan Rodgman, Ph .D . We're

9 going back on the record at 2 :42 p .m .

10 BY MR . SHELLER :

11 Q . Dr . Rodgman, if Reynolds disagreed

12 with anything the FTC was doing about its method

13 for measuring tar and nicotine levels, did

14 Reynolds ever go to court to argue against what

15 the FTC was doing?

16 A . I don't know .

17 Q . Did they ever ask for a hearing before

18 the Federal Trade Commission about it?

19 A . I don't know .

20 Q . Well, we know that tobacco industry

21 and Reynolds are not shrinking violets, are they,

22 when it comes to litigation?

23 MR . McDERMOTT : Object to the form of Ln


~
J
N
24 the question . m
~
J
25 MR . BLANCATO : Object to the form of
P.

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 899

1 the question .

2 BY MR . SHELLER :

3 Q . Isn't that true?

4 MR . McDERMOTT : Object to the form of

5 the question .

6 BY MR . SHELLER :

7 Q . So if it's something they didn't like,

8 they wouldn't hesitate to take on the Federal

9 Trade Commission, would they?

10 MR . McDERMOTT : Object to the form of

11 the question .

12 MS . EASON : Object to the form of the

13 question .

14 MR . BLANCATO : Object to the form .

15 MR . McDERMOTT : No foundation .

16 THE WITNESS : I don't know .

17 BY MR . SHELLER :

18 Q . Isn't it true they're taking the Food

19 and Drug Administration to court because the Food

20 and Drug Administration has said that nicotine is

21 a drug? And they're in court right here in North

22 Carolina, their own ballpark, right?

23 MS . EASON : Object to the form .

24 MR . BLANCATO : Object to the form .

25 MR . McDERMOTT : Object to the form of

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 900

1 the question ; no foundation .

2 THE WITNESS : I don't know .

3 BY MR . SHELLER :

4 Q . You don't know?

5 MR . McDERMOTT : Dr . Rodgman, just a

6 moment . Let me finish my objection .

7 Counsel well knows Dr . Rodgman was an

8 employee at Reynolds from 1954 to 1987 . He's here

9 to answer factual inquiries with respect to that

10 time period .

11 If you want to give little speeches

12 about what the tobacco industry has done, that's

13 fine ; but it has nothing to do with Dr . Rodgman or

14 the information in his possession . You're wasting

15 our time, and this line of questioning is

16 improper .

17 MR . SHELLER : Well, I don't think it's

18 improper . I think the jury is entitled to know

19 that the -- Reynolds can go to court in

20 North Carolina any time they wanted to if they

21 didn't like what the Federal Trade Commission was

22 doing . And they didn't .

23 MR . McDERMOTT : Object to the form of

24 the question . That's why God made closing

25 argument .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 901

1 MR . SHELLER : Oh, yeah?

2 BY MR . SHELLER :

3 Q• Now, the next exhibit that I'd like to

4 mark is "Comments, Re FDA Nicotine Report

5 General" . Dated -- it says "Revised 11/2/95" .

6 Did you re -- prepare that report?

7 MR . SHELLER : Can you give the witness

8 a copy of it? I believe copies were made .

9 MR . BLANCATO : What's the exhibit

10 number on this?

11 MR . SHELLER : This will be 7 .

12 (Plaintiff's Exhibit Number 7 was

13 marked for identification)

14 BY MR . SHELLER :

15 Q . That was in your documents that you

16 gave us, Doctor .

17 A . Yes, I prepared this .

18 Q . And what was the purpose of re --

19 preparing this?

20 A . I was asked to read the -- some report from

21 the FDA or some comments about the FDA, did I have

22 any thoughts of what they had written and anything

23 I might come up with that might be usable to

24 respond to them . And I -- as you know, it's sort

25 of choppy . I just put this together and --


~
r
J

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 902

Q• Well, who asked you to put this

together?

A. The folks at R & D .

Q. At Reynolds?

A . Yes .

Q . So this was prepared for Reynolds . So

you were doing work for Reynolds in 1995, then ; is

that correct?

A. No . I just did it for -- I wasn't paid for

10 it .

11 Q . You weren't paid for it . I see . But

12 you were doing work for them .

13 A. (Witness nods head .)

14 MR . MoDERMOTT : Object to the form of

15 the question . Misstates prior testimony .

16 BY MR . SHELLER :

17 Q . Now, you had testified that you were

18 not an expert on nicotine .

19 A . That's right .

20 Q . Yet, Reynolds is asking you to give

21 the m a repor t on n i co ti ne ? Ln
N
~
~
22 A . Well, they knew that I had considerable m
~
23 background in the literature . And , as you notice , ~
N
CO
24 most of it is things pulled out of the literature .

25 I don't consider my -- still don't consider myself

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 903

1 an expert on nicotine .

2 Q . Would you look at what appears to

3 be -- I'm sorry . I have two different reports .

4 And I -- which one -- let me just see which one

5 you do have . Do you have the one marked 11/25/95

6 or 11/2/95?

7 A . Well, I've got them back-to-back here .

8 Q . Okay . Look at the one marked

9 11/25/95 .

10 A . Uh-huh .

11 MS . KNISELY : Actually, when they were

12 doing the copying, they put them, obviously,

13 together .

14 MR . SHELLER : That's all right .

15 MR . McDERMOTT : Do you want to keep it

16 as one exhibit? Or do you want 7A,'7B or --

17 MR . SHELLER : It doesn't matter .

18 MS . KNISELY : Why don't we make it 7A

19 and 7B .

20 MR . SHELLER : Okay . So the

21 comments .

22 (Plaintiff's Exhibits Numbered 7A and

23 7B were marked for identification)

24 (Discussion off the record)

25 BY MR . SHELLER :

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 904

1 Q . Now, Doctor, on page 1 of the revised

2 11/25 report, it states : (Reading)

3 Tobacco treated with

4 ammonia/steam (the process

5 used by RJR to reduce the

6 nicotine level in

7 high-nicotine tobaccos)

produces the following

9 changes in the tobacco .

10 So, remember I asked you before if you

11 knew what system RJR was using?

12 A . Yeah . I'd forgotten about that, sir .

13 Well, that case was the

14 denicotinization case, which has always been

15 ammonia and steam .

16 Q . I see .

17 And is there anything in these two

18 reports that you now disagree with or think is

19 incorrect?

20 A . It's been some time since I've looked at

21 them . As I say, they were sort of pulling things

22 together that might be of use in responding to the

23 FDA . And I'd have to read them . As you notice,

24 it's very choppy . It wasn't one of my better

25 efforts .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 905

1 Q . Well, do you see the portion under

2 that, it says : (Reading)

3 In the mainstream, MS,

4 from the ammonia treated

5 tobacco?

6 A . Right .

7 Q . It says : (Reading)

8 On an equal weight of

9 tobacco smoke basis, the

10 nicotine delivery is lower in

11 the mainstream from the

12 processed tobacco than in the

13 mainstream from the control .

14 Is that correct?

15 A . That's usually the case with ammoniated

16 tobaccos .

17 Q. Right . Well, how did you measure

18 that, though?

19 A . Well, there's a set analytical procedure for

20 measuring nicotine in tobacco .

21 Q . How did you measure it in the

22 mainstream smoke? MS, is it -- what is that?

23 A . Mainstream smoke .

24 Q . I thought you can't measure it in

25 mainstream smoke? j

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 906

1 MR . McDERMOTT : Object to the form of

2 the question . You're misstating the witness'

3 testimony .

4 BY MR . SHELLER :

5 Q . Only by particulate?

6 A . Yeah, it's in the --

7 Q . Just the particulate matter .

8 A . It's the nicotine done by the FTC procedure .

9 Q . I see .

10 So, you don't know, then, whether

11 there's more nicotine in the smoke, then, because

12 you -- you'd have to calculate a value for that,

13 right?

14 A . I -- I don't get the message .

15 Q . If you treat tobacco with ammonia to

16 reduce the nicotine, this is your -- you're

17 reducing levels of nicotine, right, so you're

18 saying?

19 A . Right .

20 Q . And you're treating the tobacco with

21 ammonia, right?

22 A . Right .

23 Q . And there's still ammonia in the

24 tobacco that's treated, right, left in there?

A . A little bit .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 907

1 Q . A little bit .

2 Do you know what portion, if any, of

3 that nicotine, after burning or pyrolysis, remains

4 in the smoke that's not picked up by the filter?

5 A . We're back to that again? As I said this

6 morning, the -- we looked at some very clever

7 chemists, both in our company and others, tried to

8 determine free nicotine, if that's what you're

9 trying to get, or nicotine, per se, in the vapor

10 phase that passes through the Cambridge filter

11 pad, and nobody has been able to find it .

12 And just to maybe round off and make

13 you feel better about it . If you have a reservoir

14 or a flask with nicotine in it that leads to a

15 Cambridge filter pad holder with a Cambridge

16 filter pad in it, and you vaporize the nicotine

17 and let it go along, so that when it hits the

18 Cambridge filter pad that it's about the same

19 temperature as the Cambridge filter pad in the FTC

20 procedure, you collect a lot of the nicotine on

21 the -- Cambridge filter pad . If you then check

22 what can go through the filter pad - because


Ln
~
J
23 there's nothing else to hold it, there's no acids ~
m
24 or anything - we can detect down to nanograms, 0.
J
N
W
25 micrograms of nicotine that will come through

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 908

1 that, and we could never find it with cigarette

2 smoke .

3 Q. I see . So anybody who finds it is

4 mistaken?

5 A . In the mainstream smoke that goes through to

6 the filter pad?

7 Q . Uh-huh .

8 A . I've never heard of anybody who's found it .

9 Q . I see .

10 A . As I said, it's been looked at by everybody

11 that I can think of .

12 Q . So you're saying there's no such thing

13 as free nicotine, the way I'm referring to it, in

14 this smoke that's not collected in the filter .

15 A . There is no nicotine that goes through the

16 Cambridge filter pad . And if it goes through the

17 Cambridge filter pad, it has to be nicotine by

18 itself . No salt .

19 Q. No salt . And you're saying, to your

20 knowledge, no nicotine by itself, free of salt,

21 does not go through that pad or it does?

22 A . That's right, it does not go through .

23 Q . It does not go through .

24 A . I guess that's --

i 25 Q . But you're not an expert on nicotine,

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 909

but you know that .

A . Well, I -- I know that -- I happened to have

some people that looked at that for about a year

and a half and tried all sorts of very fancy

methods .

The reason we did it is the -- some

people at Tennessee Eastman found out a way to

measure free ammonia in smoke, and we thought it

was adaptable to free nicotine . But it doesn't

10 work . They couldn't get it to work . Hoffmann

11 can't get it to work .

12 Q . Well, do you know any researchers at

Reynolds, like Dr . Robinson or -- who actually can


• 13

14 measure increased levels of nicotine -- I forget

15 what they're called -- indicators in the urine?

16 Cotinine levels, is that --

17 A . Well, a lot of the things that Dr . Robinson

18 has done on nicotine metabolism and so on were

19 done after I left . I don't know --

20 Q . You don't know about that?

21 A . I don't know about --

22 Q . So you don't know whether Dr . Robinson

23 has actually found that nicotine in

24 ammonia-treated tobacco has higher levels than in

25 the control without it?

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 910

1 MR . BLANCATO : Object to the form .

2 MR . MCDERMOTT : Object to the form of

3 the question .

4 THE WITNESS : I think you're jumping

5 from apples to oranges again, sir .

6 BY MR . SHELLER :

7 Q . I'm talking about the way Dr . Robinson

8 measures things .

9 A . I don't know . I just finished telling you, I

10 don't know how he measures .

11 Q . You don't know . You don't know . All

12 right .

13 A . I mean, if I don't know, I don't know . I'm

14 sorry, I can't -- I won't make up an answer for

15 you .

16 I understand . I understand .

17 MR . SHELLER : This is going to be the

18 next exhibit I refer to .

19 (Plaintiff's Exhibit Number 8 was

20 marked for identification)

21 BY MR . SHELLER :

22 Q . Doctor, this is a report that you Ln


1~
23 prepared in 1956, September 28th . Do you recall ~

24 preparing that? It's called "RDR, 1956, No . 9" .

0 251 And it's Exhibit 8 .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 911

1 MS . BRACHTL : Give us a second to

2 catch up with you .

3 (Witness reviews document)

4 BY MR . SHELLER :

5 Q . Did you prepare that report?

6 A . Oh, yes .

7 Q . So you recall it .

Would you please look at page 36 .

9 This was when you were a young chemist, right,

10 Doctor?

11 A . When I was young?

12 Q . Some 41 years ago .

13 A . Right .

14 MR . MCDERMOTT : We were all young .

15 BY MR . SHELLER :

16 Q . Now, Doctor, in the discussion it

17 says : (Reading)

18 The main interest in .the

19 presence of the polycyclic

20 aromatic hydrocarbons in

21 cigarette smoke condensate is

22 that many of these compounds

23 are known to be carcinogenic

24 to various species of

animals . The current

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 912

1 controversy concerning the

• 2 influence of cigarette

3 smoking on the increasing

4 incidence of cancer of the

lung in the human male (and

6 it lists a bunch of numbers] .

7 Animal data indicate there is

8 a carcinogenic factor in

9 cigarette smoke condensate .

10 MR . BLANCATO : Objection . You've

11 skipped over a portion of the --

12 MR . SHELLER : "However, animal

13 data" --

14 MR . BLANCATO : No, beyond that --

15 before that : "It has not yet been settled ."

16 MR . SHELLER : Where are you reading

17 f rom?

18 MR . BLANCATO : After the numbers in

19 the parentheses end .

20 MR . SHELLER : Oh . (Reading)

21 Has not yet been

22 settled -- the increasing

23 incidence of cancer of the

24 lung in the human male has

25 not yet been settled .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 913

1 However, animal data indicate

2 that there is a carcinogenic

3 factor in cigarette smoke

4 condensate . This

5 carcinogenic factor resides

6 mainly in the neutral

7 fraction of the smoke

8 condensate and is produced

9 primarily by the pyrolysis --

10 THE WITNESS : Pyrolysis .

11 MR . SHELLER : (Reading)

12 -- pyrolysis of the

13 tobacco during the smoking

14 process .

15 Is that a true statement?

16 MR . McDERMOTT : Is that now, or was it

17 then?

18 BY MR . SHELLER :

19 Q. Was it then, and is it today?

20 A. Well, the carcinogenic factor that causes

21 skin cancer in mice is probably due to that . It's

22 true now as it was then .


Ln
Q. Would you change that any way today? ~
23 ~
~
m
24 A. The last two sentences? (Reading) ~
~
N
25 However, animal data kD

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 914

1 indicate there is a -- there

2 is a carcinogenic factor in

3 the cigarette smoke

4 condensate .

5 Q . You'd change that?

6 A . No, are those the two --

7 Q. No . Is there any part of it you'd

8 change?

9 A . No, I wouldn't change that . Because you can

10 still do it with mouse skin .

11 Q . Now, on the top of page 37, you say :

12 (Reading)

13 It has been demonstrated

S 14 that the carcinogenic

15 activity of the whole

16 condensate -- condensate, or

17 the hexane-soluble, neutral

18 fraction, is apparently much

19 greater than that due to the

20 individual carcinogenic

21 hydrocarbons, anthracene,

22 pyrene, chrysene?

23 A . Chrysene .

24 Q . (Reading)

• 25 1, 2-benz --

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 915

1 A . "Benzanthracene" .

2 Q . Do you want to help me here? I can't

3 pronounce these things .

4 A . m 3,4-benzpyrene" .

5 Q . (Reading)

6 -- present . Three --

7 these explanations of this

8 apparent anomaly appear

9 plausible at present .

10 And then it lists the following :

11 (Reading)

12 The carcinogenic

13 activity of the

14 hexane-soluble, neutral

15 fraction (or whole

16 condensate) is due mainly to

17 some hitherto unknown

18 powerfully carcinogenic

19 polycyclic aromatic

20 hydrocarbon .

21 A synergistic effect is

22 obtained from the known

23 hydrocarbons . This fact --

24 phenomenon has been described

25 by numerous workers in the

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 916

1 cause -- case of the

• 2 polycyclic aromatic

3 hydrocarbons .

4 Some compound present in

5 the neutral fraction of

6 cigarette smoke condensate is

7 behaving as a cocarcinogen

8 either for some compound in

9 cigarette smoke or for some

10 compound present as a

11 pollutant in air .

12 (Witness reviews document)

13 Do you agree with those? Anything you

14 disagree with?

15 A . Well, I now know, for example, that number 1

16 is wrong .

17 Q . Number 1 is wrong?

18 A . That the -- there was a proposal that,

19 because they could not explain the fact with the

20 known polycyclic hydrocarbons that would cause

21 tumors on mouse skin, they couldn't explain what

22 they were getting with cigarette smoke condensate,

23 that Dr . Wynder and Dr . Wright - Dr . Wright .

24 happened to be my major professor - had proposed

25 that there is some other polycyclic hydrocarbon in

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 917

1 smoke that's as potent as benzo[a]pyrene, at --

2 but present at 25/30 times the level of

3 benzo [a] pyrene .

4 Q . We went through that before . So this

5 is the same thing before?

6 A . Well, no, this is different .

7 The -- or there was a polycyclic

8 hydrocarbon, which was 30 times more potent than

9 benzo[a]pyrene, present at the same level as

10 benzo[a]pyrene . And Dr . Wright, who I say was my

11 major professor, spent 18 months looking for what

12 they call the super carcinogen and, of course,

13 never found it .

14 But then, I say, looking back at what

15 we know now, back to 1956 -- and in the mid '70s

16 the group at USA -- USDA in Athens, Georgia, under

17 Dr . Chordik did the most complete study of

18 polycyclic hydrocarbons in smoke ever done and

19 could account for the whole fraction . And there

20 was no compound potent, like benzpyrene, present

21 at 30 times the level or no super carcinogen .

22 Q. Well --

23 A . So that is, you know, a premise that was in

24 the works at that time, and went down the drain

25 subsequently .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 918

1 Q . I see . Is two and three correct?

2 A . The --

3 Q• Synergistic effect .

4 A . In a way it is . Because what was found

5 shortly after 1956 -- for example, if you have

6 benzpyrene at a given amount and paint mice with

7 it, you get a certain number of tumors . But then,

8 if you paint another group of mice with the same

9 amount of benzpyrene but with a non-tumorigenic

10 polycyclic, like anthracene, the tumorigenicity

11 goes down . In other words, it's not synergism,

12 it's inhibition . And, of course, this was not

13 known when I wrote this .

14 Q . How about synergistic effects? How

15 about --

16 A . That has never been demonstrated with

17 polycyclic hydrocarbons .

18 Q . Has it been demonstrated with other

19 substances and stuff?

20 A . Not that I know of .

21 Q . Well, did Reynolds, to your knowledge,

22 ever do any studies on animals, either by contract

23 or otherwise, to see if the various constituents

24 of smoke, when mixed together in different

25 mixtures --

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 919
r

1 A . No, we didn't .

2 Q . -- create a synergistic effect?

3 A . No, we didn't .

4 Q . You didn't . Do you know if anybody

5 did?

6 A . Oh, yes .

7 Q . Who?

8 A. Dr . Wynder .

9 Q . And what did he say?

10 A . Well --

11 Q . He says it does, doesn't it?

12 A . It doesn't say synergism .

13 Q . It doesn't? So if Dr . Wynder and

14 Dr . Hoffmann agree with you, you're going to have

15 a problem with it?

16 A . No, I don't have a problem with it . Because

17 they -- what they did -- at the time they did the

18 experiment, there were, I don't know, a dozen

19 polycyclic hydrocarbons which had some degree of

20 tumorigenicity to mouse skin . And they figured

21 out how much was in the smoke condensate . And

22 they added -- and I forget whether they doubled Ln


~
~
23 the amount or tripled it . I forgot . I think it m
~
~
24 was doubled . w
Ln

251 In other words, if they had X

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 920

1 nanograms of benzpyrene, they put 2X . And they

2 said, when you painted the skin of the mice with

3 this enhanced thing, you got double the tumors --

4 not quite double, but --

5 Q . But that was an enhancement .

6 A . -- but -- yeah .

7 The thing was, it was done by four

other laboratories and nobody could confirm it .

9 Q . I see . I see .

10 Well how about -- do you know what

11 the -- what do you understand, from your

12 background, are the tumor promoters in cigarette

13 smoke?
• 14 A . Well, the tumor promoters were -- the first

15 group that was proposed were the phenols .

16 Q . Are they still -- some of them still

17 in smoke?

18 A . Well, I don't -- yeah . They're always in

19 smoke .

20 Q. I see .

21 A . And the thing was, as I said yesterday, that

22 several people have shown that, if you have a

23 smoke condensate intact and you paint it on mice

24 and get a certain number of tumors, if you then

• 25 prepare that same smoke condensate in a way that

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 921

1 strips out the phenols from the smoke, paint that

2 on mice, you get the same number of tumors . Which

3 means that there's no -- the promoter, that they

4 claimed, is not promoting .

5 Q . I see .

6 A . And Dr . Van Duuren at -- I think he's at

7 New York University -- showed that actually the

8 phenol, which some people call promoters, actually

9 inhibited the behavior of poly -- of

10 benzo [a] pyrene .

11 Q . Is nicotine a tumor promoter?

12 A . Not that I know of .

13 Q . You don't know that?

14 A . Huh-uh .

15 Q . Did you know that it was Dr . Minna

16 from a medical school in Texas, who was funded by

17 the Council for Tobacco Research, concluded that

18 nicotine was a tumor promoter?

19 A . No, I did not .

20 Q . You didn't know that .

21 What are the other tumor promoters?

22 A . There are a couple of the indoles --

23 substituted indoles in smoke that have been shown

24 to be tumor -- ~J
W
J
25 Q . How about nitrosamines? Is that a

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 922

1 carcinogen or a tumor promoter?

2 A . It's a tumorigen, yeah .

3 Q . It's actually not just a promoter? It

4 actually causes cancer?

5 A . Right .

6 Q . Do you know if anybody has painted

7 nitrosamines on animals and gotten tumors beyond

the skin? In other words, of the lung and other

9 parts of the animal's body .

10 A . Usually they don't -- because of the fact

11 that painting -- skin painting with nitrosamines

12 has -- but many of them done and rather fruitless,

13 they don't get tumors on the skin --

14 Q . I didn't ask about skin tumors .

15 A . -- and, as you pointed out, they do get them

16 elsewhere .

17 Q . I see .

18 A . So most people who study nitrosamines don't

19 paint them, they feed it .

20 Q . They feed it .

21 Well, if you -- how about painting --


cn
22 has Reynolds ever looked at humans to find out, -J
N
m
23 those who smoke, if they're, you know, getting AD .
-J
24 those nitrosamines in their mouth, whether it o

251 causes tumors in the lungs or someplace else?

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 923

1 A . No . Reynolds has not done that kind of work .

2 Q . Anybody? In the tobacco industry?

3 MR . McDERMOTT : Objection ; no

4 foundation .

5 THE WITNESS : I don't know .

6 BY MR . SHELLER :

7 Q . Wouldn't that be logical and important

8 to look into?

9 MR . BLANCATO : Objection .

10 MR . McDERMOTT : Objection ; no

11 foundation .

12 MS . EASON : Objection .

13 BY MR . SHELLER :

14 Q . Your answer?

15 A. No . Well, there have been speculations that

16 they're causative, but nobody's shown it .

17 Q. I see . Nobody's studied it for the

18 humans .

19 A . Not with humans . But he also --

20 Q . Well, we know if we put them on a

21 mouse it will get cancer of the lung, right?

22 A . Yeah . But it's not the type caused by --

23 it's mostly attributed to smoking .

24 Q. I see . Adenomas, though, right?

25 A . Well, you get mice that are --

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 924

1 Q . What kind of cancers do they get of

2 the lung?

3 MR . McDERMOTT : Counselor, you keep

cutting the witness off . Would you let him finish

5 his answer .

6 MR . SHELLER : I'm letting him finish .

7 MR . MCDERMOTT : No, you're not . The

8 record will reflect that . Let him finish .

9 THE WITNESS : Will you let me finish?

10 If you won't, I'm leaving .

11 MR . SHELLER : I'm letting you finish .

12 THE WITNESS : I'm finished .

13 MR . SHELLER : Good .

14 BY MR . SHELLER :

15 Q . Doctor, at the -- sir, as I understand

16 it, then, you know of no testing that Reynolds has

17 done to take, say, a tumor promoter and

18 nitrosamines and test them together to see if they

19 increase the risk of cancer in animals .

20 A. No . I don't -- I don't know -- I don't think

21 they've ever done it . Unless they've done it

22 since I've left .

23 Q . Now, Doctor, at the last paragraph

24 here you say : (Reading)

25 Since it is now well

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 925

established that cigarette

smoke does contain several

polycyclic aromatic

hydrocarbons --

A . Where are we?

Q. Page 37 . (Reading)

In considering the

potential and actual

carcinogenic -- (you say]

10 actual carcinogenic activity

11 of a number of these

12 compounds, a method of either

13 complete removal or almost

14 complete removal of these

15 compounds from cigarette

16 smoke is required .

17 Do you now disagree with that view that

18 you had in 1956?

19 A. No . You got to remember, this was written

20 when there was a big controversy about all this,

21 saying that it would be opportune to remove -- to

22 cut down the argument and the bad press we were

23 getting .

24 Q . Well, you don't say that there . You

25 say -- you were a young scientist then, trying to

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 926

1 do the right thing, right? You weren't worried

2 about the controversy ; you were worried about what

3 was right, weren't you?

4 A . Well, the other thing, too, sir, is that,

5 when I wrote something like that, the people knew

6 what I was talking about .

7 Q . They did . 1956 .

8 By the way, I looked in your

9 background . I saw, when you were a young man, you

10 taught Sunday School, didn't you?

11 A . I did?

12 That's what it said, somewheres . You

13 didn't teach Sunday School? Do you belong to

14 church?

15 A . Yes .

16 Q . Which church?

17 A . If it's any of your business, I'm an

18 Episcopalian .

19 Q . Do you believe in God?

20 MR . BLANCATO : Objection . This is --

21 BY MR . SHELLER :

22 Q . Well, Doctor, I'm just asking you . If

23 you know that something is a carcinogen, don't Ln


N
~
24 you -- you don't believe anymore that it's N
~
~
* 25 required to be removed -- complete removal or ~
N

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 927

1 almost complete removal of these compounds from

• 2 cigarette smoke is required? You don't believe

3 that anymore? Is that true?

4 A . Well, I believe in what we have done . If you

5 look at what we have done, we have reduced it

6 substantially in cigarette smoke over the years .

7 And the fact that that has been done has gotten,

8 actually, commendation from the Surgeon General .

9 Q . I see .

10 You got a letter to that effect from

11 him?

12 A . No, it's in the Surgeon General's report .

13 Q . Oh, I see . Now --

14 (Discussion off the record)

15 MR . McDERMOTT : Are we moving to a new

16 exhibit?

17 MR . SHELLER : Yes . We're moving to --

18 THE WITNESS : If you'll excuse me, I'm

19 going to go to the restroom .

20 MR . SHELLER : Sure .

21 VIDEOGRAPHER : We're going off the

22 record at 3 :15 p .m . . Ln
FA
J

23 (Recess taken from 3 :15 p .m . to 3 :24 m

24 p .m . )

25 VIDEOGRAPHER : We're going back on

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 92 8

1 record at 3 :24 p .m .

2 BY MR . SHELLER :

3 Q. Doctor, I'm going to give you a lette r

4 that you wrote to Dr . Hoover, Dr . Kenneth Hoover,

5 in July -- on July 25th, 1962 . And this would be

6 Exhibit 9 .

7 (Plaintiff's Exhibit Number 9 was

8 marked for identification )

9 (Discussion off the record )

10 MR . SHELLER : While they're waiting ,

11 I'll just -

12 BY MR . SHELLER :

13 Q . Kenneth Hoover is who ?

14 A . He was the director of research when I came

15 to Reynolds, and I guess he was director till 1965

16 when Dr . Willard Bright took his place .

17 Q . Now, you were making a submission of

18 abstracts of papers to be presented at the 16th

19 Tobacco Conference Research Conference, in

20 Richmond, Virginia, in September 1962 .

21 A . Right .

22 Q. And you had to get permission fro m

23 Dr . Hoover as to what you could present ; is that

24 correct ?

25 A . Yes .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 929

Q . And in it -- and I take you down to

2 the third paragraph . It says : (Reading)

3 The findings presented

4 in this manuscript have been

5 described in RDR, 1962,

6 No . 14 .

7 And you say : (Reading)

8 The discussion given in

9 the RDR of the testing of

10 indoles and carbazoles for

11 carcinogenic activity has, of

12 course, been deleted from the

13 manuscript, even though all

14 of these tests gave negative

15 results . The review of other

16 heterocyclic nitrogen

17 compounds identified in

18 tobacco smoke, example, [and

19 again, my pronunciation is

20 not great] pyrido indole

21 methyl-something . Indole

22 dibenz acridine -- [on and

23 on] was omitted from our

24 manuscript because of the

- 25 reported carcinogenic

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 930

1 activity of the latter three

2 compounds .

3 A . Right .

4 Q . Why did you feel compelled to have to

5 omit any compound that could be carcinogenic from

6 this presentation?

7 A . Well, we didn't omit any, we just didn't

8 discuss them in the presentation, their biological

9 activity in the presentation .

10 Q . Well, why didn't you want to do that?

11 A . Well, as I explained to you before . If you

12 look at the last ones, dibenz[a,h,]acridine,

dibenz [a, j] acridine and dibenz [c, g] carbazole . If

• 13

14 you notice the date on this is 1962 . These were

15 the three aza-arenes that had been reported in

16 1960 by Benjamin Van Duuren . And as I said

17 earlier, they had been described as tumorigenic to

18 mouse skin . But they're -- already some question

19 as to whether they were in cigarette smoke .

20 And as I said, Dr . Wynder, if you look

21 at his book and some of his writing in his review

22 articles, they couldn't find those . And then,

23 since then, seven other studies done in Germany,

24 Japan, the United States, they can't find them .

25 So -- and the other thing is, sir,

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 931

1 this was a -- not a biological conference, it was

2 a chemist conference . And they were primarily

3 interested in chemical analysis, chemical

4 identification, and not on the discussion of

5 biological issues .

6 Q . Well, "May we" -- you say, "May we

7 submit the manuscript to Tobacco Science for

8 Publication?"

9 You were submitting it, not just to

10 the conference, but you were submitting it to

11 Tobacco Science for Publication . Weren't you

12 planning to do that?

13 A . Yes . And it was published .

14 Q . It was published . With the omission

15 of any compound that was thought to have --

16 A. No .

17 Q . -- carcinogenic activity in cigarette

18 smoke .

19 A . Not compounds we had identified .

20 Q . Not ones you had identified .

21 A . That other people had discussed . And I say


Ln
r
J
22 here, Tobacco Science was primarily a chemical ~
m
23 journal . ~
J

J
24 Q . Well, how about -- were there any of

25 these compounds that you agree were still -- are

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 932

1 still in tobacco smoke and are carcinogenic?

2 A . The norharmane and harmane, the first two

there, are, if you will, borderline tumorigens,

4 and they're in tobacco smoke .

5 Q . So, your description, then, was you

6 were going to admit -- omit even the ones that

7 even today you agree are borderline carcinogenic?

8 A . Omit discussion .

9 Q . Was that the standard practice at --

10 MR . McDERMOTT : Excuse me .

11 Dr . Rodgman, had you finished your answer?

12 THE WITNESS : I guess .

13 MR . McDERMOTT : Okay . I'm sorry .

14 BY MR . SHELLER :

15 Q . Was that the standard practice, to

16 omit any compound -- discussion of compounds at

17 any of these Tobacco Science conferences that were

18 carcinogenic compounds at that time?

19 A . At this particular one, it was . This

20 conference .

21 Q . How about after that?


Ln
22 A . Well, I'm sure you've mulled through all my ~
~
m
23 reports on the composition of smoke, including the ~
~
24 ones on the polycyclic hydrocarbons, and so on and co

~ 251 so forth . By sometime in 1965, we had presented

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 933

1 almost all of that stuff at different conferences .

2 Carcinogenic or non-carcinogenic, inhibitory,

3 promoting, and --

4 Q . How about publishing them?

5 A . Well, by the time we got to presenting

6 them -- the whole thing -- are you listening?

7 Q. Yes . I didn't forget . I'm here .

8 A . That -- when we determined the polycyclics

9 and identified them, we then set out on a -- as

10 you know, a series of studies of ways to reduce

11 polycyclics in cigarette smoke, which involved the

12 extraction procedure I mentioned before, the

,~ 13 addition of combustion additives, the use of


I I_I I
14 filter tip additives, the effect of things in

15 paper and so on . And one of the major reasons we

16 had not published too much about the polycyclics,

17 since our work was fairly sophisticated, that --

18 this would have been a pretty good clue to anybody

19 that, if Reynolds knows that much about

20 polycyclics, they're probably doing something to

21 reduce it, and what are they doing?

22 As I told you before, many of the

23 methods that -- where we were looking at selective

24 reduction of class of compounds, whether it be

25 polycyclics or phenols or what have you, ended up

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 934

1 in causing other problems that -- you know, you

2 solve one problem, or partly solve it, and then

3 you raise several others . And by the time we

4 finished all that work and went to the premise

5 that, if we're going to do something with smoke,

6 let's lower everything uniformly, or as nearly

7 uniformly as we can . Most of what we had found

8 had all -- was already published . I think, by the

9 time we got to that point in time, in the -- '65,

10 or whenever it was, there was only one compound

11 that I had found that was not in the literature,

12 and I wasn't too sure of that one either .

13 Q. That was carcinogenic?

14 A . I don't know -- it may be borderline

15 carcinogenic .

16 Q. What one was that?

17 A . A compound called cholanthrene .

18 Q . Did you ever publish on that?

19 A. No . It appeared in something else, shortly

20 thereafter .

21 Q . How long thereafter?


Ln
A . Oh, I don't know . A year or two . You ~
22 ~
N
m
23 usually wouldn't -- ~
~
Ln
24 Q . Doctor -- m

25 MR . BLANCATO : Finish your answer .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 935

MR . McDERMOTT : Doctor, finish your

answer .

MR . SHELLER : A year or two

thereafter, I think he said .

THE WITNESS : But, here again, you

know, by this time, there were -- by 1965, there

were probably a hundred polycyclics in smoke .

'What more would one do?

9 BY MR . SHELLER :

10 Q . I see .

11 Doctor, wouldn't it have been

12 appropriate for Reynolds to say : There are

13 carcinogens in tobacco smoke --

14 MR . BLANCATO : Objection .

15 BY MR . SHELLER :

16 Q . -- and here they are, that we have -

17 that have been reported by others? Rather than

18 saying, publicly : We're going to deny that we

19 know about them .

20 MR . BLANCATO : Object to form .

21 MR . McDERMOTT : Object to the form of


! c„
N
22 the question . Assumes facts not in evidence . ~
m
23 THE WITNESS : I don't understand . ~

24 BY MR . SHELLER :

! 251 Q . Well, why didn't -- is the only reason

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 936
,

1 Reynolds never told the public that there are

2 carcinogens in our smoke and published it was

3 because others, outside of the tobacco industry,

4 had published that information and, therefore,

5 there was no need for Reynolds to acknowledge it?

6 MR . McDERMOTT : Objection, no

7 foundation .

8 THE WITNESS : Well, as I say, we

9 eventually did acknowledge it . And I gave it four

10 times .

11 MR . BLANCATO : Objection .

12 THE WITNESS : Twice in Georgia, and

0 13 over here in Greensboro, North Carolina, and once

14 here at Wake Forest University .

15 BY MR . SHELLER :

16 Q . In a publication?

17 A . No, a presentation . As I say, everything had

18 been published by that time . But --

19 Q . When did you -- there were four times

20 you did this . When was it?

21 A . I think -- the first time, I think, was '65,-

22 somewhere in there .

23 Q . So you agreed that there were

24 carcinogens in tobacco smoke? Ln


N

25 A . Well, as -- as I've said, many, many times 1

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 937
I

1 here, sir, there are carcinogens in tobacco smoke

2 that are carcinogenic to mouse skin .

3 Q . Doctor, I'm going to give you a

4 report . We're going to refer to this as Exhibit

5 10 .

6 MS . EASON : May we please have a

7 description, please --

8 (Plaintiff's Exhibit Number 10 was

9 marked for identification)

10 BY MR . SHELLER :

11 Q . This is entitled "The Smoking .and

12 Health Problem, A Critical and Objective Appraisal

• 13

14
of RDM, 1963, No . 4 ." The copy where it's marked

"voided by KHH" .

15 (Discussion off the record)

16 MR . McDERMOTT : Do you want to do the

17 same thing? Do you want to do an A and B here?

18 Or you're not going to use .

19 MS . KNISELY : I don't know if we'll

20 get to the next one, but we can just give it a

21 different number .

22 MR . McDERMOTT : If memory serves, I

23 think these are already in the record for this

24 deposition from the first session .

• 25 MS . KNISELY : Not that particular one .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 938
I

1 MR . LEE : Only in the boxes, not

2 individual . I talked about it . It was never

3 introduced . And they're not on top --

4 MS . KNISELY : It's not been attached,

not that particular one .

6 MR . McDERMOTT : All right . I thought

7 it was introduced in the Minnesota deposition, the

8 Minnesota portion, was it not?

9 MS . KNISELY : No . The one attached to

10 the subpoena -- the Arch subpoena was ; but that

11 did not have the "voided KHH° on it .

12 MR . McDERMOTT : All right .

13 BY MR . SHELLER :

14 Q . Doctor, you, in this -- do you recall

15 this report?

16 A . Oh, yes .

17 Q . And this -- what do you mean by

18 "voided by KHH°?

19 A . Mr . Hoover voided it .

20 Q . Meaning what?

21 MR . McDERMOTT : Objection . Asked and


Ln
N
22 answered . This was all gone into -- ~
~
m
23 BY MR . SHELLER : IN
~
~
24 He rejected it ; is that correct? ~

MR . McDERMOTT : Objection . Asked and

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 939

1 answered . This was all gone into at length by

2 Mr . Lee .

3 BY MR . SHELLER :

4 Q . All right . The -- page 7 of the

5 report -- and before I get to that, let me

6 introduce another exhibit, 'cause I'm going to ask

7 you to refer to them together . This is a 1962 --

8 it says "RDM 1963 No . 1," also voided by KHH .

9 MR . McDERMOTT : I believe that's

10 Number 4 .

11 MR . SHELLER : Previously Number 4?

12 MS . KNISELY : No, I don't think it is .

13 THE WITNESS : The one that's got

14 "first" on the top is number 1, 1963 . The one

15 that's got second --

16 MR . McDERMOTT : Yeah, but let me see

17 this one .

18 THE WITNESS : It's the short one?

19 MR . McDERMOTT : Is that a "one" or a

20 "four"?

21 THE WITNESS : That's a "one" and this

22 one's the "four" .


Un
23 MR . McDERMOTT : Okay, I'm sorry . I r
J
F-'
0
24 misspoke . ~
~
~
~ 25IBY MR . SHELLER : Ln

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 940

1 Q . Now, Doctor, I want you to look at

2 page 4 of what's number 1, research report 1 .

3 MR . BLANCATO : Are you going to mark

4 this short one as an exhibit?

5 MR . SHELLER : Yes .

6 (Plaintiff's Exhibit Number 11 was

7 marked for identification)

8 BY MR . SHELLER :

Q . If you look at E, the "Evidence to

10 Date m on report number 1, you say : (Reading)

11 Obviously the amount of

12 evidence accumulated to

13 indict cigarette smoke as a

14 health hazard is

15 overwhelming . The evidence

16 challenging this indictment

17 is scant . Attempts to shift

18 the blame to other factors

19 (example, air pollutants)

20 necessitates acceptance of

21 data similar to those denied

22 in the cigarette smoke case .

23 MR . MeDERMOTT : I'm not going to

24 object at this time, but I will point out this was

25 covered in the first session of the deposition .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 941
r

1 MR . SHELLER : Not this particular

2 statement .

3 MR . HOLTON : Oh, yes, it was .

4 MR . SHELLER : You'll see, when I get

5 to it .

6 MR . HOLTON : Not the variation .

7 MR . SHELLER : Right, not the

8 variation .

9 BY MR . SHELLER :

10 Q . Now, Doctor, that's what you said in

11 your first report . And then, if you look at page

12 second (sic) of your -- this one, 1963 report,

13 number 4, when you -- what did you do? Did you

14 resubmit it to Mr . -- to Dr . Hoover?

15 A . No . No .

16 MS . EASON : What page are you on?

17 MR . SHELLER : Page 7 .

18 THE WITNESS : If you had read the

19 deposition, you'll find why there are two . You

20 haven't read the deposition .

21 MR . SHELLER : Yes, I have .

22 THE WITNESS : Well, do you know why

23 there are two, then?

24 MR . SHELLER : I may not remember it

25 accurately, I'm sorry .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 942

1 THE WITNESS : Well, if you notice, one

2 is very brief ; no citations . And the reason they

3 were written this way is, I knew management --

4 scientific management would appreciate the longer

5 version annotated, and so on and so forth . And

6 the other one, if it marched on outside of the

7 research department, that people wouldn't want to

8 have a whole bunch of numbers rattling around, and

9 a long bibliography, and so on and so forth . So

10 one is a -- if you will -- a brief summary of the

11 other one .

12 BY MR . SHELLER :

13 Q . Well, Doctor, look at the top of page

14 1 of the report number 4 .

15 A . Uh-huh .

16 Q• You say on the top of the page, first

17 paragraph : (Reading)

18 This report is an

19 extension of a companion

20 memorandum, which presented

21 my position as briefly and as

22 concisely as possible . The


Ln
~
~
23 two memoranda have identical m
~
24 schematic organizations . As Ln
00

25 mentioned before, if

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 943
r

1 requested, a thorough,

2 fully-documented exposition

3 of the ideas will be

4 prepared .

5 Is that why this -- is there any

6 inconsistency between these two?

7 A. No . As I say, one was a shorter version of

8 the other . And, if you notice, they fairly well

9 follow the same plot and --

10 Q . Well, on page 7 -- could you look at

11 page 7 of the report 4 . "The Evidence to Date,"

12 which is now being amplified in your report 4, you

13 say : (Reading)

14 Obviously the amount of

15 evidence accumulated to

16 indict cigarette smoke as a

17 health hazard is

18 overwhelming .

19 A . Yes, I said that . And I explained it before .

20 Q. Right . Now you say : (Reading)

21 However the evidence

22 from epidemiological,

23 pathological, biological and

24 chemical studies . Supporting

25 the proposition that lung

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 944

1 cancer is caused by or

2 associated with cigarette

3 smoke, is paralleled by

4 similar evidence supporting

5 the proposition that lung

6 cancer is caused by or

7 associated with air

8 pollutants . In some

9 instances, the evidence seems

10 to be stronger in support of

11 cigarette smoke as a

12 causative or associated

13 factor ; in other instances

14 the evidence seems to be

15 stronger in support of air

16 pollutants as a causative or

17 associated factor .

18 (You then go on and say]

19 Any criticism leveled at the

20 lung cancer-cigarette smoke

21 proposition, statistical

22 studies cannot prove

23 cause-and-effect

24 relationships between two

25 factors, mice are not men,

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 945
y

1 (criticism of biological

2 evidence) .

3 You say : (Reading)

4 Metaplasia and

5 hyperplasia do not become

6 cancerous (a criticism of the

7 pathological evidence) ; and

8 no experimental evidence to

9 show that any cigarette smoke

10 constituent is carcinogenic

11 to human lung tissue at the

12 level present in cigarette

13 smoke (a criticism of the

14 chemical evidence) is equally

15 applicable to the lung

16 cancer-air pollutant

17 proposition .

18 Is that how you amplified it then?

19 A . Well, as you can see, one is much longer than

20 the other . And, of course, as I explained before,

21 that my concern was that -- when I said evidence Ln


~_j
_j
22 was overwhelming, is all we were hearing was one ~
m

23 side of the arqument . And this is late '62/early tj

24 '63 .

251 And as I said before, my concern was

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 946

1 we had developed a pretty good reputation for

2 being good chemists . And what I wanted to do, and

3 what this is really aimed at, is persuade

4 management to let us get into biological work .

5 Q. Right .

6 A . And -- because I felt, with the competence of

7 the people we had or people we could acquire, that

8 if we could be that good in chemistry - and we

9 were considered very good in chemistry r then we

10 could do the same thing with the biological

11 studies . And already, by this time, in 1963, we

12 had demonstrated in-house -- unfortunately we

13 hadn't published some of it . But many of the

14 assertions in the -- that -- in this overwhelming

15 evidence was wrong .

16 Q . All right, sir .

17 Doctor, look at your recommendations

18 on page 14 . And you say : (Reading)

19 Recommendations : After

20 consideration of the evidence

21 available on the cigarette Ln


r
~
22 smoke-health problem and the ~

23 Company's obligation to its

24 customers [and you have an

asterisk there] it is

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 947

1 interesting to note remarks

2 like "Why don't 'they' do

3 something about the liquor

4 industry? After all, there

5 are an estimated four million

6 Americans classified as

7 alcoholics . Alcoholism not

8 only is a health hazard to

9 the drinker but also causes

10 untold anguish to his

11 family ." Or "What about the

12 meat-packing industry and the

• 13

14
supposed relationship of

saturated animal fat to

15 cholesterol-caused

16 circulatory disorders and

17 heart disease? After all,

18 many more persons die of

19 heart disease than lung

'20 cancer ." These remarks [and

21 this is your statement] may

22 have some justification, but

23 attempts to minimize our

24 obligations by pointing an

• 25 accusing finger at others is

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 948

1 no solution to the cigarette

2 smoke-health problem!

3 A . Right .

4 Q . Do you agree with that today?

5 A . Yeah .

6 Q . Then you go on to say, after you say,

7 "To its customers, stockholders, and employees :"

8 (Reading)

9 It is recommended that

10 facilities, animals, and

11 personnel (where necessary)

12 be acquired to study

0 13 biological cigarette smoke,

14 tobacco, tobacco and

15 additives .

16 This recommendation has

17 been made previously by

18 Teague, by Rodgman [and it

19 lists -- you list all these

20 dates] . Data from such

21 studies may be invaluable, if

22 government restrictions are

23 imposed as a result of the

24 conclusions of the Surgeon

25 General's Committee on

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 949
,

1 Smoking and Health . It is, I

2 believe, more urgent than

3 ever that we acquire

4 dexterity in biological

5 techniques .

6 Do you still agree with that today?

7 A . Yes . And of course we do have biological

8 things in place, now, some of them .

9 Q . And between 1970 and '84 you had none,

10 right?

11 A . Well, we did a lot of contracting outside .

12 Q . I see .

13 Then you say, on page 15 : (Reading)

14 It is recommended that

15 data already available on

16 physiologically active

17 cigarette smoke components,

18 example, polycyclic

19 hydrocarbons, phenols be

20 published . It is recommended

21 that analytical procedures

22 concerning such components be

23 published . These

24 recommendations are made

25 because I believe they

WAGA'& SPINELLI (201) 992-4111


Vol . 5, Pg 950

1 t represent the best answer to

2 the questions : What effect

3 would immediate publication

4 of these data have on this

5 Company's economic status?

6 What would be the effect on

7 this Company of not

8 publishing these data now,

9 but being required at some

10 future date to disclose such

11 data, possibly in the

12 unfavorable atmosphere of a

13 lawsuit?

14 What happened? Did they agree with you?

15 Did Mr . Hoover -- Mr . Hoover voided this, didn't

16 he?

17 A . Right .

18 MR . McDERMOTT : Counselor, I don't

19 mean to rain on your parade, but this has been

20 covered already, and this is getting repetitive

21 and quite time consuming .

22 MR . SHELLER : By the way, I'm going to

23 give you a letter that Dr . Teague wrote to

24 Dr . Hoover .

251 MS . KNISELY : If you want to mark

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 951

1 these next A and B?

2 THE WITNESS : By the way it's not

3 Dr . Hoover, it's Mr . Hoover .

4 MR . SHELLER : Mr . Hoover . All right .

5 THE WITNESS : Believe me, there's a

6 difference .

7 MR . SHELLER : That's obvious .

8 MS . KNISELY : One is typewritten and

9 one is handwritten, if you want to mark the next

10 number A and B .

11 MR . SHELLER : Okay . What number are

12 we up to? 12 A and B .

13 MS . EASON : And which is the A and

14 which is .the B?

15 MR . SHELLER : A is the typewritten

16 version, the letter from Dr . Teague to Kenneth

17 Hoover -

18 MR . McDERMOTT : This is 11 A and B?

19 MR . SHELLER : Right . And 11 -- 12 .

20 And the handwritten is -- 12 is the handwritten

21 copy by Dr . Bruce .

22 (Discussion off the record)

23 (Plaintiff's Exhibits Numbered 12A and

24 12B were marked for identification)

25 BY MR . SHELLER :

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 952

1 Q . Now, Doctor, Dr . Teague was your

2 supervisor, right?

3 A . At one time .

4 Q . At one time .

5 And what was he at this time, in 1963?

6 A . He was manager -- 1963, he was manager of the

7 chemical research division . He was my boss .

8 Q . And he says : (Reading)

9 I believe he has a right

10 to be heard, despite my

11 honest disagreement with him

12 on certain minor points .

13 Accordingly, I recommend that

14 the reports be accepted and

15 distributed . I also might

16 suggest that copies be made

17 available to members of our

18 legal department .

19 And he's referring to "RDM, 1963, No . 1"

20 and °RDM, 1963, No . 4 .°

21 A . Right .

22 MS . EASON : For the record, which

23 version were you reading? ~


0,
00
24 MR . SHELLER : I was reading the typed

251 version .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 953

MS . EASON : Thank you .

2 BY MR . SHELLER :

Q . And even though Dr . Teague supported

you, he -- Hoover rejected it too . Did Hoover

tell you why?

A . He called me in -- actually, they were all

typed and of course had been assigned a number --

you might as well hear the whole story .

And in those days we didn't have Xerox

10 copiers . We had an original and five or six

11 carbons . And he had the typed version on his desk

12 and a couple of copies of my -- if you notice,

13 this typing on the ones we just finished, it's

14 pretty terrible . And I have to -- I was never

15 much of a typist . I did these at home .

16 And he said, "Alan, I'm not going to

17 issue these ." And he didn't say why . And I

18 noticed the copies on his desk . I didn't know if

19 there were two copies or three copies there with

20 the "voided KHH" on it . And I just reached over

21 and I said, "Okay, if you're not, then these are

22 mine," and walked out .

23 So these -- I think, if you look in

24 the list of RDM's, you'll find a place there where

25 these two are voided .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 954

1 Q . So he really didn't tell you much, he

2 just voided them?

3 A. No .

4 Q . All right .

5 Doctor, I'm going to give you a report

6 that you wrote in 1964 that wasn't voided by

7 Hoover, apparently . It's an analysis of cigarette

8 smoke condensate, summary of an eight-year study .

9 MR . McDERMOTT : Hang on . Do we have

10 copies of that?

11 MS . KNISELY : Yes, you do .

12 MR . HOLTON : We don't have that one

• 13

14
copied, do we?

MS . KNISELY : Yes, you do .

15 (Discussion off the record)

16 BY MR . SHELLER :

17 Q . Doctor, would you please refer to --

18 this is RDR number 1964, Plaintiff's Exhibit 13 .

19 (Plaintiff's Exhibit Number 13 was

20 marked for identification)

21 BY MR . SHELLER :

22 Q . And I'm referring you now to page 56,

23 entitled "Discussion" .

24 You start a rather lengthy discussion,

25 and you say : (Reading)

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 955

1 During the past decade

2 and a half, considerable

3 scientific evidence has been

4 presented which relates

5 tobacco smoking, particularly

6 cigarette smoking, to

7 specific diseases . This

8 evidence consists of four

9 types : Namely, statistical,

10 pathological, biological and

11 chemical . Our studies have

12 been concerned solely with

0 13 the latter - the chemical

14 composition of smoke . For a

15 consistent picture to be

16 painted of the tobacco

17 smoke-disease problem, the

18 evidence from each discipline

19 must agree with that from the

20 other three . With respect to

21 the composition of tobacco

22 smoke, are our chemical

23 evidence and the chemical

24 evidence reported by others

25 consistent with the reported

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 956

1 statistical, pathological,

2 and biological data?

3 You asked this question .

4 And then I take you over to page 58,

where you say --

6 MR . McDERMOTT : Hang on, let me catch

7 up with you . All right .

BY MR . SHELLER :

9 Q . (Reading)

10 The known composition of

11 tobacco smoke is not

12 inconsistent with the

13 statistical finding that

14 cigarette smoke may be

15 associated with lung disease,

16 heart disease, et cetera .

17 The next paragraph, you go on and you

18 say -- and -- I'm sorry, lung cancer, heart

19 disease, et cetera .

20 You then say in the next paragraph :

21 (Reading)

22 The known composition of

23 tobacco smoke is not

24 inconsistent with the

0 25 pathological findings that

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 95 7

1 fluorescent components of

2 cigarette smoke --

3 MS . KNISELY : Biological .

4 MR . SHELLER : (Reading)

5 -- are absorbed b y

6 respiratory tract tissue, or

7 that metaplasia and

hyperplasia are produced in

9 the respiratory tract by

10 cigarette smoke, or that

11 ciliastatic -- ciliastasis is

12 produced by cigarette smoke .

13 Then you go on and you say : (Reading)

14 The known composition of

15 tobacco smoke is no t

16 inconsistent with the

17 biological findings, that

18 cigarette smoke is

19 carcinogenic, cocarcinogenic,

20 and ciliastatic .

21 You say, on page 59 : (Reading)

22 It is often argued that

23 the amount of benzo [a] pyrene

24 or arsenious oxide i n

cigarette smoke i s

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 958
r

1 insufficient to account for

2 the observed carcinogenicity

3 of cigarette smoke . This, of

4 course, is true! But no one

has yet conducted the obvious

6 experiment to determine

7 whether the amounts of the

carcinogenic polycyclic

9 hydrocarbons plus the amounts

10 of the carcinogenic

11 heterocyclic nitrogen

12 compounds plus the amount of

0 13 arsenious oxide plus the

14 amounts of the cocarcinogenic

15 phenols and fatty acids are

16 sufficient to account for the

17 observed biological results .

18 Calculation has indicated

19 that the known carcinogens

20 and cocarcinogens in tobacco

21 smoke -- in cigarette smoke

22 can account for about

23 90 percent of the observed

24 activity . Such a mixture

25 could behave synergistically,

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 959

1 additively, or inhibitively .

2 It is obvious that concern

3 with relative concentration

4 in cigarette smoke of one, or

5 at most, of a few of the

6 components is ridiculous . As

7 an absolute criterion of

8 safety insofar as health is

9 concerned, chemical analysis

10 of cigarette smoke, while

11 highly suggestive, is

12 physiologically meaningless .

13 You then -- I take you to page 62 . You

14 say on page 62, number 7 : (Reading)

15 None of the --

16 You say several things ; I'm just pointing

17 out to you one of them . (Reading)

18 None of the chemical

19 data acquired in our study or

20 in studies conducted

21 elsewhere is inconsistent

22 with reported biological, ~


v
~-•
23 pathological, or statistical m
~
~
24 data indicting cigarette ~

25 smoke as a health hazard .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 960

1 Recommendations . Future

2 Work, 1 .

3 All additives of tobacco

4 smoke should be tested

5 biologically for their

6 adverse effect, if any, on a

7 host .

8 Was that ever done by Reynolds?

9 A . The additive thing?

10 Q . Your recommendations .

11 A . Well, the additive thing was eventually done .

12 Q . All additives were tested on a

13 biological host?

14 A . They were tested in the Ames test .

15 Q . All of them?

16 A . As far as I know .

17 Q . As far as you know .

18 A . Dr . Chin Lee was the --

19 Q. Oh . Okay . And how about your other

20 recommendations about -- that it's ridiculous if


Ln
21 you don't mix the different things together? Do N
-j
N
6
22 you recall that?
~
~
23 A . Well, that's an interesting exercise, because -j
rn

24 at one time I thought that would be really the way

25 to look at it . And in looking at some

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 961

1 calculations done by one of the masters in the

2 cancer field, I thought, well, if we have this

3 number of polycyclics that are tumorigenic to

4 mouse skin, and if we had this number of this

5 compound and these compounds, what kind of an

6 experiment would you have to do?

7 Well, I plotted it all out and I was a

8 little stunned to find, to do the experiment that

9 I thought would be the ultimate in solving the

10 question or showing the effect would require three

11 times the number of available mice at all the

12 laboratory supply companies in the United States,

13 because of the extent .

14 And then it goes over the cost . In

15 those days, it doesn't sound like much, but I

16 think I figured it out : It cost about

17 $12 million . And I just -- you know, nobody's

18 going to do that .

19 And, of course, some of the things I

20 suggested there -- although, I -- I have a little

21 problem . I don't know where I got that

22 90 percent . But that's all right .

23 Q . So it was never done, because it cost

24 too much ; is correct?

25 A . Well, nobody ever did it .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 962
I

1 Q . Nobody ever did it .

• 2 A . And --

3 Q . Except it's done on humans .

4 MR . BLANCATO : Object to the form .

5 MR . McDERMOTT : Object to the form .

6 MS . EASON : Objection .

7 BY MR . SHELLER :

8 Q . Isn't that correct, Doctor?

9 A. What?

10 Q . It's done on humans . Every human who

11 smokes is a human guinea pig .

12 A . I wouldn't say that, sir .

13 Q . No?

14 A. No .

15 MS . EASON : Object to the form .

16 MR . McDERMOTT : Object to the form .

17 BY MR . SHELLER :

18 Q . So you'd, rather than run the test and

19 spend the money, which was $12 million in 1964 --

20 A . Well, I never proposed that to anybody, sir .

21 Q . -- because it was too expensive .

22 MR . McDERMOTT : Object . You're

23 mischaracterizing his testimony . He said it would

24 take three times the number of animals that

25 existed in the United States, laboratory animals .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 963
r

1 BY MR . SHELLER :

2 Q . Laboratory . How many animals would it

3 take, Doctor?

4 A . Well, I forget the -- in here I used 100 mice

5 per group . And it was in the hundred thousands of

6 animals . Well, you can phone some of the animal

7 supply place and say, "Well, you know, if I were

8 to need so many animals by such-and-such a date,"

9 they were nowhere close to what you need .

10 Q . How did you determine that? Did you

11 contact anybody who had knowledge to do this

12 testing, to give you an estimate on how many

' 13 animals they need and what the cost would be?

14 A . Well, as I say, the way I looked at it -- and

15 it was very simplistic ; I was just curious . That

16 if you had compound A, B, C, D, E, whatever - they

17 listed them - what was their effect singularly?

18 What were their effect in pairs? What were their

19 effect in triplets? And you can see, it just

20 snowballs .

21 Q . How about sticking to just triplets?

22 A . Well, I say, I was doing -- I mean, you're

23 asking me something I did 33 years ago and say

24 "Why didn't you do so-and-so?" I didn't do it .

25 Q . And Reynolds never did it . And to

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 964
r

1 your knowledge -

2 A. No . I never even turned that calculation in

3 to anybody .

4 Q . And to your knowledge, no one in the

5 tobacco industry --

6 A . Nobody in any place has ever done it .

7 Q. Right .

8 Now, Doctor -- you say Dr . Chin did

9 Ames testing?

10 A . Dr . Chin Lee .

11 Q . Chin Lee, on additives that are in

12 tobacco?

13 A . He -- he looked at all the components of

14 flavor formulations, I understand .

15 Q . Well, which ones? Do you know?

16 A . I don't know that much about all the -- the

17 flavorants by name . I know a few of them .

18 Q . You don't know whether Dr . Chin Lee

19 actually looked at all of the additives in

20 tobacco, do you?

21 A . Well, I used to see some of the things he

22 wrote that he did . And of course, in those days,

23 a lot of the flavorants and the flavor formulation

24 were coded, for obvious reasons . And there were

25 75, 100 of them, and he had run them all and found

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 965
r

1 no problem with all of them .

2 Q . Seventy-five or a hundred .

3 A . Something like that .

4 Q . Additives .

5 Now, how many additives are there in

6 tobacco?

7 A . Additives in tobacco?

8 Q. Uh-huh . Do you know?

9 A . Tobacco per se?

10 Q . In cigarettes .

11 A . Well, I just told you .

12 Q . You said there was only 75 or 100?

13 A. No . There may be 75 or 80, whatever the

14 number of compounds used in flavor formulation .

15 But'each blend -- brand, I should say, not blend,

16 has its own flavor formulation, and there may be

17 40 in this brand and 50 in this, and 30 in this .

18 And -- but they'll be different ones .

19 Q. I see . Well, are you able to tell the

20 jury today whether Reynolds tested all the

21 additives for Ames testing, that's mutagenicity on

22 animals in their cigarettes? ~


a
23 A . Well, as far as I know, Chin -- Dr . Lee did m
0
24 it . But then we had another experiment that ~

251 actually was a much simpler one and more

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 966

meaningful, I guess, if you will, in terms of

product .

Q . What was that?

A . Well, this will take a little explanation .

And we did it with five products . But let's just

concentrate on one product .

Q . When you say "a product," you mean a

cigarette brand?

A . Yeah . Like Winston or -- I'm sure you've

10 seen this someplace . It's all written up .

11 Q . Is that the one where you found --

12 when you tested one of your products, 37 and a

13 half percent of the mice got skin cancer?

14 MR . McDERMOTT : Object to the form --

15 BY MR . SHELLER :

16 Q . Is that one of the tests you did?

17 MR . McDERMOTT : -- of the question .

18 You're interrupting Dr . Rodgman's answer .

19 Dr . Rodgman, complete your answer .

20 BY MR . SHELLER :

21 Q . I'm just asking if that's one the --

22 A. No . This is -- this was a mutagenicity test,

23 Ames test, done by a contract laboratory, with

24 unimpeachable reputation . And what we did was

! 25 very simple .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 967
r

1 We had the Winston cigarette, as it is

2 marketed, which has a certain amount of what we

3 call casing materials and a flavor formulation .

4 Then we had the Winston cigarette with the casing

5 materials, no flavorants . Then we had some

6 Winstons made with no casing material, and the

7 flavorant formulation the same as on the marketed

8 product . Then we had the Winston cigarette with

9 no casing, no flavorings .

10 And the Ames test showed that, when

11 you took out the flavorants of the -- the casing

12 material, the mutagenicity went up . And the

13 minute I saw the results, I -- I won't say I

14 panicked, but I was a little thunderstruck . Until

15 it hit me . We already knew why it went up,

16 because six -- it just went up a little bit .

17 Six or seven percent of this tar,

18 which is used in the -- or TPM, which is used in

19 the Ames test, is humectants, glycerol and

20 propylene glycol, and they are non-mutagenic . So

21 we -- you weren't getting those in the smoke, you

22 didn't have -- their dilution effect . So the

23 mutagenicity went up a few percent .

24 Flavorants had no effect on

25 mutagenicity .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 968

1 Q . Doctor, you did this with Winston .

2 What other products?

3 A . Winston, Vantage, Now, Camel and something

4 else ; there were five brands .

5 Q . Did you do it with any of the other

6 brands?

7 A . Well, if you did it five times and you get

8 the same answer --

9 Q . But in all instances there was

10 mutagenicity, right?

11 A . Well, cigarette smoke itself is mutagenicity .

12 Q . I see . I see .

13 Did you do any other test --

14 biological testing, other than the Ames test, on

15 any of your products? The biological testing

16 A . Well, we did the biological testing on puffed

17 tobacco, we did it on one of our tobacco

18 substitutes .

19 Q . On your product line .

20 A . Well . . .

21 I was trying to think if one of our

22 products was the control for a substitute test we u+


~
-J
23 did . I-- I don't -- m
4
24 Q. You just don't know? ~
~P-
251 A . I've forgotten, apparently .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 969

1 Q . There's a whole lot of biological

2 tests that one can do, right, on a product?

3 A . Right . And of course the one that is part

4 and parcel of the definition is mouse skin

5 painting .

6 Q . And that wasn't done on your products,

7 other than -- which one did you did do -- which

8 product did you do the mouse skin painting?

9 A . Well, we did it on the tobacco substitutes .

10 Q . On the substitute .

11 In a prior exhibit, it's already been

12 marked, Plaintiff's Exhibit 1056 . I'll have to

13 show you the one that I have, 'cause it's the only

14 copy I have handy .

15 You -- you had said that you didn't

16 recommend testing the mixtures of the different

17 parts of the tobacco smoke . I'd like you to look

18 at page 2 . And this is a -- April 16th, 1982,

19 from you, is it Dr . Giles, Dr . Colby and

20 Dr . Nystrom are "Misters" there?

21 A . Giles is a Mister .

22 Q. To Dr . DiMarco . And who's

23 Dr . DiMarco?

24 A . He was vice president of R & D . He had just

25 come to Reynolds about that time, early '82,

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 970

1 something like that .

2 Q . You say : (Reading)

3 Project Area 3 . In

4 spite of its high complexity,

5 most of the chemical

6 carcinogenesis literature

7 deals with experiments

8 involving one - or at most

9 two - 'carcinogens' (plus

10 cocarcingoens, promoters,

11 et cetera) ; the real-life

12 situation is obviously much

13 more complex than this .

14 Therefore, we propose

15 standardized animal

16 carcinogenesis tests

17 involving varying proportions

18 of first, three chemical

19 carcinogens and, later, four

20 chemical carcinogens,

21 et cetera, to,determine

22 interrelationships more

23 closely related to real-life

24 situations .

25 First, who was Dr . Giles -- or was it

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 971
I

1 Mister? I'm mixed up . Is that a Mister or

2 Doctor?

3 A . Yeah, he was at one time -- he was manager of

4 analytical research at one time .

5 Q . I see . Is he a doctor?

6 A . Mister .

7 Q . Mister . And who is Dr . Colby?

8 A . He was head of the science information

9 division at that time .

10 Q . At 1982?

11 A . Right . And -- and Dr . Nystrom worked under

12 him at the library and eventually became manager

13 of the science information division .

14 Q . And what was your com -- position at

15 the time?

16 A . Director of fundamental research .

17 Q . Did Reynolds ever do what you

18 recommended?

19 A . No .

20 Q . They give you a reason why not?

21 A. No . You got to re -- well, this was written

22 because Dr . DiMarco had just gotten there and we ~


-j
I-A

23 were showing him some of the things -- or ~


0.
J
24 outlining some of the things that we thought ~

251 should be done . And some he did, some he didn't .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 972

1 And, of course, he eventually got us back into the

2 biological work again .

3 Q . But he didn't do this, did he?

4 A . I'm sure they didn't do this, no . They had

5 other things they wanted to do, I guess .

6 Q . Do you know if any -- anybody has ever

7 done that? In the tobacco industry or elsewhere .

8 A . I don't think it's ever been done anyplace .

9 MS . KNISELY : Do you have the copies

10 of the RDR's index -- '54 to '91? I think they're

11 out on the table .

12 (Discussion off the record)

13 (Plaintiff's Exhibit Number 14 was

14 marked for identification)

15 BY MR . SHELLER :

16 Q . Doctor, while we're waiting for one

17 more exhibit, I would like you to look at what I

18 am now marking exhibit, whatever, 14? And it's

19 entitled "R & D Long-Range Planning, Smoking and

20 Health : Product and Smoke Components, Dr . Alan

21 Rodgman, October 8, 1976 ." Is that a report that

22 you prepared?
Ln
H
J
23 A . I assume so . Let me look at it . ~
6

24 MR . McDERMOTT : Do we have copies of ~

25 this?

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 973

1 MS . KNISELY : We don't . Sorry about

2 that .

3 MR . HOLTON : Shall we go make some

4 copies?

5 MR . SHELLER : We didn't know we were

6 going to get to it . That's the problem .

7 MR . HOLTON : Shall we go make some

8 copies?

9 THE WITNESS : I'm only going to refer

10 to one sentence . It's not going to be a big deal .

11 MR . McDERMOTT : Okay . What's the date

12 on that?

13 THE WITNESS : October the 8th, 1976 .

14 BY MR . SHELLER :

15 Q . Doctor, look at page 43 . Now, is this

16 a document you've prepared? Has your name on it?

17 I mean, the whole document .

18 A . I assume so . I mean, it's got my name in the

19 front and my signature . Sometimes you get

20 something like that and it may be a combination of

21 different people working on it .

22 Q . Would you look at the top of page 43 .

23 It says (Reading)

24 I .A ., Product .

25 Condemnation of nicotine as a

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 974

1 health hazard by some

2 smoking-health proponents

3 increased demand for

4 low-nicotine tobaccos,

5 probability of occurrence

6 70 percent .

7 And then you say "Qualitative" over in

8 the right . (Reading)

9 Lowered "tar" and

10 nicotine on established

11 brands ; if lowering of "tar"

12 and nicotine progresses too

13 far, customers weaned from

14 smoking with subsequent sales

15 decline .

16 Is that your statement?

17 A . Yes, sir .

18 Q . Why would lowering tar and nicotine on

19 established brands too far wean smoke -- wean

20 customers from smoking with subsequent sales

21 decline?

22 A . Well, it has been shown that, in many Ln


~
~
23 instances where people have come out with a very ~
m

24 low tar cig -- very low nicotine cigarette or a

25 zero nicotine cigarette, that they just don't

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 975
r

1 sell .

2 Q . Why did you use the word "wean" them

3 from smoking, rather than "stop" them from -- they

4 just won't buy it? What did you mean by that as

5 this -- you don't say "they won't buy the

6 cigarette," you say it will "wean" them from

7 smoking .

8 A . Well, it may be a--

9 Q . That's your word, right?

10 . Right . That's my word .

11 Q . You could have used different

12 language, couldn't you have?

13 A . Oh, certainly .

14 Q . What did you -- do you mean by "wean"?

15 A . Well, I think you know the meaning of "wean,"

16 don't you?

17 (Discussion off the record)

18 BY MR . SHELLER :

19 Q . Now, Doctor, I'm giving you a list of

20 RDRs, that's research reports, from 1954 to 1991

21 of Reynolds' research department reports . I'm

22 only -- because -- yeah, mark the whole thing,

23 because we'll refer to others . But I'm only, for

24 now, because I know time is short --

25 I want to refer you to page -- there's

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 976
r

1 no page number . Nineteen -- the year 1970 . Did

2 you make that list, Doctor?

3 A . No .

4 Q . Who made that list?

5 A . The library .

6 Q . So this is a list from the Reynolds

7 library . And they gave you a copy of it? How did

8 you have, in your possession, a copy?

9 A . Well, if you look back, about 1976, '75 --

10 let's see, where are we? 1970, '71, '72 . The

11 typewritten part . When I took over as director of

12 research, there was a folder -- Dr . Senkus had

13 been my predecessor, and before him, of course,

14 was Mr . Hoover .

15 And if you notice -- I'm sure you've

16 looked at some of the RDR's/RDM's . And at the

17 bottom of the last page there's a distribution

18 list, and usually it's to the authors, the

19 manager, the director of research, and a couple of

20 copies to the library . And if it's a report that

21 has patentability things in it, it may go to the

22 patent lawyer .

23 Well, periodically Mr . Hoover, and

24 then subsequently Dr . Senkus, they got all these

25 copies and -- and had them on file . But,

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 977 '

1 obviously, we've only got so much filing space,

2 and there were two copies up in the library, so

3 periodically they would tell their secretary "get

4 rid of so -- so many years of this stuff" .

5 And -- and I'm sure you've noticed in

6 several places it says -- for example, on -- you

7 flip the page, "1954, destroyed 4/9/57" . And that

8 means they took those copies from Mr . Hoover's

9 files and destroyed them .

10 Well, they kept the list of all these .

11 And when I took over from Dr . Senkus, I happened

12 to get this folder, and here's this list of -- of

13 the RDR's, and there was a similar list for RDM's .

14 And I thought, gee, this is a handy thing to have

15 to check things .

16 So, after that, I went up to the

17 library and they had a ledger book that, as new

18 RDR's were phoned in, the secretary or the

19 clerical person up there would say, "Give me the

20 title," and they would write down the date and

21 assign it a number and write it down . That's why

22 it's all handwritten .

23 And then I'm sure you'll probably come

24 across places where you may see something crossed

25 out . Well what would happen is somebody would

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 978

1 phone up and get an RDR number or RDM number,

2 suddenly have reservations or a problem with what

3 they were going to write, phone up and say, "Hey,

4 void that one ; I'm going to redo it," or give it a

5 new title or something . And then you'll notice,

6 sometime later on, there may be something with a

7 very similar title . You know, sometimes an

8 experiment goes wrong and you get it screwed up .

9 Q . I understand .

10 Look at the year 1970 in this list, in

11 the typewritten part .

12 A . Uh-huh .

Q . And from 1970 it says "Smoking

14 exposure studies, not in file . E .R . Fluck ."

15 There's a checkmark next to that one . Whose

16 checkmark is that?

17 A . I don't know .

18 MS . EASON : For the record, could you

19 please read the Bates number that appears on that

20 page .

21 MR . SHELLER : There is none .


. Ln
22 MR . McDERMOTT : Yes, there is
J
N

23 MS . EASON : Yes, there is . m


~
J
24 MR . SHELLER : Not on the page I'm ~

25 looking at .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 979
I

1 MR . McDERMOTT : 501524764 . If you

2 look on the cover -- it's probably covered by your

3 hand .

4 MR . SHELLER : Oh . Okay . Sometimes

5 these help .

6 MS . BRACHTL : Repeat that .

7 MR . SHELLER : 501524764 .

8 MS . BRACHTL : Thank you .

9 BY MR . SHELLER :

10 Q . So you don't know who put that

11 checkmark there?

12 A . No .

13 Q . And what does it mean, "not in file"?

14 Is that your writing?

15 A. No . I don't know whose writing that is .

16 Q . Then you -- there's a checkmark at

17 number 4 . An attempt to establish a simple

18 procedure for determination of a drug's addicting

19 properties . And that says, "not in file," and<

20 there's a checkmark .

21 A . I have no idea what it --


Ln
N
22 Q . And then there's a checkmark -- and ~
m
23 these are the only three checkmarks on this whole ~

24 page . (Reading)

251 Number 15, "Development

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 980

1 of a New Screening Procedure

2 Which Detects and

3 Differentiates Major and

4 Minor Tranquilizing and

5 Sedative Hypnotic Activity ."

6 "Not in file" .

7 You don't know why, on the entire page,

8 those three have the words "not in file" written

9 next to them and checkmarks next to them?

10 A. No . I notice, over the next page, number 25

11 has a checkmark beside it but "not in file" is not

12 written on it . So I don't see any connection .

13 Q . Well that's "90-day Toxicity Study on

14 Glucose Fructose Syrups"?

15 A . Well, I think that's a good example of

16 showing the people were wrong . I said the only

17 thing the bio division was doing was smoke

18 studies .

19 Q. Right . But that's in the file, huh?

20 A . Well, 319 is not a smoke study either .

21 Q . Would you mind telling me why -- who

22 are Thompkins and Thornloe? Do you know, who are

23 the authors?

24 A . They were some -- they were some of the

25 people that were let go in the '70 incident .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 981

1 Q . Are they still around, alive? Do you

2 know?

3 A . I don't know .

4 Q . How about -- well, Thompkins also did

5 number 15 .

6 Now, do you know why Reynolds is

7 researching an attempt to establish a simple

procedure for determination of a drug's addicting

9 properties?

10 A . I have no idea, sir .

11 Q . Do you know why smoking's exposure

12 studies from E .R . Fluck -- where's Fluck these

13 days? Do you know? E . R . Fluck?

14 A . He left -- he actually wasn't in the group

15 that left in 1970 ; he had already left . He had

16 done some work on ciliastasis, but I don't know

17 whether that's what it refers to or not .

18 Q . Where is he now?

19 A . I have no idea . I mean, you're talking 27

20 years ago, sir .

21 Q . Well I -- I just was -- so you have no

22 idea why those three studies are not in the file .

23 A . Well, I don't know what you call by "in the

24 file" and in whose file or --

25 Q . Who would know where those studies

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 982
r

1 are?

2 A . I think the first place to check was with

3 Reynolds' library .

4 Q. I see . And where are the -- you think

5 the originals would be in the library?

6 A . I would assume so .

7 Q . They'd still be there, right?

8 A . They should be .

9 MR . SHELLER : Could I have them

10 produced, please?

11 MR . McDERMOTT : Document production

12 has long since ended .

13 MR . SHELLER : We only found these

14 boxes six weeks ago, and we had to go -- and only

15 had them delivered a couple of weeks ago . And we

16 need to -- we can't get production of things we

17 don't know about . We didn't know this witness had

18 this material .

19 MR . MCDERMOTT : This material has

20 nothing to do with the underlying studies, which

21 have been available . Document production has

22 concluded . If you want to make a request to

23 Mr . Belasic -- I'm not the regular attorney in

24 this case . Put it in writing and give it to him,

• 25 and we'll respond .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 983

MR . SHELLER : Okay .

MR . McDERMOTT : But we don't engage in

document production exercises in a third-party

witness deposition .

MR . SHELLER : All right . At this

point I'm going to let Mr . Maistros go forward,

and I will press the issue with Mr . Belasic and

see if we have to --

MR . McDERMOTT : All right . Let me

10 raise a question, and you have me at a bit of

11 disadvantage here .

12 MR . SHELLER : I know, you wanted to

13 leave at 4 :30 .

14 MR . McDERMOTT : No . That's -- that's

15 not a problem . I'm not going to raise my schedule

16 as a barrier to your going forward .

17 Ordinarily, when two attorneys

18 question, one questions and completes his

19 questioning and the other begins, and that ends

20 it, and you don't do tag-team, switching back and

21 forth .

22 MR . SHELLER : Oh . I'm finished with

23 Dr . Rodgman .

24 MR . McDERMOTT : Has that practice not

251 been observed in this case? I just want to know

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 984

1 what -- sequential testing . Jack is coming

2 back - -

3 MR . SHELLER : Yes . And I'm not going

4 to be questioning again .

5 MR . McDERMOTT : That doesn't precisely

6 respond to my question . Mr . Maistros, having had

7 his turn at bat, does he get another turn at bat?

8 MR . SHELLER : No . He's not going to

9 repeat anything that I've repeated .

10 MR . McDERMOTT : That is not my

11 question either . Does he get a second opportunity

12 to question under the protocol that you all been

13 following --

14 MR . SHELLER : It's not a second

15 opportunity . Don't play games now, Mr . McDermott .

16 We -- to let me question because I wanted to get a

17 few hours - and I said it to the judge's law

18 clerk - and that Mr . Maistros would then continue .

19 And I said it to the judge's law clerk . And I

20 told that to you, that I only wanted a few hours .

21 MR . McDERMOTT : Are you representing

22 to me, on the record, that has been the practice

23 in this case, that the attorney first questioning

24 is then followed by the second attorney, the

25 second lead attorney designated under the case

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 985

1 management order, and then the first attorney gets

2 to return and ask additional questions?

3 MR . SHELLER : It depends on the

4 situation . We've already done this before, by the

5 way .

6 MR . MAISTROS : We have done this on

7 numerous occasions . I don't know why it was

8 agreed to and I wasn't a party to it, but it's

9 happened at, I would guess, more than half the

10 depositions that I attended .

11 THE WITNESS : I thought there were

12 only supposed to be two, if I may stick in my ore .

13 Now you're the third .

14 MR . McDERMOTT : On the strength of

15 your representation that this sort of

16 switching-off has taken place before, I will

17 permit you to continue, but without prejudice to

18 the ability of my partner, who is not here and who

19 is not reachable, Mr . Belasic, to raise objection

20 to this procedure and deem the deposition closed

21 as of this point . But I will not -- I will not

22 stop things, for the moment .

23 MR . BLANCATO : I would like to go

24 ahead, while you're moving, Mr . Sheller, and put

25 something on the record about the discussion

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 986

1 objection that I raised this morning and that

• 2 Mr . McDermott raised this morning based on

3 pretrial order number one, joint case

4 management --

5 COURT REPORTER : I'm sorry, I can't

6 hear you . Based on what?

7 MS . BRACHTL : Rustling the paper is

8 extremely distracting .

9 MR . BLANCATO : I'm sorry . Based on

10 pretrial order number one, joint case management

11 plan entered in the Arch case, particularly

12 paragraph roman numeral VI-D-1, which said that :

• 13

14
(Reading)

Each side shall

15 designate not more than two

16 attorneys to take the lead in

17 conducting the examination of

18 the deponent .

19 It's my position and, I believe,

20 Mr . McDermott's position that Mr . J . D . Lee was

21 the first attorney to be designated to take the

22 lead in questioning this case, and that

23 Mr . Maistros was the second, and that Mr . Sheller


Ln
~
24 was therefore the third and, under the terms of ~
m
25 this order, should not have been permitted to ~
N

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 987

1 question the witness .

2 We've made a telephone call to the

3 judge's chambers, learned that the judge is on

4 vacation, and spoke with his law clerks, who

5 recommended that Mr . Sheller be allowed to go

6 forward . We agreed to abide that recommendation

7 and not disturb the judge on his vacation . But I

8 want to make it clear that, by agreeing to that

9 recommendation or allowing -- following that

10 recommendation by the law clerk, I don't waive any

11 objection to the procedure you followed here

12 today . And it's my position that your questioning

• 13

14
was improper under the orders governing this case .

MS . BRACHTL : This is Martis Brachtl,

15 for the record . I need to make a statement while

16 we are at this transition point .

17 We cross-noticed this deposition in

18 the New York action . It's 4 :30 . It's my

19 understanding that the Arch deposition will not

20 finish today, and we, in New York, have not been

21 able to ask any questions, and we will do so when

22 you let us know the date to resume the deposition .

23 Th an k you . , ~
-J
r
24 MS . EASON : May I also make a m
Ob

~ 25 statement for the record, that I believe that the m


w

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 988

1 Perry case preceded your case .

2 MS . BRACHTL : So you're saying that

3 Perry should go before --

4 COURT REPORTER : I can't hear you .

5 MS . EASON : Mr . Lee had designated the

6 Perry case for his case before your intervention .

7 I think that, even though he's not present, you

8 probably need to discuss with him if he has any

9 questions and if he would like to reconvene for

10 Perry .

11 MR . McDERMOTT : All right . Let me put

12 in my two cents worth once again .

• 13

14
As far as I'm concerned, the Arch

deposition is going to conclude today . And I will

15 leave it to negotiations with my partner,

16 Mr . Belasic, if he wishes to permit a

17 continuation . And, of course, I can't speak for

18 Dr . Rodgman or his counsel .

19 Plaintiffs in Arch have had more than

20 ample opportunity to explore any relevant issues

21 they wished, and they've spent some time doing

22 that, other time in ways that we can quibble


. Ln
23 about
J
F4

24 Be that as it may, as far as I'm m


~

• 25 concerned, this deposition in Arch will be ~

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 98 9

1 concluded as of the end of today, subject to

2 Mr . Belasic having a kinder review of things .

3 We've had three attorneys . The thir d

4 attorney has completed his examination, and we're

5 now going back to number two . This is highly

6 irregular and quite protracted .

MS . BRACHTL : Regardless of what

8 happens in the Arch case, whether it finishes

9 today or doesn't finish today, it's clear that

10 New York won't get to go today . So we'll talk to

11 you about another date .

12 THE'WITNESS : I want to go home . I

13 mean, I've been here for four days, listening to

14 all this stuff . Do I have a say in this ?

15 MR . McDERMOTT : Would you like to

16 confer with your counsel ?

17 MR . BLANCATO : Let's take a break .

18 VIDEOGRAPHER : We're going off the

19 record at 4 :30 p .m .

20 (Recess taken from 4 :30 p .m . to 4 :3 9

2 1 p .m . )

22 VIDEOGRAPHER : This is tape 6 of the Ln

23 videotape deposition of Alan Rodgman, Ph .D . We're


or.
24 going back on the record at 4 :39 p .m . CO
cn

0
25
WAGA & SPINELLI (201) 992-4111
Vol . 5, Pg . 990
I

1 EXAMINATION (Continued)

2 BY MR . MAISTROS :

3 Q. Dr . Rodgman, how are you?

4 A . I'm tired .

5 Q . I'll try not to be duplicative of

6 either my previous questions or Mr . Sheller's

7 questions . I'm sure I'11 be reminded, if I am .

8 I'd like to mention a couple of

9 topics, first of all, and ask you if -- what your

10 knowledge is of these topics, okay?

11 A . Yes, sir .

12 Q . You ever hear of a project called

13 Project RAN, R-A-N?

14 A . Yes .

15 Q . What was Project RAN?

16 A . Reduced Ames numbers .

17 S2 • What does that mean?

18 A . Well, in the test for mutagenicity, they --

19 what is used is the test that was developed in

20 1973 by Dr . Bruce Ames, and it was used to test

21 the mutagenicity of compounds . And, for a while,

22 it was thought to be a -- an alternative to


vn
23 lung -- large-scale lung -- running biological H~
m
24 studies, but there wasn't a complete coordinatioi,p .
00

• 25 or relationship between mutagenicity and


m

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 991
r

1 tumorigenicity . But it's a way to get a result on

2 something very quickly ; it takes a week or less

3 than -- I never ran it ; Dr . Chin Lee did all that

4 work in-house .

5 And there was a project to develop a

6 cigarette whose smoke condensate showed reduced

7 Ames numbers . And the Ames numbers are usually

8 proportional to some of the components in the

9 tobacco smoke .

10 Q . What was that project?

11 A . Pardon?

12 Q . What was the project that you

13 mentioned? You said there was a project to

14 develop a cigarette .

15 A . R-A-N .

16 Q . No, you said there was a project to

17 develop a cigarette with reduced --

18 A . R-A-N was the project .

19 Q . That was to develop a cigarette

20 with -- with reduced --

21 A . Well, it was a -- the -- yes . It was to

22 develop a cigarette with reduced Ames numbers, and ;

23 it was called Project RAN .

24 Q . What was the name of the actual

• 25 cigarette that was developed? J

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 992

1 A . I don't think there was one developed . If

• 2 there was -- if anything was developed, it was

3 probably incorporated in something I know nothing

4 about .

5 Most of that work - I don't know what

6 date you have on that - was started just about the

7 time I was leaving . It may have started in '86 .

8 It was not done in fundamental R & D -- in

9 fundamental research . And I believe a fellow

10 called Dr . William Rice was in charge of it .

11 Q. Okay . Have you heard of Project XDU?

12 A . If I have, I don't -- I don't know it by

• 13

14
those initials . I mean, I don't know exactly what

it does or what it's supposed to do . I may have

15 heard of a project -- I don't know of an XDU .

16 Q. Have you heard of Project R-E-S-T?

17 A . I have a feeling I should -- I've heard the

18 name someplace recently, but I couldn't tell you

19 what it does .

20 Q. Reestablishment of solubles ; does that

21 ring a bell at all?

22 A . No, it doesn't ring a bell .

23 Q Have you heard of Project EW?

24 A. No .

• 25 Q . What was the Chemosol study?

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 993
r

1 A . Oh, the Chemosol study . The Chemosol study

2 was based on a patent -- issued to a man called

3 Bindig, B-I-N-D-I-G, a German . He obtained

4 patents in Germany, Canada, and the United States .

5 And sometime in the late '60s, this patent was

6 issued in the United States, and some noted

7 government officials found out about this patent .

8 And what it involved, sir, was the

addition to tobacco of citric acid, which is

10 already in tobacco, dissolved in water containing

11 some deuterium oxide and -- heavy water .

12 Well, we had looked at the patent and

13 figured well, this is not going to do anything .

14 Because the amount of citric acid -- that's a very

15 plentiful component of tobacco ; it's about two and

16 a half/three percent of tobacco is citric acid .

17 And Bindig recommended adding enough citric acid

18 to the .tobacco to, say -- and here I'm just

19 picking a figure . Say it was 3 .00 percent citric

20 acid, that when you put what he recommended, it

21 would be 3 .002 . And the amount of deuterium oxide

22 he recommended adding was like doubling the water


~
23 that comes out of your tap at home . And this J
N
m
24 Chemosol additive was supposed to reduce the

25 tumorigenicity of cigarette smoke condensate to

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 994

mice, and the benz -- polycyclic hydrocarbon

content of the smoke .

We -- I looked at it, from my

background, and said to management : It isn't

going to do a darn thing . Philip Morris' people

looked at it, they told their management it isn't

going to do a darn thing . American's people

looked at it, Lorillard, and so on . But these

three very powerful individuals in the government

10 said : You will do it .

11 And at a cost of three years' time and

12 several million dollars, Reynolds made the

13 cigarettes with Chemosol people standing there,

14 watching how the cigarettes were made .

15 The animal work was done, which takes

16 about two years . The chemistry was done on the

17 smoke with regard to polycyclic hydrocarbons,

18 principally benzo[alpyrene . And, here, I've

19 forgotten the exact numbers, but there was one

20 mouse difference between the control and the

21 Chemosol-treated cigarette, which is within

22 experimental error, because you could have a

23 difference of three and not make a difference .

24 The benzpyrene difference was .84

0 251 micrograms per gram of condensate versus .83,

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 995

1 which is an experimental error .

2 Now, this is all written up by James

3 Gargis in a reputable journal . He did all the

4 work .

5 And the, of course, the high-powered

6 officials, as soon as they learned this -- their

7 aim was, if it had worked, they would buy the

8 patent from Bindig and charge the tobacco industry

9 royalties . And of course, when it didn't work,

10 the whole thing dropped .

11 And if you're wondering who one of the

12 major proponents of it is, it was Hubert H .

13 Humphrey . The father of the man pushing Minnesota

14 all over the place, from the tobacco company .

15 And you may say : Well how does Alan

16 Rodgman know this? In 1968 or '69, when this

17 started, the monitoring of this whole experiment

18 was done by Dr . Eldon Nielson . And when he left

19 in -- Reynolds, late in 1970, I was assigned to

20 take his place on the monitoring committee, which

21 included Dr . Robert Carpenter from Philip Morris

22 and Dr . Preston Leake from American Tobacco

23 Company, and myself replacing Dr . Nielson .

24 And after Gargis published his work,

25 the Chemosol people had enough nerve to say :


i

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 996
r

1 Well, the cigarettes weren't made properly . And

2 they stood there and watched every step of the

3 preparation . And the Reynolds factory is just up

4 the street from here . And agreed that everything

5 was done properly .

6 Q . Let me show you what's been marked as

7 Exhibit 16 .

8 MR . MAISTROS : I don't know if there's

9 a quick way to pull that or not .

10 MR . HOLTON : This is -- this is not in

11 those boxes . This was produced by Reynolds . So

12 we need to make copies .

13 MR . MAISTROS : Well, while you're

14 doing it, then, please make this one as well . I

15 have two of this, if that's enough . You want

16 more?

17 MR . McDERMOTT : Yeah, let's make a

18 couple of copies .

19 MR . MAISTROS : Let me put a sticker on

20 it, first, Mark .

21 (Plaintiff's Exhibits Numbered 15 and


Ln
22 16 were marked for identification)

23 BY MR . MAISTROS :

24 Q . While they're making those copies, if

! 25 you wouldn't mind browsing -- let me see if -- if

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 997
r

1 that's the -- that will be the next one . Maybe we

2 can save some time if you read it now :

3 (Witness reviews document)

4 The document I've marked as Exhibit

5 16, is it not?

6 A. Yes .

7 Q . It's dated January 4th, 1978?

8 A . Right .

9 Q . It's to you?

10 A . Yes .

11 Q . And it's from a D . H . Piehl?

12 A . Dr . Donald Piehl .

13 Q . Who was Dr . Piehl?

14 A . He was manager of the chemical research

15 division .

16 Q . What was your title on January 4th of

17 1978?

18 A . Director of research .

19 Q . And take a minute to look at this

20 document . Do you recall receiving this document

21 on or about January 4th of 1978?

22 A . Yes, I -- yes, I did, sir .

23 Q . And is this a document that appears to


~
24 be a complete and accurate copy of the document °~°
w
251 you received on or about January 4th of 1978?

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 998

1 A . I assume so . Page numbers seem to be all

2 right .

3 Q . And was this document kept by you in

4 the ordinary course of business as an employee of

5 Reynolds?

6 A . I don't know whether I kept it in my file or

7 not . I really don't know . I've forgotten if I

8 did .

Q . What do you mean by your file? You

10 mean in those six boxes over there?

11 A . Yeah -- no . I don't think it was in those

12 boxes . It may have been, but I don't think it

13 was .

14 Q . But, you do recall receiving this

15 document on or about January 4th of '78?

16 A . Yes . I mean, I wouldn't swear to the date,

17 but I remember seeing this before .

18 Q . What is the objective that Dr . Piehl

19 advises you that he had in '77/'78?

20 A . This is the taste of nicotine, the tar and

21 nicotine ratios . Those ones, you mean?

22 Q . What is the stated objective,

23 underneath "Objective"?

24 A . (Reading)

25 The ultimate goal of

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 999

1 this research is to provide

2 the means to maximize smoker

3 satisfaction for all Reynolds

4 cigarette brands, with

5 particular emphasis on low

6 "tar" cigarettes .

7 Q . And then the four specific objectives

8 that he lists below there . First one is :

9 (Reading)

10 Determine the taste

11 characteristics of nicotine

12 in factors that affect its

perception .

What's the second objective of head of

15 chemical research at RJR in 1978?

16 MR . McDERMOTT : Object to the form of

17 the question .

18 THE WITNESS : I didn't understand you,

19 sir .

20 BY MR . MAISTROS :

21 Q• Well, I'm reading below the heading

22 that says m Specific '77/'78 objectives," correct?

23 A . Right .

24 Q . What's the second listed '77/'78

25 objective by Dr . Piehl, manager of chemical

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 1000

research at RJR?

2 A . (Reading)

3 Determine the means to

4 alter and control "tar" and

5 nicotine ratio and increase

6 nicotine transfer efficiency .

7 Q What did Dr . Piehl mean by "increase

8 nicotine transfer efficiency"?

9 A . Well -- I'd have to read this again . I

10 don't .

11 Q . It's on the second page .

12 (Witness reviews document)

13 A . I assume that's what he meant, is what he

14 wrote there . On page 2, item 2 .

15 Q . On the second page, Dr . Piehl goes

16 into some detail explaining what he means by

17 nicotine transfer efficiency?

18 A . Yes . I assume -- I assume that's what he

19 meant because that's what he wrote .

20 Q . What's the first paragraph, second

21 sentence say underneath that?

22 A . First paragraph?

23 Q . If you could just read slower for the

24 court reporter .

0 25 A . (Reading)

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 1001

1 It has been demonstrated

2 that blending alone can

3 greatly alter T/N ratio,

4 while, to date, other

5 techniques such as adding

6 nicotine or other additives

7 have been less expedient .

8 Q . What research was the chemistry

9 department -- or the chemical department doing in

10 '77/'78, that related to adding of nicotine?

11 A . I think they're shown on page 3 . And the . .

12 Q . Why was RJR doing research in '77/'78

13 with respect to adding nicotine to tobacco?

14 A . Well, a lot of this was experimental . I

15 don't know whether -- I'm pretty sure it was never

16 included in a product . But I guess he wanted to

17 see how it behaved under different circumstances .

18 Q . Do you know what the "Reynolds' number

19 one cigarette" is? It's referred to on the third

20 page, second paragraph .

21 A . Which paragraph, sir?

22 Q . Third page, second paragraph . Last

23 line refers to "Reynolds' number one cigarette"

24 A . No, I don't know what that is .

• 25 Q . Are you suggesting that, in 1978, the

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 1002

1 only addition of nicotine that Reynolds was doing

2 to its tobacco was experimental?

3 A . As far as I know .

4 This was about the same time as the

5 thing I mentioned yesterday to you, was when

6 people like Dr . Russell in England and Dr . Jarvik

7 here - maybe it was this morning I mentioned it -

were recommending leaving the nicotine alone and

9 reducing the tar, or reducing the tar and

10 increasing the nicotine . And that was discussed

11 by him at the Banbury Conference in 1979, which

12 was published in 1980 .

13 And, subsequently, there were problems

14 with consumer acceptance or test paneling of such

15 prototypes . And as far as I know, we dropped

16 them .

17 Q . And the third objective listed on the

18 first page says what?

19 A . (Reading)

20 Define the optimum

21 nicotine level in cigarette

22 smoke required to maximize

23 smoker satisfaction .

24 Determine the existence of a

25 minimum or a threshold value

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 1003

1 of nicotine required for

2 satisfaction .

3 Q. Was Dr . Piehl advising you of this

4 objective to get your approval or just to advise

5 you of what he was doing?

6 A . He was just telling me what -- some of the

7 things they were looking at that would run from

8 '77 into '78, possibly .

Q . And do you know if Dr . Piehl carried

10 these studies forward, that is, to determine the

11 minimum or threshold value of nicotine required

12 for satisfaction?

0 13 A . I really don't remember it . But, you know --

14 but, you know, if he did, I'm sure there's a

15 report on it .

16 Q . On the fourth page of this document,

17 do you see where he is listing the -- it's under

18 the heading "Optimum and Threshold Nicotine

19 Values" . The heading is on the previous page .

20 MR . McDERMOTT : I'm sorry, where are

21 you?

22 MR . MAISTROS : On page 3, he's got the ~


~
~
23 heading "Optimum and Threshold Nicotine Values," m

24 but it caries over to page 4 on the second

25 paragraph .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 1004

1 BY MR . MAISTROS :

2 Q . He states that : (Reading)

3 The preliminary data

4 above apparently reveal an

5 optimum nicotine value of

6 .12 milligrams per puff .

7 These results should be

8 regarded as unconfirmed at

9 this point . However, it is

10 of interest to speculate,

11 since the value for Winston

12 has usually been over

13 .15 milligrams puff and the

14 value for Marlboro

15 .13 milligrams puff or less .

16 Were you aware in 1977/'78 that Dr . Piehl

17 was doing that research?

18 A . I'm sure I was . I notice, on the preceding

19 page, they were talking about the consumer study,

20 and I was trying to think of where that was

21 conducted . It wasn't in Winston . It was

22 someplace else .

23 Q . Do you know if consumer studies were

24 done, subsequent to this period of time, to

25 determine the minimum nicotine values that were l


WAGA & SPINELLI (201) 992-4111
Vol . 5, Pg . 1005

1 acceptable to consumers?

2 A . They may have, sir . I don't remember them .

3 I think that's one of the things that

4 everything -- this is '78, of course ; a couple of

5 years went by, we were into 1980, and the whole

6 R & D thing got changed around and things were

7 dropped . Don Piehl became a director . And I

8 really don't remember some of this work, if it was

9 done .

10 Q . When you would do -- did you do,

11 yourself, consumer tests with test cigarettes?

12 A. No . I -- when I was involved experimentally,

13 most of my work was in the chemical end . I was

14 trying to think .

15 You might say it was sort of test

16 paneling, consumer testing, is when we were

17 looking at the substitutes, the Sutton smoking

18 material, as I mentioned before and the -- we had

19 a problem with some of our test panels who are --

20 people who had become very perceptive to tobacco

21 smoke . And they really couldn't tell us much on

22 tobacco substitutes, particularly when the

23 cigarette was a hundred percent . They didn't know

24 what to look for .

25 And so we had some small groups that

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 1006
I

1 we sort of trained, they were in-house groups, to

• 2 test substitutes .

3 That's really the only one I was

4 involved with in the Sutton smoking material .

5 We had supposedly bought a finished

6 product, but we really ended up having a year-long

7 research exercise to improve it and get the right

8 formulation for the Sutton thing . And so we had

9 to keep testing it and changing the manufacturing

10 process . And I had about six or eight people that

11 did all that . That was -- but they were all

12 in-house people, not external .

• 13

14
Q . Could you look at page 4, at the

bottom . Dr . Piehl states : (Reading)

15 It has also usually been

16 assumed that smoke pH

17 determined "free nicotine"

18 content of the smoke, and it

19 is calculated on that basis .

20 However, recent evidence

21 suggests that "free nicotine"

22 in the mouth is determined by

23 the pH of the smoker's

24 saliva .

• 25 Do you know if any work was done,

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 1007

1 subsequent to this date, to either verify or

2 confirm that hypotheses?

3 A . I think -- and this -- we went through this

4 with Mr . O'Fallon . That there's a report by

5 Dr . Rix on this subject -- at least it's also in

6 the report by Dr . Rix, that it was done with some

7 experiments in which human saliva was tested with

8 nicotine salts . And the saliva -- the pH of the

9 saliva is the controlling factor, not the pH in

10 the smoke or anything like that .

11 Q . In this same period of time, wasn't

12 Reynolds doing other testing to determine how to

13 increase the ability of the nicotine to transfer

14 into the human respiratory system?

15 A . If it was, I don't remember it .

16 Q . Do you know what I mean by -- do you

17 have a specific understanding of what Dr . Piehl

18 meant by "nicotine transfer efficiency," separate

19 and apart from this memo you just read?

20 A . Yes . It's -- tobacco has a, you know,

21 certain level of nicotine in it and -- for

22 example, in -- just taking a one-gram tobacco

23 cigarette, if it's got two and a half percent

24 nicotine in it, that means you've got

• 25 25 milligrams of nicotine in the tobacco . And,

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 1008

1 normally, maybe 1 .5 milligrams of that would end

2 up in the mainstream smoke and maybe twice that in

3 sidestream smoke, and the rest of it's destroyed .

4 And so the transfer is, say -- one and

5 a half milligrams from 25 is the transfer rate of

6 nicotine from -- to tobacco to the mainstream

7 smoke .

8 Now, one of the things that could

9 possibly be involved in some of these things that

10 we were doing that, when you puff tobacco, the

11 nicotine level goes down in the puffed tobacco ;

12 which, at some -- at one point, was 15/16 percent

13 of the blend . So, actually, your total nicotine

14 in the tobacco blend is down .

15 Then, when you increase the level of

16 reconstituted tobacco sheet, the total nicotine in

17 the overall blend goes down . And to -- if you had

18 been making a cigarette, for example, that

19 delivered 1 .3 or 1 .5, whatever number you were

20 looking for, and you ended up having, say -- in

21 one case had 25 milligrams of nicotine in the

22 tobacco, and the other you had 20, well, if you Ln~
~
23 increased the transfer rate, you could keep m
~
OD

24 n i cot i ne i n th e smo k e at the same level . ~

251 Q . Okay . Let's start, first, the

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 1009

1 principle that expanded tobacco has the effect of

• 2 reducing the nicotine content of the tobacco .

3 A . It does .

4 Q . Before it's burned, correct?

5 A . Before it's burned .

6 Q . And Reynolds had to develop a means to

7 compensate for that reduction of nicotine, did

8 they not?

9 MR . MaDERMOTT : Object to the form .

10 BY MR . MAISTROS :

11 Q . In the reconstituted tobacco .

12 MR . McDERMOTT : Object to the form of

13 the question .

14 THE WITNESSs Are you suggesting they

15 added nicotine to the --

16 BY MR . MAISTROS :

17 Q . Well, I don't want to limit it to

18 adding nicotine, because no one's going to admit

19 that, I'm sure .

20 What I'm looking at is did Reynolds

21 engage in other processes whereby the nicotine F-A

1J
N
m
22 that was lost during the expansion process could
0
CO
N
23 be regained by some other process later on? Ln

24 A . Not that I know of . As I say, I think I just

25 explained it, that -- by increasing the transfer

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 1010

1 rate, you could make less nicotine in the tobacco

2 behave as it had before .

3 Q . That -- that's much more accurately

4 worded than I attempted .

5 You have less nicotine in the tobacco ;

6 but, because you increase the transfer rate, the

7 exact same amount of nicotine enters the human

8 system, correct?

9 A . Yeah -- pretty well . I mean, you could --

10 you could arrange it that way . I don't recall

11 that it was actually ever done that way, but .

12 Q . When the tobacco is expanded, and

13 before the tobacco is burned, there's less

14 nicotine, correct?

15 A . Right .

16 Q . After the tobacco is burned, expanded

17 tobacco, didn't Reynolds have to devise a method

18 whereby the end product in the human system

19 remained some sort of constant to the pre-expanded

20 tobacco?

21 A . Well, you've got to remember one thing, that

22 expanded tobacco was not the whole blend . You had

23 unexpanded tobacco in the blend . So you're not

24 looking at a great difference of the total --

• 25 total nicotine in the tobacco -- as I say, it

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 1011

might -- we've reconstituted tobacco sheet,

juggling it and so on .

(Ms . Eason leaves deposition)

MR . MAISTROS : Let me show you what

I've marked as Exhibit 17 .

(Plaintiff's Exhibit Number 17 was

marked for identification)

MR . McDERMOTT : Let me ask a question

here . I see that counsel for Lorillard in another

10 case has just left . This is marked as

11 confidential under the Arch protective order . Is

12 the -- is the practice to type up this portion of

13 the transcript separately and not circulate it to

14 counsel for other defendants, or what? I'm not

15 sure how you all have been treating confidential

16 documents .

17 MR . MAISTROS : Let me keep this short ;

18 we're running out of time . Protocol has been :

19 You decide what you want to do, run it by Belasic,

20 he calls us and we sign off on it . Whatever

21 the -- the defendant's desire has been .

22 MR . McDERMOTT : All right .

23 MR . HOLTON : Is that part of the

24 review -

251 MR . MAISTROS : I'm not sure it's part

WAGA & SPINELLI 1 (201) 992-4111


Vol . 5, Pg . 1012

1 of it ; it's just as a courtesy . I have

2 represented that I will not share a deposition, my

3 notes, the transcript, anything till that's

4 resolved .

5 MR . McDERMOTT : All right, we'll take

6 it up with Mark, so we don't waste time here .

7 He'll get back in contact with you .

8 BY MR . MAISTROS :

9 Q . Exhibit 17, which I've showed you, is

10 dated January 30th, 1978?

11 A . Uh-huh .

12 Q . It's Bates stamped on the right

13 508880315 through 508880316, correct? And there

14 is a -- in between, a 3158 that somebody wrote on

15 in handwriting . Do you see that?

16 A . Yeah .

17 Q . Now, it appears as though, on my copy

18 at least, the way it was produced, that pages 1, 2

19 and then a page in the middle was just reversed ;

20 it should be at the end .

21 A . Yes .

22 Q . Would you agree, though, that this


Ln
H
23 appears to be a complete three-page document of a

24 report authored by Thomas Perfetti and Lawrence

25 Hayes, and --

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 1013

1 A. Right .

2 Q . -- copied to you?

3 A . Right .

4 Q . And do you recall receiving this

5 report on or about January 26th of 1978?

6 A . I really don't . But if my name was on there

7 I probably did .

8 Q . And again, at this point in time you

9 had supervisory responsibility over both Perfetti

10 and Hayes, correct?

11 A . Right .

12 Q . Is there any relationship between

13 Lawrence Hayes and Wallace Hayes?

14 A . No .

15 Q. What does the summary of this report,

16 which you were copied on state, on the first page?

17 A . (Reading)

18 Chemically-bonded

19 ammonia as the pectate amide

20 and nicotine as the pectate

21 salt into ammoniated

22 reconstituted sheet should

23 improve the nicotine transfer

24 and flavor of RJR tobacco

25 products .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 1014

Q . Were you aware, that on or about this

date, that Perfetti and Hayes were working on

improving the nicotine transfer and flavor of RJR

tobacco products through the use of ammoniated

reconstituted tobacco?

A . I knew they were working on it . This was the

time we were -- I believe, around the time we were

working on the ammoniation of our reconstituted

tobacco sheet and -- in an attempt to see if we

10 could figure out why Marlboro was doing so good --

11 so well .

12 Q . Did you agree that -- and I'll read

• 13

14
from -- I'm reading from the document

page, underneath "Memorandum" . Fourth line :


on the first

15 (Reading)

16 It is known that ammonia

17 is used to break down the

18 pectin in tobacco .

19 Is that a generally known principle in

20 January of '78?

21 A . Well, that was the -- the basis -- somewhat

22 the basis for the Philip Morris patent, except Ln


J
H

23 they use ammonium phosphate not ammonium gas or m


A
00
24 aqueous ammonia . So it had been known for W
~

9 251 some time, you know, since 1967 .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 1015

1 Was it known by you and others at RJR

2 that : (Reading)

3 It is believed that

4 pectin chemically binds the

5 ammonia and available

6 nicotine as the amide and

7 nicotinic salt -- I'm

8 sorry -- amide and pectin

9 chemically binds the ammonia

10 and available nicotine as the

11 amide and nicotinic salt,

12 respectively?

13 A . Well, that was a theory . I don't know

14 whether you know what a CIM is .

15 Q . What's a CIM?

16 A . It's a conception of invention memorandum .

17 And what it is, is a -- an idea that Lawrence

18 Hayes and Tom Perfetti had to -- as sort of an

19 outline of a possible invention .

20 And if you notice, there's a lot of

21 °mays," and "it is believed" and so on in this .

22 What they're saying is : Is this possible and

23 should we look at it?

24 Q . Why was Reynolds interested, in '78,

25 in creating an invention or a patent related to

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 1016

1 enhancing nicotine transfer?

2 A . Well, it may -- it may have been -- these are

3 individual concepts, sir, that, whether Reynolds

4 was interested in this or not, had no bearing on

5 the fact that Thomas Perfetti and Lawrence Hayes

6 made this proposal . Whether we were seeking a

7 method of this or not, I don't know .

8 But there were a lot of times -- if

9 you look at the conception of invention

10 memorandum, there were a lot of things that were

11 proposed over the years, and some of them Reynolds

12 had never expected (sic) an interest in . I think,

13 if you look through the list -- in fact, somebody,

14 one time, suggested : Hey, we should have colored

15 cigarettes, orange and pink and so on, to match

16 the ladies wardrobe . Well, Reynolds never

17 expressed an interest in that . Somebody just

18 thought it might be a good idea and proposed it .

19 Q . And was the underlying premise of such

20 an invention, or a potential invention, that,

21 because of the process used to make reconstituted

22 tobacco, you lost some of the nicotine?

23 MR . McDERMOTT : Object to the form of

24 the question . No foundation .

25 THE WITNESS : Well -- say that again,

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 1017

1 sir . I'm sorry .

2 BY MR . MAISTROS :

3 Q . I'm trying to figure out why -- what

4 was the premise behind the desire to figure out a

5 method to increase nicotine transfer . Would --

6 A . Well, as I say -- as far as I know, any time

7 you ammoniate the tobacco, whether it be sheet

8 or -- or tobacco itself, like burley or

9 flue-cured, you lose ammonia -- lose nicotine .

10 And I say again that, if you do that, you get an

11 acceptable reconstituted tobacco sheet that's

12 ammoniated . If you -- that has lost nicotine

• 13

14
if -- there's a possibility the ammonia will help

in increasing the transfer of nicotine and

15 maintain it at what it had been before you lost

16 the nicotine .

17 Q . Earlier, I got into this in some

18 detail with you . . But you explained that one of

19 the purposes of expanding tobacco was to reduce

20 the end compounds that were produced during the

21 smoking process, correct?

22 A . Yes .

23 Q . At least in so far as nicotine was

24 concerned, although the nicotine content of the

• 25 tobacco itself may have been reduced as a result

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 1018

1 of the expansion process, wasn't it the goal of

2 Reynolds to make certain that the nicotine that

3 ended up in the human system was not reduced?

4 MR . McDERMOTT : Object to the form of

5 the question . No foundation .

6 THE WITNESS : Well, I guess all I can

7 go -- say about that is, if -- when you go back to

8 when we introduced expanded tobacco - it was in

9 '68/'69, sometime around there, the cigarette was

10 made - it was the Winston - with about ten or --

11 eight to ten percent expanded tobacco . And

12 nothing was ever done at that point to either

13 increase the transfer of nicotine or to add

14 nicotine . They just sold the product and people

15 bought it .

16 BY MR . MAISTROS :

17 Q . And is it your testimony -- if you

18 know, was anything similar done, such as the

19 ammoniation process, to increase the transfer of

20 nicotine from '68 to the present?

21 A . Well, as I -- as I said, ammoniation usually

22 reduces the nicotine, and it also increases the

23 transfer . So if you've lost nicotine and

24 increased the transfer, you may have offset some

25 of the effect of the loss . 1

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 1019

1 Here again, I have no idea that -- you

2 know, if you lost a small percentage -- dropped

3 the nicotine in the tobacco from two and a half to

4 two percent, whether the ammonia would drive

5 enough nicotine over to make up for what it -- was

6 lost . There's a possibility it could ; but there's

7 a possibility it wouldn't, either .

8 Q . Does the FTC testing method, that

9 you've discussed previously, measure the nicotine

10 content of the tobacco smoke?

11 MR . MeDERMOTT : Object to the form of

12 the question . Asked and answered .

13 BY MR . MAISTROS :

14 Q . It does, doesn't it? In some fashion

15 it measures the nicotine content?

16 A . Right .

17 Q . Does it measure the transfer

18 capabilities of the nicotine?

19 A. No . Because they don't ever analyze the

20 tobacco . You got to analyze the tobacco in the

21 mainstream smoke if you want to figure out the

22 transfer rate .

23 MR . BLANCATO : Dr . Rodgman, it's about

24 5 :20 . You said you want to go to about 5 :15 . If

251 you'd like to go a little longer, it's up to you .

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 1020

1 THE WITNESS : Do you want to finish

2 this one?

3 MR . MAISTROS : Let me ask you this .

4 Your answer is what your answer is ; we'll debate

5 it with Belasic later . Are we stopping at 5 :15

6 because of the witness' desires or because counsel

7 believes we should stop?

8 MR . BLANCATO : No . Dr . Rodgman just

9 blurted out, before the last break, he's going to

10 go to 5 :15, and that's the first I heard of it .

11 It's really up to the witness .

12 THE WITNESS : I mean, I've been here

13 four days .

14 MR . MAISTROS : I understand . I'm not

15 going to debate it, because it's not going to

16 accomplish anything ; the judge isn't here . I will

17 say on the record that there are numerous

18 documents I'd like to go through with this

19 witness, have them identified, try to get a

20 stipulation that they're business records, and ask

21 him questions about . It will take longer than I'm

22 sure he's willing to sit here for the rest of the

23 day or evening to do . And I would --

24 MR . BLANCATO : How long do you think

25 it will take?

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 102 1

1 MR . MAISTROS : It's at least anothe r

2 day .

3 And I would request -- rather tha n

4 debate it here on the record, is we'll discuss it

5 with Belasic . The record is what it is, and

6 somebody wiser than me can decide .

7 I just want to note for the record

8 that there is previous testimony about how much

9 time he spent preparing for the deposition . I'm

10 sure you all agree he's an important witness . And

11 I think, if you take the total time of the Arch

12 examination as opposed to whoever was doing it

13 from Minnesota, including my time yesterday,

14 Steve's time today, Doctor -- or J . D . Lee's time,

15 that it's probably not as much as Minnesota's

16 time .

17 THE WITNESS : They took exactly te n

18 hours .

19 MR . MAISTROS : I'm guessing we're -

20 THE WITNESS : What are you on, tap e

21 what?

22 MR . MAISTROS : Close . Close .

23 THE WITNESS : So you're over te n

24 hours . And that doesn't count the hour and a half

25 that Mr . Lee -- i

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 1022
r

1 MR . MAISTROS : It accomplishes nothing

2 by us debating it . But I am not done and I would

3 object if the position is going to be taken that

4 this is the end of the deposition . You've

5 preserved all your objections as to why it should

6 be .

7 VIDEOGRAPHER : We're going off the

8 record at 5 :24 p .m .

9 (Deposition adjourned at 5 :24 p .m .)

10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

25

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 1023

1 JURAT

2 I, Alan Rodgman, Ph .D ., do hereby

3 certify that I have read the foregoing transcript

4 of my testimony, taken on Tuesday, August 5, 1997,

5 and have signed it subject to the following

6 changes :

7 PAGE LINE CORRECTION

10

11

12

14

15

16

17

18

19

20

21 DATE :

22 Sworn and subscribed to before me on this

23 day of -----------------•

24 NOTARY PUBLIC ------------------------------


25

WAGA & SPINELLI (201) 992-4111


Vol . 5, Pg . 1024

1 STATE OF NORTH CAROLINA


COUNTY OF YADKIN
2

3 REPORTER'S CERTIFICATE

4 I, Linda N . Russell, a Notary Public in and

5 for the State of North Carolina, do hereby certify

6 that there came before me on Tuesday, August 5,

7 1997, the person hereinbefore named, who was by me

8 duly sworn to testify to the truth and nothing but

9 the truth of his knowledge concerning the matters in

10 controversy in this cause ; that the witness was

11 thereupon examined under oath, the examination

12 reduced to typewriting under my direction, and the

13 deposition is a true record of the testimony given

14 by the witness .

15 I further certify that I am neither

16 attorney or counsel for, nor related to or employed

17 by, any attorney or counsel employed by the parties

18 hereto or financially interested in the action .

19 IN WITNESS WHEREOF, I have hereto set my

20 hand and affixed my official notarial seal, this the

21 12th day of August 1997 .

22 ~~.~y. e1e6 T

WIti.13C 5;?:I

23 N oth ~ r.rdina . Yadkin Cou


ELI . ----------T -----I ------- --
LIN Notsry Pubsc Linda N . Russell, Notary Public
My Commfssbn Expl__ rex_ Q•~?
24 My Commission Expires 8/25/97

25

WAGA & SPINELLI (201) 992-4111


EXHIBITS
4
Arch, et al . vs . The American Tobacco Co ., et al.
Civil Action No. 96-5903-CN
4

As Attachment to Deposition of.•

ALAN RODGMAN, PH . D . Tuesday, August 5, 1997


(VOL . 5)

0 I I CONFIDENTIAL

Exhibit Nos . 1 - 17

PREPARED FOR :
MARTINL. HOLTON, III, ESQUIRE

PREPARED BY:
WAGA & SPINELLI.
FOUR BECKER FARM ROAD
ROSELAND, NEW .IERSEY 07068
Phone : (201) 992-4111
njn° CONf1DE1-11 1 AL
Subject: 5.okin9-itealth Research ProOrIR ' Dete : April 16 . 1982

Alem RodpKan
J . A . Gtl es
Tos Or . G . R, Dlrkrco F . 9 . Colby
C . it . Mystro+e
t
in response to your request, this .eoorandua outlines opportunities
for a substantial research proOrem related to the tookin and health
controversy . In the ekta, these are tn eddition to outs~de tndnstrr-
sporsored research (see Appendix A) end do not necessarily coestder
past 1lrftations .
Concerning the outside Industry- and RJR•sponsored reseerch the
following reco .meadattoas are ottered :
o, RJJtT ALO oersonael be more Intimately inrolved In decisions
VAapt, discussions end monitoring ef thtpr oQress of this
~Y!lbardh . tn the post, these activities Aave been ltatted
~ to R 1e9e1 personnel sad/or upper w ne9e .ent with 1t«tted
''••tlu~to devote to tbe saokinp•Meelth controversy .
Rf0 aersoanel be involved in the conteaplated euJor RJR
to fund iundiaental research on diseases alleged to be
ted to saokinq without, however, necesserily involvinQ
tn' as such .
Rt0 personnet be sore involved in the existing RJRi-
rted pro0rAe on basic research adetnistration by Kessrs .
eier and tecon .
,_.._ _ . elopAent ot detailed reco~anendettons= t .e ., prol ect proposels/
wlthiri+iRMeElrort ttee tri .e is essentially impossibte because of the
bresdt/iq;,p*doinp bfoe~edtcel research which t•pects on the se~oktn9 and
hea)th~l[troYersy . The attached tables of contents froa the lest coepre-
hensiYfT~ir eon lienerai's Report (1979) illustrate this breadth .
of aress have beea identified which constitute gaps or
weekain the present state of knowled e . Eecb Is addressed below i
with a<~;d~ stete~Kat ot background and t~e, pyerill thrust of research t
~eor~t~. It~1s clear that soeu of this research could be eonducted tn-house,
ire facilities not presently on h :nd . Other areas will be
best addressed by tuadia9 competent outside researchers aad, providing I
RJA tohnicel support as appropriate .

V
V

nPN /OnV eM-AMe,1pe


.. ..

r4AuwY/rra•~~C~~XH181T~
pwv[ ....~..~/A ]>
WiLLIAM C . L .AB0ROt
RCgIilTtRC• rRor• RCPORTtII
s
•2•

PROJECT AREA I1 :
The literature contains ewvr studies on animal (rouse skin, tnstil•
lation, Inhalation, etc .) tests of Individual s+noke components and/or
smoke lroctions, shacing positive or negative results with reference to
the so•called Initiation and/or pro.otion of earclnogenesls . 1fe propose
to test all knorm s .oke eoweonents (present above a certain Qusntitative
level~ for entl•earttao?enle ectivlty In one or sort general eerclno-
genes s testing systems s
a) Initiation phase
b) prowtion phase, etc .

tw" PROJECT ABE/l Itt


lbst of the titerature on chemical carctnogenests isqltcttly or
.(
,w n-;rr
explictt suaes that results of experiments with a high level ef a
::Zc A cheRlc~~r dsinp relatively few antalt, can be extrapolated to a
~~ reei•1 e situttion . There is also to date unresolved controversy
r+bethe eAeral toxteolo4tul prtnctple that there is a threshold
'" level substance's biological action, does or does not apply to
carcinogenes s . therefore we propose standardized enial circtnoeeacsis
~ tests, tftereAt species, iRvolving different strength proups of
~ _ ehee~k tno9enf wet~ es 'strong' earelnogen~ s, "aediua• arciaoQens,
•n0 ret eas tetttnp e~xle~u . tolereted dou9es involving a
.oS anisa1=,1/(e levels of ax~ chemical entittes
~i volvp~
n a=r ~~ue+bol=r
tSoee of tbe:e axpertants e~
,~a. pi~rrea underwn~r tl~rou~h see,e Oovern .ent tunded researct:.) Ye
maan~ ther st to exaanQ these projects to test the validity of the
~ aifo th• hypothesis of chemical earcinolenesis .

"" PRQJECT' /1 :
tn'ttde of its bi9h complexity, =st of the c,heoical carclno-•
9eneststtt+erature deals with experiments involving one • or at srost
~ two •`n=" (p1us co•carcinotens . prOpotSrf, ete .)s the real-
~ life songls ObvloNsly «ucb ebre complex then this . Therefere
We pro~andardited eniewl earclnopeneslt tests Involving
=w+vP varying proportiont of first, three chemical carcinogens and leter,
four cIM~MRI earcinoQens etci, to deteraine lnterretationships more
closely related to reat•1{fe stwttons .

PROJECY AREA 84 :
ozb r ' One of the chief antagonists of smoking, tn the past, has published
*-Awau rouse skin tests, elaiMing to show that 'tar' frorn c!~arettes to whi~,h
nitrate has been added, proved_less carcinog+nic_tn these tests . Hore
recently_, that seae tea~e has elUiaed thet high nitrate tobaccos yield ©
ille9ed toainer+tise ea Cinogenieity . ~lherittore .wa roposetto teste A
•3-

high nitrate versus low nitrate tobiccos 1n a suitable, to be developed .


aniwl imalation sodel which wt11 assay simultaneously the so•called
'putfculate aed gas phasa' of cigarette uroke .

Mt4JECT AMA IS :
,, .
relitlirely 1loitea nuaber of studiei~bii sbownthit ir~antait
experiaents the results are very contradictory and roy not depend on the
chemical and/or other factors which an experiAentsr wiy ennt to tett*
but on the design protocol of the study, and, most specifically, oa the
rethode by whlch the anixul : are 'hendled" . Thsrefore we propose to
deterrine effects of vurinp handling procedures such as caging, feedin9,
foAdiinp, itrefs, etC ., on the outco .oe of animal models ettperiaeats
related to diseases alleged to be associated with s .okin4 .

Mo,1ECT AM fi : .
TMire'~are some li .ited epfdeafelo0tCa1 data iR the litsrature
Mhich ~{odi te that prepupt women have a~eReral cencer Incidence
way be oir~ xpected' levels . Therefore we suggest to determine
plVrsf 1 parametert of prepnency which euy have a eancer preventing
sffectiF: ,,~
l~~
pROJEC~ /7 !
'weak lunp' hypothesis . It has been postulated that
ia of lcmp eancer, other respiratory system eaaesrs,
hrente breeehiti : . atc. . are essentfallr oeoale who in
__ s Mould lwve betA affected by pulaoniry tbbeiYUlosfs,
ci--- lwre an fa-bor+a 'weak tunp• . Therefore we propose to
Iete tber or aot en :yrwatie or other piraaoters can be tdeatftied
W ch terNfne that an individuel has a'penetiully' determined
sus ty to lung diseases in 9eneral,

PROJEcu.0A is: .
A'ili"*ity of scientists working on non•wwliQnent chronic
respi .• diseases believe 1n a hypothesis that~~ eo is due
to a 1atbalance in poi .onery eniy.es in that smoking, through an
oxidative effect, either proaotes depradatfon of the protein laycr of
elastic 1ong tissue framework, end/or inhibits lung constituents,
which prevent such destruction . Therefora we suggest to Investigate
which saokscoa1 onent or coeponents or fraction •if any'eould
exert the so-ulled 'oxidetiw' effect postulated by the 'elastese' a
egplt4se.x1~pothtsis . This project could possibly be done in•tiovse, 0
If proper aefwl facilities were available . x

.
i
. . . . ,~
~ ~-- ---------_ _-____--_ ._._.- -- - - -- -- -- ---- - - 1W
~
PRAJECT AREA IQ :
C1aiMs that carbon monoxide an0 ntcotine eey be responsibte for the
association between saohinp and urdiovesculer disase ere ottee made .
These clai .o are given support by oxperiments conducted with either
carbon sonoxide or nieotine separately .
ihere is some evidence In the literature wl :ich suggests that nicotine
ewy actually counteract soNe of the physiological effects of carbon
etonoxide . It is suggested that tM synergtsm andJor anteWisNS between
carbon monoxide sad nicotine be tested In snieel eadels using a battery
of epecitic cardtovaculer parameters .

-: nv Pao,>ECT AREA tla:


Certain Individuals may be oore suscepttibte to s .okinp sssociated
resptr and other diseases . The suscepttblllty may be reflected in
the 0gtui~ties of these individuals . It /s, theretore .
prsPo d~, et the tesMinoZO01N1 protilet of se~okers and aon-sMOktrs
harir~ihete dtstases be tmrestlpated and Eo.pered to Mealtl~y non•saokcrs .
as wel~aeet healthy sNOker : . .

rRDJl~~b /11s

v. ••r " MW*sous one million + men Anericen tancer Socie~r (Ita :onond) stqQy
Is 61 ted as the a~or evidence of the association bet+teen lun4
~cancse~oicfn9 . Noa+ever, the study has beeR criticized and is knarn
"'°to ~ butlt•iA b/eses, inconststeectes In the data, support for
~the ttonel 1{tpotbes/s, ttc . (You will recall that the consti-
~+sau tutt 1 tMstsproposes that the hiOher 1evels of the diseases
Itr,v,t ess with saokip ts due to the fact ttat sookers are different
« . kir:ds ple than non•s+rokers, i .e ., they ara eare vnlnerable i
eons 1 types .) It 1s proposed this an en•de th study of the :+
. : raw to carried out In ordcr to expose these veeCne :ses etc .,
and r+llablt study of similar or larger scope be desi9ned to
;. test,,1D~'~constitutlonel hypothesis . (Potential cost ) S2 tailiton/year t
, ; for ~ ysers . ) i
i
~
E+
Much evidence exists india tin9 thatQe nettc susceptibility fs an
leportant factor In chronle diseases assoeieted with sMokiaq . It Is, t
i therefore, proposeA that as epide+aioloQtcal study be conducttd of the ~
; causes ot deat * in tirst and seeond back 9eneration biood repitives of '
smkers and non•sokers having sote allepedly ukoking associated dtsease, o ~
such as lwy cancer, other respiratory cancert, chronic bronchttis, ~
emphysea, etc .
v
~
V
}
.;.

PROJECT AREA 813 :


Evtdence iw= been presented sup4est1n9 that sihokin9 my affect the
R+etaboilsa of cheRicals In mn . These effects eoy be desirable or
undesirable and tuy be quite different In certain indtviduils . tt ts,
therefore, proposed that the e~etabolisw or a coor+Otnated, ltatted number D
of cher1ci11y different non-toxtc substances be determined in groups of
smokers, as well as In groups of non•taokers .

PROJECT AREA 114 :


A major thrust against the tobacco industr hit been claims of
alleged effects of slde :trem s.oke . These iac~ude both Naltw claims,
~ as will as those due to ennoyance or ct~~rette s .oke in the at .osphere .
This problem could be alleviated by techniques which would remove the
anaoyence etrects of cigarette s+.oke . it is proposed that we spopsor
.,~ . electrtcal/eaecAsntcal research oo tnexpensive, energy efficient and
uaobtrmtve equipeent for removing cigarette s .oke and cigarette saoke'
odors fpfthe Indoor indestrtal, public, and home environments .

M
'* ~ t!~t r unS e ocyi ot r
• Knp,
e ttr Rpent
at ! np,1 anc r- ont
d lttt d t on
i Ap
Engtne~nc . IASIIRAE) us recently released aew standards for
rentti requ raeents for smoking and non•smoktng, areas tn Industrial
butldt The raqutreN eat : tA arees whert snottap ts pemtttea 9reatly
qacree apital investment and subsetuent operattn9 costs tor the
~ :ainildt ~ltneertn9 and other studies should be undertaken to test
~adt,e ve ty ot these requirewrentt end new e~etAodt of dea11w9 with these
'8 ~eQui t Moula be reseerched .

..AIxsul4

k•

Attaclaents
APVERDIx A
WR7tEKT MUNC-NEA1T11 RESEARCN VENICLES

Two tyDes of projects are twwed by the Council for Tobacco Research .
There ere also Plens vnder consideratlon by R,MT to cowatt svbstantial
fuRds to fundaoe, :tal research ion diseases alleged to be associated with
s.*kinR .

The e+ost t .portent effort by the Meriun Industry ts eide through


the Council for Tobacco Research-USA 1n New York . This orRaRi :ation
handles generally t•ro types of projects :
a) Cener.l projects eDO+''ored by an independent peer
~~i9rouD of scientists, the •Scientific Advisory

b) Specill projects ~enerally inltiatel, discussed and


. approved p~r tndvitry counsel and/or outside litigating
,.•, . w,a,, attorneys lror firfss such as dacob, /~elinper i iinne'ant
frSbok . 14sr4y i RacoA .
Ati:.. . .
Es

Ses ::J. .

!L ."••i •t!:
r
.215 546_0942 .,,_• 5HELLER, L& B au . 1~~a P. 2
7j~i*/97 MON 17 :52 FAX

.
ALAN RODGMAN, Ph .D

~• Dr. Rodgman was, formerly employed In the Research and Development Department
at R.J. Rqnolds Tobacco Company ("Reynolds") . He is a fact witness who may also offer
expert testimony . Dr. Itodgrnan has a A .A . in chemistry and qs, M .A, and Ph.D in organic
~ chemistry from the Unlversity, of Toronto . He vka$ employed„iii scarlous capacities at .
' Reynolds from 1954 undl •1987. - .

Dr. Rodgman is expected to testlfy or opine concerning the development over time
of scientific knowledge relacing to smoking and healrh. Dr. Rodgrnan is ('Itrther expected mw
testify cottcernitig historical activities of the Research and Development bepatbrae~nt at
Reynolds, includfng research conductad by or for Reynolds, in the areas of smoking sad
health, including the subject of the constituents of cigarette staoka,

Dr. Rodgman fs further expected to testify concerning the design, aoasttvstion atyd
manufacture of cigarems, incluoiag tbe state-of-the-art in c,igarette design, and goveromattal
regutatioA/pazticipation with respect thereto . Dr. Rodgtnan ts expected to tes} ify dtat, In the
design of cigarettes . Reynolds speciticaUy. and rhe manufacturers of cigarettes generally,
have responded both to the scientific criticisms of cigarettes and .the demands of smokers.
Indeed, the tobacco irbdustry, ineludina Reynolds, were leaders in inventing or developing
such cigarette designs .

Finally, Dr. Rodgman may be asked to comment upon the opinions expressed by
other witncsses, as well as the evidence upon which they rely, to the extent that such
opinions and evidence related to his areas of expertise . -

Dr . Rodgman will base his testirnony on his education . training and experience, his
review of scientific information and literature concerning the subject matter described above
that are reasonably relied upon by members of his profession, his review of documents from
Reynolds concerning the subject matter described above made in connection with the expert
opinions he itatends to offer in this case during the tenure of his em131oyinent at Reynolds
and, as appropriate, documents either produced by other defendants in this fawsuit
concerning cigarette design or relied upon by plaintiffs experts oA these subjects, and his
review of testimony atld . evidence in this case . ~
FTC SMOKING METHOD

USED FOR

" TAR" AND NICOTM

DATA

Alan Rodgman, MA, Ph.D .


2828 Birchwood Drive
Wiaston-Salem, NC 27103 3410

30 August , 1994 Ln
~
~
~
m
~
HEALTH ASPECTS OF POORLY DEFINED "TARS"
OBTAINED FROM TOBACCO BY A VARIETY
OF METHODS 35

APPENDIX B : INFORMATION PROVIDED RJRT MANAGEMENT


IN THE MID-1960s FOR COMMUNICATION TO
THE FEDERAL TRADE COMMISSION re ITS
CIGARETTE MS "TAR" AND NICOTINE
LABELING PROPOSAL 7

APPENDIX C: DETERMINATION OF "TAR" YIELD FROM


ULTRALOW-"TAR" CIGARETTES :
SPECTROPHOTOMETRY 44

REFERENCES 46

m
FTC SMOKING METHOD USED FOR "TAR" AND NICOTINE DATA

SUMMARY

In the mid-1960s, the Federal Trade Commission (FTC) announced its intention to have cigarette packs
labeled with the "tar" and nicotine yields from the packaged cigarettes because of the reports issued between 1950
and 1964 on the following :

• The dose-response relationship reported in retrospective and prospective studies on the association
between smoking and lung cancer
• The production of epidermal carcinoma in laboratory animals skin-painted with cigarette smoke
condensate (CSC)
• Reports that nearly all the tumorigenicity of tobacco smoke resides in the CSC
• The demonstration of a dose-response relationship between the amount of CSC applied to the animals'
skin and the number of tumor-bearing animals (TBA)
• The demonstration of the presence in CSC of extremely small quantities of several polycyclic aromatic
hydrocarbons (PAHs) and aza-arenes reported to be tumorigenic to the skin of laboratory animals
• The publication in 1964 of the Advisory Committee's Report to the Surgeon General Report in which,
on the basis of the evidence noted above, cigarette smoke - particularly its particulate phase - was
classified as a health hazard of sufficient importance to warrant appropriate remedial action

To rank cigarettes marketed in the U.S . according to their MS "tar" and nicotine yields so the consumer
could select, from the labeling data, the cigarette that spoke to his/her individual smoking-health concerns, the FTC
proposed the development of a precisely defined protocol which would permit the reproducible determination of
yields of cigarette mainstream smoke total particulate matter (MS TPM), MS TPM nicotine, and MS TPM water,
and "tar," the latter entity to be calculated from the equation

MS TPM - MS "tar" + nicotine + water .

Both the FTC and the cigarette manufacturers recognized from the very beginning that the FTC's publication of
cigarette "tar" and nicotine yields was to serve solely as a ranking of the cigarettes . ?he values determined had
nothing to do with ranking the smokers and were never intended to do so.

The details of the analytical procedure specified by the FTC in its protocol and how some of them differ from
human smoking parameters are shown below :

• ®
FTC SMOKIlKG PARAMETERS vs HUMAN SMOKIIVG PARAMETERS
Param¢ler or Condition FTC Soecification Smoker

• conditioning ojthe cigarette prior to smoking and analysis

• time of conditioning, hr • 24 • variable ; depends on individual


smoker
• temperature of conditioning area, °C • 23 .9 (75•F) • variable ; depends on environment
encountered by Individual smoker
• relative humidity (RH) of 0 • variable; depends on environment
conditioning area, % encountered by individual smoker

• nature oJthe smoking machine • 20-port • NA

• major smoking parameters=

• puff volume, nd • variable ; dependent on individual


smoker
• puff duration, aec • variable; dependent on individual
amoker
• puff frequency, no ./min • variable ; dependent on individual
smoker

• other smoking parameters

• depth of Insertion of cigarette in • 11 • variable ; dependent on individual


holder, mm smoker
• temperature of smoking laboratory, • variable ; dependent on
eL. environment encountered by
Individual smoker
• RH of smoking laboratory, % • variable ; dependent on
environment encountered by
individual smoker
• number of cigarettes to be smoked • NA
• butt length of a non8ltered cigarette • 23 • variable ; dependent on individual
to be smoked, mm smoker
• butt length of a filtered cigarette to • overwrap length + 3 • variable ; dependent on individual
be smoked, nun smoker

• method of trapping q f TPAf • Cambridge filter pad • oral cavity and respiratory tract

• analytical procedurea jor determination oJTPM, TPM nicotine, and TPM water jor calculation of cigarette "tar" yield

• TPM, mg/cigt • gravimetric • NA


• nicotine in TPM, tttg/cigt • originally the Griffith still • NA
procedure ; later a OC
procedure
• water in TPM, mg/cigt • originally, Karl Fischer • NA
titration; later a CiC
procedure

• 7PM behavior

• TPM retained by trap, % • 100 • 50-90


• TPM emitted from tap, % • 0 • 10-s0

' Theae are essentially the values described In a publication issued almost 30 years before (Bradford et al ., 1936) and used in
USDA studies in the early 1960s (Ogg et al ., 1962 ; Ogg, 1964).


iv
The FTC was adamant about the details of its smoking procedure . Its analytical protocol was written almost
on "tablets of stone" despite the fact that personnel from the individual cigarette manufacturers informed FTC
personnel that the consumer may be more misled than informed by the "tar" listing for a variety of scientifically
valid reasons . Each of the reasons was communicated to the FTC by representatives of one or more members of
the Industry . Information communicated from the Industry to the FTC included the following :

• The smoking parameters defined in the FTC protocol are not those of either an average smoker or of most
individual smokers (see preceding Table) .

• The FTC "tar" yield determined for, a specific cigarette brand is not the "tar" yield to which the
individual smoker is exposed because each individual consumer does not :

condition his cigarettes prior to smoking as is specified in the FTC protocol for cigarettes to be
analyzed ; the moisture content of the consumer's cigarettes is dependent on moisture content at time
of manufacture, transportation conditions, shelf time, time between opening of the pack and
consumption of the last cigarette ; ambient conditions while smoking the cigarettes successively,
smoke a cigarette in a regimented fashion ; thus, the number of puffs, the pressure drop across the
cigarette, its burning temperature will vary from smoker to smoker and with individual smokers from
cigarette to cigarette,
smoke each cigarette under conditions identical with those in the FTC procedure,
retain the total intake of MS TPM as does the smoking machine .

• The "tars" from two different cigarette brands that yield the same amounts of "tar" are not
compositionally the same .

• Specific "tar" components from a cigarette brand that yields say 30 mg of "tar" are not present at twice
their level in the "tar" from a brand that yields 15 mg of "tar". The cigarette design technologies used
to control "tar" yield also markedly influence the MS composition, including that of the "tar ."

Since the implementation of the FTC procedure in 1967, cigarette have changed markedly because of the
introduction of new design technologies . Also, consumers' smoking regimen has changed since the mid-1960s and
is substantially different from the 35-m1 volume, one 2-sec puff per minute specified by the FTC .

The FTC protocol is no longer appropriate for analysis of many current cigarettes, particularly those with
low- and ultralow "tar" yields . Despite the fact that these inadequacies in he FTC procedure were pointed out by
the Surgeon General in his 1979, 1981, and 1982 reports, the FTC has made no effort to modify the major smoking
parameters (puff volume, duration, frequency) prescribed in its procedure for "tar" and nicotine determination to
counteract these criticisms . However, the FTC has made several other changes in the FTC procedure : It has
incorporated carbon monoxide (CO) determination into its procedure and CO values are now reported in the FTC
reports on "tar" and nicotine yields of cigarettes marketed in the U .S . The FTC also approved the use of automated
gas chromatographic procedures for the determination of the nicotine and water in the MS TPM . These latter
modifications were demonstrated to be significant improvements (less time consuming, less expensive, more
accurate) over those originally dictated in the FTC protocol . These improved analytical procedures were proposed
by Industry R&D personnel, not by FTC personnel .

Detailed studies involving 1979 85-mm Winstons and Marlboros, 1984 100-mm Winstons, and 1984 120-
mm Dawn cigarettes of the effect on MS "tar" and nicotine yields of changing the three major smoking parameters
revealed the following :

• Variation in puff duration has little effect on the "tar" and nicotine yields of the 85-mm Winston or
Marlboro . -

v
• Variation in puff volume or puff frequency has a significant effect on the two yields . Increasing either or
both increases the "tar" and nicotine yields .

• The "tar" and nicotine yields for the 85-mm Winston were greater than those for the 85-mm Marlboro .

• For a given increase in puff volume or frequency the "tar" and nicotine yields increase for both the 85-
mm Marlboro and the 85-mm Winston but the % difference between the Marlboro and Winston "tar" and
nicotine yields decreases .

Thus, if the FTC does modify the three major smoking parameters, particularly increasing the puff volume and puff
frequency, the "tar" and nicotine yields for marketed cigarettes will increase over the values obtained currently .

To reiterate several points mentioned previously : the following aspects of the protocol for the so-called FTC
procedure for the determination of cigarette MS nicotine and "tar" yields (and subsequently carbon monoxide yield)
should be remembered :

• The final protocol was a product of the FTC which dictated every detail of the protocol .

• Its implementation was ordered by the FTC .

• Its purpose from the very beginning was to rank marketed cigarettes according to "tar" or nicotine yield
to permit the consumer to choose a cigarette whose deliveries satisfied his/her concerns about the effect
of cigarette smoke on the smoker .

• The "tar" and nicotine yield data obtained by use of the FTC smoking and analytical procedures were
never considered by either the FTC or the cigarette manufacturers as a means to somehow rank smokers .

vi
FTC SMOKING METHOD USED FOR "TAR" AND NICOTINE DATA'

I. INTENDED USE OF SMOKING METHOD RESULTS

A. Statement of Purpose

The results from the FTC analyses of the "tar" and nicotine yields in the mainstream
smoke (MS) from cigarettes marketed in the U.S. were intended to accomplish the following :

To permit the cataloging or sequential listing of the cigarettes for their MS yields of
these two smoke entities (c, f. FTC, 1967b, 1978) generated under standard and
reproducible conditions. Subsequently, a third MS entity, CO, was added to the FTC
listing (FTC, 1981) .

• To permit the consumer who wished to continue smoking to select a cigarette whose
MS lltar" and/or nicotine yield was compatible with his/her concerns about the
effect(s) of cigarette smoking on his/her health .

It was never anticipated by the FTC or by the cigarette manufacturers that the FTC lists could .
serve as a means to catalog or rate cigarette smokers .

The following factors were known or suspected from the very beginning of discussions
among the FTC and the representatives of the cigarette manufactureres on a standard,
reproducible procedure for the determination of cigarette MS "tar" and nicotine yields :

• Individual smokers do not smoke a cigarette under the precise smoking regime
dictated in the FTC procedure .

• Unlike the smoking machine used in the FTC procedure, individual smokers may
miss one or more puffs during the smoking of a cigarette because of involvement with
other activities (writing, telephoning, discussing, etc .).

• Unlike the smoking machine used in the FTC procedure, the individual smoker does
not smoke his/her cigarette to the butt length dictated in the FTC procedure for
untipped and filter-tipped cigarettes .

• Unlike the smoking machine used in the FTC procedure, the individual smoker
exhales a portion of the MS .

• It is highly probable that the per milligram compositions= of the MS "tars" from two

~'I1ro original FTC procedure for smoking cigarettes to determine "tar," nicotine, and water deliveries in mainatream .moke (MS) (values
first reported in 1967 ?PTC, 1967), was subsequently modified for the simultaneous determination of MS carbon monoxide (cf . FTC, 1981)
2 In addition to the differences between the compositions of the particulate phases, the compoaidons of the vapor phases will differ .

1
different brands of cigarettes whose "tar" yields are 20 mg are entirely different .

• It is highly probable that the per milligram compositions' of the MS "tars" from two
different brands of cigarettes whose "tar" yields are 20 and 2 mg, respectively, are
entirely different .

B. Other Analyses Similar to FTC Smoke Analysis

In the U.S. there are numerous analyses of consumer products similar to the FTC
analysis for "tar" and nicotine in cigarette mainstream smoke (MS) :

• Composition of vitamin pills in terms of weight or units of Vitamin A, vitamin C,


thiamin, riboflavin, niacin, vitamin D, vitamin B,,, etc .

Even though the analysis for the levels per pill of various vitamins appears on
the label, the consumers absorption of the each vitamin will depend on the
individual consumer's metabolism . The label listing only indicates how much of
each vitamin is ingested when the consumer swallows the pill, not how much is
actually effective in and beneficial to the consumer .

• The urban and highway mileage per gallon of gasoline expected for an automobile
model tested under certain driving regimes representing the average driving habits of
and conditions encountered by the American driver, e .g., 20 mpg under urban
conditions, 28 mpg under highway conditions . These two mileages are listed annually
for each new automobile model and are listed in numerous publications as information
to enable a potential automobile buyer select the automobile of his/her choice .

Depending on his/her driving skills, individual drivers may get more or less mpg
than the reported 20 mpg in city driving and more or less mpg than the reported
28 mpg on the highway.

• The mileage rating of automobile tires, e .g., 40,000-mile tires, 50,000-mile tires .
These ratings are determined by testing the tires under specified driving conditions
and ensuring that they are periodically and properly maintained during testing .

Here again, how many miles are obtained with a given set of tires depends on
the driving skills and habits of the owner, the terrain over which the tires are
driven, and whether or not the tires were maintained at proper inflation and
rotated according to prescribed schedule .

• The content of fat in dairy products expressed as % butterfat .

• The levels of various components in foodstuffs are determined by approved analytical


procedures and the results listed on the marketed packages, e .g., on the package of

• 3 In addition to the differences between the compositions of the particulate phases, the compositions of the vapor phases will differ .

2
a popular cereal are listed the amounts per serving of protein, fat (saturated, fat
(unsaturated), carbohydrate, cholesterol, sodium, potassium, iron, zinc, magnesium,
calcium, copper, phosphorus .

It is known that the nutritional effect of each of these components is not the
same for each consumer but depends on the individual consumer's metabolic
processes.

II. CHRONOLOGY

A. Introduction

While the concern about the particulate phase of cigarette mainstream smoke (MS)
received particular emphasis in the early 1950s, numerous investigators between the late 19th
century and the early 1950s had commented on its possible effect on the health of the smoker
(see Appendix A) .

Six major events in the 1950s and early 1960s escalated the concern about the MS
particulate phase' and triggered the FTC's proposal to have the U .S. cigarette manufacturers
report the "tar" and nicotine deliveries of individual cigarette brands :

• The epidemiological data from both retrospective and prospective cigarette smoking
studies that indicated a dose response relationship between the number of cigarettess
smoked per day and specific disease entities, particularly cancer of the lung (see
summary of the epidemiology studies in the Advisory Committee's report to the 1964
Surgeon General (USPHS, 1964)] .

• The first reported production of skin carcinoma in susceptible strains of laboratory


animals painted periodically with massive doses of mainstream smoke cigarette smoke
condensate (MS CSC) prepared under conditions more or less simulating the human
cigarette smoking regime' (Wynder et al ., 1953a, 1953b, 1955, 1956 ; Wynder and
Wright, 1957) .

• Reports that nearly all the tumorigenicity (mouse-skin painting) of tobacco smoke

4 Even though they differ in composition, MS total particulate matter (rpM), cigarette smoke condensate (CSC), and "tar" (water- and
nicotinafree TPM as detined by in the FTC procedure) became almost equivalent when referred to In d'ucuuiona of the effects of cigarette
MS particulate phase on the health of the conaumer .
s Fewer than two dozen cigarette brands were marketed In the U .S . in the 1950s and their per cigarette deliveries of "tar" and nicotine were
remarkably uniform, ranging from 33 to 40 mg "tar" and 2 .7 to 3 .0 mg of nicotine . In the late 1950. and early 1960s t t hese values showed
progressive decreases .

6 To collect large amounta of cigarette smoke condensate for the akin-painting studies, the puff frequency used was three puffs per minute
rather than one puff per minute, the frequency closer to that used by smokers . The MS was trapped in Dry lce-chilled vessels .

3
resided in the MS CSC' . The MS vapor phase was subsequently shown to possess
very little tumorigenicity .

• Reports that the MS CSC contained several polycyclic aromatic hydrocarbons (PAHs)
and aza-arenes' previously demonstrated to be tumorigenic to mouse skin and several
phenols, nontumorigenic per se, previously reported to enhance or "promote" the
tumorigenicity of tumorigenic PAHs applied to laboratory animals at subtumorigenic
levels (see summary in Wynder and Hoffmann, 1967) .

• Reports from several laboratories (Wynder et al ., 1957a, 1957b ; Bock et al ., 1962)


that carcinoma production showed a dose response in laboratory animals skin-painted
with various levels of cigarette smoke condensate and that no carcinomas were
generated below a certain dose level .

The publication of the Advisory Committee's report to the 1964 Surgeon General
(USPHS, 1964) in which it was stated that "Cigarette smoking is a health hazard of
sufficient importance in the United States to warrant appropriate remedial action ."

The latter event provided the FTC with an official statement of the government's position
on tobacco smoking, particularly cigarette smoking, and a virtual mandate to require the
reporting of the "tar" yields from all U .S . cigarette brands .

In response to these reports, the U .S. cigarette manufacturers subsequently marketed


newly designed cigarette brands which provided a range of "tar" (and nicotine) yields, thus
enabling the consumer to choose a brand whose "tar" yield satisfied his/her concern about
smoking and health .

It should be noted that at the time of publication of the 1964 Report of the Advisory
Committee to the U .S. Surgeon General, nicotine in cigarette MS was not considered to be a
significant health hazard . It was stated (USPHS, 1964) :
Nicotine is rapidly changed in the body to relatively inactive substances with low toxicity . The
chronic toxicity of small doses of nicotine is low in experimental animals. These two facts, when
taken in coqjunction with the low mortality ratios of pipe and cigar smokers, indicate that the
chronic toxicity of nicotine in quantities absorbed from smoking and other methods of tobacco use
is low and probably does not represent an important health hazard .

7 MS CSC, closely related compusitionaily to the nnaterial subsequently defined as "tar," was reported to contain numerous tumorigenic
(mouse skin) polycyclic aroroatic hydrocarbons (PAHs) such as benzo(a1PYrend (Bap), tumorigenie au-arenes, and tobaeeo-speeifie IK
nitrosamines (rSNAs) such as N-nitrownornicotine (NNN) and 4-(*methyWunsamita)-t-(3-pyridinyi)-1-butanone (NMq . It is claimed
that the PAHs are responsible for the tumorigenicity of CSC to mouse skin, but their concentntions in CSC account for less than 296 of
the observed response . The renuinder of the observed tumorigenicity In such studies has not been accounted for . The /Knitrosamines are
organ specific tumorigene and play little, if any, role in the tumorigenicity of CSC to mouse skin .
~ Of all the groups itrve Wgating the aza-arenes in tobacco nnoke, none has been unable to duplicate the findings of Van Duuren et al . (1960a,
1960b) who reported the presence of dibenz[a,hjact4dine, dibenz(a,JJacddine, and 7R-dibenzo(c,glcarbazoie (see Rodgman, 1991, 1994) .

4
Subsequently, however, nicotine was alleged not only to be involved in coronary and
circulatory problems but also it was defined as the precursor of several tumorigenic tobacco and
MS components, the so-called tobacco-specific N-nitrosamines (TSNAs) such as N'-
nitrosonornicotine (NNN) and 4-(N-methylnitrosamino)-1-(3-pyridinyl)-1-butanone (NNK)
(Hoffmann et al ., 1984, 1985, 1991a, 1991b ; Hoffmann, 1989) .

Soon after the publication of the 1964 Surgeon General's report (USPHS, 1964), the
following events occurred :

• The FTC began its activities to implement a labeling system for "tar" and nicotine
yields from cigarettes marketed in the U .S. As communications between the FTC and
the cigarette manufacturers proceeded, RJRT R&D personnel provided management
with pertinent information on the status of the analysis of MS for 'tar" and nicotine
(see Appendix B) . This information was used in attempts - obviously all
unsuccessful - to dissuade the FTC from pursuing its plan of implementing cigarette
pack labeling .

• The FTC alerted the U .S . cigarette manufacturers of its intentions (FTC, 1966),
vigorously pursued the implementation of an appropriate analytical method for the
determination of MS TPM, defined MS "tar" in terms of MS TPM, water, and
nicotine (Equation 1), promulgated the protocol of FTC procedure for the
determination of MS "tar" and nicotine yields (FTC, 1967a ; Pillsbury et al ., 1969),
and published the first FTC list of the MS "tar" and nicotine yields from 59 cigarette
brands marketed in the U .S. (FTC, 1967b) .

TPM = "tar" + nicotine + water Equation 1

The FTC procedure originally incorporated the best aspects of various methodologies
developed during the preceding three decades and subsequently was modified slightly
to include new and improved analytical techniques such as the determination of TPM
water and nicotine by gas chromatography . E.g ., the FTC procedure included the
smoking parameters (puff volume, duration, and interval) of Bradford et al. (1936),
collection of TPM on the Cambridge filter (Wartman et al ., 1959), pertinent aspects
of TPM nicotine analysis of Pfyl et al ., (1927), Pfyl (1933a, 1933b), Willits et al .
(1950), Griffith (1957), Ogg et al . (1962), Ogg (1964) and TPM water analysis of
Holmes and Cridlin (1960), Crowell et al. (1961), Jarrell and Wickham (1961, 1962),
Sloan and Sublett (1964, 1965), Schultz and Spears (1966) .

Because many of the analytical procedures to define the yields of cigarette MS TPM,
nicotine, water, and "tar" had been used for some years in the laboratories of
Tobacco Industry members in their product development studies, R&D representatives
from five of them° collaborated on a publication (Bates et al ., 1967, 1968) in which

9 L&M, Inc ; BdtW Tobacco Corp . ; American Tobacco Co . ; RJ Reynolds Tobacco Co. ; Philip Morria, Inc .

5
appropriate and Industry acceptable procedures for the determination and reporting
of MS TPM, TPM water, and TPM nicotine were described . The procedures were
essentially identical with those presented in the FTC protocol (Pillsbury et al ., 1969) .

• At the 1967 World Conference on Smoking and Health, a workshop involving some
30 presentations was devoted to the subject "Toward a Less Harmful Cigarette"
(Wynder and Hoffmann, 1968) . About two-thirds of the presentations dealt with the
composition and alleged adverse effects of "tar" in experimental situations .

• Under the auspices of the National Cancer Institute Smoking and Health Program, a
study, "Toward a Less Hazardous Cigarette," was implemented in 1968 and
continued for more than a decade . The summary report on the study was issued in
1980 (NCI, 1980) . R&D personnel from several of the major U .S. cigarette
manufacturers10 served on the NCI Tobacco Working Group as private citizens
knowledgeable in cigarette design and tobacco and tobacco smoke analysis,
composition, and properties .
1956 1960 1964 1968 1972 1976 1980 1984
Numerous technologies 50 3 .0
introduced sequentially from the 45
mid-1950s to the late 1960s were n,tar Tlp. .!
42.5 °
40 Raoonatftut.d Tob .ooo She .t
incorporated into cigarette design P.p.r Additt...
P.per Porosity
to control MS delivery and I 35 ~ lspaad .d Tobaooo
0 1. -l 2 .0
composition. All are considered ~ V.nUlatlon
e~e 30
to contribute to what some have ~
characterized as a "less 25
ir
hazardous" cigarette when 20
included in cigarette design 8
15
(USPHS, 1979 ; NCI, 1980 ; Gori
and Bock, 1980 ; USPHS, 1981) . r 10 - Tar
••••••••• Nicotine
These technologies include : 5
• tobacco blend and 0 1956 .0
. 1960
L 1964
L L 1968 L
1972L 1976
L1980
AI1984 0
weight
• tobacco rod length and Figure 1 . "Tar" and Nicotine Deliveries, Sales Weighted Average
Basis
circumference
filter tips (material type
and additives)
• processed tobaccos (reconstituted tobacco sheet, expanded tobacco)
• paper (type and additives)
air dilution (increased paper porosity, filter tip perforations) .

The chronology of introduction of these technologies and their effects on sales weight average

10 LdtM, Inc . ; B&W Tobacco Cocp . ; P. Lodllard Co., Inc . ; RJ Reynolds Tobacco Co . ; Philip Morsis, Inc .

6
nicotine and "tar" yields are shown in Figure 1 . Over the years, the introduction and use of
these technologies in concert and to various degrees in cigarette design have provided the
consumer with a great variety of products whose number has increased from about a dozen in
the early 1950s to nearly 200 presently . The cigarette is a system : All the technologies used
in cigarette design are interactive . Le., inclusion of or change in the level of use of any
particular technology may require other adjustments in the cigarette design to maintain certain
attributes acceptable to the consumer . In contrast, by current technology, SS delivery is
controlled almost totally by tobacco blend and weight . The SS is not subjected to filtration, the
effect of filter-tip additives which specifically remove certain MS components from MS (phenols,
volatile N-nitrosamines), or air dilution effects .

In a continuation of their earlier reported mouse skin-painting studies, Wynder et al .


(1957a, 1957b) examined the effect of application of lower and lower total annual doses of MS
CSC on tumor production in skin-painted mice . They reported that skin painting of mice with
a total annual dose of 10 g/mouse produced papilloma in about 60% of the mice ; at a total
annual dose of 7 .5 g/mouse the percentage of papilloma-bearing animals was reduced to about
35 % . Only a small percentage (< 10%) of papilloma-bearing animals (but no carcinoma-
bearing) animals was observed when the total annual amount of MS CSC applied was less than
5 g/mouse; further reduction of the annual dose to 3 g/mouse resulted in no papilloma- or
carcinoma-bearing mice . These data are presented graphically in Flgure 2 . Thus, in this study,
reduction of the total annual dose from 10 g/mouse to 3 g/mouse reduced the percentage of
tumor-bearing animals from 60% to 0% . This represents a 3 .3-fold reduction in the dose of the
applied material, CSC . so r

These data from the dose- ro


response study (and the threshold
limit value for MS CSC) were
subsequently reported several 30
times by Wynder and Hoffmann ~
(1962, 1963, 1964, 1967) who ~ 40 stated in 1964 and again in 1967
: ,~ „
}~f
It is apparent that a V
reduction of
tumorig enic t0
components can be
most readily °a 3 4 6 e 7 s Y 10
accomplished by arams of Cisaratta smotce/llouae/Year
reducing the total Figure 2 . Relationship of Tumor Yield and Dose (Wynder et al .,
amount of smoke con- 1957b)
densate. . . to which one
is exposed . This has
been clearly shown
experimentally by dose-
response studies
[Wynder et al:, 1957a, Wynder and Hoffmann, 1962a, 1962b ; Bock et al., 1962] .

7
Wynder and Hoffmann (1965) determined the effect of MS CSC dose on tumor yield by
conducting lifetime sldn-painting studies in mice (50 mice per dilution) with various dilutions
of CSC-acetone suspensions. The results are shown in FIgure 3 . Skin painting with a fixed
volume of successive dilutions of a 50% CSC-acetone suspension reduced the percent tumor-
bearing animals from 45% with a 5096 suspension to 34 % with a 33% suspension, to 2036 with
a 25 % suspension, to 8% with a 10% suspension, and to 2% (one tumor-bearing mouse) with
a 5% suspension, i.e., a 10-fold dilution of the CSC-acetone suspension produced a 25-fold
diminution in % tumor-bearing animals . From their results, Wynder and Hoffmann (1965)
noted:

It is apparent. . .from
laboratory studies . . .that so
exposure to tobacco - 60X
-- 33X
smoke condensate and $ax
tumor yield are -- 109
quantitatively - - 5%

correlated . 51

A few years earlier,


Wynder (1961) had commented on
the effect of dose reduction on
tumor yield in laboratory animals
painted with CSC . Because he
................ .`
used much more reasonable doses _._. . ..-
. .. . . .
of CSC in his slcin painting, . . ..-•
.
.~ , ,
Passey in England was unable to 1 s a 7 0 0 m 11 /u 13 14 1s 16 17 ls

confirm the findings of Wynder et YONTHS


al. (1953a,, 1953b) . Wynder's
explanation was as follows :

What reAlly happened Figure 3 . Tumor Response to Different Doses of Cigarette Smoke
was that y applied Condensate in Acetone (Wynder & Hoffmann, 1965) .
too weak a coneent-
ration of to smoke
condensate to his
animals. Of course,
since tobacco ke is
only a weak carc ogen
to begin with, if u
dilute its concentra too markedly, it is no wonder that you do not obtain any cancer . It would
be just like a human , ing smoking one or two cigarettes a day without inhaling it . His risk of
developing lung cancer`would certainly also not be greater than that of a non-smoker . . .

[From] a study which we have done on the dose response of different amounts of smoke condensate to the
production of skin cancer in mice . . . (y]ou will note that, if we applied to the mouse 5 g or less per year
of tobacco smoke condensate we were not able to produce any cancers . This of course explains the failure
of Dr. Passey_to repeat our work . But it clearly shows that tobacco smoke condensate is not a very strong
carcinogen .

8
The importance of dose (exposure) was reiterated in tlie same language by Wynder and
Hoffmann in their lengthy 1964 review article (Wynder and Hoffmann, 1964) and 1967 book
(Wynder and Hoffmann, 1967) on tobacco :and tobacco smoke:

Since 1953, when the first large-scale prod4ction of epidermoid cancer was reported, many
investigators have verified these findings . Some ri~ativeftndings (Shotadze, 1953 ; Gwynn, 1954 ;
Passey et al., 1954; Kakhiani, 1955 ; Hamer and Wbpdhouse, 1956 ; Gwynn and Salaman, 1956)
are largely, if not exelusively, a result of tnadequate~dQse . (Emphasis addedr AR)
.,

Wynder and Hoffmann (1964, 1967) also noted that Gritsiute and Mironova (1960)
reported only 3 (1 .7%) tumor-bearing animals (TBA) out of 174 animals treated with between
1 .4 and 2 .6 g of CSC over a 10-month period whereas their own studies gave 44% TBA in
animals treated with 11 .7 g of CSC over a 15-month period . When the difference in treatment
time is disregarded, a dose reduction ranging from 4 .5 to 8 reduced the % TBA by a factor of ~
26!

Because of the dose-response relationships reported in the human epidemiological studies


and the dose-response relationships in the biological studies conducted with CSC-painted
laboratory animals, the FTC proposed that the consumer should know the "tar" deliveries of
marketed cigarettes in order to make an informed choice of his/her brand, depending on his/her
degree of concern about the reported relationship between smoking and certain disease entities .

In the period 1964-1966, numerous memoranda were prepared in which reasons for the
FTC not to continue with its efforts to label cigarette packages were outlined . The salient points
advanced by RJRT R&D personnel to dissuade the FTC are summarized in Appendix B . These
arguments and similar ones advanced by other Industry members were unsuccessful .

On 25 March 1966, the FTC (FTC, 1966) announced it had sent identical letters to each
of the major U .S . cigarette manufacturers in regard to factual statements of "tar" and nicotine
content on labels and in advertising of cigarettes :

Gentlemen :

. The Cigarette Advertising Guides promulgated by the Commission in September 1955


provided that no representation should be made that "any brand of cigarette or the smoke
therefrom is low in nicotine or tars * * * when it has not been established by competent scientific
proof applicable at the time of dissemination that the claim is true, and if true, that such difference
or differences are significant ." On the basis of the facts now available to it, the Commission has
determined that a factual statement of the tar and nicotine content (expressed in milligrams) of the
mainstream smoke from a cigarette would not be in violation of such Guides, or of any of the
provisions of law administered by the Commission so long as (1) no collateral representations
(other than factual statements of tar and nicotine contents of cigarettes offered for sale to the
public) are made, and (2) the statement of tar and nicotine content is supported by adequate
records of tests conducted with the Cambridge Filter Method, as described in an article entitled
"Determination of Particulate Matter and Alkaloids (as Nicotine) in Cigarette Smoke," by C .L .
Ogg, which appeared in the Journal of the Association of Official Agricultural Chemists, Vol . 47,
No. 2, 1964- It is the Commission's position that it is in the public interest to promote the

9
/
dissemination of truthful information concerning cigarettes which may be materia) and desired by
the consuming public .

By direction of the Commission. Joseph W . Shea, Secretary .

During discussions between U .S . cigarette manufacturers and the FTC in the mid-1960s,
it was pointed out by industry representatives that labeling cigarette packs with the amounts of
MS "tar" and nicotine delivered by the cigarette smoked under standard laboratory conditions
would not inform the smoker of the precise amount or composition of the "tar" received during
his/her smoking of the cigarette (see Appendix B) .

The reporting of nicotine as a separate MS component derived from the fact that it and
water are the two most plentiful components in MS TPM . In the early 1960s when the FTC
began its efforts to require "tar" and nicotine reporting, extensive studies were underway to
define MS composition . The number of identified MS components had increased from about 80
in 1954 (Kosak, 1954) to about 800 in 1965 . Currently, the number of identified components
in MS exceeds 4,500 . Thus in the early 1960s, MS "tar," except for nicotine and water, was
a poorly defined material .

B. Origins of Smoking Parameters (Puff Volume, Puff Duration, Puff Frequency, etc .)

As noted previously, the FTC's desire to catalog cigarettes by their "tar" and nicotine
delivery stemmed from the various claims in the scientific and medical literature that certain
health problems arose in cigarette smokers as a result of their inhalation of the components
constituting MS "tar" and the dose response relationships reported in epidemiological studies
with smokers and biological studies with laboratory animals . The following relationship has been
used for over three decades to calculate the value of the "tar" delivered in cigarette MS :

total particulate matter = "tar" + nicotine + water

The values for the major smoking parameters (puff volume, duration, and frequency) can
be traced to the publication of Bradford et al. (1936) who selected a puff volume of 35 ml, a
puff duartion of 2 sec, and a puff frequency of 1 puff/60 sec . Actually, only the puff duration
of 2 sec 'was similar to that observed with cigarette smokers . The other two values were less
than the observed average puff volume and frequency . The values for these three cigarette
smoking parameters persisted for the next three decades .

For a given cigarette brand, the FTC numbers for "tar," nicotine, and more recently
carbon monoxide are obtained via a precisely defined smoking regime and analytical methods
[preconditioning of cigarettes (23 .9°C; relative humidity, 60% ; conditioning time, 24 hr) ;
smoking parameters - 35-ml puff volume, 2-sec puff duration, 1 puff/min ; 23.9°C, 60%
relative humidity, cigarette smoked to a defined butt length].

In contrast to the rigorously defined FTC smoking and analytical procedures for the
determination of cigarette MS "tar," nicotine, and more recently carbon monoxide :

10
• Few smokers, if any, in the smoking of a cigarette take in the TPM amount found
in the FTC determination .

• Few smokers smoke their cigarettes to as short a butt length as in the FTC procedure .

• Because of involvement in other tasks, the smokers often place their cigarette in an
ash tray for a brief time, thus missing one or more puffs on the cigarette . Few
smokers take the number of puffs obtained for a given cigarette brand in the FTC
procedure. The smoking machine used in the FTC method is relentless ; it never
misses a puff on the cigarette under test!

• Whereas the smoking parameters (35-ml puff, 2-sec duration, 1 puff/min) in the FTC
procedure are those originally proposed by Bradford et al . (1936), proposed again by
Ogg (1964), accepted by the tobacco industry (Bates et al ., 1967, 1968) and the FTC
(FTC, 1966 ; Pillsbury et al., 1969), individual smokers varied considerably from the
FTC-dictated values, e .g., puff volumes ranged from 32 .8 to 53 .4 ml, puff durations
ranged from 1 .53 to 2 .77 sec at 1 .8 puffs/min in a study conducted close to the time
of the FTC activities (Adams, 1966) .

• In contrast to human smokers, the smoking machine used in the FTC procedure does
not "exhale. " It has been reported in numerous studies that individual cigarette
smokers vary considerably . They were found to exhale between 10 and 75 % of the
TPM inspired during the puffs taken to consume the cigarette, thus retaining between
25% and 90% of the inspired TPM" (cf., Piehl, 1970) .

Another problem, long recognized by tobacco scientists but ignored by the FTC, is the
fact that the MS "tars" from two different cigarette brands delivering the same weight of "tar,"
e.g., 25 mg, may be quite different compositionally because entirely different technologies were
incorporated in the design of the two brands to achieve the 25-mg "tar" delivery. Examples of
this are found in the reports of the National Cancer Institute on its 10-year study on "less
hazardous" cigarettes . Various cigarette design technologies were investigated to determine their
effect on MS yield, MS chemical composition, and MS CSC biological activity (mouse-skin
painting) (Gori, 1976a, 1976b, 1977, 1980 ; NCI, 1980) . Overall, the relationships among
tobacco blend compositions, MS compositions, and biological activities of the CSCs from nearly
100 test and some 30 standard and reference cigarettes were studied . Nine of the cigarette
samples showed "tar" yields ranging from 27 .0 to 27 .4 mg. As shown in Table IA, despite the
uniformity in "tar" deliveries from these cigarettes, their MSs - both the particulate phases and
vapor phases - were quite disparate compositionally as shown by the data, normalized to "tar"
yield, and the ranges listed for the normalized data .

t~ % retentiona of MS TPM much lower then the 90% described in the literature were reported by Whisnant and Stevenson (1969c) at RJRT .
In a detailed in-houae studies at RJRT R&D, .rooken were found to retain between SO and 65 % of the TPM inspired .

11
Table 1
Variations In Mainstream Smoke Composition for Cigarettes Delivering 27 .2 f 0 .2 mg of "Tar"

AnalyldCigt. No. Id,' 1-23° II-42' 1I-44' 1II-74a III-81' IV-26' IV-31a IV-67° Range

Per Cigarette Dedvery

`Yar" i mg 27.4 27.4 27.3 27.4 27 .4 27.3 27.0 27.1 27.2 27.0-27. 4
'tar"P'taq.d" 1 .007 1 .007 1 .004 1 .007 1 .007 1 .004 0 .993 0 .996 1 .000
nicatinei mg 2 .07 1 .39 1 .93 1 .80 1.80 1 .91 3 .25 0 .89 1 .84 0.89-3 .2 3
'Yar"/nioot6ne 13 .2 19.7 14.1 15 .2 15.2 14.4 8.3 30.4 14.8 8.3-30 . 4

Amount ofComponent Relative to "Tar "

BaPj µg/g 0.91 0 .68 0.58 0.79 1 .04 1 .18 0.72 0.82 0.64 0 .38-1 .1 8
BaA ° µglg 1 .40 0 .92 1 .08 0.90 1 .49 1 .64 1 .01 1 .00 1 .42 0 .90-1 .64
pheaol mg/g 3.95 2.98 3.83 3.90 4.28 4.62 4.85 3.07 6.10 2 .98-6 .1 0
ocresol mg/g 0.72 0.51 0.62 0.63 0.77 0.79 0.72 0.57 nd 0.51-0 .79
aoetaldehyde 39.1 42 .6 37.9 36.1 38.4 39.9 19.6 25.1 34.9 19.6-42.6
mg/g
HCN mg/g 6.11 4.2' 12.2 12.0 13.3 12.1 9.8 13 .0 12.5 9.8-13 .3 °
NO' mg/g 9.6 8.0 9.4 8 .7 10.8 10.0 33.7 11 .3 12.8 8.0-33 .7

Tschnology Investigated; other notes :

' I!i contained double the nitrate level of control blend SRH-I (1).
° Higb deosity reooos<itutad tobacco (RTS), slurry process (1 b
` Dupllcate aatnplea ofoonttol blend SE&I1(2}
° Cantrol blend SEB-III (aoatained 3 .2 Bti glyoaol) (3).
' Olycerol omitted from control blend SEB-1II (3).
Full redum of cut rolled burley rtmn (4).
a Niontine in SFR-IV blend adjuRed iu► that dgarette delivered MS nicotine at 1 .0 mg/ciQl. (4).
" SEB-IV blend with 1 .3l5 of m additive to reduoe MS iartstion.
' MS "ur' and nicotine deiamined by the FTC prooedure .
BaP - benno[a]pynaw t BaA - benz[a]anthraome
~ Subeaquaot HCN malyua for the 2nd, 3rd, and 4th series involved an improved and more accurate analytical prooedura
° Becauae of analytical problem . HCN data from SEB-1 samples were omitted from ranga
In the original e epocts, nrtrogien oiddea were expnxsed as NO= . Sinoe it has been demwstrated that more than 95 %
of the nitrogen oxides in tobacco smoke is nitric oxide (NO) (5), the nitrogen oxddes data were recalculated accordingly .
Table 2
Variations in Mainstream Smoke Composition for Cigarettes Delivering 25 .5 f 0 .4 mg of "Tar"

tlaaavtolCiai Nu. jx 11-53~ ID-73` -ITI g2° fII-93e IV-13t IN'-29a [uV,-32a $em

Per Cigarette Detivery

"tar" ° mg 25 .9 25 .9 25 .5 25 .5 25 .1 25 .4 25 .1 25 .7 25 .1-25 .9
`har"PYarW3 " 1 .016 1 .016 1 .000 1 .000 0.984 0.996 0.984 1 .008
nivulvne ° mg 1 .68 0 .38 1 .67 1 .78 1 .18 0.16 2.02 1 .91 0.16-2 .02
"lar'Yniaatide 15.4 68 .2 15 .3 14.3 21 .3 158.8 12.4 13.5 12 .4-159

.4mount ofComponent Relative to "Tar"

BaP I µg/g 0.72 0.54 1 .06 1 .16 1 .56 0.76 0 .78 0 .66 0 .54-1 .56
BoAJ µglg 1 .20 0.87 1 .56 1 .54 2 .35 1 .03 1 .05 1 .72 0 .87-2 .33
pheaol mg/g 4 .35 3 .26 4.05 4 .89 3 .71 4 .99 4 .44 3 .53 3 .26-4.99
otresol mg/g 0.78 0.57 0.86 0.82 0 .73 0.40 0 .59 0 .63 0 .40-0 .80
aataldehyde 41 .1 35.0 46.0 41 .8 36 .7 30 .6 39,2 39 .3 30.6-46.0

HCN ~gg 7 .e 11 .3 12.6 12 .0 9.7 11 .1 12 .7 12 .6 9.7-12 .7'


NO ° mg/g 9 .2 2.0 10.5 10.8 7 .4 10.9 11 .4 11 .4 2.0-11 .4

Technology fmrutlgated .• other nota:

' Cigarotte faFxioetad with SRR-1 Mend and medium panMity, citrrtetrcated parer (1).
° Cigaralte fabricated with Iow-0loat6te flue aued tobacco grown with nonnal nitrogea feftifuatian (2) .
' Contr+ol SE&III blend (3).

• ° SEB-III blend with added cocoa (1 .0 %) (3).


' Tobaoco subatituta (Cytrelm):SEB-III blard - 30:70 (3).
~ Datioatiaized SEBd1I blend (3) .
' SEB-IV control blend (4) .
h MS "tar" and niootitta detecmined by the FTC prooedure .
' BaP - beivo[a]pyrene ~ BaA - benz[a)anthraane
k Subsequent HCN analysea for the 2nd, 3rd, and 4th series involved an improved and more aoourate analytial
p~a
' Hecaux of analytical problem, HCN result from SEB-1 sample 1-2 was omitted from range .
'" In the origina/ repocts, nhrog,ea o)ddes were expressed as NO3 . Sinx it has been demaostnnad that more tban
95% of Ihn nilrulgnn uxides 6n tubauw wrxukn ia nilriu oxide (NO) (S), the nilnVe oxidex data were reuslwlatexl
aooordingly.

~ . Gori, G .B. (Editor) Report No . 1. Toward Less Hazardous Cigarettes. The FJrst Set of Experimental
Cigarettes. DHEW Publ. No . (NIH) 1976, 76-905 .

2. Gori, G .B. (Editor) Report No. 2. Toward Less Hazardous Cigarettes. The Second Set of
Experimental Cigarettes. DHEWPubI. No. (NIH) 1976, 76-1111 .

3. Gori, G.B. (Editor) Report No. 3. Toward Less Hazardous Cigarettes The Third Set of Experimental
Cigarettes. DHEW Publ. No. (NIH) 77-1280.

4. Gori, G.B . (Editor) Report No. 4. Toward Less Hazardous Cigarettes. The Fourth Set of Experimental
Cigarettes. DHEW PubG (NIH) March (1980) .

s. Cooper P.J. ; and Hege, R.B. The Oxidation of NO to NO= in Cigarette Smoke . 32nd Tob . Chem. Res. Ln
Conf., Montreal PQ, Canada, 1978 : Paper No . 34 . N
~
N

CO
m
-j
Table 3
Component:"Tar" Ratios of Deliveries of Selected Components in Fresh Mainstream Smoke
from Commercial Cigarettes Designed to Yield Different "Tar" Levels'

AnalytelCigt . Type Cigt A (NF) b Cigt B (F) Cigt C (F) Cigt D(P17

Per Cigarette Delivery

"tar" mg 20.1 15 .6 6 .8 0.90


nicotine mg 2 .04 1 .50 0 .81 0.15

Amount of Component Relative to "Tar"

"tar" g/g 1 .00 1 .00 1 .00 1 .00


nicotine 919 0 .10 0.10 0 .12 0.17
benzo[a]pyrene µg/g 1 .30 1 .14 1 .79 2.44
N-nitrosodimethylamine µg/g 1 .55 0.20 1 .78 4.46
N-nitrosopyrrolidine µg/g 3 .21 0.65 4 .81 14.67
N'-nitrosoanatabine + 6.37 47.69 77.06 113 .3
N'-nitrosoanabasine µg/g
.N'-nitrosonornicotine µg/g 50.10 31 .28 40.15 73.67
4-(N-methylnitrosamino)-1- 21 .14 11 .54 8 .26 19.22
(3-pyridinyl)-1-butanone µg/g
catechol mg/g 2.08 4 .56 3 .96 10.11

' Dats from Adanu et aL (g .


"NF - nao6haed dgarene; F - 6ha4ipped aguatta
PF - perfaated 6halippad dgaette

~ . Gorl, G.B . (Editor) Report No . 1 . Toward Less Hazardous Cigarettes. The F7rst Set of Experimental
Cigarettes. DHEW Publ. No. (NIH) 1976, 76-905.

2. Gori, G.B. (Editor) Report No. 2. Toward Less Hazardous Cigarettes . The Second Set of
Experimental Cigarettes. DHEW PubL No. (NIH) 1976, 76-1111 .

3. Gori, G .B . (Editor) Report No. 3. Toward Less Hazardous Cigarettes. The Third Set of Experimental
Cigarettes. DHEW PubL No. (NIH) 77-1280.

,. Gori, G .B. (Editor) Report No. 4. Toward Less Hazardous Cigarettes. The Fourth Set of Experimental
Cigarettes. DHEW Publ. (NIIQ March (1980) .

s. Cooper P.J. ; Hege, RB. The Oxidation of NO to NOZ in Cigarette Smoke . 32nd Tob. Chem . Res.
Conf., Montreal PQ, Canada, 1978 : Paper No. 34.

6. Adams, J .D. ; O'Mara-Adams, K.J. ; Hoffmann, D . To)dc and carcinogenic agents in undiluted
mainstrcam smokc and sidcstrcam smoke of different typcs of cigarittcs . Carctnogenesis 1987, 8,
729-731
TABLE 1A : VARIATIONS IN MS COb1FOSITION FOR CIGARETTES
DELIVERING 27.2 ± 0.2 mg OF "TAR"
AxWYtc/Sjai .Ns, L-o: L-= I-C II-W IDZ4°. ID w 1.:3e w-31' e Am
Per Qgareae Dellrery

"ur"' cog/ci8t 27 .4 27.4 27 .3 27 .4 27 .4 27.3 27 .0 27 .1 27.2 27.0-27 .4


•'ur' y' 4ary,e„ 1 .007 1 .007 1 .004 1 .007 1 .007 1 .004 0.993 0.996 1 .000

nkotinet mg/clgt 2.07 1 .39 1 .93 1 .80 1 .80 1 .91 3 .25 0.99 1 .94 0.89-3 .25

"ar"/nicotine ratio 13 .2 19 .7 14.1 13 .2 15 .2 14 .4 8 .3 30.4 14.8 8 .3-30.4

Amount oJ Component Re(ative w'7or••

BaPi Itg/j* 0 .91 0 .68 0 .58 0.79 1 .04 1 .18 0 .72 0 .82 0 .64 0 .58-1 .18

BaAt µg/g 1 .40 0 .92 1 .08 0 .90 1 .49 1 .64 1 .01 1 .00 1 .42 0 .90-1 .64

phenol aWg 3 .95 2 .98 3 .83 3 .90 4.28 4 .62 4 .88 3 .07 6 .10 2 .98-0 .10

ocrerol mg/= 0.72 0.51 0.62 0 .63 0.77 0 .79 0.72 0.57 ad 0 .31-0 .79
aceWdehyde ng/g 39 .1 42 .6 37.9 36 .1 38 .4 39.9 19 .6 25 .1 34 .9 19 .6-42 .6

HCN n4g/j 6 .11 4.21 12.2 12 .0 13 .3 12 .1 9.8 13 .0 12 .5 9 .8-13 .3°

NO' aS/j 9 .6 8 .0 9 .4 8.7 10.8 10 .0 33 .7 11 .3 12 .8 8 .0•33 .7

Technofogy tnvrrdgaad; other norer:

• 1-6 coataiued double the nitrate level of control biend S8&I (God, 1976a) . I so 3~ ~
b High density reconstituted tobacco (ATS), slurry procew (God, 1976a) .
° Duplicate samples of control blend SBB-11(Ciod, 1976b) .
e Control blood SB&lII (contaiaed 3 .2 !i glyceroq (Ooei, 1977) . ~ C L ~ J
• Olyceroi omitted fmm control blood S88-m (God, 1977) . i S1 ~
r Full retura of cut rolled burley aems (()ori. 1980) . ~ S 3
s Nieotine In SB&N blood adjusted so that eigareua delivered MS nicotine at 1 .0 mg/cigt (Ciorl, 1980) .
~ S8B-N blood .vith 1 .5 % of an additive to reduce MS irdtation .
t MS "tar" and aicodns determined by the FTC procedure .
J B.P = benzo(aJpyeww k BaA - beoz(a)aat6ncane
~ Sub .equent HCN aaalysas foe the 2nd, 3rd, and 4th asria involved an iaaproved and nwn accurate analytical procedure .
m Becauss of analytical probbm, HCN data fi= S88-1 smopies Mm omitted 6om raa`e .
° In du oeiSiaal roports, aioropa osid .a .rorev exprewd as NOp Sioce it hu been deawa°trated that more than 9S9i of the
nitrogeu oxides In tobacco soatA is s3teia oxide (NO), dw nierojea oxides data were recalculated aoooedaqtly .

In the same NCI study, another set of eight cigarette samples whose "tar" yields were
equivalent at 25 .5 f 0.4 mg showed similar disparate compositions in their MS particulate and
vapor phases (Table IB) .

12
TABLE 1B : VARIATIONS IN MS COMPOSITION FOR CIGARETTF.S
DELIVERING 25.5 t 0.4 mg OF "TAR"
,AnaIXJ2/S' .tio. L-Z D'- r L3£9 IYUL& Bi!oe4
Per agarette Deuvery

"tar"e mg/cigt 25 .9 25 .9 2S .S 25 .5 25 .1 25 .4 25 .1 25 .7 25 .1-25 .9

"tar"/"urtp,.q•' 1 .016 1 .016 1 .000 1 .000 0 .984 0 .996 0 .984 1 .008 ~


~ ;.
nicotined mg/cigt 1 .68 0.38 1 .67 1 .78 1 .18 0 .16 2 .02 1 .91 0 .16-2 .02
"tar"/nicotine ratio 15 .4 68.2 15 .3 14 .3 21 .3 158 .8 12 .4 13 .S 12 .4-158

Amount oj Compor+ent Relatrve to "Tar"

Ba0 µg/g 0 .72 0 .54 1 .06 1 .16 1 .56 0 .76 0 .78 0.66 0 .54-1 .56

BeAI µg/g 1 .20 0 .87 1 .56 1 .54 2.35 1 .03 1 .05 1 .72 0 .87-2 .35

phenol mg .r .".,3; 3 .26 4.055 4 .89 3 ;71 4,99 4 .33 3 .53 3 .26-4.99•

acreaol mg/g 0 .78 0.57 0 .86 0 .82 0.73 0 .40 0 .59 0 .63 0.40-0 .80

acetaldehyde mg/g 41 .1 35 .0 46 .0 41 .8 36 .7 30 .6 39 .2 39 .3 30 .6-46 .0


9.I .' I

HCN mg/g 7 .8k 11 .3 12 .6 12 .0 9 .7 11 .1 12 .7 12 .6 9 .7-12 .7'

NO1O mg/g 9 .2 2 .0 10.5 10 .8 7 .4 10 .9 11 .4 11 .4 2 .0-11 .4

Technology tnvest/gated; other notes:

' Cigarette fabricated with SEB-I blend and medium porosity, citrate-treated paper (Gori . 1976a) .
b cigarette fabricated with low-nicotine flue cured tobacco grown with normal nitrogen fertilization (Oori, 1976b) .
° Control SEB-III blend ~(t3~ori, i~~'7):
e SEB-III blend with addZd-o" (1 .0 %) (Gori, 1977) .
• Tobaceo substitute (GytreN) :SEB-m blend - 30:70 (dori, 1977) .
t Denicotinized SSB-III blend (Qod, 1977) .
a SEB-IV control blend (God, 1980) .
b MS "tar" and nicotine determined by the FfC procedure .
I BaP - benzo[alpyrene 1 BaA - benz[a)anthracene
4 Subsequent HCN anaiyaea for the 2nd, 3rd, and 4th aeriea involved an improved and more accurate analytical
procedure.
t Beeau.e of analytical problem, HCN result from SEB-I sample 1-2 was omitted from range .
m In the original reports, nitrogen oxldes were expressed as NO= . Since it has been demonstrated that more than 9596
of the nitrogen oxides in tobacco smoke ia nitric oxide (NO), the nitrogen oxides data were recalculated accordingly .

Cigarette design technologies for the cigarettes listed in Tables 1A and 1B included RTS
inclusion, stem inclusion, tobacco substitute inclusion, nitrate enhancement, humectant (glycerol)
effect, tobacco additives, e .g., cocoa, nicotine adjustment, use of high porosity citrate-treated
cigarette paper . Several of these together with other technologies (expanded tobacco, perforated
filter tips, filter-tip additives) have been used in concert and to different degrees to attain specific
"tar" yields . ranging from 0 .1 to over 40 mg .

Another anomaly ignored was the fact that the "tars" from different types of cigarettes
i .e ., those cigarettes rated ultralow-, low-, medium-, and high-"tar" on the basis of "tar" yields
• determined by FTG analysis, may be quite different compositionally . The consumer smoking a
15-mg "tar" cigarette is inhaling "tar" entirely different in composition from the "tar" in the

13
MS of a cigarette whose "tar" yield is 20 mg or 7 mg . Examination of the data (Adams et al.,
1987) in Table 2 for four different U .S. commercial cigarettes indicates the significant variations
in individual component : "tar" ratios for several MS components of interest .

TABLE 2: COMFONENT :"TAR" RATIOS OF DELIVERIES FOR


SELECTED COMPONENTS IN FRESH MAINSTREAM
SMOKE FROM COMMERCIAL CIGARETTES DESIGNED
TO YIELD DIFFERENT "TAR" LEVELS'
CiQt A(NF1° Cigt B (F) Cigt C (F) Cigt D(PF)

Per Cigarette Delivery


. . r„ mg/cigt 20.1 15 .6 6 .8 0 .90
ta

nicotine mg/cigt 2 .04 1 .50 0 .81 0 .15

Amount of Component Relative to "Tar"


. .tar,t g/g 1 .00 1 .00 1 .00 1 .00

nicotine g/g 0 .10 0.10 0 .12 0 .17

benzo[a]pyrene Ng/g 1 .30 1 .14 1 .79 2 .44

N-nitrosodimethylamine Ng/g 1 .55 0.20 1 .78 4 .56

N-nitrosopyrrolidine .Ug/g 3 .21 0 .65 4 .81 14.67

N'-nitrosoanatabine +
N'-nitrosoanabasine llg/g 6 .37 47 .69 77 .06 113 .33

N'-nitrosonornicotine IiS/g 50 .10 31 .28 40.15 73 .67

4-(N-methylnitrosamino)-1-
(3-pyridinyl)-1-butanone Ng/g 21 .14 11 .54 8 .26 19 .22

catechol mg/g 2 .08 4 .56 3 .96 10 .11

' Data from Ad .ma er al . (1987) .


b NP - nonfiltered ; F- filtered; PF - perforated filter

14
III. REPRODUCIBLE ANALYTICAL METHODS

Between the Bradford et al. (1936) publication and the implementation of the FTC
smolring method for the determination of cigarette MS "tar" and nicotine yields, there were
other analyses used for this purpose . The details of the five most commonly used procedures are
summarized in Table 3 . Other details of these procedures plus comments on the events occurring
at the time of the FTC's involvement in the "tar" and nicotine labeling are summarized in
Appendix B .

TABLE 3 : METHODS FOR DETERMINATION OF TOTAL SOLIDS AND NICOTINE

L&M Tobacco Co .
Method (Keith and
The Consumer Newsome, 1956,
Union's Method Cambridge Filter 1957, 1958 ;
Smoking Wolman Method (Consumer Method (Wartman Foster D . Snell Newsome and Keith,
Condjtiona, ete . (Wolman . 1953) Reoorta . 1955) sr al. . 1959) Method (Kimball) 1936 . 1957)

cigarette length 47 variable ; depends 47 variable ; depends variable ; depends on


smoked, nvn on length of on length of length of cigarette
cigarette being cigarette being being tested
tested tested

butt length, mm variable ; depends 23 variable ; depends 23 variable ; depends on


on length of on length of length of cigarette
cigarette being cigarette being being tested
tested tested

number of puffs number required to number required to number required to number required to 14
consume 47 mm of attain 23-mm butt consume 47 nun of attain 23-mm butt
cigarette length cigarette length

puff volume 33 35 35 35 44

puff duration 2 .0 2.0 2 .0 1 .9

puff frequency, I 1 1. 1 2
no ./min

lab temp ., °C 25° not specified not apecified not specified 23 .90

lab RH, %- 45% not specified not specified not specified 60%

cigarettes smoked 5 8 10 5 10'


per determination

cigarette selection selected for selected for selected for selected for selected for
uniformity in uniformity in uniformity in uniformity in uniformity in
moisture content, moisture content, moisture content, moisture content, moisture content,
cigarette aize (if cigarette aize (if cigarette size (if cigarette size (if cigarette size (if
feasible), weight, feasible), weight, feasible), weight, feasible), weight, feasible), weight,
firmneu, and other firmness, and other firmness, and other firnuxaa, and other firmness, and other
chancteriatica characteristics characteristics characteristics characteristics

15
Table 3. Continued :

L .dcM Tobacco Co .
Method (Keith and
The Consumer Newsome, 1956,
Union's Method Cambridge Filter 1957,1958 ;
Smoking Wolman Method (Consumer Method (Wntnun Foster D. Snell Newsome and Keith,
Conditions, etc . (Wolman . 1953) Reoons. 1935) er o1 . . 1959) Method (Kimball) 1956, 1957)

determination of SoHds (designated Smoke for deter- Cigarette MS Is To determine soUds The smoke in this
total solids as tars in the mination of both collected on a glass (tar content In the method is retained
publication) are nicotine and solids fiber filter material, communi-cat'wn), on an a-cellulose
determined by Is absorbed in Cambridge filter smoke is collected trap . The a-cellulose
gravity deposition acidified alcohol . medium CM-1 13 . in acidified alcohol . Is washed with hot
of smoke over 25 One portion of the The weight of The alcohol acidic methanol . The
m1of0.1N acidified alcoholic material retained in solution Is heated solution Is extracted
sullbric acid . The solution Is diluted the filter represents on a steam bath with chloroform . To
mixture is extracted with water, then total solids (total (100'C) to deter-mine soUds
with chloroform, extracted with particulate matter) . evaporate the (termed tar in the
and the chloroform chloroform. The Part of the material alcohol. After publications), the
extract Is heated to aqueous layer ia retained on the about 5 hr, the chloroform solution
evaporate the nude alkaline and Cambridge filter Is residue is heated in is evaporated on the •
chloroform . The re-extracted with water. Thus . this the beaker at steam bath and
residue Is then chloroform. The method includes 105°C for 7 hr. heating is continued
heated, or dried, two chloroform water In the value The weight of for 3 hr at 105°C .
for 3 hr at 100°C. extracts are com- for total aolida, material remaining Tar value is
The weight of bined, and the whereas the in the beaker Is determined by
remaining material chloroform Wolman Method designated as the weighing the
after the heating ia removed by and the Consumers tar content. residue .
reported as tars . evaporation to yield Union Method do
the tar, which Is not. .
weighed .

determination of Solids for deter• Another portion of To determine To determine The extracted
nicotine mination of the acidified nicotine, the nicodne, an aliquot methanol solution is
ntcodne are alcoholic solution is Cambridge filter of the acidified made alkaline and is
collected over 10 treated with base with the retained alcohol solution steam-distilled .
ml alcohol acidified and steamdistilled . solids is extracted containing the Mcodnt is deter-
with sulfuric acid Mcodne in the with 0.1 Nsulfuric smoke solids is mined In the steam
in a 300-m1 steam distillate Is acid . The solution, heated to remove distillate spectro-
1Cjeldahl flask. measured spectro- after washing with the alcohol, the photometrically.
Solution ia treated photometrically. chbroform, Is residue Is made
with alkali and then made alkaline and alkaline and Is
steam-distilled . The Is steam-distilled. steam-distilled.
distillate Is treated Nicotine in the Wlcodns is deter-
with silicotungstlc steam distillate Is mined gnvimetri-
acid to precipitate determined either cally in the steam
the silicotungaute . by the aiGcotungstio distiWte (siGco-
The silleotungatate acid method or by tungstic acid
Is aeparated and Is the spectrophoto• method) .
ignited to an ash metric method .
whose weight Is
used to calculate
the nicotine valueb .

' The authors recommended that three to six such determinations be carried out and the results averaged .
b Since other alkaloids coprecipitate with nicotine as silicotungstates, thia determination yields the alkaloid or total alkaloid
value .


16
Table 4 summarizes the chronology of the various analytical procedures proposed and
used for the determination of cigarette MS "tar" and nicotine yields .

TABLE 4: MAINSTREAM SMOKE "TAR" AND NICOTINE DETER-


MINATIONS
The Pre-FTC Era' The FTC Era T6e Ultralow-"Tar" Era
Wolman Method (Wolman, 1953) FTC Methodab (FPC, 1%7a) Spectrophotometcic Methodad : For
determining "tar" yield of cigarettes
designed to deliver < 2 mg/cigt

Consumer Union's Method - No . I ISO Methods (ISO, 1986, 1987s, 1987b,


(Consumer Reports, 1955) 1989a,198b)

Cambridge Filter Method (Wartman et al., CORESTA Methods (CORESTA, 1966s,


1959) 1966b, 1966c, 1966d, 1969s, 1969b,
1986, 1987, 1989s, 1989b)

Foster D. -Sneil MethoJ (Kimball)° DIN Methods (Verband, 1965)

LecM Tobacco Co . Method (Keith and UK Methods (Bentley and Burgan, 1961)
Newaome, 1956, 1957, 1958; Newsome
and Keith, 1916, 1957)

' For complete details on these five methods, aee Appeodt : B .


b FTC methods Incotporate contributions of Bradford et al. (1936), Griffith, (1957), Wartman et ol . (1959), Ogg et al .
(1960, 1962), Ogg (1964) ; rf. Bates et al . (1967, 1%8) .
° 7he Reader'r Digest (Riia, 1950; Norr, 1952; Miller and Monahan, 1957s, 19S7b, 1957c, 1958s, 1958b, 1959, 1961, 1966,
1968• ; Miller, 1958, 1%2 ; Ratcliff, 1959) in ita continued attack against cigarette smoking had retained Foster D . Snell,
Inc . to determine the "tar" and nicotine yields from U .S . (Miller and Monahan, 19S7b, 1958s, 1958b, 1959, 1961, 1966)
and Canadian (Miller and Monahan, 1957c) cigarettes .
d For details on these methods, aee Appmdbc C .
• in thia article, Miller and Monahan (1968) cite FTC (6TC, 1968) not Foater D . Snell data .

IV. DI]FFERENCES BETWEEN FTC AND OTHER METHODS

Debardeleben et al . (1991) presented a very fine review of the determination of "tar"


and nicotine in cigarette smoke from an historical point-of-view . They included discussion of the
following topics and how certain procedures eventually were included in standard methods of
analysis such as the FTC procedure and the CORESTA and ISO procedures :

• Smoking machines

• Smoking parameters

- the origins of puff volume, puff duration, puff interval, butt length'=

• Smoke trapping systems (cold traps, Cambridge filter pad)

12 DeBardeleben et al . (1991) nude no mention of the depth of insertion of the cigarette into the cigarette holder . It was eventually set at
I 1 nun (7/16 in) . This insertion depth ensured that in most products with perforated filter tipa, the perforations were not covered, i .e . .,
the perforations were external to the cigarette holder .

17
~ Analytical procedures

- water (Karl Fischer titration, gas chromatography)


- nicotine (silicotungstic acid method, spectrophotometric methods,
titration, gas chromatography) .

Table S summarizes information from Bradford et al . (1936), Wynder and Hoffmann


(1967), Johnson (1986), DeBardeleben et al., (1991), and others on the similarities and
differences in the smoking parameters used by various investigators or institutions in the
determination of cigarette MS "tar" and nicotine .

Table 6 compares the smoking and parameters and analytical procedures prescribed for
use by the cigarette manufacturers (Bates et al ., 1967, 1968), by the USDA (Ogg et al ., 1964),
and by the FTC (1967b).

18
(A

TABLE 5: SMOKING PARAMETERS PRESCRIBED FOR USE IN VARIOUS


DETERMINATIONS OF CIGARETTE MS "TAR" AND NICOTINE

Source
p~ Bradford CORESTA 24 PPl 3m 4Qe FM
puff volume, ml 35 35 t 0 .3' 35 33 35 3S t 0.5 35 t 0 .5
33 t 0 .25"
puff duration, .ec 2 .0 1 .8-2 .2 f 0 .0t3' 2 2 2 2 t 0.2 2 t 0 .2
2 .0 t 0.05b

puff fcequency, puff/min 1 1° 1 1 1 1' l


bua lenyt6, mm 23 23 23 23 20 30 23
OW + 3• OW + 3• OW + 3' OW + 3a OW + 31 OW + 3'
F+81 F+Br F+Bt OW+Sh
air flow, mVaec 17 .5 17.5 17.3 17.5 17.5 17 .5 17 .3

aample aize, no . of ci8areaea 200 100

ia.eRion depth, mm 11 11
TPM trappinp tyatem CFI+i CFFi CF14 CFFi CFpi CFpi
SSPti BSFt ESpk

TPM water analyaia llC' Oct Oct Oct OC1 Oct


KFl• KEtm KFI° K1tN KFl° KF I°

TPM nicotine andyaia STAF" GC1 QC1 ClC! Od OCi ad


OSpo OSpo

laboratory conditions 22'C 22'C 22'C 22•C 23 .9'C 23 .9'C


60% RH 60% RH 60% RH 60% RH 60% RH 60% RH

ci8arette conditioning 22'C 22•C 22•C 22'C 24 hr @ 24 hr 0


60% RH 60% RH 60% Wi 60% RH 23 .9'C 23 .9'C
60% RH 60% RH

' ptrior w 1989 ` Atter 1989


° 1 puff every 60 t 1 aec ° 1 puff every 60 t 0 .5 aac
• OW - overanp ; 23 mm or overweap + 3 mn% whichever Ia longer
r F - flher ; 23 mm or Sher + 8 mm, whichever Is loag .r
e For cipralba s 75 nM 20 aom a oveewpp + 3 me% whichever ia lon8er
k For ci8aauea > 75 mm,10 mm ar ovenvap + 5 mm, whichever ia looSer
1 OW m overnc .pp 30 mm or aver.vrap + 3 mm, whichever ia lon`er
J CFP - Cambridje mter pad k BSP ~ electroatado precipitation
~ OC - gas cbromatojrapby ~ KFT ~ Karl Fiacber BtnBoo
e BTAp - ailioowo8 .dc aaW pencedur.
o OSP - OeitFith still procedure. 'lbis procedure was uaed for war yean In the U .S . but .vaa
replaced by a ps cbeom .w;eapbio met6od, wbsequeofly approved by the FTC

19
TABLE 6: COMPARISON OF SMOKING PARAMETERS PRESCRIBED FOR
USE BY THE TOBACCO INDUSTRY (BATES et al, (1967, 1968),
OGG et ot. (1964), AND THE FTC (1967b) IN THEIR
DETERMINATIONS OF CIGARETTE MS "TAR" AND NICOTINE

Source

Parameter Bslgs ti.el, 2u Fn


puff volume, ml 35 t 0.5 35 t 0 .5 35 f 0 .5

puff duration, sec 2 .0 t 0 .2 2 ± 0.2 2 ± 0 .2

puff frequency, number l per 60 ± 1 I per 60 ± l I

butt length, mm NP: 23, 30b, or 47 NF : 30 NF - 23


F- OW+3° F:OW+3° F- OW+3d
F+OW+3°

air flow, ml/sec 17 .5 17 .5 17 .5

sample size, no . of cigarettes 200' 200 100

ineertion depth, mm 11 11 1l

TPM trapping system CFFr CFFt CFFr

TPM water analysis Kb'1'e KFre K1TTe


GC6 ()Ci

TPM nicotine analysis GS>J GSFi GSPi


()Cb

laboratory conditions 23 .9 ± 1 .1°C 23 .9°C 23 .9°C


60 f 2%RH 60%RH 60%RH

cigarette conditioning variablet at 24 hr at 24 hr at


23 .9° ± 1 .1°C 23 .9°C 23 .9°C
60t2%R13 60%RH 60%RH

' NF - nonfiltered cigarette ; F - filtered cigarette


6 30 mm or overwrap + 3 nun was the preference of Bates er al (1967, 1968)
° OW - overwrap ; 30 mm or overwrap + 3 nun, whichever Is longer
d OW - overwrap ; 23 mm or ovenvrsp + 3 mm, whichever Is longer
• 40 determinationa on S cigarettes
r CFP - Cambridge filter pad
e KFT - Karl Fischer titration
b OC - gee chromatography ; the procedure of Schultz and Spears was recommended
~ Eventually a gas chromatographic procedure was implemented in the FTC procedure to
determine water and nicotine In the particulate matter
1 OSP - Griffith still procedure
k it was recommended that cigarettes be conditioned under laboratory conditions
specified until they "come to moisture equilibrium with the atmosphere of the
conditioning chamber ."

Both prior to and after the implementation in 1967 of the FTC analytical procedure for
cigarette MS "tar" and nicotine, numerous investigators reported on their determinations of total
particulate matter, water, nicotine, and "tar" in cigarette MS . References are indicated in Table
7. Surprisingly, most of the studies conducted pre-1967 dealt with methods of determining

20
TABLE 7: CHRONOLOGY OF ANALYSIS OF MS TPM AND NICOTINE AND
WATER IN MS TPM
tinatlon TPM Nicotine Determtnation TPM Water Determination
~.
Pre-193Q
~ ~ I{iaeling, 1882s, 1882b
\, Lowenthal, 1892
~ Schmidt, 1904
Theodorovita, 1905
~ Warburg, 1906
Biederbeek, .1908
\ Toth, 1908, 1909
Toth and Krampera, 1910
Van Leeuwen, 1919

Hahn and Langer, 1920


Bogner, 1921 _/n •
Popp,1922
Baumberger, 1923a, 1923b
Ptyl and Schmidt, 1927
Wenuach, 1928
Winter.tein and Aronaon, 1928

193Qs
Preiu, 1936 Bodnar, 1930s, 1930b

• Heiduachaka, 1930
Batu and Toole, 1931•, 1932a', 1932b'
Hahn and IfiriamaM, 1931
Kovalenko, 1931
Malaquin, 1931
Pydki, 1931a, 1931b, 1932 .
Wenusch, 1931a, 1931b
Heiduachaka and Poat, 1932
Molinati, 1932
Nagy, 1932a, 1932b
Hofmann, 1933°
Nagy and Dickmann, 1933a, 1933b
Pfyl, 1933a, 1933b
Pyriki, 1933, 1934, 1935
Schloumann, 1933
Toole, 1933
Kopericu, 1934
Pretu, 1934, 1935, 1936
Wenuach, 1934s, 1934b, 1934c, 1934d,
1934e, 1936a, 1936b, 1937a,
1937b
Wulfert, 1934a, 1934b
Bodnar et at ., 1935
Jensen and Haley, 1935

~
Hofmann, 1942b ~
Pyriki, 1943 ~--j
Griffith and Jefl'rey, 1948 ~'
Dabrowaka, 1949 S

tp
J
tp

21
Table 7. Continued:

TPM Nicotine Deterrnination TPM Water DeterminatioC


19SOs

Schmihl et at., 1954b Willita ct at., 1950 Cogbill et al ., 1959


Schmihl, 195Sb Marchand and Zenard, 1951 Fiahel, 1959
Schmihl and Schneider, 1955b Cundiff and Markunaa, 1953', 1955'
Keith and Newaome, 1956, 1957 Laurene and Harrell, 195Sb
Aksu and Fneroan S, 1958s, 1958b izawa and Kobashi, 1956
Morgareidge, 1958, 1959 lzawa et at ., 1956s, 1956b
Trifu and Dumitreacu, 1958s, 19S8b, Grittith, 1957d
1959 Aksu and Enercan S, 1958s, 1958b
Wartman and Harlow, 1958 Laurene and Harrell, 1958"
McConnell et at., 1959b, 1960P Mathur, 1958
Monod and DuPont, 1959 Trifu and Dumltreacu, 1958s, 1958b
Staberg, 1959 Wartman and Harlow, 1958
Wartman et at ., 1959 Kuhn, 1959b
Pleaaanta et al ., 1959b
Staberg, 1959
Waltz er al., 1959b

L2&
Bentley and Burgan, 1961 Barkemeyer and Seehofer, 1960b Crowell, 1960b
Bock et at., 1962 Ogg ct al ., 1960, 1962 Fishel, 1960
Ogg et at., 1962 Kuhn and Marek, 1961 Holmea and Cridlin, 1960
Harrell and Sullivan, 1963t Aamua et al ., 19626 Crowell et al ., 1961b
Smith and De Souza, 1963° Pyriki and Moldenhauer, 1962 Jarrell and Wickham, 1961°, 1962°
1964 biopm (fatnn/'r Reporr Artho and Grob, 1963, 1964d Ogg et al ., 1962
Ogg, 1964 Harrell and Sullivan, 19631 Harrell and Sullivam, 1963r
Okada and Shibayama, 1964b Seehofer and Borowaki, 1963a Waltz et al., 1963b
Senkus, 1960 !%{ SSageaai (ienerol'c Report 1964 b5ogoow Gsewertil'c Reporr
TTokura and Furakawa, 1964 Mann et al., 1964° Neurath et al ., 1964
Rodgman, 196Sa, 196Sb, 1965c Ogg, 1964 Okada and Shibayama, 1964s, 1964b
Yamazaki tt at ., 1965 Senkua, 1964t Sloan and Sublett, 1964°, 1965°
CORESTA, 1966a Tokura and Funkawa, 1964 Neuath, 1966
Batea et at., 1967, 1968 Lyerly, 1965a°, 1965b° Neurath er al., 1966
MOller and Moldenhauer, 1967 Pyrikl and Moldenhauer, 1965a, 1963b° Schultz and Spears, 1966°
Wynder and Hoffmann, 1967r Rodgnun, 1965s . 1965b, 1965c Thome, 196Sa°, 1965b°, 1966°
Dalhamn, 1968 Verband,1963 Bates et al., 1967, 1968
CORESTA, 1969a Yamazaki et al., 1965 Graves, 1967°
Georgiev, 1969 Lyerly and Gilleland, 1966 Wynder and Hoffaunn, 1967r
Gilea, 1969t CORESTA, 1966b, 1966c, 1966d CORESTA, 1969a
Gilea and Sullivan, 1969 Harvey et al., 1966' , 1967'
Ogg, 1969 Bates et al ., 1967, 1968
Viart, 1969 Lyerly 1967°
M811er and Molden6auer, 1967
Wynder and Hoffmann, 1967t
Dalhamn, 1968
Charles et al ., 1969b
Pillsbury et at., 1969
CORESTA, 1969b
Georgiev, 1969
Gilea, 1969r
Gilea and Sullivan, 1969
Ogg, 1969

22
Table 7. Continued :

TPM Determination TPM Nicntine Determination TPM Water Detennination


1970s
Ogg and Schulz, 1970 Cano et al., 1970° Watson et al., 1970°
Smit, 1972b Ogg and Schulz, 1970 Hartung and Stewart, 1973
Hartung and Stewart, 1973 Sadler et al., 19704 Roberta, 1975°
Norman, 1973, 1974 Diffee and Sheppard, 1971° Rix, 1979
Rothwell and Grant, 1974t Bourlas and F.aperdy, 1972b
Harbin and Stamey, 1975 Hartung and Stewart, 1973
Williamson et al., 1975 Schulz and Seehofer, 1973
Bronnemann et al ., 1976r Randolph, 1973°, 1974°
Hammond et al., 1976 Rothwell and Orant, 1970
Keith, 1976 Wagner and Thaggard, 1974°, 1979°
Owen, 1976 Diffee, 1975
Wakeham, 1976 Roberts, 1975°
Burton et al., 1977 Williamson et al ., 1975
Maeda et al ., 1978 Bourlas et al ., 19766
Rix, 1979 DeVriea et al ., 1976"
Bmnnemann et al ., 1976"
Hammond et al ., 1976
Keith, 1976
Leonetti and Carugno, 1976°
Lyerly and Greene, 1976°
Owen, 1976
Wakeham, 1976
Campbell, 1978
Oaivoromchi et al., 1978°
Maeda et al., 1978
Ma.kninec et al ., 1978a
Rix, 1979

1980.r
Hege, 1980b Shoffner and Ireland, 1980°, 1982° CORESTA, 1987°, 1989b°, 1990'
Norman et al., 1980a, 1980b McMuttrie et at., 1981 ISO, 1987a, 1987b
Thomaa, 1980b Wald et al ., 1981
Herning et al ., 1981 Yamamoto, 1981
McMurtrie et al., 1981 Baskevitch and Ferrer, 1982
Sloan and Curran, 1981b Dobbins, 1984
Wald et al ., 1981 Yamamoto et al ., 1984
Yama111100, 1981 CORESTA, 1986°, 1989b°
Baakevitch and Ferrer, 1982 ISO, 1989a°, 1989bb
Dobbina, 1984
Yamamoto et al., 1984
ISO, 1986
Johtuon,1986t
Williamson et al., 1986s, 1986b
ISO, 1987s, 1987b
CORESTA, 1989a, 1989b


23
Table 7. Continued :

TPM Determination TPM Nicotine Determination TPM Water Determination

1M
Yamamoto et al ., 1990 Ayres et at ., 1990b Deldardeleben et al ., 1991t
DeBardeleben et al., 1991t Yamamoto et al., 1990
DeBardeleben et al., 1991t
Deutach and RobeR.on, 1991°
Deutech and Jefton, 1994°

• Titrimetric method b Spectrophotometic method °(3aa chromatognphic method


d Distillation method ° Extraction method t Review
a High pressure liquid chromatograph

nicotine or total alkaloids in cigarette MS . Those described post-1967 include improved


procedures (e .g., gas chromatographic methods instead of gravimetric, titrimetric, or
spectrophotometric procedures for nicotine ; gas chromatographic methods instead of the Karl
Fischer titrimetric method for water), spectrophotometric methods for determination of "tar"
in the MS from ultralow-"tar" cigarette, automation of existing procedures, reviews, and the
like.

VI . HISTORICAL TRENDS

1956 1960 1964 1968 1972 1976 1980 1984


A. Sales-Weighted 50 3 .0
Average MS "Tar" 45
Deliveries 1711.r Tlpe
40 Raoonaututad Tobacco Sbaat
Papar Addithes
Papar Porodty
From the mid-1950s 35 i:panded Tobaaoo
through the late 1980s, the sales- V.atllatlon
30
weighted average "tar" yield of
U.S. cigarettes has declined as 25
~ . . . . . .... . . . .
shown in Figure 4 .
15 ~ • . .. ..~
This decline in "tar" yield
is the result of inclusion of various 10 - Tar
••••••••• Nicotine
combinations of these technologies 5
to varying degrees in the design of
0I I I I I L_ I I I 0.0
cigarette. As noted previously, 1956 1960 1964 1968 1972 1976 1980 1984
these technologies include :
Figure 4. "Tar" and Nicotine Deliveries, Sales Weighted Average
Basis
• tobacco blend and weight
• tobacco rod length and
circumference
• filter tips (material type and additives)

24
• processed tobaccos (reconstituted tobacco sheet, expanded tobacco)
• paper (type and additives)
• air dilution (increased paper porosity, filter tip perforations) .

In Figure 4 are indicated the approximate dates when these technologies were introduced
and subsequently became used routinely thoughout by U .S . cigarette manufacturers .

It has been noted by the U .S . Surgeon General (USPHS, 1979, 1981, 1982) that the
following changes in the properties of the "tar", actually CSC, accompanied the decrease in
sales-weighted average "tar" produced by inclusion of the various technlogies in cigarette
design:

• The BaP per mg of CSC decreased over the same time period .

• The tumorigenicity, as measured in mouse-skin painting studies, of the MS "tar" (CSC)


decreased over the same time period .

B . Sales-Weighted Average MS Nicotine Deliveries

From the mid-1950s through the late 1980s, the sales-weighted average nicotine yield of
U. S. cigarettes has declined as shown in Figure 4 .

This decline in per cigarette nicotine yield is also the result of inclusion of the various
technologies to varying degrees in the cigarette design .

VII. EFFECT OF VARIATION OF MAJOR SMOKING PARAMETERS ON FTC MS


"TAR" AND NICOTINE YIELDS

An individual cigarette smoker generally does not consume his/her cigarette by the major
smoking parameters (puff volume = 35 ml, puff duration = 2 sec, puff frequency = 1 puff/60
sec) defined for use in the FTC smoking procedure . Data are available from several RJRT in-
house studies to show the effect on MS cigarette "tar" and nicotine yields of keeping two of the
three parameters constant and varying the third .

In 1979, Rix (1979), using Response Surface Methodology, conducted a detailed study
on the effect of puff volume, duration, and frequency on puff number plus the MS TPM, MS
nicotine, MS water, MS "tar," and MS carbon monoxide yields from 85-mm Winston and
Marlboro cigarettes . Table 8 summarizes the 'tar" and nicotine data on the 85-mm Winston .
"Tar" and nicotine yields are increased by increasing the puff frequency and by increasing the
puff volume. Examination of the data in Table 8 reveals that of the three major parameters
changes in the puff duration have the least effect on MS "tar" and nicotine yields: See
comparisons of Sample No . 17 vs Sample No . 18 and Sample No . 1 vs Sample No. 3 where the
puff durations of 1 .5 vs 2 .5 sec were studied .
TABLE 8: THE EFFECT OF VARIATION IN SMOKING PARAMETERS (PUFF VOLUME,
DURATION, FREQUENCY) ON THE FTC "TAR" AND NICOTINE YIELDS
FROM AN 85-mm W7W!nN
Puff Puff Puff FTC FfC No . of
Samole No. Volume, ml Duration, sec Freauencv "Tar" . ma tlicotine . ma rt

16 35 1 .5 30 42 .1 2 .26 15 .2

1 3S 1 .3 60 23 .7 1 .60 9 .3

16 35 1 .5 30 42 .1 2 .26 15 .2

17 60 1 .5 30 62 .2 2.85 12 .2

2 3S 2 .S 30 38 .7 2 .31 13 .5

18 60 2 .S 30 61 .1 2 .72 11 .4

3 3S 2 .S 60 24 .1 1 .43 9.1

20 60 2 .5 60 41 .8 1 .96 8.4

11 47.5 2 .0 30 43 .9 2 .21 10 .8

S/l0° 47 .5 2.0 45 40 .7 2 .11 10 .3

47 .5 2 .0 60 32 .4 1 .81 8 .2

13 26 .3 2 .0 43 24 .0 1 .48 12 .5

S/lOb 47 .5 2 .0 45 40 .7 2.11 10.3

14 68 .8 2 .0 4S 50 .7 2 .31 9 .1

2 35 2 .5 30 38 .7 2 .31 13 .5

© 35 2 .S 60 24 .1 1 .43 9 .1

18 2 .S 30 61 .1 2 .72 11 .4

20 2 .S 60 41 .8 1 .96 8.4

17 60 1 .5 30 62 .2 2 .85 12 .2 cn
N
18 60 2 .5 30 61 .1 2 .72 11 .4 J
N
m
~
OD
26 W
Table 8. Continued :

l 35 1 .5 60 23 .7 1 .60 9 .3

3 35 2 .5 60 24,1 1 .43 9 .1

' Data are from Rix (1979) who also presented similar data for the 85-mm Marlboro . Rix also presented data on the
yields of TPM, TPM water, and carbon monoxide .
b Data represent the average "tar^ and nicotine yields from Samples Noa . 5 through 10.

Rix (1979) also compared the effect on the carbon monoxide, nicotine, and "tar" yields
from the 85-mm Winston and 85-mm Marlboro of changing the major FTC smoking parameters
(35-m1 puff volume, 2 .0-sec puff duration, 60-sec puff frequency) to more "realistic""
smoldng conditions (65-m1 volume, 2 .0-sec duration, 45-sec frequency) . Table 9 summarizes
the results obtained . At the higher puff volume and frequency, the % differences between the
Winston and the Marlboro become less for MS "tar" and nicotine yields, with the Winston yield
being the higher . In the 150-page report by Rix, there are numerous plots of the relationships
between carbon monoxide, nicotine, and "tar" yields and puff volume, duration, and frequency
for the 85-mm Winston and Marlboro . Also included are plots (2-sec puff duration, 1 puff/min)
of the "tar"/nicotine ratios vs puff volume for the following brands : Winston, Camel, Vantage,
Now, More, Real, and Marlboro .

TABLE 9 : 85-mm WJVSTiDN AND MARl.8OR0: COMPARISON OF FTC CARBON


MONOXIDE, NICOTINE, AND `-TAR" YIELDS AT STANDARD AND MORE
"REALISTIC" SMOKIING PARAMETERS
FTC "Tar", FTC Nicotine, FTC CO, "Tar"/Nicotine
cjgg agg ale/ciat me/ciet m !Q Ciat Rado

FTC smokfng condidons (3J-ml pkQ', 2.0-sec puff durotion, one pi}D'every 60 see)

WAsron 20.6 (20.9)' 1 .43 (24 .3) 19 .1 (15 .2) 14.4 (-4.8)

Marlboro 16 .3 1 .08 16 .2 15 .1

' ReallsNe" snaokIng eondidons (6J-rnd pqf. 2.4see pr}Q'durotion, one pr{Q'every 45 sec)

Wlnsron 35 .7 (15 .7) 2 .35 (16 .8) 33 .9 (15 .3) 13 .2 (-2 .6)

Marlboro 30.1 1 .93 28 .7 15 .6

' Numbers in parentheses represent % difference between WINSTON and MARLBORO :

% Difference - 100(Wtnsron - Marfboro)l Wlnrton

In a similar study on the 100-mm Winston and the now defunct 120-mm Dawn, Dobbins
(1984) elected to vary the puff volumes at different puff frequencies with the puff duration

• 13 Whether the "realistic" conditions for 1979 smokers would apply to current (1994) smokers is not known . Two years later, Henning et
at. (1981) observed that filter cigarette smokers took a 35 .9- to 47 .8-m1 puff of 1 .94 to 2 .06 wc every 26.9 to 30 .0 sec .

27
• maintained throughout at 2 .0 sec because of the findings of Rix (1979) on the minimal effect of
variation in puff duration . His data on number of puffs plus MS "tar," and MS nicotine yields
are summarized in Table 10 . In addition to the data summarized, Dobbins also reported the MS
TPM and TPM water yields for the cigarettes . The effects of variation of puff volume (puff
duration and puff frequency constant) and puff frequency (puff volume and puff duration
constant) observed for the 100-mm Winston and the 120-mm Dawn were similar to those
reported by Rix for 85-mm Winston and 85-mm Marlboro .
Herning et al.
Sm4king Parameter Rix (1979) Dobbins (1984) (1981)
,
cigarette type 85-mm filtered cigarettes 100-mm and 120-mm smokers of filtered
filtered cigarettes cigarettes

puff volume, ml 26 .3, 35 .0, 37 .5, 15, 25, 35, 40, 45, 55 35 .9-47 .8
60.0,68 .8
puff duration, seo 1 .15, 1 .5, 1 .0, 2.5, 2 .85 2.0 1 .94-2.06
puff frequency, sec 30, 45, 60 30, 45, 60 26 .9-30 .0

28
TABLE 10: THE EFFECT OF VARIATION IN SMOKING PARAMETERS (PUFF VOLUME,
FREQUENCY) ON THE FT C "TAR" AND NI COTINE YIELDS FROM A 100-mm
W11VSTrIN
Puff Puff Puff RCC FTC
Volume. ml fluration. aeo Freauencv "Tar" . me Nicotine, mQ No . of Puffi

15 2 .0 30 13 .5 1 .08 20.7

1S 2 .0 45 10 .0 0 .81 15 .2

15 2.0 60 7 .8 0 .63 12 .0

2 .0 30 23 .2 1 .77 18 .4

25 2 .0 45 17 .4 1 .19 13 .5

2 .0 60 13 .8 1 .02 11 .1

35 2 .0 30 30.6 2 .24 16,6

35 2 .0 45 23 .0 1 .72 12 .6

35 2 .0 60 18 .6 1 .36 10.5

1 40 2.0 30 32 .0 2.32 16 .0

45 2 .0 30 34 .6 2 .44 15 .8

45 2 .0 45 25 .9 1 .89 12.2
45 2 .0 60 21 .3 1 .52 10 .1

SS 2 .0 30 38 .0 2 .68 14.2

SS 2 .0 45 31 .4 2 .09 11 .4

55 2 .0 60 24 .1 1 .62 9 .4

' Data from Dobbina (1984)

29
VIII. RELATIONSHIP TO HUMAN SMOKING

USPHS, 1979 :

The "tar" and nicotine content of cigarettes is measured by machines which smoke cigarettes
according to a predetermined puff rate, butt length, duration of puff, and volume of puff . An
individual smoker does not necessarily consume cigarette in this standardized manner .

Depending on the makeup of the cigarette, the wet particulate matter that issues with the [MS]
from the butt end amounts to 0 .2 to 9 .0 percent of the weight of the [MS] . The. ..FTC issues
reports semiannually on the "tar" content of all U .S . commercial cigarettes . In those reports
"tar" is defined as total particulate of [MS], minus water and nicotine, and is determined by
smoking cigarettes under standard conditions in a 20-channel machine [Pillsbury et al ., 1969] .

[From 1955 to 1977], the "tar" and nicotine contents' of cigarettes have declined . This trend is
illustrated in [F'igure 5] which depicts the sales-weighted average "tar" delivery per cigarette
from 1955 to 197T. . . For the years after 1967, periodic measurements of cigarette "tar" by the
[FTC, 1967b] permit reliable calculations of sales-weighted average "tar" delivery .

From 1954, sales-weighted average "tar" decreased from approximately 37 mg to approximately


23 mg . Although this change paralleled the rapid increase in filtertip market share, it also reflected
a decrease in the "tar" content of both filtertip and nonfilter cigarettes . . . Since 1966,the sales-
weighted average "tar" has continued to decrease . . . The observed decreases in sales-weighted

• "tar" have been paralleled by declines in the sales-weighted nicotine [yield] per cigarette .

a A cigarette does not have a"tu" content; Its MS does.


b FiQnre S is in an extension of that ahown In the 1979 Surgeon General's report (USPHS, 1979) ;
it represents data from 1954 through 1985 .

USPHS, 1981 :

There is evidence that machines that measure "tar" and nicotine content are not suitable for
measurements of smoke from lower "tar" and nicotine cigarettes with perforated filter tips . . .and
that the "tar" and nicotine in the inhaled smoke may be more than indicated by the test
procedures .

The FTC ratings of "tar" and nicotine yields measure an implied risk to the smoker . Smoking-
maehine"data guide experimenters in elucidating the mechanisms of induction of smoking-related
disease . Absolute levels of smoke constituents my be very important for experiments, so the
experimenter must have reliable information about the comparability of machine and human
smoking . The use of machine data to monitor risk has somewhat different requirements . If the
relative yields of different cigarettes are not greatly affected by smoking conditions, present
smoking-machine standards will be adequate to indicate relative risk of new cigarettes . We know,
however, that the relative yield of many constituents is affected by butt length, puff frequency,
and degree of ventilation . We need to determine how the variations in these smoking parameters
affect relative yields of the several substances in smoke that are of toxicological interest .

Methods for determining "tar"' and nicotine yield were developed before very low yield
cigarettes were an important segment of the market . It is questionable whether existing procedures
can measure accurately the "tar" delivery of the cigarettes yielding 0 .1 mg of "tar." Other
techniques giving acceptable results must be developed . Procedures for determining "tar" yields

30
• of low magnitude through measurement of fluorescence have been recommended (Thomas, 1980) .
[see Appendix C, this memorandum]

USPHS, 1982 :

The composition of the [MS] and [SS] depends greatly on the smoking conditions and the methods
of collection and analysis . This has long been realized; more than 20 years ago, standardized
smoking conditions were established for machine measurements of cigarette smoke [Wartman et
al., 1959] . Since then, the . . .FfC, research institutions, and the U .S . cigarette industry have used
the same standardized parameters for cigarette smoking [Bates et al ., 1968 ; Pillsbury et al .,
1969] . . . The standard cigarette smoking conditions reflect the average smoking habits of a male
smoker of nonfilter cigarettes as determined 25 years ago (Brunnemann et al ., 1976] . The average
smoking parameters recently recorded for filter cigarette smokers were one puff of 1 .94 to 2 .06
seconds duration, repeated every 26 .9 to 30 .0 seconds, with a puff volume of 35 .9 to 47 .8 ml
[Herning et al., 1981] . Nevertheless, FTC-standard cigarette smoking conditions continue to be
used for comparisons of tar and nicotine yields in the smoke of present cigarettes and those made
years and even decades ago .
1956 1960 1964 1968 1972 1976 1980 1984
The trends for the 50 3 .0
sales-weighted average
tar and nicotine 45
171ta Ttpr
deliveries of U .S . 2 .5 °•!
40 R4ooo.ttlut.a ToDaooo Sh ..t
cigarettes since 1955 . . . ~ Pap .r Addlu...
Pap.r PoroalLy
are shown in [Figure ~ 35 lspaadad Tobaoao
~ v.nw.u.o 2 .0
5] . . . During this time,
the percentage of filter- 30
~
tipped cigarettes in 25
U .S . cigarette
production increased S5 20
from 18 .7 to 90 a
15 ~'`~ ...
percent . . .
- Tar
••••••••• Nicotine
The reported data are
based on measurements 5
obtained by machine 0 I 1 1 I 0 .0
1 I I

smoking of cigarettes 1956 1960 1964 1968 1972 1976 1980 1984
under standard Figure S . "Tar" and Nicotine Deliveries, Sales Weighted Average
conditions . As Basis
discussed before, these
conditions may have
reflected the average smoking habits of individuals 25 years ago, but today [1982] they appear to be
representative of less than 10 percent of U .S . smokers .

Despite the repeated criticisms and deficiencies noted above (USPHS, 1979, 1981, 1982)
of the FTC analytical procedure for "tar" and nicotine yields, a procedure imposed on the U .S .
cigarette manufacturers (FTC, 1966, 1967), no serious attempt has been made by the FTC
during the past decade to modify the analytical procedure it put in place in 1967 . Because of a
B&W uniquely filtered cigarette product that behaved differently when smoked in the holder on


31
the FTC-recommended smoking machine and when smoked by mouth", an attempt was made
to introduce a new holder that would circumvent the problem . The original rubber diaphragm
holder on the FTC smoking machine is still in use.

IX. PERTINENT EPIDEMIOLOGICAL DATA : DO PEOPLE WHO SMOKE


REDUCED-"TAR" CIGARETTF.S HAVE A LOWER INCIDENCE OF
SMOKING-RELATED DISEASE?

In 1976, Hammond et al. (1976) described the decrease in mortality ratios in low-
nicotine, low-"tar" smokers compared to high-nicotine, high-"tar" smokers for lung cancer .
Several years later, Hammond (1980) wrote :
Wynder and I drafted a resolution that . . .was quoted in the Congressional Record [U .S . Congress,
1967] and by the Surgeon General . It said, "The preponderance of the scientific evidence strongly
suggests that the lower the 'tar' and nicotine contenN [sic] in cigarettes, the less harmful would
be the effects . . . The statement has been relevant ever since . Today I would change this wording .
Instead of saying that "the preponderance of evidence strongly suggests," I'd now say "the
preponderance of scientific evidence very strongly suggests" and I'd leave the rest of the wording
unchanged .
' A cigarette does not have a"ur content" ; its MS does .

In a comparison of the cellular changes (hyperplasia, metaplasia, carcinoma-in-situ) found


in the respiratory tract of smokers who died from lung cancer during the periods 1955-1960 and
1970-1977, Auerbach et al . (1979, 1980) reported that the epidemiological data reported by
Hammond et al. (1976) were paralleled by pathological data . They reported :

Although we do not have the tar and nicotine content [sic] of the cigarettes smoked by the subjects
in this study, all those who died in the 1955-1960 period had to have smoked cigarettes up to the
time of their death that were higher in tar and nicotine, than those who died during the years
1970-1977 . . . [F]or the last 5-10 years of their lives none of the 1970-1977 group could have
smoked cigarettes with as high a tar and nicotine content [sic] as those smoked by the 1955-1960
group .

Whenever we have found an early microscopic invasion in the tracheobronchial tree


epithelium in our previous studies of lung cancer cases, it was always next to and probably arose
from an area of carcinoma-in-situ . The changes in the cigarette over the 15 years from the time
the average group A person died [the 1955-1960 group] to the time the group B people died [the
1970-1977 group] has resulted in the changes demonstrated. . . These changes seem to be the result
of decreased tar and nicotine and they correlate with epidemiological data already presented . . .

With regard to reduced-"tar" cigarettes, Wynder (1980) noted :

A number of retrospective epidemiological studies have shown a decreased risk of disease


associated with filtered cigarette smoking . . . In our studies we calculated risk among persons who
smoked filtered cigarettes . . . [T]he risk of developing either epidermoid lung cancer or larynx

• 1s Mouth smoking of the cigarette generated much higher "tar" yields than when the cigarette was smoked In the FfC smoking
machine because of compression by the smoker's lips of longiwdinal dou In the filter tip .

32
cancer is reduced up to 33 % in long-term (Z 10 yr) smokers of filtered cigarettes, compared to
smokers of nonfiltered cigarettes.

The retrospective study from our group included more than 1000 cases of lung and larynx cancer
and showed a reduction in risks among long-term filter cigarette smokers of 10 years or more of
between 25 % and 33 % for both men and womea . . . This finding has been confirmed by the
prospective studies of the American Cancer Society . . . ([¢1 discussion to Russell (1980a)]

~
~
_j
~
m

OD
~
m

33
ITEM TO BE INSERTED :

In 1964, nicotine was essentially given a clean bill of health in the first Surgeon
General's report on smoking and health (USPHS, 1964) . Fifteen years later, nicotine was not
described in overly adverse terms. E.g., in the 1979 Surgeon General's report it was stated :

For the habitual smoker, the smoking of a cigarette is a rewarding experience ... Because of the
myriad compounds present in cigarette smoke, it should be kept in mind that the pharmacological
effects of smoking are not related solely to nicotine ; rather, it is the combined effect of the whole
smoke . Nevertheless, nicotine is generally accepted as the principal constituent responsible for
cigarette smokers' pharmacologic response. . .

Because "tar" rather than nicotine was considered to be the most hazardous part of the
particulate phase of MS, there was an era when it was proposed to fabricate a "less hazardous"
by redesigning it to deliver a substantially reduced "tar" level but deliver the same or an only
slightly reduced nicotine level, i .e., decrease the "tar" :nicotine ratio (Russell et al., 1973,
Russell, 1976, 1980b ; Schacter, 1978) . Russell et al. (1973) noted :

[T]he least harmful cigarettes for heavy smokers may be those with high, rather than low, nicotine
yield. . .

[A] cigarette with a high nicotine yield would enable heavy smokers to curb their tobacco
consumption, and harmfulness would be further reduced if, at the same time, the tar and CO
yields were low . . . To reduce tar yield without lowering the nicotine yield presents a challenge to
cigarette technology but is one which the skill and resources available are no doubt capable of
meeting . . .

and Russell (1980) in a conference on "safer cigarette" design wrote :

[A] low-tar, low-CO, but medium-, rather than low-, nicotine cigarette might reduce tar and CO
intake more than occurs with low-tar, low-CO, low-nicotine cigarettes . It might also be more
acceptable to smokers .

A problem with this concept was consumer acceptance when "tar" :nicotine ratio was less than about 7 . The
consumer re " from inhaling because of the harshness of the MS . Perforated filter-tip
cigarettes with" 1" :nicotine ratios between 9 and 11 or other filtered and nonfiltered cigarettes
with "tar" :ni e ratios above 10 are not perceived as too harsh to smoke's .

1s The following ia my recollection of In-house experiments conducted by Harris with a modified NOW with 2-mg "tar" delivery : Its
nicotine delivery was enhanced by nicotine ask addition to the blend so that'4ar" :nicotine ratio was decreased from about 9 to about 3 .

• Even though the MS nicotine delivery per cigarette was about 0 .6 mg and the MS nicotine delivery per puff was only about 0 .1 mg,
panelists repotted the modified cigarette to be totally unacceptable because of the harshness of the smoke . Cigarettes with deliveries of
18 mg "tar" and 1 .5 mg nicotine (a "tar" :nicot'ux ratio of 12 and a per puff nicotine delivery of about 0 .1S mg) are rated acceptable .

34
APPENDIX A : HISTORICAL COMMENTS ON THE POSSIBLE HEALTH
ASPECTS OF POORLY DEFINED "TARS" OBTAINED
FROM TOBACCO BY A VARIETY OF METHODS

Prior to the first production of carcinoma in laboratory animals skin-painted with the tar
from cigarettes smoked under conditions supposedly simulating human smoking (Wynder et al .,
1953a, 1953b), there were various comments and studies described in the literature on changes
produced in laboratory animals by application of various tobacco products (tars, juices, extracts)
and the possible relationship of tobacco smoke tars to respiratory tract cancer . No malignant
tumors were produced in studies with tobacco tars or any other industrial tars such as coal tar
prior to 1915 when Yamagiwa and Ichikawa (1915, 1918, ef . summary 1965) developed the
procedure to produce tumors in laboratory animals skin-painted with coal tar solutions . Between
1915 and 1953, numerous studies were described of attempts to produce tumors with v' t~tS e~S
tobacco products . None of the tobacco products (tars, extracts, etc .) in a smoking
process simulating the human smoking of cigarettes . Table APP A-1 summarizes representative
tobacco product studies conducted between 1880 and 1953 and their results .

TABLE APP A-i : MISCELLANEOUS TOBACCO TAR STUDIES PRIOR TO


WYNDER et al. (1953a, 1953b, 1955)
Year Event
1880 Tillmanns (1880) suggested that tobacco amoke particulate matter was of interest in cancer research from an etiological
standpoint because it possibly contained the aenx products of incomplete combustion as In coal tar and aoot .

1900 Broach (1900) observed cellular proliferation in guineas pigs painted with "tobacco juice ."

1911 Wacker and Schminke (1911) iqjected tobacco tar from pipes into rabbits and reported cellular proliferation .

1915,1918 Yamaglwa and Ichikawa (1915, 1918) produced carcinoma in robbta by repeatedly painting their sMn wlth a solution
ojeoaf tar. 7hts was the first nporred tneident ojthe production ojearetnoma In laboratory animals and was the basLs
for the all the research on chemical tumorigenesls In subsequent years .

1923 Hoffman et al. (1923) reported that tobacco tar which was not nicotinatree produced strong acute toxic aymptoma
when painted on mouse akin .

1928 Helwlg (1928) reported that rabbits injected with tobacco tar from pipes developed extensive cellular proliferation ;
mice akin-painted with the same solution developed ulceration at painting site .

1930, 1931 Roffo (1930, 1931) painted 30 rabbits with a tobacco tar, one rabbit developed a tumor . Roffo claimed that this was
the first production of cancer In a laboratory animals with a tobacco tar . However, his tobacco tar was obtained by
destructive distillation of tobacco, not In a smoking process (cf. Wynder st al., 1953 ; Wynder and Hoffmann, 1964,
1967) .

1932 Bogen and Loomis (1932) concluded that tobacco tar did not possess the necessary irritating or stimulating properties
to induce cancerous growths when painted on mouse skin .

Cooper et al . (1932) collected tobacco tars from tobacco mechanically smoked at 400-500°C and at 700-800°C and
applied the tars as 10-50% aolutiona in benzene, ethanol, or glycerol . Only one tumor-bearing animals was observed .
He concluded that tobacco was relatively unimpoetant In cancer causation, especially when the data were compared
with those obtained with aimila coal tar solutions.

1935 Schurch and Winteratein (1935) reported that mice treated with cigar tobacco tar or cigar tobacco tar fractions did not fLn ,
develop cancer either treated with the tar or tar fractions alone or subjected to a combination of tar treatment plus v
irritation (thermal or mechanical) . ~
_ G
1P
tb
tO
N
35
Table 1 (Appeadibt A) . Continued:

1937 Taki (1937) reported a squamous cell tumor on the skin of mice treated with a tar extracted from tobacco pipes .

1946 Jaffe et al . (1946) questioned the validity of Roffo's results because of the fact he had used a destructive distillate of
tobacco rather than a tobacco tar generated by a smoking process .

1949 National Cancer Conference panel (American Cancer Society, 1949) reported that the tobacco smoke tar painted on the
skin of Strain A mice, injected subcutaneously, or itoected intravenously did not induce tumon of the lung (adenomas)
or any other organ .
1953 Shotadze (1953) treated mice (lower lip) with a tobacco pyrolyate for 1 l months . No precancerous or cancerous
conditions were observed .

1953, 1955 Wynder er al. (1953a, 1953b, 1955) rreported the production of carcinoma In laboratory animals (highly tusceptible
mouse strain) painted with massive doses of cigarette smoke condensate generated under conditions simulating human
smoking conditions .

• The Strain A mouse is extremely susceptible to development of lung adenoma; 90% of them will die with adenoma
of the lung .


36
APPENDIX B: INFORMATION PROVIDED RJRT MANAGEMENT IN THE
MID-1960s FOR COMMUNICATION TO THE FEDERAL
TRADE COMMISSION re ITS CIGARETTE MS "TAR"
AND NICOTINE LABELING PROPOSAL

Below is presented the essentials of a 1965 memorandum prepared for RJRT management
by Rodgman (1965c) . It incorporates information from memoranda by Senkus (1964) and
Rodgman (1965b) and a draft memorandum by Rodgman (see also 1965c) .

A Short Explanation and Analysis of Methods for Measuring "Tar and Nicotine"
in Cigatette Smoke fJan/Feb . 19651

Introduction

Suggestions have been made from time to time that cigarette packages should indicate the
amount of "tar and nicotine" produced by smoking of the cigarettes in the package . Even if it
were established that "tar and nicotine" have some relationship to health, there is no method by
which a smoker can be accurately informed of either the amount or the composition of the "tar
and nicotine" he receives from the cigarette he smokes .

The term "tar and nicotine" requires clarification . Cigarette smoke consists of the particulate
phase and the gas phase. The particulate phase has been referred to in scientific and other
literature by a variety of terms, such as tars, smoke solids, solids, total solids, particulate matter,
total particulate matter, smoke condensate, total smoke condensate, and smoke condensables . One
of the components of smoke solids is nicotine ; the nicotine fraction of smoke solids is sometimes
referred to as alkaloids, or total alkaloids . It seems more meaningful to use the term "total solids"
instead of "tar," and such term will be used in this memorandum .

Summary and Conclusions

Various methods exist for determining in the laboratory the total solids and nicotine in the
smoke from cigarettes smoked by a machine under laboratory conditions. Although the different
methods produce different results, one method could be arbitrarily selected as the standard . But
the total solids and nicotine received by any individual smoker would vary from that produced by
the smoking machine in the laboratory using the same brand of cigarettes, even if it were assumed
that the cigarettes smoked by the individual and those smoked in the laboratory are exactly alike .
This is because the smoking habits of individual vary, and because the conditions under which
cigarettes are smoked vary .

It may not be assumed, however, that cigarettes smoked by the smoking machine in the
laboratory are the same as the cigarettes of the same brand purchased by the smoker . Because of
unavoidable variations in the manufacture and storage of cigarettes, differences exist in the
tobacco, paper, filter, and condition of cigarettes so that measurements of total solids and nicotine
in the smoke of one sample of cigarettes will differ from measurements obtained with another
sample of the same brand, assuming that all possible steps are taken to assure as much uniformity
as possible . The measurements appearing on a package of cigarettes would relate to the cigarettes
used in the test and would not be accurate as applied to the cigarettes contained in the package .

• Even if two cigarettes of the same brand, or of two different brands, were to deliver precisely

37
the same amount of total solids, variations in the cigarettes, in smoking habits, and in smoking
conditions would generate total solids in the smoke of one of the cigarettes composed of different
quantities and kinds of chemical compounds from those found in the total solids from the other
cigarette . Since it is not known which, if any, chemical compound in the total solids is harmful,
it is not helpful to the smoker to furnish him a quantitative measurement of total solids, especially
one which, as has been stated in the two preceding paragraphs, cannot be accurate .

The conclusion is therefore inescapable that labeling the amount of "tar and nicotine" on a
cigarette package cannot give to the smoker meaningful information as to the amount or
composition of the total solids and nicotine he receives from the cigarettes he smokes . He is more
likely to be misled than informed .

Methods for Measuring Total Solids and Nicotine

The following five methods for measuring total solids and nicotine are described in Table
APP B-1 :

(1) The Wolman method [Wolman, 1953]


(2) The Consumer Union's method - No . 1[Consumer Reports, 1955]
(3) The Cambridge filter method (Wartman et al., 1959]
(4) The Foster D . Snell method' [Kimball]
(5) The Liggett and Myers Tobacco Company method [Keith and Newsome,
1956, 1957, 1958; Newsome and Keith, 1956, 1957] .

• It should be recognized that a number of variations of such methods are possible, and there may
be other methods . Those described [below], however, appear to be the ones most commonly
reported.

The five methods described in Table APP B-1 have not been compared on the same lot of
cigarettes . Three of the methods, however, have been compared by Keith and Newsome (1957a,
1957b, 1968) . The results of such comparison show distinct variations and were reported to be
as follows:
Consumer Union' .
Method - No . I Foeter D. Snell Method L.dcM Tobacco Co . Method

Solids, rtg/ciyt 18 .8 34.2 19.1

Nicotine, nglclat 2 .2 2 .9 3 .S

It is of course clear even apart from such comparisons that the various methods described in Table
APP 13-1 necessarily will produce different results because they do no start with the same smoking
conditions .

Generally speaking each of the methods require five to ten cigarettes for testing purposes . The
cigarettes are smoked by machine, which is designed to retain 100% of the particulate phase of
the smoke . Each method proceeds on the basis of smoking the cigarette using a fixed volume of
puff, a puff of specific duration,a fixed frequency of puffing, and a specific amount of the
cigarette to be smoked . All methods other than that of Liggett & Myers use a 35-m1 volume puff .
The most common duration of puff is two seconds, and the most common frequency of puff is one Ln
~
~
~

~P
~ The Foster D. Snell Labontory performed many of the cigarette smoke anelyaes for ?he Reader's Digest .
Co
~
. 38 Ln
per minute . The Wolman method and the Cambridge filter method2 smoked a fixed length of
cigarette (47 mm) regardless of the length of the cigarette being smoked and regardless of whether
it is a filter cigarette or not . Some of the methods smoke to a predetermined butt length, e .g ., 23
mm ; in such methods the length of cigarette smoked would vary depending upon the initial length
of cigarette being tested and whether or not it is a filter cigarette . The Liggett & Myers method
smokes fourteen puffs of each cigarette, so that the number of puffs taken determines the length
of the cigarette smoked .

TABLE APP B-1 : METHODS FOR DETERMINATION OF TOTAL SOLIDS AND


NICOTINE

1.&M Tobacco Co.


Method (Keith and
The Consumer Newsome, 1956,
Union'a Method Cambridge Filter 1957, 1958 ;
Smoking Wolman Method (Consumer Method (Wattman Foster D. Snell Newsome and Keith,
Conditions . etc . (Wolman . 1953) Reoocta . 1955) ft ol . . 1959) Meth (Kimbalb 1956 . 1957)

cigarette length 47 variable ; depends 47 variable ; dependa variable ; depends on


smoked, mm on length of on length of length of cigarette
cigarette being cigarette being being tested
tested tested

butt length, tnm variable ; depends 23 variable ; depends 23 variable ; depends on


on length of on length of length of cigarette
cigarette being cigarette being being tested
tested tested

number of puffs number required to number required to number required to number required to 14
consume 47 mm of attain 23-mm butt consume 47 mm of attain 23-mm butt
cigarette length cigarette length

puff volume 35 35 35 3S 44

puff duration 2 .0 2 .0 2 .0 1 .9

puff frequency, l l 1 1 2
no ./min

lab temp ., °C 25° not specified not specified not specified 23 .9°

lab RH, % 45% not :peeified not specified not specified 60%

cigarettes smoked 5 8 10 S 10°


per determination

cigarette selection selected for selected for selected for selected for selected for
uniformity In uniformity in uniformity In , uniformity In uniformity in
moiature content, moisture content, moisture content, moisture content, moisture content,
cigarette size (if cigarette aize (if cigarette size (if cigarette aize (if cigarette uze (if
feasible), weight, feasible), weight, feasible), weight, feasible), weight, feaaible), weight,
firmness, and other firmness, and other firmness, and other firmness, and other firmneu, and other
characteristics characteristics characteristics characteristics characteristics

2 It should be noted In the Cambridge filter method as outlined by Ogg et ai . (1962) the cigarette under teat is smoked to a 30-mm butt
length . Further modificitiona of this method, including length of cigarette to be smoked, are under consideration by the Analytical Methods
Committee of the Tobacco Chemists' Research Conference .

39
Table APP B-1 . Continued :

L&M Tobacco Co .
Method (Keith and
The Consumer Newsome, 1956,
Union's Method Cambridge Filter 1957, 1958;
Smoking Wolman Method (Consumer Method (Wartman Foster D. Sne11 Newsome and Keith,
Conditiona, etc . (Wolman. 19531 $Sports . 1955) t! 9 Method (Kimball) 1916, 1957)

determination of Solids (designated Smoke for deter- Cigarette MS is To determine solids The smoke in this
total solids as tan in the mination of both collected on a glass (tar content In the method is retained
publication) are nicotine and solids fiber filter material, communi-cation), on an a-cellulose
determined by is absorbed in Cambridge filter smoke Is collected trap . The a-cellulose
gravity deposition acidified alcohol. medium CM-! l3 . in acidified alcohol . is washed with hot
of smoke over 2S One portion of the The weight of The alcohol acidic methanol . The
m1of0.1N acidified alcoholic material retained in solution is heated solution is extracted
sulfuric acid . The solution is diluted the filter represents on a steam bath with chloroform . To
mixture Is extracted with water, then total solids (total (100°C) to deter-mine soltds
with chloroform, extracted with particulate matter). evaporate the (termed tar in the
and the chloroform chloroform . The Part of the material alcohol . After publications), the
extract ia heated to aqueoua layer ia retained on the about S hr, the chloroform solution
evaporate the made alkaline and Cambridge filter ia residue is heated in is evaporated on the
chloroform . The re-extracted with water. Thus, this the beaker at steam bath and
residue is then chloroform . The method Includes 105°C for 7 hr. heating is continued
heated, or dried, two chloroform water in the value The weight of for 3 hr at 105°C .
for 3 hr at 100°C . extracts are com- for total solids, material remaining Tar value is
The weight of bined, and the whereas the in the beaker ia determined by

• remaining material
after the heating ia
reported as tars .
chloroform
removed by
evaporation to yield
the tar, which is
Wolman Method
and the Consumers
Union Method do
not. .
designated as the
tar content.
weighing the
residue .

weighed .

determination of Solids for deter- Another portion of To determine To determine The extracted
nicotine mination of the acidified nicotine, the nicodnt, an aliquot methanol solution is
ntcodne are alcoholic solution is Cambridge filter of the acidified nude alkaline and is
collected over 10 treated with base with the retained alcohol solution steam-distilled .
ml alcohol acidified and ateam-diadlled . solids Is extracted containing the NTcodnt Is deter-
with sulfuric acid Mcodne in the with 0. 1 N aulfitric smoke solids is mined in the steam
in a 300-mi steam distillate ia acid . The solution, heated to remove distillate apectro-
i(ieldahl flask . measured apectro- after washing with the alcohol, the photometrically .
Solution Is treated photometricdly . chloroform, ia residue ia made
with alkali and then made alkaline and alkaline and is
ateatn-0iatilled . The is ateam4iatilled . ateam-diatilled .
distillate ia treated Nicotine In the Mcodne ia deter-
with ailicotungatic steam distillate ia mined gravimetri-
acid to precipitate determined either cally in the steam
the ailicotungatate . by the silicotungstic distillate (silico-
The ailicotung.tate acid method or by tungstic acid
la separated and ia the apectrophoto- method) .
ignited to an ash metrie method .
whose weight Is
used to calculate
the nicotine valueb .

' The authors recommended that three to six such determinations be carried out and the results averaged .
b Since other alkaloids coprecipiute with nicotine as ailicotung .tatea, this determination yields the alkaloid or total alkaloid
value .


40
From the foregoing it is apparent that each of the methods has adopted arbitrary smoking
habits for the smoking machine, which habits do not correspond with the habits of each individual
smoker . The volume of puff taken in smoking [Derr et al ., 1937 ; Cigarette Components, Ltd .,
1957 ; Schur and Rickards, 1955, 1957 ; Cuzin et al., 1958], the frequency of puffs [Derr et al .,
1937 ; Cigarette Components, Ltd ., 1957 ; Cuzin et al., 1958 ; Staub and Furrer, 1957 ; Bentley and
Burgan, 19613, and the duration of the puff [Derr et al ., 1937 ; Hilding, 1956 ; Schur and
Rickards, 1955, 1957 ; Cuzin et al ., 1958 ; Staub and Furrer, 1957 ; Bentley and Burgan, 1961]
vary among individuals. The length of the cigarette smoked, or the butt length to which cigarettes
are smoked also varies among smokers [Hilding, 1956 ; Cigarette Components, Ltd ., 1957; Schur
and Rickards, 1955, 1957 ; Finkner et al ., 1957; Bentley and Burgan, 1961] . These variations
necessarily mean that the amount of total solids and nicotine collected by the smoking machine
is not the same as what individual smokers receive .

It is obvious of course that all smokers do not retain 100% of the particulate phase as a
smoking machine is designed to do . The degree of inhalation differs appreciably among individuals
(Cigarette Components, Ltd ., 1957] . Moreover, smokers who inhale hold the smoke in the lungs
for different times, some exhaling more quickly than others [Mitchell, 1962] . The Amount of
particulate phase retained in the lungs obviously depends in part upon the time elapsing between
inhaling and exhaling . Smokers who do not inhale admit the smoke to their mouths ; the duration
of retention of the particulate phase in their mouths obviously affects the extent of retention of
solids [Mitchell, 1962] .

Other variations between smokers include the following :

• The burning temperature of cigarettes varies from smoker to smoker because of


differences in smoking habits [Cuzin et al ., 1958] .

• The pressure drop across a cigarette differs from smoker to smoker [Bradford et al .,
1936; Hilding, 1956 ; Schur and Rickards, 1955, 1957 ; Staub and Furrer, 1957 ; Cuzin
et al ., 1958] .

• The total number of puffs per cigarette and the time necessary to consume a cigarette
varies from smoker to smoker [Hilding, 1956 ; Bentley and Burgan, 1961] .

Successive puffs of an individual on the same cigarette may differ with respect to puff
volume, puff duration, and frequency, degree of inhalation, temperature change by puffing, and
pressure drop produced by smoking [Staub and Furrer, 1957] . The manner of smoking successive
cigarettes by an individual may also vary . These differences include length of cigarette consumed,
total number of puffs per cigarette, and time required to consume a cigarette (Staub and Furrer,
1957] .

All of the variations so far mentioned have been the subject of comment in the scientific
literature, and all would affect the amount of total solids and nicotine received by the individual
smoker as compared with a smoking machine . In addition, there are other variable factors, which
have not been reported in the scientific literature and which may affect the amount or composition
of total solids and nicotine delivered to or retained by a smoker . Some of the factors are :

• Smoking at very low temperatures and very low humidity . These conditions would
prevail in the winter in the northern states .

• Smokin,g at reduced pressure, e .g., in the mountainous states . There is some indication

41
NUMBER CONTROL PAGE
BATES NUMBER
NOT USED

517104899
that the rate of burning of a cigarette will differ depending upon the altitude at which the
cigarette is smoked .

• Smoking in areas which are either abnormally humid or abnormally dry.

• Smoking from a pack which has been opened for more than a day . The cigarettes may
lose appreciable moisture under and conditions . Although loss of moisture will not affect
weight of solids produced per cigarette', it is believed to affect the chemical composition
of smoke.

Variations in Cigarette s

The following variables affect the yield of total solids per gram of tobacco product consumed
and the composition of the smoke and total solids :

• Tobacco [Wynder and Hoffmann, 1963, 1964] .

Since tobacco is an agricultural commodity, it is not homogenous . Its characteristics vary from
leaf to leaf of the same plant and within the same leaf . And of course a variety of types, grades,
and blends of tobaccos are used in the manufacture of cigarettes, such as flue-cured, burley, and
Turkish tobaccos, and blends of such tobaccos .

• Processed tobacco (Wynder et al., 1959 ; Nicod, 1961 ; Cuzin et al, 1963 ; Uhlman,
1963] .

Just as different tobacco types and blends yield different amounts of total solids, homogenized
tobaccos (reconstituted tobacco sheet), on a per gram of processed tobacco consumed, yield
different amounts of total solids than does tobacco . Extraction of tobacco decreases the yield and
alters the composition of the total solids in MS and alters . Steaming of tobacco produces similar
changes .

• Number of cuts/inch [Wynder and Hoffmann, 1964] .

With the same tobacco type or the same blend, increasing the number of cuts per inch decreases
the total solids in MS .

• Filtration and pressure drop [Wynder and Hoffmann, 1960 ; Bock et al., 1962 ; Ayres et
al., 1963 ; Waltz and Hausermann, 1963] .

The higher the degree of filtration the lower the total solids ; the higher the pressure drop, the
lower the total solids. The efficiency of filters of the same design will vary from filter to filter
depending upon the construction or the manner in which the filter tow is packed.

• Paper porosity [Schur and Rickards, 1955,1957 ; Lipp and Van Hooy, 1962 ; Wynder and
Hoffmann, 1964] .

The cigarette paper which is normally supplied to the cigarette manufacturer usually has an

3 This has been shown to be Incorrect . Loaa of moisture from the tobacco filler affech the yields of both "tar" and nicotine .
• The study by Green et a! . (1982) showed that moisture loss from the cigarette filler had profound effects on the MS composition .

42
appreciable range of porosity . The solids in MS usually decrease as the porosity increases .

• Number of pt~`'s taken to consume a given length of cigarette [Newsome and Keith, 1956,
1957 ; Segelken et al., 1962] .

E.g ., burley tobacco buras at a greater rate than other tobacco types ; thus, a different number of
puffs are required to consume the same cigarette length of burley, flue-cured, and Turkish
tobaccos .

• Moisture content of cigarettes [Newsome and Keith, 1956, 1957 : Sato et al ., 1961 ;
Wynder and Hoffmann, 1964] .

The age of the cigarette, e.g., the length of time on the retailer's shelf, may affect the moisture
content of the filler.

• Variations in amounts of total solids and nicotine In each puff [Lindsey, 1959, 1962 ;
Kotin and Falk, 1960 ; Wynder and Hoffmann, 1961 ; Ayres et al., 1963] .

It has been suggested in the scientific literature that the amount and composition of total solids in
later puffs markedly exceeds that in earlier puffs [Lindsey, 1959, 1962 ; Kotin and Falk, 1960] ;
other investigators report finding very little difference between the mounts in the early and late
puffs [Wynder and Hoffmann, 1961 ; Ayres et al ., 1963] .

• Additives on tobacco [Alvord and Cardon, 1956 ; Lindsey et al ., 1959 ; Bentley and
Burgan, 1960 ; Candeli et al., 1960; Wynder and Hoffmann, 1961 ; Cuzin et al., 1963 ;
Scherback et al., 19631 .

The amount of total solids and composition of MS and solids vary with the amounts of additives
such as licorice and glycerol . It is impossible to apply these to tobacco uniformly .

• Humidity of analytical laboratory [Newsome and Keith, 1956, 1957 ; Sato et al ., 1961 ;
Wynder and Hoffmann, 1964] .

It is quite obvious that some of these variable are interdependent, e .g., filtration, paper porosity,
cuts/inch, filling capacity, and pressure drop .

Chanaes in the Comcosition of Smoke and Total Solids

It has been pointed out that the amount of total solids and nicotine produced by smoking can be
changed by a large number of variable factors, including the type of tobacco, the efficiency of the filter,
and the porosity of the cigarette paper. As has been mentioned in connection with such factors, they (and
probably others) may also change the ratio of various components of the smoke . As a result, the ratios of
the components in the total solids may be different .

43
f- -
APPENDIX C : DETERMINATION OF "TAR"' YIELD FROM
ULTRALOW-"TAR" CIGARETTES: SPECTROMETRY

The following paragraphs, slightly modified, are from a 1988 memorandum written
by Rodgman :

In the mid-1950s, Watson (1954) investigated the fluorescence of cigarette smoke and related
the difference in fluorescence between inhaled and exhaled cigarette MS to the degree of
particulate matter retention and the possible relationship to lung cancer causation . At the same
time, Schmghl and co-workers reported on their studies of the fluorescence of cigarette MS,
particularly with respect to the fluorescence of its particulate matter (SchmBhl et al ., 1954 ;
/
SchmAhl, 1955 ; SchmAhl and Schneider, 1955) . In fact, they used this analytical procedure to
estimate the degree of absorption of MS by the smoker during consumption of the cigarette . From
their fluorescence measurements on inhaled and exhaled MS particulate matter, Schm1hl et al .
(1954) estimated that as much as 90% of the MS particulate matter was retained in the lungs and
bronchi during deep inhalation. Subsequently, Wynder and Hoffmann (1960) claimed they had
confirmed the findings of SchmAhl et al . Neither Watson nor SchmBhl commented on the findings
of Bruce (1941) who reported that there was no correlation between fluorescence in general and
carcinogenicity .

Bentley and Burgan (1958) described the use of fluorescence techniques to estimate the levels V/
of several PAHs, including BaP, in a PAH-rich fraction derived from CSC . The use of
fluorescence spectroscopy to estimate PAHs (or BaP) is not surprising : UV fluorescence
spectroscopy was used by Hieger (1930, 1933) and Cook et al . (1932, 1933) in their concentration ~Ie ,/
of the PAHs in coal tar and the isolation of BaP and other tumorigenic PAHs from the PAH-rich
coal-tar fraction in the early 1930s .

However, it should be noted that the fluorescence of a solution of cigarette MS particulate


matter is not due solely to the PAHs contained therein . E.g., Duggan et al. (1957) noted in their r
study of the fluorescence properties of compounds of biological interest that, in addition to the
PAHs and structurally similar heterocyclic compounds, many classes of compounds such as
phenols, aromatic amines, and conjugated polyenes exhibited pronounce fluorescence properties .
All of these classes of compounds are now known to be present in CSC . Glycerol and propylene
g.lycol, major tobacco additives which appear in MS, are .UV transparent at the absorption or
fluorescence wavelengths used .

McConnell et al . (1960r'used fluorescence techniques in their method to evaluate the r


efficiency of various cigarette filtefs-in particulate matter removal from MS . They did note that
the fluorescence intensity of solutions of cigarette MS particulate matter was linearly proportional
to the weight of MS particulate matter . However,'ate the high-"tar" deliveries (about 30 mg/cigt)
of the 1960 cigarettes, it was noted that the gravimetric method was more rapid and slightly more
accurate than the fluorescence method . A similar procedure ftc described by Smit (1972) in his P/
determination of filter tip efficiency for particulate matter removaTfratQMS .

Burton et al. (1977) confirmed the findings of McConnell et al . (1960) on the linearity
r
between fluorescence and particulate matter weight and also noted the fluorescence method was
more accurate and less time consuming for low-"tar" cigarettes than the gravimetric method used
in the FTC procedure . Three years later, Thomas et al . (1980) described an automated method,
base on fluorescence technology, for the determination of FTC "tar" in the MS of low-"tar"
delivery cigarettes .
ILe UV absorption method described by Sloan and Curran (1981) for estimation of per
cigarette "tar" yields is similar to the UV fluorescence procedure . A modification (Hege, 1980)
of the Sloan-Curran UV procedure was used at RJRT R&D in low-"tar" studies and in Premier
studies (R.J. Reynolds Tobacco Co ., 1988). K

45
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50
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63
DRAFT • January 22, 1965

A Short Explanation and Analysis of Methods of Measuring


"Tar and Nicotine" in Cigarette Smoke

Introduction

. Suggestions have been made from time to time that

cigarette packages-should indicate the amount of "tar

and nicotine" produced by the smoking of the cigarettes

in the package . Even if it were established that "tar

and nicotine" have some relationship to health, there is

no method by which a smoker can be accurately informed of

either the amount or the composition of the "tar and

nicotine" he receives from the cigarettes he smokes .

The term "tar and nicotine" requires clarification .

Cigarette smoke consists of the particulate phase and the

gas phase . The particulate phase has been referred to in

scientific and other literature by,a variety of terms, such

as tars, smoke solids, solids, total solids, particulate

matter, total particulate matter, smoke condensate, total

smoke condensate and smoke condensables . one of the components

of smoke solids is nicotine ; the nicotine fraction of smoke

solids is sometimes referred to as alkaloids, or total

alkaloids . It .,seems more meaningful to use the term "total


solids" instead of "tar", and such term will be used in this

memorandum .

w
N
r
~

. .._... ..~. .~ ..._ ...~. _ ..._ . . . . . . . . ., ___. ..~. .. . . ..._ . , • .• _-


-2-

Suand-Conclusion

Various methods exist for determining in the laboratory

the total solids and the nicotine in the smoke of cigarettes

smoked by a machine under laboratory conditions . Although

the different methods produce different results, one method

could be arb_itrarily
. selected as the standard . But the

total solids and nicotine received by any individual smoker

would vary from that produced by the smoking machine in the

laboratory using the same brand of cigarettes, even if it

be assumed that the cigarettes smoked by the individual and

those smoked in the laboratory are exactly alike . This is

because the smoking habits of individuals vary, and because

the conditions under which cigarettes are smoked vary .

.It may not be assumed, however, that cigarettes smoked

by the smoking machine in the laboratory are the same as the

cigarettes of the same brand purchased by the smoker . Because

of unavoidable variations in the manufacture and storage of

cigarettes, differences exist in the tobacco, paper, filter

and condition of cigarettes so that measurements of total


I•
solids and nicotine in the smoke of one sample of cigarettes

will differ from measurements obtained with another sample

of the same brand, assuming that all possible steps are taken
• -3-

to assure as much uniformity as possible . The measurements

appearing on a package of cigarettes would relate to the

cigarettes used iii the test, and would not be accurate as

applied to the cigarettes contained in the package .

Even if two cigarettes of the same brand, or of two

different brands, were to deliver precisely the same amount

of total solids, variations in the cigarettes, in smoking

habits and in smoking conditions would generate total solids

in the smoke of one of the cigarettes composed of different

quantities and kinds of chemical compounds from those

found in the total solids from the other cigarette . Since

it is not known which, if any, chemical compound in the

total solids is harmful, it is not helpfuli to the smoker to

furnish him a quantitative measurement of total solids,

especially one which, as has been stated in the two preceding

paragraphs, cannot be accurate .

The conclusion is therefore inescapable that labeling

•the amount of "tar and nicotine" on a cigarette package

cannot give to the smoker meaningful information as to the

amount or composition of the total solids an$ nicotine he

receives from the cigarettes he smokes . He is more likely

to be misled than informed .

_ . .... .. .~. .. ...._....-...~.,.,...~_ ......... .. .... ....r.~.. .. .. . . .. ;~ ...__.__ . ..._ .__.__._ .. . .. .. .r. .~_ , _ . .
Methods for Measuring Total Solids and Nicotine

The following five methods for measuring total

solids and nicotine are described in Appendix A hereto :

the Wolman method ; the Consumer's Union method - No . I ;

the Cambridge Filter method ; the Foster D . Snell method ;

and the Liggett & Myers Tobacco Company method . It •

should be recognized that a number of variations of such

methods are possible, and there-may be other methods .

Those described in Appendix A, however, appear to be the

ones most commonly reported in the scientific literature .

The five methods described in Appendix A have not

been compared on the same lot of cigarettes . Three of

the methods, however, have been compared by Keith & Newsome

(Tobacco Science II, 14-19 (1958)) . The results of such

comparison show distinct variations, and were reported to

be as follows :

Consumer's Union Foster D . Snell Liggett and Myers


Method - No . 1 Method Tobacco Co . Method

Solids, mg ./cig . 18 .8 34 .2 19 .1
Ln
~
Nicotine , mg ./cig . 2 .2 2 .9 3 .5 ~
~
m
It is of course clear even apart from such comparisons that ~
~
N
the various methods, described in Appendix A necessarily LA

will produce different results, because they do not start N


O

-, .
-S-

with the same smoking conditions .

Generally speaking each of the methods requires from

five to ten cigarettes [query, Liggett & Myers method?]

for testing purposes . The cigarettes are smoked by a

machine, which is designed to retain 1007. of the particulate

phase of the smoke . Each method proceeds on the basis of

smoking the cigarettes using a fixed volume of puff, a puff

of a specific :duration, a fixed frequency of puffing, and

a specific amount of the cigarette to be smoked . All methods

other than that of Liggett & Myers use a 35 ml . volume-of

puff . The most common duration of puff is two seconds, and

the most common frequency of puff is one per minute . The

Wolman method and the Cambridge Filter method smoke a fixed

length of cigarette (47 mm .), regardless of the length of

the cigarette being smoked and regardless of whether it

is a filter cigarette or not . Some of the methods smoke to

a predetermined butt length, for example, 23 mm . ; in such

methods the length of cigarette smoked would vary depending

upon the initia7l length of the cigarette being tested and

whether or not it is a filter cigarette . The Liggett & Myers

method smokes fourteen puffs of each cigarette, fo that the

number of puffs taken determines the length of the cigarette

smoked .
-6-

From the foregoing it is apparent that each of the

methods has adopted arbitrary smoking habits for the smoking

machine, which habits .do not correspond with the habits of

each individual smoker . The volume of puff taken in smoking

a cigarette, the frequency of puffs, and the duration of

the puff vary among individuals . The lengths of cigarettes

smoked, or the butt length to which cigarettes are smoked


:- -
also varies among smokers . These variations necessarily

means that the amount of total solids and nicotine collected

by the smoking machine is not the same as what the individual

smoker receives .

It is obvious of course that all smokers do not take

in, or retain, 100% of the particulate phase, as a smoking

machine is designed to do . The degree of inhalation differs

appreciably among individuals . Moreover, smokers who inhale

hold the smoke in the lungs for different times, some exhaling

more quickly than others . The amount of the particulate

phase retained in the lungs obviously depends in part upon

the time elapsing between inhaling and exhaling . Smokers

who do not inhale admit the smoke to their mouths ; the duration

of reteption of the particulate phase in their mouths obviously


0
determines the extent of retention of solids . o
r
Other variations between smokers include the following : w
N
U
O

! ; 51710 4927
the burning temperature of cigarettes varies from smoker

to smoker because of differences in smoking habits ; the

pressure dro,p across a cigarette differs from smoker to

smoker ; and the total number of puffs per cigarette and

the time necessary to consume a cigarette varies from

smoker to smoker .

Successive puffs of an individual on the same cigarette

may differ with respect to puff volume, puff duration, degree

of inhalation, temperature change by puffing, and pressure

drop produced by puffing . The manner of smoking successive

cigarettes by an individual may also differ with respect

to number of puffs per minute, length of cigarette consumed,

total number of puffs per cigarette and time required to

consume a cigarette .

All of the variations so far mentioned have been the

subject of comment in the scientific literature, and all

Would affect the amount of total solids and nicotine received

by the individual smoker as compared with a smoking machine .

In addition, there are other variable factors, which have

not been reported in the scientific literature, and which

may affect the amount or composition of total so~lids and

nicotine delivered to or retained by a smoker . Some of


these factors are :
,

a. Smoking at very low temperatures and very low


humidity . These conditions would prevail in
the winter in the northern states .

b . Smoking at reduced pressures, for example in the


mountainous states . There is some indication
that the rate of burning of a cigarette will
differ depending upon the altitude at which the
cigarette is smoked .

c . Smoking in areas which are either abnormally


humid or abnormally dry .

d . Smoking from a pack which has been open for'more


than a day . The cigarettes may lose appreciable
moisture under arid conditions . Although loss of
moisture will not affect weight of solids produced
per cigarette, it is believed to affect the
chemical composition of smoke .

Variations in Cigarette s

The following variables affect the yield of total

solids per gram of tobacco product consumed :

a . Tobacco . Since tobacco is an agricultural


commodity, it is not homogeneous . Its
characteristics vary from leaf to leaf of
the same plant, and within the same leaf .
And of course a variety of types and grades
of tobacco are used in the manufacture of
cigarettes, such as flue-cured, Burley and
Turkish tobaccos .

b . Filtration and pressure drop . The h ;gher the


degree of filtration, the lower the total
solids ; and the higher the pressure drop, the
lower the total solids . The efficiency of
filters of the same design will vary from
filter to filter depending upon the construction
or the manner in which the filter tow is packed .

.. . _ . . _ . . _..._.~ ..,.. ._..-. __ ~ . --- . ••- .~.-. _~, _,.. .. . . . .. . .. _ ... ~.. .
\
~J .

-9-

c . Paper porosity . The solids usually decrease


,as the porosity increases .

d . Number of puffs taken to consume a given length


of cigaz'ette . For example, Burley tobacco burns
at a greater rate than other tobacco types ; and
thus, a different number of puffs are required
to consume the same cigarette length of Burley,
flue-cured, and Turkish tobaccos .

e . Humidity of analytical laboratory .

f . Moisture content of cigarettes . The age of the


cigarettes (e .g .•, the length of time on the
retailer's shelf) may affect the moisture
content . Moreover it is not possible to
manufacture cigarettes with a constant moisture
_ content .

g . Variations in amounts of total solids and/or


nicotine in each puff . It has been suggested in
the scientific literature that the amount and
composition of total solids in later puffs markedly
expeeds that in earlier puffs ; others report
finding very little difference between the amounts
in the early and late puffs .

h . Number of cuts/inch . With the same tobacco type


or blend, increasing the number of cuts per
inch of tobacco in the manufacturing process
decreases the total solids in the smoke, and
changes their composition .

i . Additives on the a er and/or the tobacco can


elter the amount of smoke solids and or nicotine .
Additives include flavoring materials .

Of course some of the above mentioned variables are

interdependent, e .g ., filtration, paper porosity, cuts/ inch

of tobacco, and pressure drop .

. . . .._ . . . .- .~--• . .- ..._.. . . .._ . . . . . . .. . . .~ _ . . . .. . . .,. . . . . . . . . .. .~_ .. ..~ . . . . . . . . . ._ . .. . . . .... . .~ ... ..... . ~ .. .
-9A-

It should be emphasized that variations between

cigarettes exist between practically all cigarettes . That

is to say, cigarettes manufactured at the same time, from

the same tobacco and other materials, will show many of

the variations described, and would on testing generate

total solids of different amounts and composition . This

is perhaps best illustrated by the fact that the five

test methods d'escribed in Appendix A all produce an average

reading for all the cigarettes tested, rather than a reading


for each cigarette .

1.
~. :

-10-

Changes in ~
the Composition of Smoke and Total Solids

It has been pointed out that the amount of total

solids and nicotine produced by smoking can be changed

by a large number of variable factors, including the type

of tobacco, the efficiency of the filter, and the porosity

of the cigarette paper . As has been mentioned in connection

with some of the factors named, they (and others) may also

change the ratios of the various components of the smoke .

As a result, although the amount of total solids may remain

the same or be reduced, the ratios of the components in

the smoke might be different .

.,

t.

.. .~ .~ ..r« . . . . .. . . . . . . . . . . .. .~.~ .~. . . .~ . ... .~ . . .- . . . ~ . ~. .. . . . . . .


. - ..- .... . .~
A Short Explanation and Analysis of Methods of Neuuring
"Tar and Nicotine" in Cia .,rette Ss+oke ~. .~.~.~ ..~

y
Int~.i.°o .

Suggestions have been rade from time to time that cigarette

packages"should indicate the amunt of "tar and nicotine" produced

by the emoking of the cigarettes in the package . Even if it were

established that "tar and nicotine" have some relationship to

health, there is no method by which a smoker caa be sccuratelr

informedof either the snunt or the compositioa of the "tar and

nicotine" he receives from the cigarettes he ssiokea .


S The term "tar and nicotine" requires clarification . Cigarette

smoke consists of the particulate phase and the gas phue . The

particulate phase has been referred te•in scientific and other

literature by a variety of terrs, such ai .tars, saoke solids, solids,

total solids, particulate oatter,'total particulate nttter, snoke

condensate, total sooke condensate aad smoke coadensables . One of

the components of smoke solids xs jicotinei the nicotine fraction

of smoke solids is somsti .es referred'to u alkaloids, or total

alkaloids . It seems more meaningful to use the ters "total solids"

instead of "tar", 4nd such term vill be used ta this sswrandum .


f

dumaa~ and Conclusion

Yariou& methods exist for determining to the laboratory

the total solids end the nicotine in the ss+oke of cigar .ttes ssioked

by a machine under laboratory conditions . Although the different

.ethods produce different results, one method could be arbitrarily

selected a1 the standard . but the total solids and nicotine received

by any individual smoker would vary from that produced by the

ss,dcing machine in the laboratory using the sam brand of cigarettes,

even if it be assumed that the cigarettes smoked by the individual

and those smoked in the laboratory are exactly alike . This is

because the smoking habits of individuals vary, and because the

conditionsr under which cigarettes are smoked vary .

It may not be assumed, however, that cigarettes smoked by the

smoking machine in the laboratory are the sa .ro as the cigarettes

of the same brand purchased by the smoker . Because of unavoidable

variations in the manufacture and storage of cigarettes, differences

exist in the tobacco, paper, filter and condition of cigarettes so

that measurements of total solida and nicotine in the ssioke of ms

sample of cigarettes will differ from measurements obtained vitb

another sample of the same brand, assuming that all possible steps "

are taken to assure as eauch uniformity as possible . Zbe measure .ents

appearing on a package of cigarettes would relate to the cigarettes

used in the test, and would not be accurate as applied to the


cigarettes contained in the package .
Even if two cigarettes of the saoe brand, or of two different

brands, were to deliver preaisely the aase aount of total solids,


,`
variations in the .eigarettes, in smoking habits and in s .oicins oonditions

would generate total solids in the a.oke of oae of the cigarettes

composed of different quantities and kinds of chemical compounds from

those fouad_ia the total solids fro* the othsr cigarette . iiace it

is not known which, if any, chemical compound in the total solida

is harmful, it is not helpful to the ss»ker to furnish his a quanti-

tative measurement of total solids, especially one which, as has beaa

stated in the two preceding paragraphs, cannot be accarate .

The conclusion is therefore inescapable that labeling the

amount of "tar and nicotine" on a cigarette package cannot fiw to

the smoker meaningful information as to the amount or composition

of the total solids and nicotine he receives from the cigarettes be

smokes . He is more likely to be misled than informed .

Mthods f,Qr Ifeasgrin;Total „fiolidg and llieotine

The following five methods for aeaauring total solids and

nicotine are described in Appendix At the Wolsisn sr thod (1) ;

the Consumer's Union method - No .' I(Z) ; the Cambridge pilter

s+ethod (3) ; the loster D . Snell method (4) ; and the Liggett i l~rers

Tobacco Company method (5) . It should be recognized that a aumber

of variations of such methods are poasible, and there may be other

methods . Those described in Appendix A, however, appear to be the

ones most commonly reported .


•4•

The five s+ethods described in Appendix A have not baen

cosQared on the s .me lot of cigarettes . Tbrea of the tsthods,

hos+ever, hive been compared by Xsith iNevsom (S) . '!be results

of such comparison show distinct variations, and were nported

to be as follows :

' Liggett i Myers


Consumer's ttaion Poster D . Snsll Tobacco Co .
h2thod _ No . 1 (2) _~th d (4) _ Method (S) .

Solids, mg ./cig . 18 .8 $4 .2 19 .1

Nicotine, mg ./cig . 2 .2 2 .9 3 .5

it ia of course clear even apart from such comparisons that the

various aethods described in Appendix A naosssarily will produce

different results, because they do not start with the same smoking

conditions .

Generally speaking each of the mthods requires from five to t•n

cigarettes for testing purposes . Tbe cigarettes are smoked by a

machine, which is designed to retain 100x of the particulate pbase

of the smoke . Each method proceeds on the basis of smoking the

cigarettes using a fixed volu .e of puff, • puff ot-srecific daratioa,

a fixed frequency of puffing, and a specific asomt of the cigarette

to be smoked . All s+ethods other than that of Liuett i lbers tisae a~

1S-ui . volume of puff . The most eoasson duration of puff is tro

seconds, and the most comson frequency of puff is otu per sinute .

The Wolsun method and the Caabridse Tilter tiatbod* s .oked a fisad

* See footnote, page 12


length of cigarette (47 na .) regardless of the length of the

cigarette being smoked and regardless of whether it is a filter

cigarette or not . tow of the methods amolc .e to a predetermined

butt length, for exanQle, 23 0 . ; in such siethods the length of

cigarette smoked would vary depending upon the initial leqgth of

the cigarette being tested and v_hether or not it is a filter

cigarette . The Liggett iWers method smokes fourteen puffs of

each cigarette, so that the number of puffs taken determines the

length of the cigarette smoked .

From the foregoing it is apparent that each of ths .rthods

has adopted arbitrary smoking babita for the smoking tachine, which

habits do not correspond with the habits of each individual smoker .

The volume of puff taken in smoking a cigarette (6, 7, 10, 11), the

frequency of puffs (6, 10, 11, 13, 14), and the duration of the

puff (6-8, 10, 13, 14) vary among individuals . The length of

cigarettes smoked, or the butt length to which cigarettes are

smoked also varies among smokers (7-9, 11, 13) . lbese variations

necessarily mean that the amount of total solids astid nicotine

collected by the smoking machine is not the aaae as what the

individual smoker receives .

It is obvious of course that all smokers do not retain 1002

of the particulate phase as a smoking machine is designed to do .

The degree of inhalation differs appreciably s,oong individuals (11) .

Moreover, smokers who inhale hold the smoke in the lungs for
different times, some exhaling more Quickly than others (15) .

The amount of the particulate phase retained in the lungs

obviously~depends in part upon the time elapsing betwen inhalini

and exhaling . Smokers who do not inhale adait the smoke to their

mouths ; the duration of retention of the particulate phase in

their mouths obviously affects the extent of retention of solids (15) .

Other variations between smokers inelude the following : the

burning temperature of cigarettes varies from smoker to smoker

because of differences in smoking habits (6) ; the pressure drop

across a cigarette differs from smoker to smoker (6-a, 12, 14) ;

and the total number of puffs per cigarette and the time necessary

to consume a cigarette varies from smoker to smoker (8, 13) .

Successive puffs of an individual on the same cigarette uy

differ with respect to puff volume, puff duration and frequency,

degree of inhalation, tes4erature change by puffing, and pressure

drop produced by puffing (14) . The manner of smoking successive

cigarettes by an individual t.ay also differ . These differences

include length of cigarette eonsurd, total nueber of puffs per

cigarette, and time required to consume a cigarette (14) .

A11 of the variations so far mentioned have been the subject , .

of comaent in the scientific literature, and all would affect tha

asount of total solids and nicotine received by the individual

smoker as compared with a smoking machine . In addition, there

are other variable factors, .fiich have not been reported in the
scientific literature, and which saay affect the asount or

composition of total solids and aicotine deliverad to or retained


,1
by a saoke : . Some of these factors are :

a . Smoking at very low temperatures and very low humidity .

These conditions would prevail in the winter in the

nb'rthern states .

b . Smoking at reduced pressures, for example in the

mountainous states . There is some indication that

the rate of burning of a cigarette will differ

depending upon the altitude at which the cigarette

is smoked .

c . Smoking in areas which are either abnormally humid

or abnormally dry .

d . Smoking from a pack which has been open for more than

a day . The cigarettes nay lose appreciable moisture

under arid conditions . Although loss of moisture

wiil not affect weight of solids produced per ci6a-

rette, it is believed to affect the chemical composition

of smoke .

Variations in Ciaarettes
~.
The following variables affect the yield of total solids per

gram of tobacco product consumed, and composition of the smoke

and total solids :


a . Tobacco (37, 38) . 6ince tobacco is aa agridiltural

comiewdity, it is sot boaogen .oua . Its cbaracteristics

~ary from leaf to leaf of t6e sa.e plamt, asd vithin

the same Laf . Aad of course a .ariety of types,

grades, and blends of tobacco are used is'the smufacture

ot.cigarettes, such as jlus-cured, burley, aad Turkish

tobaccos, and blends of such tobaccos . ,

b . Filtra_ tion aad eressuXg droD (17,9~3i, 33~5 the higher

the degree of filtration, the lowar the total solids=

and the higher the pressure drop, the lwrer the total

solids . The efficiency of filters of the sar design

vill vary from filter to filter dapending upon the

construction or the .aaner ia•vliich the filter tar is

packed .

c . Pa~er porositr (Z6, 31, 38) . The cigarette paper Mhich

is normally supplied to tha cigarette sanufacturrt

usually has an appreciable range of porosity . %e solids

usually decrease as the porosity iscrrasos .

d .. Number of euffs ~~
.~~.~.~•
taken
.
to .~i~g~leattb
oonaus a w~
... r ~~~.
of
.~..r~L

aia_ arette (t7, 32) . For axaaple, lurley tobacco burns at .: .


a greater rate than other tobacco types= aed thus, a .

different number of puffs are reqnir+N~Ro oontosr t1~s sar


,
cigarette length of lurley, flue-cur.d, md llittdsb

tobaccos .
a. Moisture content qfciasrettes (27, 29, 38) . tbe ap of

the cigarette (e .p ., the length of tir on the retailer's


,` . ., .
shelf) sry af fact the nois ture cant.at . ''

f . Va_liations to _o,i„jotal solids snd,tiicotins in

Sach f (17, 22-24, 36) . It bas bsn suuest .d ia the

scientific litarature•tbat the asawat rd corposition of

total solids in later puffs .ariudly esouds that in

earlier puffs (22-24jt others report finding very little

difference between tbe asomts in the •arlr and late

puffs (17, 36) .

t. Additives on tobacco (16, 18, 20, 21, 259 30, 36) . The

amount of total solida and oo .position of the s .dce aad

solids vary with the asounts of additives such as licorioa

and glycerol . It is impossible to apply these to tobacco

uniformly .

Of course aow of the above-msntloosd variables are ietsr-

dependent= e .g ., filtration, paper porosity, and pressure drop .

Moreover, it should be qphasiad that there viil tie tariation tros

cigarette to cigarette ia the composition of sacb cisaratte Miss

to the nature of the cigarstts-sishint process . '

IM Qe s in the gM o sitt i~~ ow=rQta L~ .=wi


.
W

It has been pointed out that the a .amt of total solids aad

nicotine produced by smoking can be chsajed by a large number of

variable factors, including the type of tobacco, the efficiency of


•10-

the filter, and the porbsity of the citarette paper . As has been

osntioned in connuction vith such factors, they (and probably oths n)

aay also ciange the ratios of the various cowposrents of the eooks .

As a result, although the a*ount of total solids .ay teaain the saoe

or be reduced, the ratios of the co .poaents in the•total solids mp

be different .
-il-

.APp
._ .EMIX
IiE1'HODS FOR DETEMNATION QZ KICOTINE A& IMDS_

I . T_h Nolman! t~ethod_ (1)

The conditions for smoking are as followss

Length of cigarette a.okad - 47 millimeters (o .)


Length of butt - variable, depending on length•of cigarette
being used in test
Volume of puff - 3f sdlliliters (or cubic centimeters ; sl . or cc .)
Frequeecy of puff - one puff`per minute
Temperature of laboratory - 71' F .
Relative humidity of air - 45%
Clgarettes smoked for each determination - Five

In this and in other methods, the cigarettes are selected for


uniformity in moisture content, cigarette sise (if feasible),•
cigarette weight, firmness, and other characteristics .

Solids for determination of cot e are collected over 10 rl .


of alcohol acidified with sulfuric acid in a 300-al . Kjeldahl fluk .
Solution is treated with alkali and is then steam-distilled . The
steam distillate is then treated with silicotungstic acid to precip-
itate the silicotungstate . The silicotungstate is ssparated and is
ignited to an ash . The weight of the ash is uaed in the calculation
of the nicotine value . However, since in this method, other alkaloids
could coprecipitate with nicotine as ailicotungstates, this datermina-
tion in reality may, depending on conditions of the experiment, yield
the alkaloid value or the total alkaloid value . Mother itss to note
is that the silicotungatic procedare can also be described as the
gravimetric procedure - implying that a weighing is performed in tLe
determination of nicotine .

Sol~tds_ (designated as tars in tbe article) are determined by ,


gravity deposition of smoke aver 25 rl . of 0 .11 aqueous sulfuric
acid . The mixture is extracted with chloroform . The chloroford
solution is heated to evaporate the chloroform . The residue is then
heated, or dried, for three hours at 100' C . (!12' F .) . The weight :
of material remaining after the beating is reported as tars .

~_ e Consumer's Union Method - tlo . I(2)

Smoking conditions :

Length of cigarette smoked - variable, depending upon length of


cigarette being used in test
Length of butt - 23 sss .
-12-

Volume of puff - 35 ml .
Duration of puff - 2 seconds
Frequency of puff - one per minute
Room emperature - Not stated
itelat~ve Humidity - Not stated
Cigarettes smoked for each deteriination - eight

Smoke for nicotine and solids is absorbed in acidified alcohol .


One portion of the alcohol solution is treated with base and is
steam-distilled . Nicotine in steas distillate is measured by means
of a spectrophotometer . This then is a spectrophotometric proeedure,
whereas thi Wolman method described above is a gravimetric procedure .

The second portion of the alcoholic solution is acidified,


diluted with water, and is then extracted with chloroform . The water
layer is made alkaline and is re-extracted with chloroform . The two
chloroform extracts are combined . Removal of chloroform from com-
posite by evaporation yields the tar, which is then s'rrjighed .•

III L, The CambridAe Filter Nethod (3) - Sometimes referred :,to as•the
American Tobacco Co . Method or the Consumer's Union Nethod-~to . II .

Smoking conditions :

Length of cigarette smoked - 47 =m .*


Length of butt - variable, depending on length of cigarette
being tested
-Volume of puff - 35 al .
Du;ation of puff - 2 sec .
Frtquency of puff - one per minute
Temperature of laboratory - Not stated
Relative humidity of laboratory - Not stated
Number of cigarettes smoked per determination - ten

Smoke from a cigarette is collected on a glass fiber filter


material, Cambridge filter medium CM-113 . The weight of material
retained on the filter represents total solids (total particulate
phase) . A part of the material retained on the Cambridge filter is Ln
water (about 12% in smoke from a 70-mm . blended, non-filter cigarette) . ~
This method, therefore, would include water in the value for total 6,
solids, whereas the preceding two methods would not . ~
~

It should be noted that in the Cambridge filter method outlined by


~ Ogg et A1 . (39 , ~ t
® 40) ss+okes the cigarette under test to
`• a 30-am . butt length . Further modifications of this method,
including length of cigarette to be smoked, are under consideration
by the Analytical Methods Coamittee of the Tobacco Cbemists' Research
Conference .
-13-

To determine nicotine, the Cambridge filter with the retained


solids is extracted with 0 .1 N_ Sulfuric acid . The solution, after
washing with chloroform, is made alkaline and is steam-distilled .
Nicotine in the steam distillate is determined either by the gravi-
metric metAod (silicotungstic acid precipitation, aahing and weighing
of ash) or by the spectrophotometric method .

IV . The Foster D . Snell Hethod (4)

Smoking conditions :

Length"cf butt - 23 mm . -
Length of cigarette smoked - variable, depending on length of
cigarette being tested
Volume of puff - 35 ml .
Duration of puff - 2 sec .
Frequency of puff - one per minute
No . of cigarettes smoked for each determination - five
Room conditions not specified

For solids determination (tar content in communication) smoke


is collected in acidified alcohol . The alcohol solution is heated
on a steam bath (at 100' C ., 212' F .) to evaporate the alcohol .
After about five hours, the residue is heated in the beaker at 105' C .
for beven hours . The weight of material remaining in the beaker is
designated as the tar content .

To determine nicotine, the acidified alcohol solution containing


the smoke solids (on aliquot portion) is heated to remove the alcohol,
the residue is made alkaline and is steam-distilled . Nicotine is
determined gravimetrically in the steam distillate (ailicotungstic
method) .

V . The Li,ggett and Myers Tobacco Co . Method (5)

Smoking conditions :

Number of puffs - 14 - the only method of the five enumerated


here which uses the number of puffs as the controlling factor
in the amount of cigarette to be smoked .
Length of cigarette to be smoked - Variable, depending on length
of cigarette being tested,
blend of tobacco, pressure drop,
and other factors
Length of butt - Variable, as in preceding item
Volume of puff - 44 ml . (all preceding methods above, 35 al .)
Duration of puff - 1 .9 sec .
Frequency of puff - One every 30 seconds (all preceding methods
above , one pe r ssin . ) .
-14 -

Room temperature - 75' F .


Relative humidity of room - 60 2
Cigarettes smoked for each detersiaatioa - ten ; however . it is
Oecoamended that three to six such determinations be carried
out and the results averaged .

The smoke in the present a+ethod is retained on an alpha-cellulose


trap .

The alpl .a-cellulose is washed with hot acidic sk thyl alcohol .


The solutioii is extracted with cf -iloroform .

To determine solids (termed tar in the articles) the chloroform


solution is evaporated on the steam bath and heating is continued for
3 hours at 105' C . Tar value is determined by weighing the residue .

The extracted methanol solution is made alkaline and is steam-


distilled . Nicotine is determined in the steam distillate apectro-
photometrically .
-17-

Lindsey, A . J ., Persaud, K ., and Candeli, A ., Reducti,on of


Benzpyrene in Cigarette Smoice . BRIT . MED . J ., i= (ii), 821 . f
Lipp, 6 ., and Van Hooy, H ., lieue tiethoden sMr Nn,~,ssuaQ der_Foro_,_ at
von Ciaaretten,pauier ,u,n¢ des Ve,Btia,t, laaeara es von Ciaaretten . Y
BEITR . TABAKFORSCH .,,1962L (9), 369-384 .

Newsod; J . R ., and Keith, C . H ., 0uantitativ* Studies dies oa Ciaa,rette


Smoke . II . The Effect of Phvsica,l Variab es gA the iJe,ieht s~f,, Smoka .
TOBACCO SCIENCE, t, 58-63 (1957) .
:- -
Nicod, J . L ., The Acute To,gdcitv and Carcinoaenic Povej of obacco
Extracted by CC14 . Z . PRAVENTIVMED ., ¢,, 444-454 (1961) .
.
Sato, T ., Fukuyama, T ., Suzuki, T ., Takayanagi, J . and Sakai, T ., ~
Difference in Mortality Rate from Luna Cancer betzveen Several_Countries
Where Cigarettes Are Smoked,~and Observations the Low Humidityof
Qarett~es, in Winter in Heated Rgc, . SULL . INST . PUB . HEALTH
(Japan), 1, 31-35 (1961) .

Scherbak, M ., Rice, R . L ., and De Souza, J . E ., An llbsolute #Igthod


for the Aeternination of 3 .4-Bensvvrene in Ciaarette Ssroke . Paper ,~
Presented at 17th Tobacco Chemists' Research Conference, Montreal, P .Q .,
Canada, September 22-24 (1963) .

Schur, M . 0 . and Rickards, J . C ., Design and Overation of a Plultivle ~


Cijzarette Smokinjt Machine . TOBACCO SCIENCE, l, 13-20 (1957) .

Segelken, D ., Schroder, R . and Seehofer, F ., The Effect of Number


of Puffs and .of Puf f Serial Number on Ciaarette Smoke Condensate . ~
TABAK TECHNIKUM E{AMBURG TECHNISCHE-WISSENSCHAFTLICHE SCHRIFFTENREIHE,
1962, 1-7 (September) .

Uhlman, W ., Statistical Remarks o_ n,the Research of_ J . L . Nicod on


the Carcinogenic Effects of Pre-exticted Tobacco . Z . PR*VENTIVMED .,
8 140-144 (1963) .

Wa1t .., P . and Hauaermann, M ., Modern Filter Cigarettes and Their ~


Effects on Smoking Habits and Inh ql,ed . ~ . .PRAVENTIVM$D .,
Substaa sS~
. .-....~_..
8, 73-98 (1963) :Y

. . L . and
.Wynder,E Hoffmsn, D ., So` Practical Aspects of the .; ~
Smoking-Cancer Problem . NEW ENG . J . MED ., 2 2, 540-545 (1960) . `'

Wynder, E . L . and Hoffman, D ., Present Status of LaboratoryStudies 5 ;


on Tobacco Carcinogenesis . ACTA PATHOL . MICROBIOL . SCAND ., 2 a/,
119-132 (1961) . cr
0
M
~
r

W
N
5171 0 4947 r
r.
wynder, E . L . and Hoffman, D ., 152erimental Conttibution l~frt~
Concerning Tobacco S,moke, CanceroRenesis . DBtJT . MED . WOCHSCHR ., ~8
623-628 (1963) .

Wynder ; E . L ., and Hoffmaa, D ., E~eriaental Tobacco Carcinoaenesis .


ADV . CANCER RESEARCH, 8, . 249-453 (1964) r

Ogg, C . L ., Bates, W . W ., Jr ., Cogbill, 8 . C ., Blackmore, R . H .,


and Petersen, E . L ., Determination,of Total Paiticulate !latter . /
Nicotine, and Water in Ciaarette Smoke . J . ASSOC . OFF . ACR . CM . V,
45, 540,545 (1962) . _

Ogg, C . L ., Determination of Particulate Natter and Alkaloids ,~


(as Nicotine) in Ciaarette Smoke . J . ASSOC . OFF . AGR . CHEM .,
.4_7_v ~/
356-362 (1964) .
ELI OCRAPHY

Wc,iman, W ., A Study of Cigarettes . Ciaarette .Smoke, and Filters . l


ls Fi__ ]~ter-Tip Cigarettes . J . AM . MED . ASSOC ., 152, 917-920 (1953)
. v

Consumer Reports, Cistarettes : A Three oart Report . CONSUMER


REPORTS, 20, (2), 56-74 (1955) .

Wartman, W . B ., Cogbill, E . C ., and Harlov, E . S ., Determination /


of Particulate Matter in Concentrated Aerosols . Application t Vo
M a1vsiT of Cigarette Smoke ._ ANAL . CHEM ., 31, 1705-1709 (1959) .

Sk)ecial communication from Cyril S . Kimball (of Foster D . Snell) on :


Methodolo v Employed in Determination of Tar and Nicotine Content
of Cigarette Smoke for Reader's Digest .

! 5 . Keitl :, C . H ., and Newsome, J . R ., Quantitative Studies on Cigarette ~ o


~ A Smoke
i S . 1ki
. M Mutoma140t c TOBACCO
mo n ac : n SCIENCE
. 1 .51-57
. ~
(1957~• 2 The Effect of Phvs i ca l V ar i abl es on the WeiAht of Smoke .
d ., 1, 58-63 (1957) ; a Methods of Ana Lvsis for Filter Ciaarettes . 1
Ibid ., 2, 14-19 (1958) . (' 1<41\1

Cuzin, J . L ., et al ., L'Acte Saecifiaue du Fumer . PROC . 2ND


INTERNAT . SCI . TOBACCO CONGRESS, 1958, ,-521-535 .
~
t
Schur, M . 0 ., and Rickards, J . C .,Design d Oaeration of Multiale ,~A
n
Ciaarette Smoking Machine . TOBACCO SCIENCE, 1, )3-20 (1957)

. C ., On Cigarette SmokinA, Bronchial Carcinoma, and


.hildng,A
Cilinry Action I . Smoking Habits And Measurement of Smoke Intake .
'7Et; ENC . J . MED ., 254, 776=781 (1956) .

Finkncr, A . L ., Horvitz, D . C ., Foradori, C . T ., Fleischer, J ., and


Monroe, J ., M_ Investig,ation of the Measurement of Current Smokina
by Individuals . July (1957) . •

Derr, R . B ., Riesmeyer, A . H ., and Unangst, R . B ., Ramoval o


Undesirable Constituents from Tobacco Smoke . IND . ENG . CHEM .,
f
2y, 771•776 (1937) .

Cigarette Components, Ltd ., Ci aarette Smokina : StudX of Certain


Asgects of Human Smokin Ha s . October, 1957 .
~
Bradford, J . A ., Harlan, W . R ., and Hanmer, H . R ., Nature re of_
Ci arette Smoke : Technic of Exaerimenta S,moking . IND . ENG . CHEM ., J
28, 836-839 (1936) .

51710 4949
Bentley, it . R ., and Burgan, J . G ., Cigare ke Condensate :
Prepar~tion and Routine Laboratory Esti :nation . TOBACCO MANUFACTURERS'
STANDING COWITTEE, RESEARCH PAPER NO . 4, 2ND EDITION, 1961 .

.Sta+ib,"M ., and Furrer, H ., Tobacco InvestiAatiqg . _ e Reoroduci-


bilitv of Smoke Investixations . MIT . LEBENSHIT . HYG ., J1, 94-116 V
(1957) .

Mitchell, R . I ., Controlled Measurement of fim6,ke-particle Retentioa V


in the Respiratory Tract . AM . REV . RESPIRATORY DIS ., jj, 526-532
(1962),.
I

Alvord, E . T ., and Caxb6n, S . Z ., The Inhibition f F_ormatiot~of


3 4;BenzpYrene in Cia~rette Smoke . BRIT . J . CANCER, }s,, 498-503 (1956) .

Ayres, C . I ., Fordyce, W . B ., and Hughes, I . H ., Ciaarettes : The v


Potential of a Tobacco to Produce Smoke . Paper presented at 17th
Tobacco Chemists' Research Conference, lbntreal, P . Q ., Canada,
September 22-25 (1963) .

Bentley, H . R ., aad Burgan, J . G ., Polynuclear Hydrocarbons in l'


Tobacco and Tobacco Smoke . Part III . The Inhibition of the Formati Von
of 3 .4-Benzpyrene in Ciaarette Smoke . ANALYST, IL, 727-730 (1960) .

Bock, F . C ., Moore, C . E ., Dowd, J . E ., and Clark, P . C ., Carcino¢enic


Activity of CaaLette Smoke Condensates :: Bi-o_loA+ical Activity__of
Refined Tar from Certain Brands of Cigarettes . J . A . NED . ASSOC . Y
181, 668-673 (1962) .

-~; Candeli, A ., Lindsey, A : J ., and Persaud, K ., Cigarette Paper


Containing Amconiu,g Su amate and Carcinoaenic .Hvdrocarboas .
SOC . ITAL . BIOL. SPER ., a, 452-4.54 (1960) .
J
Cuzin, J . L ., Testa, A ., Testa, S ., and Anguera, C ., Chemical and
Bioloaical Control of, the Ggndensetes Rettiltinst from the Smokina of V
Tobacco Treated by the Patented Neukoom-Bonnet Procedure .
Z . PRAVENTIVMED ., B, 125-137 (1963) .

Kotin, P., and Falk, H . L ., e Role and Action of Environmental


Agents in the Pathogenesis of Luna Cancer . 11, Ci, Qaretle -$mk~.
f
CANCER, 13, 250-262 (1960) .

. Lindsey, A . J ., The Comoosition of Cigarette Smoke : Studies on


Stubs and Tips . BRIT . J . CANCER,,Us 195-199 (1959) .
~
Lindsey, A . J ., Some Observations rvations Upon the Chemistry of Tobacco
Smoke . Chapter in James, G ., and Rosenthal, T ., "Tobacco and Hea1t ',
Springfield, Illinois, C . C . Thomas, 116j, 21-32
. 1

51710 4950
L .J

• FEDERAL TRADE COMMISSIDN .


/Yasbington, D.C. 20S80
,.
OFFICE OF INFORUATlON M-6800 Ext. 197 .
• For RCLEASC: I1•:-MDIATE, Friday ttarch 25, 1956 .

~ The Federal Trade Comission today announced that it,has sent identical letters

• to each of the nation's major cigarette manufactu•rera and to Mr . Robert D . tdeyner, :


.i
Adainistrator ot Fhe'Cigarette Advertising Code, Inc ., in regard to factual state-
:
' ments of tar and • nicotino content on labcls and in advertising of cigarettes . ~
i
The text of the letter is as followss ' , .•
.i . .
i
~ Gentlaoens
The Cigarette Advertising Guides proawlgated by the Commission in
Septembor 1953 provided that no representation should be made that "any
brand of cigarette or the smoke therefroa is low in nicotine or tars *+~ *'
when it has not been established by competent scientific proof applicable
at the time•of dissemination that the elaim is true, and if true, that
such difference or differences are significant ." On the basis of the !
--•--•»•-- facts now available to it, the Commission has deterainsd that a factual
statement of theQ and nicotine content (expressed in milligre-'es) of f
the mainstream srao~ce from a cigarette trould not be in violation ot such
Guides, or of any of the ptovisions ot latr administered by the Co=issioy,
so long as (1) no collateral representations (other than factual state-
suats of tar and nicotine contents of cigarettes offered for sale to the ,
~ .
public) are made, expressly or by implication, as•to reduction or elinina-
; tion of health haaarda, and (2) the statement of tar and nicotine content
is supported by adequate records of tests conducted in accordance t+ith
the Cambridge Filter Method, as described in an article entitled "Deterai-
nation of Particulate Matter and Alkaloids (as Nicotine) in Cigarette
Smoke," by C .,L . Ogg, which appeared in the Journal .of the Asaoeiation ~ :
of Of•ficial Agricultural Chemists, Vol . 47, No . 2, 1964 . It is the
Comcaission's position that it is in the public interest to promote the
dissemination of truthful inforaution concerning ,cigarettes which may be
materi~al and desired by the consuming publie,
8y direction of the Coaoaiesion . ' .• . ~
. Joseph W . Shea,
• Seeretary . • .
. . .
., .
Table 8. Continued :

1 33 1 .5 60 23 .7 1 .60 9 .3

3 35 2 .5 24 .1 1 .43 9 .1

• Data are from Itix (1979) who also presented similar data for the 85-mm Marlboro . Rix also presented data on the
yields of TPM, TPM water, and carbon monoxide .
b Data represent the average "tar" and nicotine yields from Samples Noi . S through 10 .

Rix (1979) also compared the effect on the carbon monoxide, nicotine, and "tar" yields
from the 85-mm Winston and 85-mm Marlboro of changing the major FTC smoking parameters
(35-m1 puff volume, 2 .0-sec puff duration, 60-sec puff frequency) to more "realistic""
smoking conditions (65-m1 volume, 2 .0-sec duration, 45-sec frequency) . Table 9 summarizes
the results obtained . At the higher puff volume and frequency, the % differences between the
Winston and the Marlboro become less for MS "tar" and nicotine yields, with the Winston yield
being the higher . In the 150-page report by Rix, there are numerous plots of the relationships
between carbon monoxide, nicotine, and "tar" yields and puff volume, duration, and frequency
for the 85-mm Wlnston and Marlboro . Also included are plots (2-sec puff duration, 1 puff/min)
of the "tar"/nicotine ratios vs puff volume for the following brands : Winston, Camel, Vantage,
Now, More, Real, and Marlboro.

TABLE 9 : 8S-mm WINS'liDN AND BIARl.BORO: COMPARISON OF FTC CARBON


MONOJaDE, NICOTINE, AND "TAR" YIELDS AT STANDARD AND MORE
"REALISTIC" SMOKIIVG PARAMETERS
FTC "Tar" . FTC Nicotine, FI'C CO, "Tar"lNicotine
cjg .roue /cpyc irt pg/cIrt - lciat Ratio

FI1C smoking rondlHonr (3S,nd pqJ, 2.0•sec pulduradon, oxe p{D'every 60 sec)

Wtnatat 20.6 (20 .9)• 1 .43 (24 .5) 19 .1 (15 .2) 14 .4 (-4 .8)

Marlboro 16 .3 1 .08 16 .2 15 .1

"Realttde" snwktng condidons (6 .f-rnl pqD; 2.4see pqfdunuton, one pqfevery 45 see)

1Hnsron 35 .7 (iS .7) 2 .35 (16 .8) 33 .9 (15 .3) 15 .2 (-2 .6)

Marlboro 30.1 1 .93 28 .7 15 .6


' Numbera in parentheses represent % difference between WINSMN and JNdRLBORO :

% Difference - 100(Wfngton - Marlboro)lliRroron

In a similar study on the 100-mm Winston and the now defunct 120-mm Dawn, Dobbins
(1984) elected to vary the puff volumes at different puff frequencies with the puff duration

13 Whether the "realistic" conditions for 1979 amokets would apply to current (1994) smokers Is not known . Two years later, Herning er
al. (1981) observed that filter cigarette smokers took a 35 .9- to 47 .8-m1 puff of 1 .94 to 2.06 aec every 26 .9 to 30.0 sec .

27
c:lfdaniclnicotn-1 . fda

revised 11-02-95

COMWIM re FDA NICOTINE REPORT : GENERAL

• "tar" reduction plus nicotine reduction - graph presented by


Wakeham, Surgeon General, etc .

1954 nicotine delivery level = 2 .7-3 .0 mg/cigt

steady decrease in nicotine delivery vs time : current


nicotine delivery, even if modified slightly for low-
"tar" vs regular-'4tar", is substantially less than
the 1954 value

why did FDA elect to consider nicotine delivery


levels only from 1982 to 1991? (see p .267-270]
Are the data correct that the sales weighted average
nicotine delivery for all cigarettes increased from
1982 to 1991? Recollection : nicotine level was
decreasing gradually through 1986119871

Is it because of the substantial decrease in sales


weight average nicotine delivery from 2 .7-3 .0
mg/cigt 1954 to about 1 .0•1.1 mg/cigt in 1980 .

If the tobacco companies were so eager to "hook"


the consumer, why did they reduce the nicotine
delivery so drastically?

what was the fate of the low-nicotine or zero-


nicotine cigarettes marketed around the world (U .S.
- Sano, brand in Gennany, etc .?) Most were
withdrawn within a year or two found them
unacceptable . The Sano was marketed for many
years but eventually was withdrawn because of
extremely low sales.

why did FDA cite Imperial Tobacco Company U .S.


patent for enhancing nicotine? Imperial is not a
U.S. company and sells few cigarettes in this U .S.

. "tar"tnicotine ratio proposals of Russell and Jarvik :


substantially decrease "tar" delivery but not
nicotine delivery or substantially decrease "tar"
delivery but decrease nicotine delivery only slightly .

post-1954 it was the practice of U .S. tobacco


companies, particularly RJRT, to investigate all
suggestions from external sources pertinent to
smoking-health issues :

1 . clean bill of health from Surgeon


General in 1964 re nicotine

2. recommendation by Wynder et al .
(late 1950s, 1964 review, 1967
book, 1968 monograph) that
reducing "tar" delivery by 50% or
more would reduce respiratory tract
cancer: mouse skin-painting studies
indicated that such a reduction in
"tar" dose lowered the % tumor-
bearing animals from m45 to 0%!
more recent studies in the 1968-1980
NCI smoking-health program on the
"less hazardous" cigarette
essentially confirmed the earlier
findings by Wynder et at.

(a) when the tobacco


industry accomplished
an approximately 50
% "tar" reduction by
cigarette design, the
reduction was not
considered to be
enough
(b) When reduction of
approximately 70 %
in the sales weighted
average "tar'• was
accomplished (40
mg/cigt in 1954 vs 11
mg/cigt in early
1990s). other factors
were emphasized

2
(increased use of
flavorants in low-
"tar" cigarettes,
harmful pyrolysis
products from
flavorants, smoke
nicotine level, tobacco
nitrate level and N-
nitrosamines, blocking
of filter-tip ventilation
holes by the smoker,
environmental tobacco
smoke diversion, etc .

3 . levels of tumorigenic polycyclic


aromatic hydrocarbons in MS could
be reduced by

(a) filtration (reduction of


"tar" delivery)
(b) reduction of
polycyclic aromatic
hydro-carbon
precursors in tobacco
( s a t u r a t e d
hydrocarbons,
phytosterols,
terpenoids) by
extraction of tobacco
with organic solvents;
because the extraction
produced only a slight
lowering of the
tobacco nicotine level,
the level of MS
nicotine was only
slightly reduced
(c) addition of burn
modifies, g e,.,
nitrate, to tobacco
and/or to the cigarette
paper (citrate) ; both
these technologies
reduced the MS

3
-1

nicotine level
(d) inclusion of processed
tobaccos (RTS,
expanded tobacco) in
the blend ; both
processed tobaccos
yielded reduced
nicotine levels in the
blend and its MS
(e) air dilution (cigarette
paper porosity, filter-
tip ventilation)

4. levels of tumorigenic N-nitrosamines


could be reduced by

(a) filtration (volatile N-


nitrosamines removed
selectively from MS
by plasticized fliter
tips)
(b) use of low-nitrate
tobacco or by removal
of nitrate from
tobacco and/or stems
by extraction, etc.
(c) addition of high
molecular weight
saturated
hydrocarbons .

5. compare the changes in the anti-


tobacco investigators suggestions
over time: reduction of levels of
tumorigenic polycyclic aromatic 10
hydrocarbons in MS by removal of
their precursors from tobacco by
extraction andlor by addition of
nitrate or use of high-nitrate
tobaccos vs reduction of tumorigenic
N-nitrosamines by addition of high
molecular weight saturated
hydrocarbons (a demonstrated

4
polycyclic aromatic hydrocarbon
precursor) and/or removal of r.itrate
from the tobacco or use of low-
nitrate tobaccos

6. according to some authorities (Van


Duuren et al., 1960), level of
tumorigenic aza-arenes in MS is
related to nicotine level of tobacco ;
however, at least seven different
studies conducted in the U .S., Japan,
and Germany between 1963 and
1992 failed to confirm the presence
of the tumorigenic aza-arenes in MS
(Candeli et a1 ., 1963 ; Kaburaki et
al., 1970; Schmeltz et a1., 1972,
1979; Snook, 1978 ; Snook et al.,
1981 ; Grimmer et a1., 1986, 1987 ;
Kamata et al., 1992)

7. levels in MS of allegedly promoting


low molecular weight phenols can be
reduced by

(a) filtration : phenols are


selectively removed
from MS by
plasticized filter tips
(b) addition of nitrate or
use of high-nitrate
tobacco

levels of low molecular weight


phenols in MS are Increased by
organic solvent extraction of tobacco

RJRT efforts re flue-cured standards association (?)


and burley standards association to have acceptable
nicotine range for new tobacco introductions
modified so that a lower lower limit was acceptable :
range was altered by the associations but reduction
of lower limit was less than requested, upper limit
remained unchanged ; major opposition included the
farmers (yield per acre and revenue) and at least

5
one other tobacco company (L&M) ; L&M
maintained the position that the nicotine range
should not be modified because of the importance of
nicotine to the smoker, l .e., it was the major reason
why smokers smoked

level of nicotine in MS may be reduced by

(a) solvent extraction of the tobacco


(polar solvent more efficient in
removing nicotine than nonpolar
solvents)
(b) addition of nitrate or use of high-
nitrate tobacco in the blend
(c) inclusion of processed tobaccos
(RTS, expanded tobacco) in the
blend
(d) use of . genetically designed low-
nicotine tobaccos or low-nicotine
tobaccos grown under reduced
nitrogen/nitrate fertilization
: levels of precursors of flavorful smoke
components are usually proportional
to nicotine level of tobacco, hence
flavor becomes less acceptable to
smoker
(e) use of filters containing acidic
additives which will react with MS
nicotine, removing it from the MS
stream

6
• suggestions by investigators such as Russell, Jarvik, and others that the design of
a "safer" cigarette should involve the substantial reduction of "tar" delivery and
either maintenance of the nicotine delivery at the level it was prior to
manipulation of the "tar" delivery or only involve a slight reduction of the
nicotine delivery' . E.g., Russell and coworkers suggested that

a low-tar, low CO, but nedimr-, rather than low-, nicotine


cigarette might reduce tar and CO intake more than occrrrs
with low-tar, low-CO, low-nk+ntlne cigarmes

Finally, a case will be made for a medtian-nlcntine, low-tar,


low-carbon monaxtde (CO) ctgarette.. . [emphasis added:
AR]

I Ruaell MAR, WUwn C, PaW UA, Cde W, and Peyenbend C(1979), Compedwo of 1he BReet on Tob .ooo Coorump8on and
Carbon Moooxlde Ab .oep8oa of Cha*q to Hijh and Low Nlcado . C*reqe. . BRIT. M®. J .1973 PW): 512 ; RuaeU MAH,
Cole PV, Idle MS, and Adame L(1975), Ceebon MonoxWe Ykldi of CSpreaa and T6eir Rel .doa to Nioodne Yield and Type of
Fiher. BRIT. MED. J. 1971 ft : 71 ; Ru ..eU MAH (19M, Low-T.r, Medium-Nicodo. Clpreuee: A Nerr Appra .c6 to Safer
Smokn. BAIT. M®. J .1976 p) : 1430; (19E0), lti.k Rednodon Ao6ievemems and Fuame Direodoos .lo God 09 and Bock FQ
(8dttor.) . d Sqfs Qaaftaet danbary Repmt 3, Cold Sprioj Hubor Leboatory . Cold Spring H.ebor NY :137-177; (1950), T6e Ca .e
for Medium-Nicodne, Lo .v Tu, Low Carbon Monoxide Ci ;areaa .ln God GB and Book tO (Ediwrs) . A So Qamrael Banbwry
RepoR 3, Cold SprinS Harbor Lebor .tory, Cold Spring Harbor NY : 297-310.

7
EXHIBITNO .____~&
Wit: ^
Date:
Rptr:

C : \fdanlc\Ilico fil-2. fda

Revised 11-25-95

COMMENTS re FDA NICOTINE REPORT : NICOTINE & AMMONIA

In its 1995 report, the FDA discussed the chemical manipulation, particularly the use of
ammonia and ammonium compounds, to enhance nicotine delivery' .

• tobacco treated with ammonia/steam (the process used by RJRT to


reduce the nicotine level in high-nicotine tobaccos) produces the
following changes:

in the tobacco

(a) reduced nicotine level (% reduction


is dependent on processing
parameters set by Company to
achieve a certain nicotine level)
(b) reduced sugar level (% reduction is
dependent on processing parameters
set by Company to achieve a certain
nicotine level)
(c) increased levels of alkylpyrazines (%
increase is dependent on processing
parameters set by Company to
achieve a certain nicotine level)

in the MS from the ammonia-treated tobacco

(a) on an equal weight of tobacco


smoked basis, the nicotine delivery is
lower in the MS from the processed
tobacco than in the MS from the
control tobacco
(b) the MS from the processed tobacco
contains higher levels of flavorful
pyrazine and alkylpyrazines than the
control tobacco MS (pyrazines are
highly flavorful compounds that
impart desirable flavors to tea,
~
~~
~ United States Fc1pd and Drug Administration (FDA) (1995) Nicotine in Cigarettes and Smokeless Tobacco Products Is a Drug and ~
~
The.e Products are Nicotine Delivery Devices under the Federal Food, Drug, and Cosmetic Act . US FDA DHHS: 1-326 (August) :
249-250 .
coffee, cocoa, peanuts, roasted
meats, etc.)
(c) the MS from the processed tobacco
contains higher levels of pyridine
and alkylpyridines which, at low
concentrations, are flavorful ; the
source of the pyridines in MS is
primarily nicotine which is an
indication that more of the nicotine
in the ammonia treated tobacco is
being decomposed during the
smoking process than that in the
control tobacco
(d) the level of ammonia in MS is
increased

While the precise wording of the definition of a "safer" or "less hazardous" cigarette
as enunciated by different investigators has varied slightly during the intervening years, the
essence of it is essentially the same now as it was forty years ago, namely, a "safer" or "less
hazardous" cigarette has been defined over the past forty years or so as one whose MS
particulate matter has been reduced and whose MS particulate matter shows reduced specific
tumorigenicity as measured in mouse skin-painting studies= . Within this definition has been the
implication that the total particulate matter should show, on a per milligram basis, reduced levels
of those MS components considered responsible, at least in part, by some investigators for the
observed tumorigenicity in laboratory animaW . Much effort in the 1950s and 1960s was
directed toward the reduction of the MS delivery of polycyclic aromatic hydrocarbons shown to
be tumorigenic to laboratory animals under certain experimental conditions. Subsequent research
involved methods to reduce the allegedly promoting phenols, the ciliastatic vapor-phase
components (aldehydes, ketones, hydrogen cyanide, low molecular weight acids), and the
volatile and tobacco-specific N-nitrosamines . I

Expansion of tobacco lamina has been accomplished by a variety of processes . The first
three methods developed were the RJRT process involving the expansion of tobacco lamina with
a chlorofluorocarbon, the NCSU process involving the expansion of moistened tobacco lamina
by freeze drying, and the PM process involving the expansion of tobacco by sequentially treating

0 Wyndor BL and Hot6n.m D (1964), $xpeeimeatal Tob.ooo C.roioopo..b . ADV. CANCER RES. d: 249-453; (1967), Tobaoco
ard Tobacro Stinoks: Sawbu fn &Psri+nertai CarbWjauitr . Ik .dendo lkea, No .v York NY; dod aB (Bditoc) (1976) . Report IJo.
! . To+wd Lea Astardow Qaanaa. 711e Ptrrt Set of Bxperlamwl aaamrxa . DBEW P.bl. No. (Nffi) 76-90d ; (1976),1tePoa
No. 2. Towand Lsrt 8atardow Qjanaa. 711t Ssowj Sn 4fSxpsdnanal atanau . DHEW ML No. OM 76-1111; (1977),
Report No. d. Toward Lar flataidow Qsairaa . The 7Mrd Set tVBfepabrwrtd Qaanasi . DHEW l.bl . No. (NtEi) 77-12ft
(1980, Report IYo. 4. Toward Leu liouWdour Qaanaa . 7bs Powdr Sst qf6spsrbnenrol Qaanaa. DSEW PpDI. (MH) MareJr
(19> 0); NNloo.l C.ncer Uutiwte (19ad), Rsport Ab . S. Towond Lssn BetwdoNr Qaanwt . swwary: Powr Slhl» Palndna Bfoauayi
uslna Coidsrrsort,Jbm BsperlnenrW a6anaa . DHEW PaN. (ND!) (SePteAber 19®0).
3 Oori OB (Fdiwr) (1976), RsPort lYo. 2. Towand Lar Rauudowr aaanaa. 71u Saod Sst ofEacperieientd Qaorrau . DHEW Pobl.
No. (NID) 76 .1111 .
a

it with ammonia and carbon dioxide (in situ generation of ammonium carbonates) . Tobaccos
expanded by these three process were studied as part of the second series of experimental
cigarettes' in the NCI "less hazardous" cigarette program .

In Table 1 are shown selected data from the NCI study of these three processes and their
effect on tobacco and tobacco smoke composition . The data concerning the ammonia treated
tobacco are particularly pertinent to the FDA claims .

TABLE 1. THE EFFECT OF AMMONIA/CARBON DIOXIDE EXPANSION


OF TOBACCO ON TOBACCO AND MAINSTREAM SMOKE
COMPOSITIONs
Exoandon Procea

PM % DiK RJRT NCSU


Aaeltct4 Ssa6csl N1L42W Yt.Sontrd Fcesn.l1 W

nicotina. 96 (!ab 1) 1 .64 0 .80 -57 1 .57 1 .37


nicotine, 96 (lab 2) 1 .74 1 .03 -41 1 .63 1 .50
nicotiae, % (lab 3) 1 .33 1 .03 -44 1 .73 1 .65
aveu;e 1 .80 0.95 -47 1 .64 1 .37
ammonia, 96 0.059 0.064 8 .S 0.056 0.027

didutmenk
TPM, anS Jcijt 32.76 22.33 -32 18 .66 19 .56

nicotine, my/ci6t 1 .79 0 .74 -59 0.78 0 .92

"ar••, m6/dst 27.07 18 .20 -33 15 .63 16 .34


ntcotioeP'ue, eado 0.066 0 .041 ,9a 0.050 0 .050
pH 5 .15 6.26 21 5 .09 4.87

baazo(aJpyrone, p61s TPM 0 .73 0.45 -40 0.76 0.57


beaz[aJamhncena, µa/g TPM 0 .93 0.6S -30 0.83 0.94
pbanoi, mW` TPM 124 65 -IS 48 68

S tumorbearins aaimda, 25 mg CSC/day 47.3 36 -24 37 36

` NH~Icp=,• expaotion .yam ia ammooialcnbae dioxids


~ pD ~ fivaze dtied

t3~
~
0 Qorl 09 (Editor) (1976) . Rsport Ab. 2. rawnnilesr Ratandort aaarruei. 711s SsoaWser oEspsrirenrat aaanaa . DHER' Yabi. ~
No. QVIH) 76-1111 . B
© Oort OB (Editor) (1976), Itcport Na . 2. rowan! lsa Razonlowr aaanata. 7ris Sscart Setq/EYpsrbnenwl aaamra . DREW Pbbi .
No. (NIH) 76-1111 .
For the samples studied in the NCI program on a "less hazardowus" cigarette, the
ammonia treatment produced the following effect on the tobacco:

• a reduction (47 %) of the % nicotine in the tobacc o


• an increase (8 .5 %) in the level of ammonia in the tobacc o

These changes in tobacco composition produce changes in the smoke composition and
its biological properties :

• a reduction (59 %) in mainstream smoke nicotine delivery


• a reduction (38 %) in the nicotine/"tar" rati o
• an increase (21 %) in mainstream smoke pH
• a reduction (40 %) in the benzo[a]pyrene/TPM ratio
• a reduction (30 %) in the benz[a]anthracene/TPM ratio
• a reduction (48 %) in the phenoUTPM rati o
• a decrease (24%) in biological activity as measured in a mouse skin-painting
experiment

While the data on the flavorful aspects of nicotine per se in mainstream smoke are sparse,
data on the effect of various types of ammoniation of tobacco indicate that the levels of pyrazine
and several flavorful alkylpyrazines are increased significantly . Also, certain of the ammoniation
treatments reduce the level of nicotine in tobacco and its level in mainstream smoke not only
because of the reduced level of nicotine available for transfer from tobacco to mainstream smoke
but also because of its enhanced decomposition° to pyridine and alkylpyridines whose levels, like
those of pyrazine and the alkylpyrazines, are also increased in the smoke of many ammonia-
treated tobaccos7. If, however, the ammonia treatment of the tobacco moderately reduces the
nicotine level of the tobacco, the levels of the alkylpyridines in mainstream smoke from such
tobacco are not necessarily increased over those in the control tobacco smoke . Increasing the
reduction of the tobacco nicotine level by more prolonged ammoniation eventually results in a
decrease in the levels of alkylpyridines in the mainstream smoke, presumably because of the
paucity of their precursor .

Ammoniation of tobaccos with high sugar levels, e .g., flue-cured tobaccos with 15-20%
sugars, substantially increases the levels of allrylpyrazines in the mainstream smoke from such
tobaccos . Only a slight increase in mainstream smoke alkylpyrazines is observed with low sugar
tobaccos such as burley (sugar levels usually less than 2 %) .

The flavorful properties of pyrazines have been well documented over the years . They

0 Kaburaki Y, SuSawan S, Kobuhi U . and Doilara T (1970), Studies on the Composition of Tobacco Smoke . XIV . The Formation
of Pyridines in the Pyrolysta of Nicotine . J . AGR. CHEM. SOC . JApAN II.' 224-231 .
T areen CR, Martin JM, and Rodgman A(1976), Perwal communication on the effect of treatment of tobacco with ammonia or
various ammonium uln on levels of pyrazinea and pyridinw in ci ;arette smoke.

4
contribute significantly to the desirable flavor of a variety of foodstuffs, including tea and
coffee•, cocoa and chocolate, roasted peanuts10, roasted meats (beef, poultry, fish)", etc .

Table 2 lists some representative data on the effect of various ammoniation treatments
on the levels of various pyrazines and pyridines in mainstream smoke . In addition to the data
shown in Table 2, similar data on the increased mainstream smoke levels of pyrazines and
pyridines were obtained from tobaccos and/or tobacco stems subjected to a variety of other
ammonia treatments:

• the denicotinization of tobacco with ammonia and steam


• the denicotinization of tobacco with ammonia and an organic solvent
• the ammoniation of the RJRT proprietary reconstituted tobacco sheet
• the addition of ammonium salts (ammonium carbonate + ammonium bicarbonate
or diammonium hydrogen phosphate) to reconstituted tobacco sheet
• the addition of ammonium salts (ammonium carbonate + ammonium bicarbonate
or diammonium hydrogen phosphate) to a blend of tobaccos

0 Mafa JA and Sizer CE (1973), Pyrazinea In Food . A Review . J. AG1t . FOOD CSFAl. 21 : 27r30 .
0 Vac Fraa= M, Stein HS, and Tibbeaa MS (196E), Steam Volatile Coaadaieab of Roasted Coc°a Bana. J. AGR. FOOD CHEt.
16: 1005-1008 .
IE Newell IA, Mason ME, and Madock RS (1967), Precursors o['lypical .nd Atypical Roamed Feaaut Flavor . J. AG& FOOD CH17K
lS:767-772. -
II . A Reviev. J. AGR. FOOD CEnL 21: 22-30. tc,1MaYJAndSizerCE(1973),FyazieInod
TABLE 2. THE EFFECT OF VARIOUS AMMONIATION PROCESSES ON
THE LEVELS OF NICOTINE, PYRAZINES, AND PYRIDINES
IN MAINSTREAM SMOKE'=
% Difference from Control
NH3ICO2-
expanded Aue- Modifiedt
cured tobacco 19bossaa + l',anel PJlnr
vt o16oro 4 Sfr ACs vs
control vt vs control
moke Analvte 8u"ured soatrol RRnrton control Wbvraw Canef PJ@er

A!S "tar". rtleoNrte. and ammonia

nicotine•l"tar"• -30 -8 0 -14


ammoniab/"tar^ 547 77 ND 48

29
pH, averaye minimum 6 .98 vs 5 .67 5 .67 vs 5.73 5 .90 vs 5 .69 6 .00 vs 5.90
pH, avenpe maximum 7 .42 vs 5 .90 6 .29 vs 6.02 6 .30 vs 6 .02 6 .53 vs 6.20
pH, overall avera8e 7.20 vs 5 .79 5 .98 vs 5 .87 6 .10 vs 5 .85 6 .26 w 6.10

MS avrarJnea°

pycuine 236 38 52 93

pyrazine, 2-methyl- 345 19 57 96

pyrazine, 2,3-dimethyl- 436 32 68 95


pyrazine, 2,3,5-trlmethyl- 361 30 125 114

MS ev~idJnesd

pyrid'me, 2-methyl-• 141 30 $2 42

pyridine .2,3-dimethyi-r 34 33 44 83

• ms/ciyt b µ8lciyt
° Similar % differences between treated and control tobacco MSs were obtained for the following pyrszines : 2-ethylpyrazine ;
2,5- and 2,6-0imethylpyrazine ; 2-ethyl-S-metbylpy+&zJm
e Similar % differences between treated and control tobacco MSs were obtained for the following pyridines : pyddine ; 3- and
4-methylpyridine; 2- and 3-ethylpyridine ; 2,4-, 2,5-, and 2,6dimethylpyridwa
° 2-picoliAe r 2,3-lutidine
• AC • mibure of ammonium cuboate and bicarbonate
e Cs+ntd 1Mrw blend was modified with NHVCO~4xpanded tobacco and dianunonium hydro8en phosphate-treated stems to
simulste the Yaibero

12 Green CR, Mutin JM, and RodBaun A (1976), Personal communication on the effect of treatment of tobacco with ammonia or
various ammonium salts on levels of pyrazlnes and pyddines in ci8arette aaake .

6
"Free" (unprotonated) nicotinel"free" (unprotonated) ammonia
no method for "free" nicotine
method for "free" ammonia

Prior to the 1975 and 1976 reports by Sloan and Morie", several methods for the
determination of ammonia in cigarette smoke had been reported". However, as Sloan and
Morie noted, none of these earlier methods was suitable for the determination of "free"
(unprotonated) ammonia in cigarette smoke :

None of the published methods distinguished between ammoniam lon and free (unprotonated)
arnmonla.

From their analytical determination of ammonia in tobacco smoke by the use of an ammonia
electrode and the calculated fraction of "free" (unprotonated) ammonia vs pH, they noted :

Tfu aWrhnental -values for free ammonia agreed my well with the theoretical amounted
calculatul from total ammonia and pH of the smoke . . ?1ie oalcnlated free ammonia agreed with
the eperlmental value.

In fact, the investigators suggested that the puff-by-puff pH of cigarette smoke is dependent to
a great extent on the level of "free" ammonia in the puff :

T he Increase In pH wlth puff number is consistent with the Increase of free aaunonla . . .

Attempts to apply the technique successful with mainstream smoke ammonia to


mainstream smoke nicotine presented several problems :

• the unavailability of a nicotine electrode corresponding to the


ammonia electrode
• the difference in the physical nature of the two amines in
mainstream smoke aerosol, namely, ammonia is a highly water-
soluble mainstream smoke vapor-phase component whereas
nicotine is dissolved and/or suspended in an essentially water-
insoluble aerosol particle
• the differwee in contribution of the two amines to mainstream
smoke pH with the methods currently employed in mainstream

m Sloan CH and Moii . OP (1975), Medwd tor tb . Deteemin.doo of Unproloo.ted Ammonia in CiS.reue Smoke . 29t6 TOB . CHIIN.
RES. CONF., CaBep Puk MD: P.per No. 16; (1976), Deaeemin.tion of Unprotonated Ammonia In Whole CiSueae Smoke .
BEITR. TABAIYORSCH. d 362-365 .
14 Ayra CW (1969) Determin.tioa of Ammonia in Tobacco and Tobacco Smote . TALANTA 16: 10S.f-10t7; Co4ias PF, L.wrence
W W, and WiI1Lau JF (1972), Tide1 (Ammonia In C'g .rette Smote]. BE1TR. TABARFORBCH . 6: 167-172; Bcunoemann KD and
HotBo.na D, (1974), au Chromatographic Deteradadoo of Ammonia In Cilueae and Cij .r Smoke . 28& TOB. C1H!M . RES .
CONF., W{et¢ NCs Paper No . $3; Sloan CH and Mode OP (1974), Deteemin .Non of Ammonia In Tobacco and Tobacco Smoke
with an Ammonia Bieatrode . ANAL. CH1M. ACTA 69: 243-247 ; Btumem.m KD .nd Ho}fm .nn D(1975), Chemicd Studies on
Tobacco Smoke . 70QQV . <iu Chromacojrsp6ia Deteeminatioa of Ammonia In Cisareue and Ci ;ar Smoke . J. CHROMAT. SCi .
19: 159-163 .

7
smoke pH determination
the difference in absorption of ammonia and nicotine from
mainstream smoke vapor-phase and particulate phase, respectively,
when they contact the highly buffered fluids, e .g., saliva, coating
the surfaces of different parts of the respiratory tract

In its discussion of cigarette design and manufacture, the FDA criticizes the chemical
manipulation of tobacco to alter the pH of mainstream smoke .

• The treatment of tobacco products with basic compounds such as


ammonia, ammonium hydroxide, ammonium salts, or urea
compound, and its salts in tobacco products because :

Ammonia inaaasea the pH of the smoke and thereby enhances the absorption of
nicotine In the body." (Emphasis added : AR)

• The treatment of tobacco products with acids or acid-generating


casing materials (sugar, cocoa) :

Manufacturers also reduce harshness by routinely adding acids to tobacco to


loawer the pH of the snwke. (7f:eyJ also use conventional casing materials, such
as sugars and cocoa, to produce acids in the smoke and reduce harshness .'D
(Emphasis added : AR)

m Brunnemann KD and Hotl'mano D (1972), On the pH of Tobacco Smoke . 26th TOB . CHFM. RES. CONF., Williamsburg VA:
Paper No . 11 ; (1974), The pH of Tobacco Smoke. F'OOD COSMET. TOJQCOL.12: 115-124 .
m Bwnnemaat Im and Hoftmano D(1974), Gas ChromatoSrapbic Determinatwn of Ammonia In CiSareae and Cigar Smoke . 28tb
TOB. CEIFM. RE& CONF., ItdriS\ NCt Paper No. S3; (1975), Chemioai Studies on Tobacco Smoke . 70QC1V. Gas Chromato-
graphic Determination of Ammonia In Cigarette and Cigar Smoke . J . CHROMAT. SCL 13: 159-163 .
17
&unaamron KD, Hot6naann D, and Wynder EL (1973), Studiea on the Inhalability of Cigarette and Cigar Smoke . 27th TOB.
CHFM. RES. CONF., Winuton-S.lem NC: Paper No . 27 .
m AemitaSe AK and Turner DM (1970), Abaoeptlon of Nicodae In Cigarette and Cigar Smoke tbrouSL Orai Mueoa . . NATURE 226.•
1231-1232 ; ArmitaSe AK. Dollery CT, George CP, Hou.eaun TH, Lewia FJ, and Turner DM (1975), Absorption and Metabolism
of Nicotine from Cigarettes. BRIT. MED. J.197S nvl : 313-316 ; Armitaje AK, Dollery CT, HouaemaaTH, Kobner 8M, Leai.
FJ, and'Niner DM (1978), Absorption of Nicotine from Small CiSar . . CLIIN. PHARMACOL. THER. 29: 143-150.
m United States Food and Drug Admini .tratioa (FDA) (1993) Nicotine in Cigarettes and Smokeless Tobacco Products Is a Drug and
These Products are Nicotine Delivery Devices under the Federal Food, DruS, and Coenetio Act . US FDA DHHS : 1-326 (August):
250.
United States Food and Drug AdmWrtration (FDA) (1995) Nicotine In Cigarettes and Smokeless Tobacco Products Is a Drug and
These Products are Nicotine Delivery Devicea under the Federal Food, Drug, and Cosmetic Act . US FDA DHHS : 1-326 (August) :
232 .
Humectants such as glycerol and other polyols are used for two major reasons in tobacco
smoking products :

• To maintain the pliability of tobaccos during blending, cutting, and


cigarette fabrication in order to reduce fragmentation of the
tobaccos

• To aid in the retention of the moisture in the cigarette tobacco


blend during fabrication, shipping, shelf storage, etc .

A blend moisture level of 1246 is optimum for cigarette


fabrication, e, g. , cigarette firmness, production speed ; a moisture
level less than 12 % presents problems in cigarettte fabrication .

If the cigarette moisture content decreases below 12 % during


shipping, store shelf life, etc., the composition of the mainstream
smoke changes drastically : The per cigarette deliveries of "tar,"
nicotine, aldehydes and ketones, etc . increase markedly and the
cigarettes, because they are perceived as harsher (less smooth), are
considered unacceptable by the consumer .

The FDA noted :

Tobacco lndustry o„Q4ctals acknowledge that controlling moisture content is


essential to ensure that nicotine content [of the mainstream smoke] does not fall .

It should also be recognized that the "Tobacco industry officials"


cited by FDA were Philip Morris R&D personnel=' presenting a
review paper in symposium at the 32nd Tobacco Chemists'
Research Conference .

The FDA could have just as easily have phrased its stement as
follows : Tobacco industry officials acknowledge that controlling
moisture content is essential to ensure that nicotine content does
not rise.

If, as the FDA implies throughout its report, the cigarette


manufacturers wanted the consumer to receive more nicotine from
the cigarette, they would use less humectant so that blend moisture
would drop to a pre-calculated value, say 10 %, thus increasing
both the total per cigarette nicotine delivery and the per puff

iLn
~
~
21 DeBardeleben MZ, Clanin WE, and Oannon WF (1978), Role of CiQareqe Physical Characteristics on Smoke Composition . RECENT ,~
ADV. TOB . SCI. 4: 8S•111 . Sce 98 . ~
~
9 `°
00
nicotine delivery during smoking . The manufacturers make every
effort to select the correct humectant level so that the moisture
content of 12 % persists as long as possible .

• In its discussion of humectants, the FDA stated :

Casings often include a humectant, usually glycerine [sie] or a higher glycol,


which serves to keep the tobacco moist and less sensitive to changes in
humidtty. . .

Its statement about RJR's acknowledgment of its use of glycerol as


a humectant suggests that RJR was involved in something
nefarious :

RJR acknowledged using glycerine (sic] as a hurnectant . . .

Giycerol, used by RJR in its cigarette blends since the introduction


of the Camel, is a natural component of tobacc& . Propylene
glycol, used by some manufacturers, is not a natural-occurring
compound .

Humectants transfer from the humectant-treated tobacco to its


smoke. For a glycerol-treated cigarette, about 10-12 % of the
weight of the "tar" determined by the FTC method is glycerol ;
for filter-tipped cigarettes, the transfer is at the lower end of the
rangen.

In its analysis of the FTC data on sales-weighted average nicotine deliveries for 1982-
1991, the FDA wrotel' :

FDA. . . analyZed lr}/brmatton supplied by the FTC that was derhed from the FTC's database on
nicotine levels !n ctgarene" [sic] . . . (T/here ts an apparent tncrease in the sales-weighted FT1C
nicotine delivery rattngs, for all cigarettes, since 1982 (the earliest year for which the computer
database Is available).

To limit its discussion of nicotine delivery data only to data available from 1982 to 1991
indicates the lack of objectivity in the FDA's examination. Even though they may not be in the

22 Cundiff RH, Greeae aH, and Laureoe AH (1964), Column Elution of Humectants from Tobacco and Determination by Vapor
Chromatognphy. TOB. SCI. 8: 163-168 .
n Wynder EL and Hofi'mam D (1967), Tobacco and Tobacco Smoke : Sardiu In Esperimrnml CaicinogcnssLr . Academic Prea, New
York NY: 480482.
24 United States Food and Drug Administration (FDA) (1995) Nicotine in Cigarettea and Smokeleaa Tobacco Products Is a Drug and
These Products aro Nicotine Delivery Devices under the Federal Food, Drug, and Cosmetic Act . US FDA DHHS: 1-326 (August):
266-270 .
ss The database referred to deals with nleoNne levefs /n dganne smoke not Ncodne kvelr !n dganaesl

10
FTC computer database, much
additional data are available! FTC
data on nicotine deliveries have
been published since 196r .
Comparable data are available for
sales-weighted average "tar" and
nicotine deliveries from the mid-
1950sn. Even though data prior
to 1967 were not generated by the
FTC, they were generated by
analytical procedure which 1982 1984 L986 L988 1990
eventually formed the basis of the Ye.r
F'igure 1 . Sales-Weighted Nicotine and "Tar" Levels in
FTC procedures for the
Cigarette Smoke as % of 1956 Levels: Average of
determination of "tar" and All Brands, 1982-1991
nicotine in mainstream smoke.
Such data have formed the basis of
discussion by the U .S. Surgeon General', the National Cancer InstituteP and others of the
effectiveness of various cigarette design technologies in generating a "less hazardous" cigarette .

If the 1982 through 1991


values are compared to the 1956
sales-weighted average "tar" and
nicotine deliveries rather than with 0 .3e
the 1982 data, an important fact 3 of 0 .36
1986
emerges: As shown in Figure 1, Levets
0 .34
even with the slight increase in
sales-weighted average nicotine 0 .32
deliveries between 1982 and 1991,
the values are less than 40% of
the 1956 value, ranging from 33 RUE 1984 1986 1988 1990
to 38% of the 1956 value, i.e., Year

between 1956 and 1982, the sales- Figure 2. Sales-Weighted Nicotine and "Tar" Levels in
Cigarette Smoke as % of 1956 Levels : Average of
weighted average nicotine delivery Alt Brands, 1982-1991
decreased about 67% ; between
1956 and 1991, it decreased about

26 Federal Trade Comcpissioa (1967), "Tar^ and Nicotine of the Smoke of S9 Variedes of Cigarettes . (November, 1%7) ; Federal Trade
Commission (1968), 'Tu" and Nicotine of the Smoke of 122 Varieties of C'sa[ettes .
r Wakeham H(1976), Sales Weighted Average Tar and Nicotine Deliveries of U .S . Cigarettes from 1957 to the Preseat . In Wynder
EL and Hecht SS (Bditon). Lung Cancer, UICC TECH. RPT. SERIES 2.f: 1S1-1S2. N
28 United Stetes Public Health Service (USPHS) (1979), S1+ioMng and IteaM . A Reporr of du Swryeon Oerteral DHEW Yabl . No. ~-'
(PHS) 79-50066; United States Public Health Service (USPHS) (1981), flie lieaW Conaequenoer oj Smoktng . M changing FJ,
G7goreae. A Reporr ojthe Surgeon Oenewl . DHHS P.bl. No . (PHS) 81-S01S6. m
29 National Cancer Imtitute (1980), Report lYo . S. Toward Lea Boiardows CJgarstret . S&anmary: Four Sktn Palndng Bioaraays Ustng
Condenaaie, fhrn Erperimenta! qgarraer . DHEW FtiW . (NIH) (&ptember 1980). ~
J
m
11
have been published since 1967'" .
Comparable data are available for
sales-weighted average "tar" and
nicotine deliveries from the mid-
1950s". Even though data prior
to 1967 were not generated by the
FTC, they were generated by
analytical procedure which
eventually formed the basis of the
FTC procedures for the
determination of "tar" and 1992 19" 1996 19ee 1990
nicotine in mainstream smoke. Year

Such data have formed the basis of +''bM 1. Sdes-Weighted Nicotine And "Ter" Levels in
Cigarette Smoke as % of 1956 Levels : Average of
discussion by the the U . S. All Brands, 1982-1991
Surgeon GeneraY`, the National
Cancer Institute'° and others of
the effectiveness of various cigarette design technologies in generating a "less hazardous"
cigarette. '

If the 1982 through 1991


values are compared to the 1956
sales-weighted average "tar" and
nicotine deliveries rather than with 0 .38
. r n • Ir• I
x els~l/w~
the 1982 data,, an important fact .36
0
. ,
emerges: As shown in Flgure 1, L19,56.vt1s
0

0 .34
even with the slight increase in
0 . - -&
sales-weighted average nicotine 0 .31 0 0 , _.

deliveries between 1982 and 1991,


the values are less than 40% of I I I I I I I I I I
the 1956 value, ranging from 33 1982 1904 190i 1990
to 38% of the 1956 value; l.e., Yaar

between 1956 and 1982, the sales- F%= 2. Salae-Waghted Niootine aod "Tar" Levels in
Cigarette Smoke as % of 1956 Levels : Average of
weighted average nicotine de2ivery All Brmds, 1982-1991
decreased about . 67%, between
1956 and 1991, it decreased about

~ Fedeal Tnda Comndaioo (1967) .'Tu" Aod Niootina of 16. Smob of S9 Vudbtka of C4aeMa . (Novsmbw,1967) ; Federd Tcade
Coomdaion (1963),'Tu" aod Nicodpa ohfw aabob of 121 VaeiMi . . o(CiF.raaes.
27 Wakehanl H(1976) . Sda Wei=Med Av.rys Tar aod Moadoa D.Hv.riea o[ 11 .S. CiptWea fian 1957 to t6e Fce .ea. In Wynder
SlL and Heoht 83 (BdhM) . L+owS Cmkur, UICC TBCH. RF'1'. SFRIES 2.f: 151-131.
21 vnhee Sta/es Fublio Hahh seevk. (UsPHS) (1974), Sea6bls ed BoWIt. A Jtspert q/d,e SY/iean l7enawt . DHEW PoW. No.
MIS) W40066; Ua3ted statea FubBo EIeaph savb . (I13pHS) (19t1), fl1t HsakA CanasqMSeca of SYwkina . ifu arangi+la
aaarra. A RspeK q/dk SraFson Qensrol. DUBS h4t. No. (PH0 t1deL{ f.
29 Nadooal CaaoeAmtiau . (1980, Revw* nw. $. toward Lsa a=ntorr apnpta. Syalnlory: FoNW skln Pandna Bloa:.ayi v.fn;
CondsnsauJ)na. Bxperinard ajQnan. DHEW F.ltl. (NW) (Sepqir60r MO) .

11
62% . Such decreases hardly denote a concerted effort by the U .S. cigarette manufacturers to
"hook" the consumer, as claimed by the FDA, on cigarette smoke nicotine by supposedly
increasing the exposure to mainstream smoke nicotine . By suitable selection of coordinates in
the plotting of these data, the appearance of the sales-weighted average nicotine increase between
1982 and 1991 may by accentuated or minimized, cf. FIgures 1, 2, and 3. Figure 3 puts the
nicotine deliveries from 1956 through 1991 vs the 1956 sales-weighted average value in proper
perspective.

Numerous technologies
introduced sequentially from the
mid-1950s to the late 1960s were . .tr o • _ _
incorporated into cigarette design Mc~tIM

to control MS delivery and


composition. All are considered
to contribute to what some
authorities, even some with
pronounced anti-tobacco
sentiments, have characterized as
a "less hazardous" cigarette when U6~ 1 s 1984 r .r 3lea lfat - 1!!0
included in cigarette design (the .

U.S. Surgeon General'0, the Figure 3. Sales-Weighted Nicotine and "Tar" Levels in
Cigarette Smoke as % of 1956 Levels : Average of
National Cancer Institute", All Branda, 1982-1991
Gori'=).

These technologies include (see FYgure 4) :

• tobacco blend and weight


• tobacco rod length and circumference
• filter tips (material type and additives)
• processed tobaccos (reconstituted. tobacco sheet, expanded tobacco)
• paper (type and additives)
• air dilution (increased paper porosity, filter tip perforations) .

Some of the technologies were developed for economic reasons but later were found to
have an effect on cigarette mainstream smoke delivery and composition that were in accord with
the definition of a "safer" or "less hazardous" cigarette . An example of this was the first

30 United States Public Health Servke (USPHS) (19?9), S5noltng and Rsattb . A Rsport qf du Swgson CknsroG DREW Pribi . No .
(PHS) 79-50066 ; United States Public He .Uh Service (USPHS) (19a1) . flre 8seltlr Coerequanea q/S+Moxing . 7he Q+miging
agamu. A Repoit q/ab. dYrrgson Owau,nl. DHHS F.bl. No. (PHS) S1dGLSi.
FE Nadonal Cancer Tnatitute (1980), Rsporr nw .1. Toward Leu 8atnrdow agwrap. .Slonmaiy: Four Skn Patndng Bloasaays Uring
Qondenaaufi+om Srpcdmerual aganau. DHEw Pubi . QV>fl) (Sepasber 1980) .
n Ood OB (19E0), i,eW Hazardous Cigarottes : Tbeory and Pr.ctice.la God OB aaid Book FO (Editora), A $0 aganaet Banbury
Report 3, Cold Spria; Harbor Laboratory, Cold Spriaj Harbor NY : 261-279; (1980, A Sununary Appraisal . In Oori GB and Boot
FO (Editors), A StiJs.agoreast Baabury Report 3, Cold Sprins Harbor Laboratorp, Cold SptioS Harbor NY : 3S3-3S9 .

12
successful incorporation of 1956 1960 1964 1968 1972 1976 1980 1984
reconstituted tobacco sheet into 50 3 .0
cigarette design in 1953 by R .J. 45
Reynolds Tobacco Company with Mb• !!p . ~
2 .5 '
40 Heooortitut .d 'lb6aoso 8do.i
the Winston. The Winston was P&yp' Aad11LvM
also the first highly successful 35 P.o.r Poro.tey
iqandod loDaooo
filter-tipped cigarette . Other v.ntllaltoo 2.0
30
technologies were developed and ~

introduced by the cigarette 25 1 .5 ~


manufacturers in an attempt to 20
respond directly to a variety of ~
1 .0
15 1. `• .y.. . ... {
smoking-health claims .
t 10 -- Tar
Nieotine 0.5 x
The chronology of 5
introduction of these technologies
0 1 1 I I 1 1 . I 0.0
is noted in Flgure 4 . Over the 1956 1960 1964 1968 1972 1976 1980 1984
years, use of these technologies in
concert and to various degrees in F'igare 4 . "Tar" and Nicotine Deliveries, Sales Weighted
Average Basis
cigarette design has provided the
consumer with a great variety of
products whose number has increased from about a dozen in the mid-1950s to several hundred
presently. It should be remembered that the cigarette is a system : All of these technologies
used in cigarette design are interactive . i, e., inclusion of or change in the level of use of any
particular technology may require other adjustments in the cigarette design to maintain certain
attributes acceptable to the consumer .

Within a decade of the introduction of the successful filter-tipped Mnston with its
reconstituted tobacco sheet component, all U .S. cigarette manufacturers were using reconstituted
tobacco sheet, either in-house developed or purchased from a supplier, in their products . Filter-
tipped cigarettes had escalated from about 1 .3 96 of the U . S. market in 1953 to 64 % in 1965" .
During the period 1955-1965, the sales-weighted "tar" and nicotine deliveries decreased by 40
and 48 %, respectively . Since filter-tip ventilation had not been discovered and utilized in
cigarette design, compensation by cigarette smokers for such a decrease (48%) in nicotine intake
was almost an impossibility .

In addition to reducing the •`tar" and nicotine deliveries, what else did the incorporation
of reconstituted toba3eoco sheet into the cigarette blend accomplish? During the same period,
1955-1965, the specific tumorigenicity of cigarette smoke condensates from commercial
cigarettes containing increasing levels of reconstituted tobacco sheet decreased" as did the

" ari .e VN (1954) . Market Growth of Reducod Tar Ci=areaea . RECENT ADV.1'OS. SCL 10: 4-14 .
34 Wynder EL and Hotfnunn D(1955), Reduction of'Ylimoripeoioity of CiSaieete Smote . An Bxperimeahi Approach . J. AM. MED.
A.4SOC .19I: aE-94.

13 '
cigarettes containing increasing levels of reconstituted tobacco sheet decreased" as did the
benzo[a]pyrene per mg of smoke condensateu.
eo
In a continuation of their mouse skin-
painting studies'a, Wynder et al ." examined the 70
effect of application of lower and lower annual y„
doses of mainstream cigarette smoke condensate ~
on tumor production in skin-painted mice
. They ~50 reported that skin painting of mice with a total 40
annual dose of 10 g/mouse produced papilloma in '

about 60 % of the mice, but only a small ~'opercentage (< 1096) of papilloma-bearing animals
(no carcinoma-bearing) animals was observed K 20
when the total annual amount of cigarette smoke 10
condensate applied was less than 5 g/mouse .
Further reduction of the annual dose to did not ° L : -A-----L
3 . 5 7
----
e a o,o
J

yield any papilloma- or carcinoma -bearing mice Graav of Ci`arette Smoke/Nouse/Year


(see Fjgtu'e S) . FIgure S. Relationship of Tumor Yield and
Dose (Wynder et al., 1957)
Wynder and his colleagues used these data
as the basis for their statements that reduction of the "tar" yield of cigarettes by about 40-50%
would produce substantial reductions in the incidence of respiratory cancer in cigarette smokers :
. . .A.lthough It is d{fficult to estimate a comparable exposure leuel for man, the human data in line
with the animal data Indicate that a reduction in total tar exposure will be followed by a decrease
in tumorformation. . . Measures that can succeed in the tar exposure of man include thefollowing :
l . More e~, jj`'adive Jtltration. lt seems feasible to produce a Jilter that will remove 40 per
cent of the tar from a given cigarette and still allow the cigarette to maintain a satisfactory
pressure drop and jlauvr .
2. Mod~'ication In the types of tobacco so that the blend used Is as low as possible in
tar1t [sic] and nicotine content. . .

. . .It may be predicted that if the average smoker were erposed to only ha{f the amount of tobacco
tar to which the smoker of ngular-siz.at cigarettes ts now [1957] exposed, his cancer risk will be

~ Wyeder EL ud Hof6mtm D(1965), Reduction of Tumotigenicity of Cigarette Smoke . An Experimental Approach . J. AM. MED .
ASSOC .192: Es-94 .
u Hotriaann D and Rathkanp (7 (1966), Unpublished data cited In Wyader EL and HotYmana D(1967), Tobacco and Tobacco S7moke :
Studlet In S+rperlrnrntal CaMeogenesfi. Academic Press, Piew York NY: S31-S23 .
36 Wynder EL, aralum EA, and Cronin;er AB (1953), Study on the Esperimerual Production of Cancer with Tobacco Tar . PROC.
AM. ASSOC. CANCER RES. 1: 62-63; Bxperimenual Production of Carcinoma with Cigarette Tar . CANCER RES.13: 833-864;
Experimental Production of Carcinoma with Cigarette Tar. II. Teata with Different Mouse Strains . CANCER RES. 1J: 443-448;
Wynder 84, Lupberger A, and l}renror C(1936), 8sperimental Production of Cancer with Cigarette Tar : Strain Differences . BRIT.
J. CANCER 10: S07-S09 ; Wynder EL and Wright OF (I9S7), A Study of Tobacco Carciaogeaesi . . I . The Primary Frac6ona .
CANCER lo.• 235-271 . -
37 Wynder BL,1{opf P, and Ziegler H(1957), Dosa Response with Cigarette Tar . PROC. AM. ASSOC . CANCER RES. 2(3): 261 ;
A Study of Tobacco Careinogenesia . II . Dose-Response Studies . CANCER 10: 1193-1200 .
X Tobacco does not contaia "tar ."

14
sign{ficantly reduced. Any measure designed to thus reduce man's exposure to tobacco tar whether
through modtfieation of the tobacco or the eigarette, or through more effeetive filtration, can
sign{/ieantly c+ontribute to the decrease in risk

The data from these dose-response study (and the threshold limit value for cigarette
smoke condensate) were subsequently reported and their pertinence to the human smoking
situation -and cigarette design were discussed many times by Wynder and Hoffmann" . E.g.,
they stated in 1964 and and again in 1967 :

It is apparent that a redudion of tumorigenic components can be most readily accomplished by


reducing the total amount of smoke condensate . . .to which one is ezposed.

From the results of additional biological studies, Wynder and Hoffmann'° concluded :

It Is apparent. .,,from laboratory studies . . . that exposure to tobacco smoke condensate and tumor
yield are quantitatively eorrelated

Similar dose-response findings were subsequently reported from the National Cancer Institute's
massive 10-year "less hazardous-cigarette" study involving tests on cigarette smoke condensates
from nearly 100 experimental cigarettes and over 30 control cigarettes and the Kentucky 1R1
Reference Cigarette (Gori", National Cancer Institute') .

How did the introduction (see FIgure 4) of the various cigarette design technologies
speak to the suggestions on "tar" reduction? Table 3 discusses the various technologies
acknowledged by various anti-tobacco smoking investigators and institutions as contributing
significantly to "less hazardous" cigarettes . In addition to the beneficial reduction sought by
Wynder and others in mainstream smoke "tar" delivery, most of the technologies also produced
a decrease in mainstream smoke nicotine delivery . This reduction in nicotine delivery occurred
between 1957 and 1965, even though as late as 1964, the U . S. Surgeon General commented on
the toxicity of nicotine as follows :

Mhe chronic toxicity of nicotine in quantities absorbed from smoking and other methods of

a9 Wynder EL and Hot6n .na D(1962), Studiee with the aamoua and Paztieulate Phaae of Tobacco Smote . PROC. AM. ASSOC.
CANCER RES. !(I): 373 ; (1963), Eia experimenteUer Beitag wr Tabatrauc6kaaaerogeaeee . DEZPr.11ZD. WCHNSCHR. 8g:
623-628 ; (1964), FVerimental Tobacco CarcioogeoeaL . ADV. CANCER RES. d: 2t9-4S3: see 372-373 ; (1967), Tobacco and
Tobacco b5noke: Studia In Bxpetimentd CarobwgenesU . Academic Press, New Yort NY : S44-S03 .
40 Wynder EL and Hoffmaan D (1965), Reductioe of Tumorigenicity of Cigarette Smoke . An F.xperimeatal Approach . J. AM . MED.
ASSOC . 192: E8-94.
a ()od OB (Editor) (1976), Report No .1. Toward Less Hazardous Qganrttu . 71te Fiat set qjErpertmmwt l3garettes . DREW Publ .
No . ¢YIH) 76-905; (1976), Report No. 2. Toward Leaa Hazardous Agantus . lhs Second Set ojFrperirnenta/ Qgamus . DHEW
Publ. No. 0iIH) 76-1111 ; (1977), Report No. 3. Toward Less Hazardous Qgantus . 71:e 7ltird set oJSrperinienul Gtgamus .
DREW Publ . No. (NIH) 77-1280; (1980, Report No. 4. Toward ltst Hazardous Qgannu . Me Fowrh Set of Fxpuimmtai
Qgarette. . DHEW Pabl. (MS) Mareh (1980).
n National Cancer Institute (1980), Report No . S. Toward Leu Hazardous Qganttes . Sanunary: Four sk/n PainNng Bioassays Osing
Condentate from F.rperlmtntal Glgannes. DHEW Publ. (NIH) (September 1980).

15
signtficantly reduced . Any measure designed to thus reduce man's exposure to tobacco tar whether
through modification of the tobacco or the cigarette, or through more effectivefiltration, can
signiftcantly contribute to the decrease in risk

The data from these dose-response study (and the threshold limit value for cigarette
smoke condensate) were subsequently reported and their pertinence to the human smoking
situation and cigarette design were discussed many times by Wynder and Hoffmann'9 . E.g.,
they stated in 1964 and and again in 1967 :

It is apparent that a reduction of tunwrigenic components can be most readily accomplished by


reducing the total amount of smoke c»ndensate . . .to which one is exposed.

From the results of additional biological studies, Wynder and Hoffmanni0 concluded :

It is apparent. ., from laboratory studies. . . that exposure to tobacco smoke condensate and tumor
yield are quantitatively oorrelated.

Similar dose-response findings were subsequently reported from the National Cancer Institute's
massive 10-year "less hazardous-cigarette" study involving tests on cigarette smoke condensates
from nearly 100 experimental cigarettes and over 30 control cigarettes and the Kentucky 1R1
Reference Cigarette (Gori", National Cancer Institute'=) .

How did the introduction (see FIgure 4) of the various cigarette design technologies
speak to the suggestions on "tar" reduction? Table 3 discusses the various technologies
acknowledged by various anti-tobacco smoking investigators and institutions as contributing
significantly to "less hazardous" cigarettes . In addition to the beneficial reduction sought by
Wynder and others in mainstream smoke "tar" delivery, most of the technologies also produced
a decrease in mainstream smoke nicotine delivery . This reduction in nicotine delivery occurred
between 1957 and 1965, even though as late as 1964, the U .S . Surgeon General commented on
the toxicity of nicotine as follows :

[TJhe chronic toxicity of nicotine in quantities absorbed from smoking and other methods of

39 Wynder EL and Hoffmann D(1962), Studies with the Qa .eow and Particulate Phase of Tobacco Smoke . PROC. AM. ASSOC.
CANCER RES. 3(I): 373; (1963), Bia axperimeateUer Beitnj zur Tabakraue6kanzero8ene.e . DEUT. MED. WCHNSCHR. 86:
623-628 ; (1964), Experimental Tobacco Carotoogenwia . ADV. CANCER RES. g: 249-453 : see 372-373 ; (1967), Tobacco and
Tobacco s+noke: Sadiu fn Lsperkenui CarMogenesls . Academic Press, New York NY : 504-505 .
p Wynder EL and Hoffmana D (1965), Reduction of'i5imorigeaieity of C'Wrette Smoke . An Experimental Approach . ,/. AM. MED.
AS.SOC.192 : 88-% .
41 Ooci OB (Editor) (1976), Report JVo . 1 . Toward Lers Razanfow agantau. M F1rst set qJBcperbuntal agaroau . DHEW Publ.
No. (MH) 76-905 ; (1976), Report /Vo. 2. Toward Less RotArdoas aganau . 7/u Second Set of Fxpenlmental aganaes . DHEW
Publ. No. (NIH) 76-1111 ; (1977), Report JYo. !. Towod Less Razasdou agamui. 71u 77iin! Set of 8rputmental agarraes.
DHEW Pobl. No. (NIH) 77•1280 ; (1980), Report No. 4. Toward Less Hazardous agansaa . 7/u Founh Set of 8spsrimenro!
aganaes. DHEW Pob1. (NIH) MareL (1980) .
n National Cancer LDtitute (1980), Report No . S. Towanf Leu Hazardous agarrttes . Sunwwry : Four Skin Paindng Bloarsays Using
CondensateJhvm F.xperimental aganats. DHEW Yobl. (NIS) (September 1980) .

15
tobacco use Is very low and probably does not represent any important health hazard . . ." ?Tu
evidence. . .supports a conclusion that the chronic toxicity {fniootine in amounts ordinarily obtained
In common forms of tobacco use Is very low Indced . . ." [TJhe chronic toxicity of nicotine In
quantities absorbed from snmking and other methods of tobaecn use is very low and probably does
not represent a significant health problem`5 .

As noted previously, by 1965, several of the design technologies succeeded in reducing


the "tar" delivery by 40%, the goal sought by Wynder . However, the decrease did not stop
there. Introduction of additional technologies reduced the sales-weighted average "tar" delivery
52% from the 1955 value . Eventually, the sales-weighted average "tar" delivery was only about
33 % of the 1955 value, i . e., a 67% reduction! When the anti-tobacco smoking group realized
the tobacco industry could provide the consumer with cigarettes at almost any specified "tar"
delivery, criticisms turned from "tar" to other factors :

• Flavora,n{,g : Since the lowered "tar" cigarettes were assumed to contain additional
quantities of flavorant formulations, the fate of flavorants during the smoking process
became a point of contention, i.e., did the flavorants generate undesired pyrolysis
products during the smoking process? This question was primarily triggered by the Philip
Morris advertisements of the new flavor technology applied to the Merit16 .

A comparison of the mutagenicities (Salmonella typhlmurium) of the mainstream smoke


from a cigarette blend with no flavorants, no casing materials, and no humectants vs
smoke from the same blend with normal flavorant and casing/humectant levels vs the
smoke from the same blend with normal casing/humectant levels plus 10 times the
normal flavorant levels revealed no differences attributable to the flavorants . The
humectants, by their dilution of the 'tar", diminished the mutagenicity of the mainstream
smoke.

• 7ter- ,p ventilation and compensation „for nicotine : Despite the fact that filter-tip
ventilation provided remarkable control of "tar" delivery, this technology was criticized
because the smoker supposedly could block the ventilation holes and increase intake of
"tar" and nicotine to "compensate" for the lowered "tar" and nicotine deliveries .
Nothing is said about the apparent lack of "compensation" for nicotine during the years
(1955-1970) when "tar" and nicotine deliveries were reduced by more than 50% .

Nor was much said about any nicotine problem when several noted investigators - as

43 United States Public Health Service (USPHS) (1964), SYnoktna and Healrh . Repon of rhe Advt+ory Comndaee w ehe Surgeon (3eneral
of the Public Health Savtce. DHEW Pohl. No . (PSS) 1103. See 32.
K United States Public Health Service (USPHS) (1964), SSnoktna and Realih . lieport of du .ldviaory CoeuMlaee to the Surgeon General
of dhe Public Health Servlee . DHEW Yobl. No . M 1103 . See 74.
LS United Statee Public Health Service (USPHS) (1964). &nokfna and Neateh. Report q fthe Advtiory Caemlaee so dhe Swgeon General
of the Public Health Service. D1IEW Pabl. No. (PHS) 1103 . See 73.
46 Uoyd RA (1978), Personal communication on Nertt research . Detailed exanoination of the Merir ciSarette with particular emphasis
on the flavorant technolo8y revealed that the teehnolo8y used differed little from that employed on the 70-mm unfiltered Came! .inoe
1913 .

16
recently as 1980 - proposed that cigarettes should be designed to deliver further reduced
levels of "tar" and carbon monoxide but with nicotine deliveries either unchanged or
only slightly reduced . E.g., Russell and coworkers suggested'7 :

G, ~~low-tar, low CO, but meditrm-, rather than low-, nicotine cigarette might
ty,~-~ -reduce tar and CO intake more than occurs with low-tar, low-CO, low-nicotine
cigarettes

and

Finally, a case will be made for a medlran-nkwtine, low-tar, low-earbon


monoxide (CO) eigarette . . . (emphasis added: AR]

•Environrnental tobacco,srnoke : Switch the criticism from the smoker and supposed self-
contamination to the smoker and his purported contamination of others in the room .

47 Russell MAH, Wilson C, Fatel UA, Cole PV, and Feyenbend C (1973), Comparison of the Effect on Tobacco Consumption and
Carbon Monoxide Absorption of Chae" to HigL and Low Nicotine Cigaeettee . BRiT. MED. J.1973 nv): S 12; Russell MAH,
Cole PV, Idle MS, and Adama L (1975), Carbon Monoxide Yie1ds of Cigarettes and Their Relation to Nicotine Yield and Type of
Filter. BRIT. MED. J. 197f (Jd): 71 ; Russell MAS (1976), Low Tar, Medium-Nicotine Ciganttea : A New Approach to Safer ~
Smoldn; . BRIT. MED. J. 1976 il): 1430; (1980, Riat Raductioo Achievementa and Future Dinoctions . In l)ori GB and Bock FO ~
(Sditon), A Sq/e (aganae t Banbury Reporr 3, Cold Spt4ng Hatbor Laboratory, Cold Spt4aB Harbor NY : 157-177 ; (1980), The Case ~-'
for Medium-Nieotine, Low-Tar, Low Caebon Monoxide Ciganttea . In God OB and Boet Fa (Editors), A Sq/e Qganttef Bonbury ~
Report 3, Cold Spring Harbor Laboratory, Cold Spring Harbor NY : 297-310. ~
V
17 00
0 .075

0 .070

0 .065
NIT
Ratie
0 .060 s

0 .005

I I I I I I I I I
1955 1960 1965 1970 1975 L980 L986 1990 1995
Year

I'`igUl^8 G . Sales-Weighted Avetage Nicotine/Tar Ratios

18

0
• suggestions by investigators such as Russell, Jarvik, and others that the design of a
"safer" cigarette should involve the substantial reduction of "tar" delivery and either
maintenance of the nicotine delivery at the level it was prior to manipulation of the "tar"
delivery or only involve a slight reduction of the nicotine delivery .

a Ruueli MAH, Wilson C, Patet UA, Coie PV, and Feycnbeod C (1973), Compatiwn of the Effect on Tobacco Consumption aad
Cacbon Monoxide Absorption of Changing to HiSh and Low Nicotine CiSareae . . BRIT. MED. J.1973 pv) : S 12 ; Ruaeell MAH,
Cole PV, Idle MS, and Adama L(1975), Carbon Monoxide Yields of CiSarettea and Their Relation to Nicotine Yield and Type of
Filter . BRIT . MED . 11975 nU) : 71 ; Rw .ell MAH (1976), Low Tar, Medium-Nicotine Cigarettes : A Nea Approach to Safer
Smoking . BRIT. MED. J. 1976 p): 1430 ; (1980, iG.k-Reduction Achievements and Future Diiectan.. In C3ori (3B and Bock FO
(Editors), A Sq/e Glgarrae t Banbury Report 3, Cold Spring Harbor Laboratory, Cold SprLV Harbor NY : 157-177; (1980), The Case
for Medium=Nicotine, L9w+ Tar, Low Carbon Monoxide Cigarettes . In flod oB and Boct FQ (Bditon), A Safe Ctgarsuef Banbury
Reporr 3, Cold SprinY Harbor Laboratory, Cold Spring Harbor NY : 297-310.

19
j

c :lfdanicWcotn-3.fda

TABLE 3 . CIGARETTE DESIGN . TECHNOLOGIES


Effect
Cigarette Design on MS
TwmlQgx Qrigjpgl Goal _u_&Muent Findin¢s Nicotine
• blend of flue- • more consumer acceptable MS • TPM° less than that from an decrease
cured, burley, than that from an all-flue- all-flue-cured or all-oriental
oriental, and cured or all-oriental tobacco cigarette
Maryland cigarette specific tumorigenicity of CSC
tobaccos' from American blend less than
that from all-flue-cured or all-
oriental tobaccos
• filter tip° • esthetics (no tobacco • as efficiency of filter tip was decrease
fragmenta in mouth) increased, MS TPMb dec-
• TPM` reduction reased
• reconstituted ~ economics (tobacco leaf stem • as level of RTS was inc- decrease
tobacco sheet constitutes 20-25 96 of the reased, the MS TPM" dec-
(RTS)a purchased leaf weight ; prior to reased
1953, stems at R .J . Reynolds • specific tumorigenicity of CSC
Tobacco Company were decreased as RTS level in
discarded, sold as fertilizer, or blend was increased
processed to recover nicotine • TPM° PAHs decreased as RTS
for sale to chemical company level in blend was increased
that manufactured a nicotine- • in some instances, MS NNAs
based insecticide) and TSNAs increased as RTS
level of blend increased
• cigarette paper • to ensure the cigarette paper • slight decrease in TPM" with slight
additives char line preceded the tobacco increased use of some ciga- decrease
blend char line during the rette paper additives, a.g .,
burning of the cigarette citrate
• air dilution via • TPM` reduction • TPM' reduction proportional slight
cigarette paper to cigarette paper porosity decrease
porosity • reduction in VP component
deliveries proportional to
cigarette paper porosity
• filter-tip additives
+ improved fabrication of filter- • filter-tip additives (plasti- decrease
• triacetin, tip rods cizers) such as triacetin
carbowax, etc . selectively removed compo-
nents found primarily in the
MS VP as well as components
partitioned between the VP
and PP, e.g., phenols, VNAs

0
Table 3 (Continued) :
Effect
Cigarette Design on MS
TechnoloQV Original Goal Subsequent Findings Nico jpg

• carbon • reduction of MS VP •"carbon-filter" off-taste decrease


components (HCN, acrolein, eventually became unaccep-
acetaldehyde, acetone) table to the consumer
reported to be ciliastatic in tn • slight decrease in TPM°
vitro studies delivery : decrqase dependent
on filter-tip construction
(compartmoatalizod carbon,
carbon-impregnated cellulose
acetate fibers, etc .)
• processed tobacco
• denicotinization • reduction of nicotine level in • increase in levels of certain decrease
tobacco flavorful compounds, e.g .,
py~~
• expansion• f • reduction of per cigarette • reduction in TPMb delivery, decrease
TPM° delivery plus reduction reduction in levels of
of levels of allegedly harmful PAHs/mg TPMb, reduction in
components levels of several allegedly
• economics (the most expensive harmful VP components, e .g.,
item in a cigarette is the CO, HCN, acrolein
tobacco; any reduction in • reduction of specific
weight/cigt is reflected tumorigenicity of CSC
economically)
• air dilution via • reduction of MS TPMb plus • reductions of TPM° and VP decrease
filter-tip reduction of MS levels of VP components proportional to %
ventilatiod components (CO, NO, HCN, air dilution
etc.)
' This blend of tobaccos, the so-called American blead, was introduced by RJ . Reynolds Tobacco Co. in the C<onel cigarette
in 1913; eventually the American blend was used In cigareaes througLout the world .
b TPM - FfC "tar" + nicotine; WTPM - wet TPM - FTC'4ar•• + nicotine + water .
° Winrton, Introduced by RJ. ReynoW. Tobacco Company In 1933 . was the first tUter-tipped cigarotte to command a
signitican anarket share .
• In 1953, RJ. Reynolds Tobacco Company used its ln-house RTS In the newly Introduced NRnrten blend ; RTS use eventually
extended to other RJRT bead. (Camel, CavaUer7 ; by 1960, all U.S . cigarette as.aufacwrers wero incoeporatiqg an RTS in
their products.
• In 1965, R .I. Reynolds Tobacco Company reported the development of the first expansion peooeu applicable to tobacco
lamia .e; previously reported expansion processes were effective only with tobacco steaas . Expanded tobacco was Included in
RJRT products during and after 1965 .
t Incorporation of expanded tobacco and filter-tip ventilation in cigareue design permitted the generadon of cigarettes whose
"tar" delivery ranged 5om 0 . 1 to 10 mg.

AbbnWmiona:

CSC ~ cigarette solote condensate RTS - reconstituted tobacco abeet


MS ~ mainstream smoke TPM - total particulate matter
NNA • N-nitrosamine VNA - volatile N-nitrosamine
PP ~ particulate phase VP • vapor pbaae
In his 1979 .report, the U .S. Surgeon General, citing data present by Wynder and Hecht',
listed the major technologies that could be used in the design of cigarettes and classified their
effectiveness in the design of so-called "safer" or "less hazardous" cigarettes2 . Table 4,
adapted from the 1979 Surgeon General's report, lists each of these technologies and its
effectiveness in reducing per cigarette mainstream smoke "tar", mainstream smoke nicotine,
mainstream smoke carbon monoxide, and mainstream smoke benzo[a]pyrene, deliveries as well
as its effectiveness in reducing the tumorigenicity (mouse-skin painting) of mainstream cigarette
smoke condensate and in vitro mainstream smoke ciliatoxicity . Also indicated in Table 4 are the
tobacco industry members who originated the various technologies, particularly those considered
highly effective and which were used in 1979 in marketed products and are still used, I .e.,
cellulose acetate filtration, reconstituted tobacco sheet, air dilution via paper porosity, expanded
tobacco . The FDA in its 1995 discussion' of nicotine essentially ignores the years of effort
involved in developing these technologies and their effectiveness in reducing mainstream smoke
yield including nicotine delivery .

The categorization of the effectiveness of the various cigarette design technologies as highly
signiflcant, signtficant, insigniftcant, etc . is not that of members of the Tobacco Industry but of
institutions and investigators characterized by their anti-tobacco sentiments . These include
institutions such as the National Cancer Institute, and anti-tobacco smoking authorities such as
the U.S. Surgeon General', Wynder and Hecht', Wynder and Hoffmann', and Gori et al .'

I Wynder EL and Hecht SS (Bditora) (1476),1ung Cancer. UICC TECH. REPT. SERIES 2S: 138 .
2 United Statea Public Health Service (USPHS) (1979) . S+noAing and Reald:. A Report of the swgeon Cknernl . DHEW Pabl. No.
(PHS) 79-50066 . See Chapter 14, Table 26.
3 United States Food and Dnig Admiaiatratioa (FDA) (1995) Niootlm in Cigarettew and Smokeless Tobacco Products Is a Dn :B and
Theme Productu are Nicotine Delivery Devicea under the Federal Food, Dnt=, and Co .metic Act. US FDA DHHS: 1-326 (August).
0 National Cancer Institute (1980), Reporr No. 3. Toward Lesa Razardow aganaes . SUonmary: Four Sxin Palnting Bloaasays Using
Condensatefian Espe>imenml aganrtei . DHEW Frbl. (NN) (Septsber 1980.
© United State . Public Health Service (USPHS) (1979), Sinoling and Real& A Report of rhe Surgeon Gcnerol . DHEW Pabl . No.
(PHS) 79-50066 . See C6aptar 14, Tabb 26 ; United Suta Public Heahb Service (USPHS) (1981), 7he Realth Consequences of
&noking. 7he a:anging agaretre. A Report of the Swgeon GeneroL DHHS FttW. No. (PHS) 81-30156.
6 Wynder EL and Hecht SS (Bditoc .) (1976), Waj Cancer . UICC TECH . REPT. SERIES 2.f: 138 .
I Wynder EL and Hoffimam D(1964), 8:cperimental Tobacco Carcloo8eaeai.. ADV. CANCER RES. g: 249-433 ; (1965), Reduction
of Tumorijeaiaity of Cijantte amotce . An Bx#eeiaaatal Approach. J. AM. MED. ASSOC. 1P2: 88-94; (1967) . Tobacco md
Tobacco SMoke: Slardteu bt Zperta.attal Ca>tclnogeneaL . Academic Press, NeMr York NY ; Wynder EL and HofGnann D(Bditors)
(1968), Toward a lsa Rarafyt agantte . NATL. CANCER INST. MONOG1tAPH 28.
0 God aB (Editor) (1976), Report A6 1. Towaid Leu Roundour agorata . flie Plrtt Set oJ6xPertmenwl agaretra . DHEW Pobl .
No. (NIH) 76A03i <Iorf oB (Editor) (1976), Report 1Vo . 2. ToMand l.ur Rarartlow aganaa. Tlre Second Set q/Sxpe>rinenral
agareaa. DREW Fubl. No. (NIH) 76-1111; tioti GB (1976), Approaches to the Reduction of Total Particulate Matter (rPM) In
Cigarette Smoke . In Wynder EL, Hotl'mann D . and Qotl GB (Editor.), Proc. dnd Wor{d Car{/. on &moidrg and fleairlt, lYew York
NY.197S, DHEW Pabl. No. (NIH) 76-1221, Vol.1:431-461 ; (loti GB (1977), Leaa Hazardou . CiYarettea. In Nieburg . HE (Bdiar),
Prrwenaton and DeucrJon of Cancer. Pon 1: Preyoudon. Vol.1 : 6dology, Marael Dekker. Inc ., New York NY : 791-804 .; God OB
(Bditor) (1977). Report lYo. 3. Toward Leti Harandout aamraa. 7Ue 7Mrd Set of F-speriieentd agontut . DHEW Pabl. No.
(NIH) 77-1280; (torl aB (1977), Las Hazardous Cigaraaee . to Nieburga HB (Bdiwr), P.rNertaton ad Deteettan ojCaneer, Pat cn
1 : Pirvennton. Vol.1 : Edology, M.rcet Dekker, Inc ., New York NY : 791-80W . tioti aB (1980), Lea Hazardous CiQarotte . : Tbeory N
1J
and Practice . In God OB and Bock FO (Editon), A S* aganaet Baubury Report 3 . Cold Spring Harbor Laboatory, Cold SPting N
Harbor NY : 261-279; (1980), A Summary ApprdW . In God aB and Boct FO (8diten), A Sqfe agantu! Banbury Report 3, Cold m
Spring Harbor Laboratory, Cold Spring Harbor NY : 353-359; Dorl f3B (8ditor) (1980), Report No . A Toward !su Ratordoua ~
agarettes . T1u Fourth Set ojEcpaimental agorraea . DHEW Yabi. KH) MaeeY (1980) . ~
00
w
3
, . .

TABLE 4 . CIGARETTE DESIGN TECHNOLOGIES : REDUCTION


OF SELECTED SMOKE COMPONENT LEVELS AND
BIOLOGICAL ACTIVTTY OF CIGARETTE SMOIW
Selective Biological
Reduction
Tumori-
. .T--f f
1V\ hnologj ~ gsw 4i4X Ciliatoxicitv

To6acc+o Proc+esslnp

reconstituted tobacco sheet t 50% 0 insig sig 2 50% sig


(paper processy
expanded tobacco' L 50 % M sig Z 50 % questionable questionable

cut insig° insig insig insig questionable insig

extraction with organic sig sig insig sig sig insig


solvents

Ciparette Paran~eters

cellulose acetate Sltration• sig insig Sig ~g msig


~~
Cbarcoal filtratloRd s1g ~ insig sig sig z 50 %

air dilution:
via paper porosity' sig = 50% sig insig sig
via filter-tip ventilation! sig n 30% sig insig sig

additives (nitrates) sig sig sig sig sig increase

Tobacco Substitutas Z 50% Z 50% insig sij z 50% sig

• lntroduced into el`uott, detip In t6 . 8ltantipped W%riae and 7amm Amnsl (1953) .
b Ffnt used In marketed products by R .J . Reynolds Tobacco Caapanr ia 1968 .
• Introaucea In the siest WShlr succaaw sltertippea eisareae, nro wawron, In 1953 .
d litroduced In an LAM product, the Lork, In 1963 .
• Introduced Into R .1. Reynolds Tobacco Coaipany products In 1938.
~ IIntroduced In an American Tobsoeo Caapany product ia t96a .
s Addition of dusls or nn of hijh-aitaa tobacco Increases level of Maitro ..mines In tobacco smoke.
`dbbnvtaqoir:• CO - oasbm moaoactds ; BaP - beazo[o)pyreos ; sig - stjnt6cant reduction ; ioais - iasiSniSoant reduction ;
questioo.ble - tnduotiou .n1din .aV.eimsntd .rcos
~ H1odoted dsfm ior nioodns reeeat dfxt of tec6nolojies In use In ouanntly marketed U .S. cigarette products .
1 At kast one 1ob .ooo subidpitm swdW (CytraN) In the National Cancer lastimte's'9ea haaidow" oiSaeeae pooSram showed an
inereaae In per oipza . BaP delivery and In BoP .'1'PM eadoto.

0 United Stata Public Health Seevice (USPHS) (1979), SSwokWa ard tlsal& A Report of de SwSson (3enrral . D1iEW Pobl . No .
(PHS) 79-50066 . Ses Chapter 14, Tsbie 26 .
10 God aB (Editor) (1976), Repon 1Yo. 2. Toward Lcit floundow Qaanaa . 71u Serad Set qfFxPerGrunwl Qgantua . DHEW Publ.
No. (NIH) 76•1311 ; National Cancer Iastitws (1980), Rsport IYo . S. Toward Lesr Bazamdou r Qganau . Sw"MaT. Four W^
Palniina Bloauay. Uaina CondcnratsJian Fspai+nsnwf Qaarraei . DHEW hW . M[I (Septt<fber 1980) .

. .. , . . •.
While neither the Surgeon General nor Wynder and Hecht discussed in detail the effect of
the so-called American blend on the mainstream smoke components or properties listed in Table
4, data are available that indicate American blend mainstream cigarette smoke condensate shows
lower specific tumorigenicity than several of its component tobaccos, e .g ., flue-cured tobacco,
oriental tobacco. The polycyclic aromatic hydrocarbon delivery, particularly the benzo[a]pyrene
delivery, and the deliveries of low molecular weight phenols are less in the mainstream smoke
from the American blend than in the mainstream smokes of flue-cured or oriental tobaccos" .

In its discussion of the "manipulation and control of nicotine delivery in marketed products",
the FDA limits the bulk of its discussion to events following about 1979" . Less than 15 % (18
of 128) of the citations precede 1980, t .e., the period from mid-1950s to 1980 when the effective
technologies were developed and introduced . The FDA's attitude about the events subsequent
to 1980 appears to be What cigarette design technology have you developed lately that will
contribute to a"less hazardous" cigarette?

Considerable data are available on the effect of several of these cigarette design technologies
on mainstream smoke composition and biological properties . Of particular interest are those data
which indicate the effect of a particular technology not only on the nicotine content of the
mainstream smoke but also on the nicotine: "tar'-' ratio. Technologies studied extensively at R .J.
Reynolds Tobacco Company include :

• reconstituted tobacco sheet whose composition is essentially 60-70% tobacco stems


plus 30-40% scrap tobacco laminae (see Table 3, Footnote d)
• expanded tobacco laminae (see Table 3, Footnote e)
• air dilution produced via filter-tip ventilation (see Table 3, Footnote, f) .

Because R.J. Reynolds Tobacco Company developed the first meaningful process for the
expansion of tobacco laminae", it not only used expanded tobacco in the design of its own
cigarette products but also licensed the expansion process to other domestic and foreign cigarette
manufacturing companies who used expanded tobacco in the design of their cigarette products .
Between 1964 and the mid-1970s, considerable data were generated in-house at R.J. Reynolds
Tobacco Co . R&D on the following:

• the effect of tobacco expansion on tobacco composition


• the effect of inclusion of expanded tobacco in a cigarette blend on mainstream smoke

it Wynder EL and Hoffmann D(1967), Tobacco md Tobacco SmaAr S7wdiu tn F-spsr6nenwl Caulno ;wud . Academic Press, New
York NY .
® United S4tea Food and Dro= Adminlstratioa (FDA) (1995) Nlcodae In CiBareetea and Smokeku Tobacco Producta L a DeuB and
These Producu are Nioodne DeWery Devicea under t6e Fedeed Food, Dru=, and Caemeda Act . US FDA DHHSt 1-326 (Aajwt) :
See 232-288 . Chronoljy of Footnotes prioc to 1980 : 1964 - Footnote 404 ; 1970 - Footnotes 302; 1971 - Footnote 423 ; 1972 -
Footnote 503 ;1973 - Footnote 491 ;1975 - Footnotes 39Sa, 483a ;1976 - Foomoe" 430, 461;1977 - Footnotes 397, 398, 412 ;1978
- Footnotea 406, 457, 465 ; 1979 - Footmrote 477, 486, 48Sd
13 Fraddctwa JD ('1970), Process for lncrasinf the Fd* Capacity of Tobacco . U.s. Patst No. 3,543,451(AMguat 18) ; Moser OP
and StewaR oM (1970), Procew for Increada= db FWias Value of Tobacco . U. S. PaEe.t No . 3,S4Z,452 (AoYort 18) .

5
composition
• the effect of inclusion of expanded tobacco in a cigarette blend on the biological
properties of mainstream smoke

The data generated were summarized in a report, originally issued in 1972" . When additional
data, particularly biological data, were obtained, revisions became available in 1974 and 1977 .
Each report was provided as an accompaniment to presentations to management and R&D
personnel of the various tobacco companies interested in licensing the R .J. Reynolds Tobacco
Company expansion process . A copy of either the original report, or its first or second revision
was provided at the time of presentation . Cigarette manufacturing companies in the following
countries received copies : U.S.A., Canada, U.K., Germany, Austria, Switzerland, Japan, Korea,
China, Taiwan, and Australia . Although the data per se were not published in a scientific
journal, nearly two hundred copies of the reports were distributed worldwide . Many of the
potential licensees, using their own tobaccos and/or tobacco blends, investigated the effects of
tobacco expansion on mainstream smoke composition and properties . Except for minor
differences in the data, attributable to the minor differences between the tobaccos studied at
Reynolds vs those studied in the potential licensee's laboratory, the experimental data were
uniformly confirmed with regard to the reductions in levels of allegedly harmful components
(benzo[a]pyrene, acrolein, phenols, etc.) . The Reynolds findings on the effects of inclusion of
expanded tobacco on themainstream smoke nicotine delivery and the nicotine :"tar" ratio were
also confirmed . Most significantly, confirmation of the mainstream smoke composition and
biological findings (mouse skin-painting) was also obtained in the National Cancer Institute's
decade-long study of design technologies whose use led to "less hazardous" cigarettes" .

m Rodgman A(1972), 013-Sxpanded Tob .coo . (Deoembec), pp. 66 ; (1974). 013-8xpanded Tob.cco. lat Waion. (Febnury). pp.
77 ; (1977), 0-13 BxpaedeOTabaoco . 2nd Ravidou . (October), pp .177 . T6eee repoits are .uamoarks of data ont6e etfect of tobacco
expandon on smolce compod8on and pcopeede.. Tiw.e data .ren used io pre .eatadomi w mrn~gemeat and R&D peaonnel of vuiow
tobaceo compardea inaoeated In lioenaiog tM RJ . Reynolds Tobacco Company expan.bo process . Copies of t6e eepoeta were
peovided potential ttcen.eee at daa of praentadoo . Tobecco coaipinia Boaa tbe 6opo .viag couatdae were involved : U .S.A., Canada,
U.K., Germany, Austria, Switzerland, Japan, Koroa, China, Taiwan, and Australia .
1$ (7ori GB (Editor) (1976) . Repott No. Z. Towand Lat Rarardou pgonaa. 71rs Sarond set ofBrperbnenmt Qgarraer . DHEW Pobi.
No. (NIS) 76-1111; National Cancer In .tiwte (19E%, 8epoa /Yo. J. Towand lssa Rnundows Aganeaa. Swnnmary: Four sktn
Palnatng BJooarayr UaJng Cordenaatt finai Erpertnunta/ Qganaa . DIi3rW AW . (M (SepterDer 1980).

6
TABLE SA. EFFECT OF TOBACCO EXPANSION ON CIGARETTE
SMOKE COMPOSITION : A COMMERCIAL BLEND
(CIGARETTE SAMPLES FABRICelTFD 70 EQDIVALEM'
FIRblNES4j
Ratio of Control Tobacco B1end :Exeandad Tobacco Blend'

Anatyteb 100% :0% 90% :10% 75% :25% 50% :50% 0%:100%
partlculate nhase
. 4tar , 9, mg 28 .6 24 .4 23 .6 21 .1 20.8

2 .01 1 .60 1 .44 1 .26 1 .01


nicotine, mg
0 .0703 0 .0656 0.0610 0.0597 0 .0505
nicoane: "tar" ratio
carbon monoxide, mg 16.2 o~ b 15 .46-C'~% 13 .9 0Sl9 11 .5 O•s~ 9 .8 Q•'*1 t
t
1enzo[a]Pyreno, ng 16 .1 13 .0Q,ri'r 11 .1 tp, ,P 10.4 0• k '4 7 .1 e• %k*

formaldehy a, µg 53 48 1 q~~ 41 ~~51 39 t•~~ 36

965 955 aQ""f 925 3a • t~ 880 0' 11 790 3 7' ~ 4


acetaldehyde, µ8
' Cigareaea In each sample fabricated to eqdtAlent fir.mneat
b Per cixareae values

TABLE 5B . EFFECT OF TOBACCO EXPANSION ON CIGARETTE


SMOKE COMPOSITION : A COMMERCIAL BLEND
(CIGARETTE SAMPIES FABRIG!?ID ?10 EQUIVALEM'
PRF.SS'URE DROP)
Analvter Control Tobacco Blend ExpWW Tobacco Blend

particulafe phase
64tarp , , an 31 .0 23 .2

nicotine, mg 1 .88 1 .20

nicotine :"tar„ ratio 0 .0606 0 .0517

carbon monoxide, m8 14.0 12 .6

benzo[a]Pyrevo+ a8 20 .8 12 .4

Ys122CP~
formaldehyde, µ8 55 45

acetaldehyde+ µ8 1050 793

' Ciyareue . In each sample fabricated to eqd .aleot


b Per cisarette values

6
TABLE SA. EFFECT OF TOBACCO EXPANSION ON CIGARET'I'E
SMOKE COMPOSITION; A COMMERCIAL BLEND
(CIOARETIE SAMPLES FABRIGlTFD 7b EQUIVilIF.NP
Fm1VF.SS~
Ratio of Control Tobacco Blend :Expanded Tobacco Blend'
Analvte" 10oas :o% 90% :10% 75.% ;,2 5.% 5o%:sog~ 0% :10og~
paniculate nhase
6 .tar„ mg 28 .6 24 .4 23 .6 21 .1 20 .8
nicotine, mg 2 .01 1 .60 1 .44 1 .26 1 .01
nicotine : "tar" ratio 0 .0703 0 .0656 0.0610 0.0597 0 .0505
carbon monoxide, mg 16.2 15 .4 13 .9 11 .5 9 .8
benzoLa]Pyreno+ ng 16 .1 13 .0 11 .1 10.4 7 .1
i9w phase

formaldehyde, µg 53 48 41 39 36
acetaldehyde, µg 965 955 925 880 790
' C'iSareaea in each aampb fabricated to eqni .aieot tirmneds
b Per cigarette valuea

TABLE SB. EFFECT OF TOBACCO EXPANSION ON CIGARETTE


SMOKE COMPOSITION: A COMMERCIAL BLEND
(CIGARET4E SAMP1F.4 FABRIGlTlD 70 EQUIVAI.F.iVP
PRExSDRE DROP)
Control Tobacco Blead6 Exnanded Tobacco
Blendd
partlculate DhaSe
,. tar „ ing 31 .0 23.2
nicotine, mg 1 .88 1 .20
nicotine:' `tar•' ratio 0 .0606 0 .0517
carbon monoxide, mg 14 .0 12.6
benzoIa]pyrene• ng 20.8 12.4
MpQ,pl+'ase
formaldehyde, µg 55 45
acetaldehyde, µg 1050 793
' Per cigarette values
b CiYarauea In each wnnple fabricated to eaoi.akot prasaore drop

7
TABLE 6. EFFECT OF TOBACCO EXPANSION ON CIGARETTE
SMOKE COMPOSITION : FLUE-CURED AND BURLEY
TOBACCOS
Flue-cured Blend Burley
Ana(yte Control E38g0~ Control ExpAded
partic tg i+ase
. . ,• . mg 32 .9 18 .2
ta
27 .7 17.7
nicotine, mg 2 .75 1 .25 1 .92 1 .13
nicotine:"tar" ratio 0 .0836 0.0687 0.0693 0 .0630
carbon monoxide, mg 15 .6 7 .0
benzo[a]Pyrene . ng 28 .5 8 .7
ygpa phase
formaldehyde, µg 31 23
acetaldehyde, µg 970 575
' Fer cisacepe values

•-e burley blend


0 .090 N • nicotine
o--o flue-cured blend
T • t1tar"
x . .x coeeerclal blend

.080
N/T
Ratio
0 .070
0

X. . . . . . . . . . . . . . .
0 .060 .. X

0 .050
I 1 I I I
0 10 25 50 100
ExpandQd Tobacco, X of Blend

Figure 7 . Nieotine/"Tar" Ratios for Expanded Tobacco Blends


TABLE 7. EFFECT OF TOBACCO EXPANSION ON CIGARETTE
SMOI{E COMFOSITION : STANDARD EXPERIl1Ii~'.NTAL
BLEND (SEB)'6
Analvta, Control SEB RJRT EzpAnded SEBd PM Ezoanded Blend°
narticulauphast

"tar", mg 27 .1 15 .6 18 .2
niootine, mg 1 .79 0 .78 0.74
niootine: "tar" ratio 0.0661 0 .0500 0.0407
betuoIalPyrene, ng 19 .2 11 .9 8 .9
MM phase
formaldehyde, µg 31 .9 20.7 21 .7
acetaldehyde, }ig 985 814 720
' Per cigaroue vatue.
6 Expansion agent - chloronuorooacbon
° Expansion agent - ammonia/caebon dioxide

10 (3ori dB (6ditor){1976), Report No. 2. TowardLas Hazandow Qaanaa . ?Ja Seoond Set oj6zperimenwl Clganaes. DHEW Pobl.
No. (NIH) 76-1111 .

9
• effect of RTS on MS nicotine
• effect of expansion on MS nicotine

• low-tar, medium nicotine ; the Gori cigarette


• tobacco substitutes
• tobacco extraction/reversal of opinion - nitrate addition/reversal of view
• carbon-filtered cigarettes

• 10
TABLE A . STATUS OF ASSERTIONS MADE ABODT CIGARETTE SMOKE, ITS
FORMATION, ITS COMPOSITION, AND ITS PROPERTIES
Asswlon Statr~s

• Nontobacco Sources qf PAHs'

§ PAHs in MS due to PAHs in lighting source flame (match, lighter) false

§ Major precursor of PAHs in cigarette MS is the cigarette paper false

§ PAHs in MS result from transfer of air pollution-derived PAHs on leaf surface false

•Precursors in Tobacco of PAHs !n Tobacco Smoke

§ No BaP is present in MS ; if it is present, its *or precursor is cellulosic false


§ Major precursor of PAHs in MS is one or more tobacco components true
§ The major precursors in tobacco of MS PAHs are the saturated aliphatic hydrocarbons false
§ Tbe major precursors in tobacco of MS PAHs are saturated hydrocarbons and false
phytosterols
§?be major precursors in tobacco of MS PAHs are terpenoids and phytosterols true
• Controversies over Presence or Absence of &wRc PAhfs in Tobacco Smolu
§ No BaP is present in MS false
§ No alkylated PAHs are present in MS false
§ No cyclopentanobenz[a]anthracenes are present in MS false
§ Dibenzo[a,l]pyreno is present in MS false [caveat']

•Mechanisms of,f~=genesis of PAHs !n Tobacco Smoke

§ MS PAHs formed primarily by a degradation-combination mechanism false


§ MS PAHs formed prttnarlty by a unimolecular aromatization mechanism false
• lavels of P,4M In M$an¢ Its Thnu~(ggntcitv
§ MS PAHs ara the only major tumor initiators causing mouse skin tumors false
§ MS PAHs are major cause of respiratory tract cancer in smokers false
§ MS contains a•`supercarcinogenie„ PAH false
§ Promoters in MS augment PAHs in their tumorigenicity false
§ Increasing BaP content of CSC increases its tumorigenicity false

11
TABLE A. (Continued) :
Assertlon &g{9

• 7he "lndicator" Concent

§ BaP is "indicator" of CSC tumorigenicity, levels of tumorigenic tetracyclic PAHs false

§ Phenol is "indicator" of promoting effect of CSC false

§ Catechol is a tumorigen false

§ Catechol is a promoter false

• Control of P.lX LeNels In MS

§ Removal of lipophilic precursors from tobacco reduces MS PAHs true [careat"]


§ Addition of nitrates to tobacco reduces MS PAHs true [caveat°]
§ Increasing number of cuts/inch reduces PAHs false
§ PAHs may be selectively removed from MS by PAH complexing agents in filter false

• Control of Levels Qf MS CeMMnents Partitioned between VP and PP

$ Selective filtration impossible false


§ Selective filtration possible with MS components partitioned between VP and PP true
•ggulvalence/Noneaulvalence of PvroEysis and the Smoking Proorss
§ Fate of an individual compound during pyrolysis is equivalent to its fate in tobacco false
during smoking process
§ PAH levels in a tobacco pyrolysate can be correlated with their levels in CSC false
• &morlpenlc Threshold LlmltsQf C ;ggrette Smoke Condenaate and Some of Its Comnonet~
§ No threshold limit exists for any tumorigenic compound false
§ No threshold limit exists for any tumorigenic mixture such as CSC false
• T~umor,jgenic Arrt Arenes In Tobacco Smoke

§ The tumorigenic ais-arenes dibenz(a,h]acridine, dibenz[a, f]acridine, and dibeazo- questionable


[c,g]carbazole are present in CSC
• MS Cotnnonents Alleped to Ciliastatic to Smokers' Resn[raLW Tract Cilia
§ In vltro water-soluble ciliastats in MS impair lung clearance in smokers' lungs false

§ In vitro water-soluble ciliastats in MS removed from smoke stream by carbon

12
TABLE A . (Continued) :
Assertion Status

• MS Comvonents Alkgedlv Resnonsible or Lung Cancer Inductlon in Smoker s


§ BaP and NNK in MS are responsible for respiratory tract cancer in smokers false
• Tobacco and Tobaeeo Smoke Comnonents Class{Red as Signilicant 74norlgen s
§ Tobacco and tobacco smoke contains 43 significant tumorigens false [caveat']
•Tobaccv Smoke Comnonents Anttcsarclnogenlc to Alleged Tobacsc+o Smoke Tumorlgens
§ MS contains components that are anticarcinogenic to PAHs and/or NNAs true
§ CSC is antimutagenic to (righly mutagenic "cooked food" mutagens true
§ Nicotine and cotinine are antimutagenic to NDMA true
' The bonafide benzo(a.lJpyrene was subsequently identified in tobacco smoke, but the PAH defined as benzo(a,Qpyrene
(dibenzoldif,PJehryaene) was nor benzo(a,lJpyrene (dibenzo(de, f,p)chryaene) but was dibenzola,elfluoranthene .
b Extraction from tobacco of lipophilic precursors of tobacco smoke PAHa produces an increaae in the deliveries of low molecular
phenols, alleged by some inveadgatora to be promoters of the tumorigenicity of certain PAHa .
° Addition of nitrate to tobacco or use of high-nitrate tobacco in the blend does deceroaae MS PAHa but Increases MS NNAa, many
of which are alleged to be tumorigenic to humacu .
a There is a host of reaaona why many of the 43 smoke components listed as significant "tumocigens" should not be included in
such a list .

Abbrevfatfona:

BaP betrao(a]pyrene NNA ~ N-nitmaamiaa


CSC cigarette smoke condensate PAH ~ polycyclie aromatic hydrocaibon
MS mainstream smoke PP ~ particulate phase
NDMA N-nitroiodimethylamine VP ~ vapor phase

13
.

: eptcr.~,er Z°, 2;56

S s: cni ~er :cal stotohooY piroos 26517-26520,


26W, 265148 2790LM27,
32C67-323.CO
RDR, 1956, ?Po . 9 Previotm reForta 3
RM40 1955, Na . 23

"s~ LY'SIS CiTCI?;_W

f`~ I Eflta

'o c .acrl. :A t--e expse-=en+„a :, SzveatiEution on tho ieolat :on a.cd/or i.deati-
ficatloa of eQvvral Da7,7eyol :c arc=tio ia ; drocarbona present in the cigarette
snoko oondensate froas CA)SL blead tobcoco .

:Ao-~t

':be five pcl7c; clic ar^^


.,.•,at .e
~a~er.e ar.;: 3,G•'v= ;; -mcc, ot*ea :.oo:tatod and idantifivd in Uo ciCa-
mcte awoka condensate irco C'.N:.L blond tobacco. TbsaO 2~qdrocarbcrs vcra idon-
tif ied Y7 otandard ehecical techniques and eoe`rersioa to one or rore known
derivatives .

The arcrmt .o ty''rccarboas wore charactoricod as tol2ovas


(1.67 =g . tY= 2^, ;C0 Vit'.::L c:gr,.rottes) by cclting toint, u1t .Mvt_o1et
crd ir.f~~r~3 atcc:-; s;,octza oS' t} :e ;;dr ca,r:ar.j a .^.fl :r_rc .^..ra_c ra (4 .03 rS . f: cm
~~.
.. w . . .~ .
ln
••~~9 . .~ ~' .. :. C ft~~,.rCL+i+ ..66~.~)
. ..
) ~ ... iXtLC'0 .Al . ...••~ ~43.w 1Lt...~Vs1 { V
.t~ ~ ..1 .. : .. . ~
.. .~ 4 ~.a..~
C*.. nn . ..~`CL
C}vC :'r t .c:'1 0',oC V rZ c f a 1 0 h ,"t'.Y'Q :..r bc : : ,* ..~. . .w 3 toltir.C point cf M.r o W .M. .I M CV :A-
„ I c"' .o acid C,. .Ed.C, M . .?CVISo t :clts•7:f; point ..IId i;l: rarCd atC'.cI';`YicA a pFot~" = of
ar.t~: mciar.o: a-9,1.0 ; r-.-rc,r,e , (1 .36 sgo ircD 1L, CCO CA.•EL ' ciCc : ottoa ) by r!xt ;r e
relting poiot ar.d ul :r aviolot atcorption aFeotr= of the Yydrocur :an, s3xtvro
celting point and in ."r~ speetr~.~ of tl :o p7rono-trinitroflucrencno cor. ; lem ;
lvoranth t,rg (1 .95 age t`rom •I49CC4 Ca :'L o:gGrettes) tq u2traviolot spect .-M
and r.vctureg relting point of the ~qdrocarbca, v.±zt•ae sAltirg Foir.t,of thfl
flvorantror.e•tr•_r.itrcfltmrenone Oowplcet ( l. ee~~
w9 . f.-= 33, c,•^.
;
.. :~ L ciZ-..rnttca ) Iv7 r.ix turo mc1t'-=.g FA :nt9 ultr aviclot and L.::^•.~rod n~..: a - r ~.~. VN

sfectra of th e L-, d m carbon and r'.xtur e = l4%,N46 :g poi.:t of LMa 3 ,4 -tcr.zrj:c:.0 -


^icrio ac :,d cccYlo m .
"..̀:e ©s po17c7*1ia It/c:rcc ; rxr-s9 3-r.ct'^a3-
r;':'9 :0j `.~~.:~a i,lZ- :o : :cpcs7lono and anthan`.hm:e, ::.ve :eca
i4ent .::ed as o=sti!,•,:aata of Cs. :CL oigarette scoke eondonsato on tho ba nis
of ultraviolet abaor ;,tion epectrv.
2

T"T?IS 0F CCfi'f'FnT:Ss

11-^7 L° . . . . . . . . .. • . . . • • • • . • • • . • • • • •

L,i "J^ C? FZCIi^ES . . . . . . . . . . . . . . . . . . . . . . . . . . .

LI~:' CP r'S~'n'~A~TS . . . . . . . . . . . . . . . . . . . • . . . . •
+ ~ .~ .- .. . ...,.
Ii . . . . • 4, • • • . • • • • • • •

rwA~~.i?iJ'.:.:fLAL .• • . . . • , • • • 9 • • • . • • • • • • • • . .

S. i'iMy u"i,iiip 4ii : :•3Ct hode . • • • • • • • • • • • • •

4 , -a.-G ~~ir Uk
lIi`} . . . . . . . . . . • • • • • • • 15

L. . .oiYeIIti . . • . . . . . . . . • . • • . • . . • . . . . 15

z . . . . . . . . . . . . . . . . .
A ~arattY . . . . 15

17
d 't1'reat,aamt of aML Cigarottos Prior to Sa.old,n

Irifluer.ce of Cisunce of Cigrotta on Manifol.d tYm


. . . .•

Suction Contor on tho Totr.a. 'h=bor of R:.° :s por Cigaratte• 17

IT . Ssolation of the 1iaxane-Solublo, .':eutml Tmctioa . . . . . . 19

III. Frsationation of tho "r .excne•.:olutlap Noutral .~:̀ action . . . . 210

a. Prauvl=7 Cbtacato~raphy . . . . . . . . . . . . . . . 0410

Chrocatomaphy of the Auaae•F2uted Material (Mation 1)


of the Rmono•Coluble, Xoutral frsatSon '• • . . . • • • • 24

Cr.rorstaRraphy of tre PolMalio Aromtio 1t7drocarboa

N. ' Me Zso:aticn and IdEntilYaatioa of the Individual F ol^c7c'-=a


) r=ti 0 N.v"droCAr tOn8 . . . . . . . . . . . . • • . . . . • • 119

Na ph i.Da iG ne

b. Antt...acom . . . . . . • . . . . . . . . • ~7

•,. Vs. RC.A iC V;tA rAi . . . . . . . . . . . . . . . . . .

.ctIZATIDN CF A . :.AC''.»'iE AS AY?AFiAMMA•PIC"ruC


2. LF,ARACTF' ~
ACID CCMPS= . . . . . . . . . . . . . . • . . • • • 29
T4ryr rP ( Cont ,d) i

^? Aa:,:ro•.crM
. At A :^:w=a,
' ..
.._. ._ 3
6• A&'CRFTIOl7 ::PECTRA . . . . . . . . . . . . . . . . . . 31

3p4mPenspyrens . . . . . . . . . . . . . . . . . . . 31
1. CP.P.Mx.% TCCm PwY . . . . • . . . . . . . . . . . . 31
2• C!'.~2+ ~^~ah•1?IC .y CP 3t1,o .o''tLrMz• .' :E AS
PIC:UC ACID CCMPIE3t . . . . . . . . : . . . . . . . • 33

Ar"^•`"'R .ICtt CF :-C'jRA • 33


d . • • . • • • • . • • • • • • • . . • . • . • . 33
l. Q~P.~t %.A 1'C VPAP{a • • • • • • • • • • • • • • • • • • • • 33
.2, ~~r'C" . «AT .r.I ~'P ?L17C??A~~" .?''"~ Ac +•~t„IIro .s~,wat~ .•r~
.o • ~/. ..I V ~ W ./ . . • .W ./

~-Pi ;..~ . . . . . . . • . . ~ . . . 33
34
00 j-Yr ome 0 4 0 0 0 0 4, 0 0 . • 0 0 0 0 0 0 • . . 0 0 • 0 9 0 • 34
I. CF P'Sp..~. ;ZE AS PYR:.''P~.•TRI7I':.^•C..
34
• 2
• ~P:C"
~~ • a. • • • • • • • • • 35
I j 02. ::Elc :a a..~'.rGCBL`e 35
»

b . Aat.~.anLhrs~s . . . . . . . . . . . . . . 35
C. DIsC^vwICA• . . .•s•• .• . .•• 36
D• v^C!CC MIV!1S • . . • • • • • • 0090 • . 090 40
w ~ ..~~~.- . ..y . . .n~*c
« • i 0 0 • 0 0 0 • • 0 0 9 0 0 9 0 0, 0 • 0 0 • • 0 0 i .V

I. `Ytt r e Work • • • • • • • • •' . • • • . • • • . • • • 41


r

~ .. P•atant 0 0 a . • 0 0 0 0 9 0 0 0 0 0 0 • • . o • • 4.i

Mlcm r n 42
.. . 7l !' .ZL;Fj

P..~ ~ r~
.....
. bl "o

I Po],Tcyolio ~'ydrocarbona in Cigarette Emoks~ aad


Cicarstta Paper fcoke Coadea3ata :`~ ~ : . ~ : . . . .
16 •Vt. .d ' .%=bii C f % .,:a r= Ci rw-ot .4ro f or i nd iliLi mi
!'a::.fc,:.3 r'cea_ccs and ua :.ifold Rtr.a . . . . . . . , 19

III Preliminary
~ ~ ~ ~ Chrosat0 , ~,~~rup~ of the tIezaaoluble,
~. ~}

. .
•~Y4i"ii.~Y4i"ii"
~~Ai li'i0tion \F~7' . s • . . . . • . . . . . .

CF

Fiv~ure "~tQ,

1 :arsmtSo DSagraa of .mcking Apparatua . . . . . . .


• ar-fo l4 A . • a`r(. ....I~' :3ii , 1. .. . s -, • a •

LI!'? r`F' FI1'•.,'f?E="*Si

_F].cnrsho,,~ e ~

l Isclation of the Fozar.a.~ c2;:tIo , '!ott : a1 F: act1--,&


i: r= C :garette !7=o're 'Cor.der:,ata . . . . . . . 2:

Crscratograph7 of the F.exano•Sotnbls, Noutral


FY'Sct1oII . . . . . . • • . . • • • . . . • . . . . . 23

Chro~atorraphq of the F'cxane•Eluted Naterial


(Fraction 1) of the Aexar.e.:olublo, Feutral Praction 25 ~
~
y
• of `~'-o r rr .:;.t.io F.y drocarxn C:,ncentrata 2i m
0.
Ito isolstion r.ad Identification of F.aFhthal.en o . . 2s t.o
ko
OD
6 :fi.e Iso:ation and IdentL'' :catioa of Anthraceno . . .

4be IiolatioA and Identification of 3,1, .Benzpyrena .


5

~ . . . ....- .. ..~•~nr
..r.~.~.~...:1.~.. .5

Statistical anolysoo tcaod on rotroapoctivo (1n,35,51,60,66,67,71,72,71,,


%~,95,96,97,1C8,110,111,117,12E) nr.d pro;pcctSve (36,52) clir :cal otv3ioa r.avo
indicated that tobacco moke, and in particular oigr :rotto ea:o:ro, is a r.n.Scr
ccun 3tivo factor in the prcaeat bigh and iacreaeinC inci .'once of cs =or of tho
racpiratory eystsa 3n the humn . goceatly, Dol .l (34) has pro3cntod an oxoollont
cr.itical appr4iaal of tboae stctistical atudioo . P.e concludoe : . . . . . .tr:oro i3
the evidonce that oisr.rotte ec^aking ia an i ..Yortant factor in tho p :roduct4cn of
. . `I
rri'lw~ :C`~, ~~
:C`i ~,ta3t~'~:Bii~ Bii~ A .R.a~ ~~C~
~a.'~i . .'Vi~ .~
.~:Lwt\J w
:Lwt\J C~
C~1
w• .+n ..
., ~ 3rr4 , . t~
4
a •.. i1 `J•Z
2 A Y .L iarwr
•~, seo3 °oault 2'r :w expcsi . re to fiem or rore S.N.deFoadcnt i.~c:ust.^ral rrocococo .
:Y':et::cr t.`:o l.norease in oi g.-.rette co .wu-r rticn and the growth of the opec :fie
Sn di:strica can toget.':er account for tho roal' inarease in mort-clit7 and for tho
extant of the a:a2e preponcorance o .:nnot be soon with certainty . Fr.cvled,-e of
tho true extent of the cban p i n martality and of the i t:.^. d=octal = cc?:r.r+ ,z= s c'
.".. .`iaL :. r eI328 :a is g to 'r`or'"~t tho i^.rCpc.raticn o: a
4 ."~ ~or4. .r'
..ital;J, l .'Jtilf :ZC :eIIt
preciso Lslanco ehoot . There iQ, hovevor, no direct ovidencv to iw=,l3cato thc3o
othcr onviroa .rontal tootoro which a.Mo also knavn to havo inereased in prevslo :co
:-I tho laat tms or five docadest and it io a reasonable presuription eat the
changes which have taken place in tobacco ccx~t :ca (im a...~zr:t ard in Lot..cd)
are rc3,.ors :rle for t~:e raJcr ~.rt of '..h3 real inc :-v : se in ~:-•s11L; . 'a.^
ti~e action of oiEcr3tto enelce ls duo to ita 3,d-tera-prone contor .t or to scr, .o
other su ;stan..^e, and vt7 it shou].Y be d .Stcrcat froc that of mo :co fZ^cn pi ;ea
a.:d cid rs, is %m ..cs" n. . . . . .

atterpts to doter~...ine a particular cor..^,titsrr,t of cigarotte g: oIce possibI7


recronsib2o for the i nitiation of cancer of tho lti :ne have rorulted iz car.~i~cr-
aUo 3::vostiC-nt:cn ca tre cc=:calt:c.z cf c_CaretLo =cko ca :reroats . F.n:=l
data, e.ployi.^.g varic•,a i':rocticns of ciC:.retto =oko cor.de^oato, have Lndicatecl
that tt:o r.a~cr ,~ :~t of t!:e c:.rc! .^.c~;cwc activity of ci~rstto s=o ::o ccrce~ats
roE_dc~s in t,t:o aeut:':1 iracticn (1~1) . :7~:o nstitral frccticn wcv.?c ^cr^m::7
c: a tz :.n the „u ' of tha Fol; c; olic arcL.:tic ;;,:r̀ocs.^ t cr.o ,, «,a V o: vri ct. :: ra
la .~t.13 %Vn~1 .~. : . .m c~r.~!..~r~t.. ..l
..lr~t .~~.r :.~ \ 5I / . ~.~ir.c ti.7 pa .gt b+C : : ..J J v ... .~r,
!
Otr ir``LL:3 .~ .n.VC3 •. .~ ~ . :'9 ~. ..i w •
879 .d.t.t+ .....
. .• .,:~ tto w.,aC«~G
!
: • 3 CS:C~/Cr •.. • i.
~ ..0 Z.La .7i:"
. :l
polycycl .:e aromtlc ~4rcroczrbcns Fret ent i .z tobacco ecoke con,:cnnato . Further-
more, aa :.-sl data ha :od cn Om tar ot+t,ainod L,7 satractir.g urecokod cigr.rotto
tobacco vith not2 :ano1 co=;arcd vith theso of the tar from smokod cigarettes
ou_r€ost that the aasor part of tho carcir.oEonio activity of aissretto s~olse is
produced dtaizg the actval amoldng rroccso (L^J .) .

:.: +::. U:c: ;:.:;: t t:o ca rci:o r enie offect o : iocacco tar
(c~t,:.r.ed ty dost :^,: ..ve di z t:~acn of tohacco) in : 3 b}its ~~ r a •.s rrcr'~3~
w4
a c_.. .. ...o6e .. .c ef.cP oo •„a di:e to t h e action of 1, .•'.-bcn: ant2'r co;.o, I, der .'lmt .vo3
. .w .~~ w'. r.1

on thooe aesq sFooioe . :pvotroacopic cx n .anstion of vsrious i`r-wct : cns of t.':•_s


t;,`xcco t:.r '~icatod ».e ^s~esaace of cc- ccctainir.g t:e 1,~~Lcr~::..-s±.~^,3:0,
., a :: :. .C : :z, _

W
I-A
_j
~
m

: . ss r~
6

7r.e sar,o year, ItoPto (F2, 84) identified nv .: rouo c=poncnts of toZ:.:cco

tar and acoko obtainad t7 the dcatru.otivo distillation .of tobacco . Diati?.Ia-
ticn of totccco at 100 to .1201 C. gave the following idcntiriable
corbon monoxide, carbon dioxide, cethaao2, a=onia, acetic aeidP - ac :etatcs,
F3ridinos, ` l .=thylp7rrolidino and ft-fa•al. •Dictil3atlon of anothar sampZo oP
to~ctcco at 350" C. for two hours Cavo tho Followinat oar .bon concadc:e, crston
dioxide, .a=oniuD csrbonato, acotic aoid, ncotatosp ouccir .io acid, lLz.3.. ~ic~ic ac :d,
.oario aald~ prenolio' aeida, Frjrrolo, ohloroph7ll derivativos, . p2:onanthrcno, IZ,
an•.hraccr,o, III, a*d "von.Y,rrc=o ." It ia o : L:tcr9st to n.oto that tre trr
rrrdi:cod b~ doatrut :vo di,otiila ~on of tobrcco at 3;C" C . ~s vory hig~ cr.r-
ai,nogenio . ae oon :parod with the ta,r : obtained at lf0 - 1200 C .

L`uring the period 1933 to 1941, F.ofto (£6, 89, 92, 93) docc='itEd tho tro-
sulta obtained by the opoctroaccpic study of tho tot+zcco tar ot,tainod by de-
atrti:ctive dictill.ation of tocccco at 3£0° C . A rrarkod oi-rilaritq was noted
botween the ultraviolet absorption trasima of thia tbbacoo tar and 3,4-Dcnw .-p7ror.a)
IV, in the range ?]r0 to 310 3r.}i.

In 1947,* IYoda (54) deeoribed the identit'..ostion of vnr'.oun cctponeMta ot


taLacco a^~..0 a . Ch . polyo9alia 2ydsoearbon of intorest vas identitied, nsrol,7,
azulana, 7.

17

Cooger (24) outL•ncd varic= z^.alytical t.eehni.qucs dovised in t :ia L^bo:M..-


tory to dotercir.e the qcsantity of tho polyoyelSo 2Crdrocarbon co :otituent3 of
cirr.rotto e~oko cnd tar . A raothod was alao dovicod for the idcnti .'Ycation of ~
t,) :o heterocyclio analogs ot'tho varior.z carcinogenic 2ydrocasbor.s, o .g., 1,2, ~
5,6-diter.:acrSdino, VZ. T!^.ia oonpouA ic the nitrogon analog of 1,2,5,6-ci- G
boa:anthMcene, VII, a very potont crrcinogen . Coop©r snEtgest.ed that cortain ,,
of the hotoroo7clia cos ::o=do raCht be constituan+.s of tobacco sr,bke and t . .r. m
Ma :7 of these hstar=,ic3io ccnrounds exhibit carcinoganic acti9il .,r or.h slighV ~
less than the analogous hqdrocarboa (53)•


1-O \S 4 ' i
m vin ia
:n i?~!., ;,efe :rl ::e (2, ?, G, 63) deccz-Stcd t~e identi . :cat:cn o£ 31i -
banzpyrvne in t2:o tar obtaiced fr= tmning oiCaretto p ::por . Tho tecr.r.:c;uea
e=ployed involvod reFeated cr.rosstoeraphy on al=ina and ol•saviolot abccrp-
tion spoct :rophotc¢etry.

S.brki.ng independont37 in Englands, Coopor and iin3sey (29), and, Coorer,


Cil:ert and Linrcoy (2?) reported tho identification of various . polmclic
aror.atio bycroearbens in the moke and tar l5r= tvrnlaE eiCarotte pzper . 11l:oce
authors er :ployed standard techaiqucs Cevalopad by Cooper and co-uor :rora (l, 21,
25, . I6, S8, 31, 11:) . °cpcatr:d .cr.rc=to,-r:~r:~y on a1=i."a, in co^,)t,..^;ction
~-::,c :ct spec•.r c ;._o t,o«.ctr ;, ::"2cr.tad t.d rPQ3C nco cf t.':o :0110'JS.b?
c : r:on$i p~er8::tr.rene, :3j anthraccr.e~ S :Tf 3,4~tcr.:,.~;rer.e . IYt ~ro:e, ~'===,
!'3ucr antrcne, !~C ; acer.aFbthylane, x ; 1,12..tenzopcryl.or.e, X i j and an•..h.ant~.Mene,
xII . An alSqlpyrenw t.aa also tentativol,y identified in the tar.

S
r mo

.
a

Cccrcr, :.indcoy ar.c WaLer !?1), Ccr.:-„ina, Cooper and Lir.dsc-; ( :.1) c--A
Cacp-er and h:.r,dscy . (30) ecploycd tho above aontionod techsiqws to idcntif7
ar.whm-ceno S :I, ( :1, 30, 31), pyrc:~e, ~iIII ( :1, 30v 31)o and 3,~C .•Len::,,-~:^cne,
I9 (30, 31 ;, in ciEcrstto cr.cko condonaate . 3be procoduros involved Sn t ::eeo
'_r.vc~ . . ;:..t!crs e ..~s "zed ct~ fo71cv33 Cc,:.:,:st :cn of the c :Cc :~ot'oa tz.:3r
ccnditiors si_~uhai^F the hLw:n wm-c :ar:g pattern ; collection of the s--oke -con-
dc ::ca .o at r^: ~ed t.erpe,-_t•r.-a ; r o=oval of aci :;io and b,:aic c=j.cnent3 0 : t : o
swoko condenoato Ly ct:cr.ical fractionation ; repeated cr.rozatoCr-_ph,7 of tho
recu :::.r.g r.eutral ta~.- on Als=ina to givo fractions containing the varioi:c p o3.;-
cyclic ar=tic tydrocarbons= identi.ric.ztion of thoeo aroa:otic }~ydrocarbcra ry
ultraviolot 3poctrophotoa.otry .

:n 1955, Ca ..«-pte11 and Cooper (19) identified 3,1,,•beazp~rer.o . 17, in the


aloe snuff nsed t^7 the Pantus of the ?tarsv~,.al. 'Yie aice ia p--opared
tq ::ectir.g aloe et= . Vonda srn:f':, vhich ciso cont3 ::s toba.coo, ia u: cd ty
the :.•.u .s . :a..-rboi1 and Cooper as.so Sdent ::.od 3,/,-ter.rpyrono in tho Vorda
snu ::. "!:e quar.tit3 fotmd was sis.il.zr to that identified in e .gr.retta s=Le
ccr: e~~~te '31) .

`: :.:k, ' :.:eh.,:rt and ".'a :er ( ;> ) dcs c:- : ted the idcnti : :cc ticn of v--r3
cu-3
co Yor.en ta of cirarette aacko ccndcnr.ato . Cno of th.o conpour.ds presn=t3 .y
Sdontd fiod Las a-2 :entr'_acontano w oviouwsly idcnti,f .ed t-,~ : c . .•~ w^
1
S.~i.~ •,~...VV :~•J r<r' . .. 1 J`-~ ~ . .~.0 .~; ~V 70d ~ : c ~iMA fni -7 V• V e s
r V . .V
.~ ~:•

;.:.coo usoc cy "oFar ;1 as .


"ccs :: 2+ ;S . ; ;9) aculd not datec•., 4 . e~ ecc :ca of 3 .-~r.r,,;: ono in t:s
oic*arette awoko corsdensato . ?i:o min differonco botwoon tl :o p~occduroa c_^ :1oycd
by Fosak and CcoFer vaa the diPfetronco in the puff rato . Coopor t-& gj . c-.r,lcfcd
a 2• .aecond putY overy 0610 sooondof vhereaa, : osxk gj glo ezzFlo7od a :.-aocor.d puff
evary 60 soconde . ibo cosavstion tompcrrs tnro3 vore e : ccntiLl:y the &ara in r.oth
invoatigations .

Wripht aad Wyndor (314) dese :~ibed the chemical fractionation of c3Lpr ette
crcke cc-x'cr.:,ate . ^:o F» oli_-+-.c .-7 :.mcticr.ation in this c:.re taa ecac^t'..a~:~
t.*:o sc: s cs t~.at of :.csak ;j -i-j . (59) aad Cco ;.er ~U g,l . ( 21t 25, .26, 23- , n7, 32 ) .
W-right and Wyr.dor astawtod that the qvantity of 3,l,~bonzpyrvae in tho szoLre
corrensa'e vaa one part par ail3ion try vei&t of the ahols condonaate .

SeolsapP (91)) idonti :iod capk.t.'•.alene, XIII, anthracone, III, a.nd 3,1.-
Mccr~ :-c~, I+, in :,^e moke ccr.ycnz ate fr or cir-,,rettos using osaontla1 .:Y L: o
oc=o Fzocodu.-es deccribed Frovicua3,y. Calculation, bcsod on ultraviolet atoo:~••
tion data,, iadicatod 50 Ng . of 3,4•benr-,.,jroae per 100 g. of whole tar obt :.ir.cd
froc, 2pC0 to 4000 cigarottcs . Ibo •puff rato and snok :.ng tocraratt-mos for tho
o:6-arotta9 were eaeantislly the aar.o as those reported Sn othor inveatiFutlons .

L: .r.dcey (68) $a~ar izcd the idcati .''icaticn of the Folyc; clio arcr~tsc
y--'rccarbors i.n cigr.rotte sc .^oke ccndena.ate prepds•ed in the laboratory of Ccopcr

Wr:;.t:t and lr'y:^.der ( 5, 215) do3critoa the idontification of an+,kxacezo, 10


p7•.-orso, VIII, Ferylene, XIV, f2ucruntroae, IX, chryflora, 7(Vv and 3,lvbcn :.l, . rc,
IV, in cif-arotte scaka cor.donoate . Zhsse authors also otserved L'•.:t the c:C .r::-
inC of c-'r.ontr:,accnt^.ne cr.d similr:r. alirh.:. tic 2Udrecr .Mbons obtai .^.o3 t,7 ea'. ~c' icn
of toracco C--vo, in audition to acotylcr.o and other gucs, r.a7 of •.l
.,:rbons idontifiod in the ciraretto seoke con.'.onr3atop e .C., :ecylirdo r-;^Y:r.~?,
aa YM~YCb r.e, c".ryEenc p 3,l.- bc n:,p7re ne a M flu.:r^Y.nt.hoae . I17 turn inC c:gsrctta
- ~J~weCO ..C:... . J A
n :a S• w * fPt.Ed~~li•~
q
Y•.. . J. .~wr .~,......w.'J ~. . .. ,* . . O ..v... .. ..=.r .@ Q Z., . t. .'.~ .L, ..
rct•„e ;a;.6r sr;::ro »en~orxata t•, :t vere =.-:le to i:cntS,* t: is co"cutid I n
=oke cordor.aata obtainod tq emoldng ciearot4.e p&per under oonditioas
tka bvma =o3d,ag Froceea .

r1I IrJ
9

i:yr..:or and '~r'.;;!:t (1 .:1) fract2oratcd cij-'"rotto =^ko cc^=4cr.rate L•.to (a)
a boso-f`reo, v2:ole oondonaato, (o) niootSr:o•f1roo baaia tar# (o) an acidic tar,
W a neut:-al ter, ( e) a r.otb7ler.o chlor:do ..ir.solublo tar, and (f) a vatcr .-
solubls tar .

tiYactions (a) aad (d) ; st~.ovEd o=i.no£onic activity conparab2o to that of


tho vholo condonaato . Anirsl r.nd epootrographia data based on the oiC=otte
tar obtainod trj extracting unsnokod oigarottoa vhen oorpared vith an :ral cata
of t!-e cor.Acnsti;•„a !`:= v-..ckcd,oi,-arottos i .wicstod that the ra4or pa .-t of the
Y:'O3e . .t : .^z e :.o~+2`9 :
:to~+2`9 to .. .ciSS iJ `: t.l
};~2'~' .
.i•JB~8' i•JB~8 OP `~'.e tOt60C0 .

La= (61) had also dotcrr S ::ed ttat t.1:o ;r1rolysis at 8CC<' C . of tr.o aLphatie
h; d :rocarLone ottaiaod trom tobacco yio].ded the polycyolic arcratio tr,drccar :bns,
n. 4 .~. . ~ w ~~ TZ, ..
... .~ ~. .~, .+ ~
.4.w cA .Q~ 'aT~ Yl . .. . .j3
. :~. .•iC . .Q~ ~: .~~ ~. .+ ~ ~ 'Z~Lr

:"7 . Mo tc: porrt .~-e of E^.C° C . is appr oxizately that oncoumtored


the norra 1 cSE---rotto axoki^e. Froceca (33 ; 119) . 4hua, f: o= the data
flL-,r,pliod by hr.Grt and '4'qnc :er (5, 115) and Lzm (61), it Ss conceivable that the
alrbatic h;fdrecarbons pro : ont in tobacco are procuraers to the pol ;raqoL+o
ar cr..:.t.a `:-j--,.'r ccsrhons found in tko a«+oks cozyler•oate .

Lettre and Ja•rm (64) detocted antb :ncono, p7rerw, 1,2.-bon:antbraceno, 1,


~-rer.cYf:-cr.e cr.d 3,L,-bo^cryrer.e in tvo t:._w rrosor.t in srckod cieur tutt3 . Cae
. y ti ,. .. . ... . . _... . . . . w .w _ ./• .'.. ~.p • v . .r .rw v ... . w w a.3 Q a ~ : .ri

b j'~roc :Y'~on .7 .

I,ettr0, Jchr- ctd f!ausbuck (65) eat :.=ted the quantity of 3,ly-'.,on..~p7rcno :.:
t: e a: ke ccrr:c.^.eate S .or 1ok:'^ civ..-ottefl to bo 4G: J :g. :hiz is t : e hichest
c:l•:a otta :ncd to dato, represonti^g 26 .7 R . of 3,l.-bo=pyroro per 1L0 cir :.-
rottee (aee T`aLle I) .

Lyer.a (6, ^0) r:;oated t: o Frccc-du.^cc ca•-r3ed out t-7 other :...^vostiC-,toro
~..~. `L.. the c~c : cY :,. f_ ,~_ w. . ~. . •_~ ..o •1
._-e r!`wws . ._. ., a ~~...
nw4
,s
.,
c J_ r....; w
a w ~, cti,.a .n
a u ,.o i
:~m 7 to ~" ..:,.:utos using 4-sQCc1~Ci• Me aLit ::or tiBsL`rCd that 9arjj, .^.~,' t: e
tor ;:o of oWok'.rC coi ::ciaod roro tia:% realSty than roCulr.r or "aver a,-o" scc :ei=4
r.oth-cds uoed L-y other vor1cer3 . :bo ranCa of concentrations of tho Fol;;cycLo
arcr.atSo hyCrocarbcr.s vas oasontial.]J the came as that reported b; earlier
vorkerc . I7ors idonti ::od •aeuleno and 1#' ,-bcn:.antt,xaccno in the cccko coadcn-
oato in addition to 3,4•teazp7reae .

Cazdcn ar.C (20) e3t :r :,.t,cd t~o S :ant .tf of 3,C• .co^cr ;,:rora in ci,-a-
. or r'. :o . co^'or^
«et•„o ..
.• . rr.• •e o : o r'
4 2 ./~ Fa • ~-
per w^~
w...•
. of v .r v ;or.
!^- V vi et rCi t td s • L M'crcnt b-ra nrs of Cam -- - Vs Lr
..

t: 41- :::7 w* o aam o vrl•.:e . ~.a ast:r~4„o of t: o qi :,:nt : t7 of t! .o 3s4 -to:.. ;~-J:cr.o .=
:.csc d oa t ::e u :traviolat aLvc: rtica -:xi= of the 3,l,.•bor .;-,7r-- r.e ar.d al: o cn
tto c :ol ;::c ai rrxor ;.s involvi .~Z., ccavorr :cn at the 3,1.-bon: ry: ozo to 6-icdo-
3,4-bcn .,^ .-,7rono follcs :od b7 ostiaatioa of this lattor a =pocn3 b7 spect-'°o p2:oto-
aetrio a,ethods .
Diol:ey and Touo~~ (32) dc : crited the ic:entiriaation of aa,,hracone, ptor :n-
t2-,roaej gfrenep fh :ornntl:ar.o# scornphthylor.o, cr.r,rnone and 3,4-cori: ~,~: cca Ln
ciearette a=ke coadonnato . :2ioce autt:ora used modific:.tioT.a of 7mos+n Froce-
dures vhoreby t.':o un3aturatcd alipb :-tio rsdrocarrcra vEre , sor=rr?,ed f-.ac t'r.o
arossatio hydroor.rbcna . Ly copplox forration between the insatura ~ ;3 ?:,, 3rcc.:rb:ra
and thiourea' iind by co=plex Forratioa 'botAen the arorntic 't ;~rocaicbcns ar:d 2p
4,7-'..rinitrofluoronone. Zheoo authors also empla3rod silica eel aaa the chrc-..,a .•
to?ro~}ac adaorbont inatead of al~~.c., the adac'rhont preforrod ty caot othor
iwvest : ..tors . woy a.lso sntst : :utod : e=ne for cyclohmmme as the ¢a ::
elutir:g ;aolvont .

Z7 cka7 and Tct:oq were the on'.,7 investieator9 to rercrt th3 aotral iao?a
:ation of epocifio polyc7olio ArorAtic h7drocarbons b7 cr=.c .ntioadchrei
other than ultrav .olet otsorption or :1Loreaconco spSct= ;:hct -=t:7 . :-e-e
ant?:ora e~ploy~ad mich rethodo aa ultr.:violot and infrared ataarption etWios,
a.elting and rAxtore melting point doter•...inatioa.grp and x-ray cr7stallopfa ;hic
studioa in their cr.aractori :ation work in which thoar oharacterizod naph '~^ co,
anthraooual ph.oaznthrene, pyrene and fluoranthene .

::b1.e I e=zs the avsilab3s data on the 3 .dentif:ca;:cn of the po :,q-


c7c.lio t7drooarbons in oigaratte saoke coadaaaate and the eati=tod quantities
vh9ra az:ah data vsrQ avai2abls .

9

u

Pt`I7V (CL?C ^?rrr~'" tw)s,f .r) TN .. .• ~ . .


--_ _

4bbacco Tar Cv3atit'! PC./I00


At b ~,... TV--%O..~. Folvevelio Mi??!~=rbon .~:1 . ,~
P~~?2t tee r Pef=„vlr,°
_

Roi'!o Cs3truative "l, 2-ben : anL':racors 83


~. ~ G . L . ,~M. YY

Aoffo destructive ar.tbrscors ~ 82, 84


diatl.ll,ate pl:enuntlzeao ~
(350° C.) ebewymm" .....
o C,•1y .
no:'.•a do3t~~.:otiqo t ,-,jTO1io" © P6, 89,
cistSlLato ~92, 93
Ikoda c:xko czul.ane © ~4 ~
i
coadsr.:~ta

3,4-bana,,-yreaa .r.~ 63
:.lvc ;~: <r .~n .~nw }3wK

.I1.. :~ bY

Cooper & "Ci tt: antr.rrcone 11,


_ '

Lir.dsey .,.t
mx ww
" acora;htbqlene ©

r.he= tl:!'On0 ©
c
f1L`0:' nt .~:eT.O
~ }r,-rone a evor~.,ll
..~..
1, L^•tea : opor~l8no ..~
...r

Ccopor, _ tte 8 CBr.Brht~^flOne E.32 27


Gilbort & M= Sie anthrnco-ze 4 .32
Lind$ay ghea:nthrene 26 .82
V.vrone 17.12
fluorantbene 16.8Z
3,G•tenz-.7rera 4 .C?
1,12-Leaaoperrlene 2 .2'`.

Ccoper , s» oke sw•Y~


P. . . ~W{w
i~ 33
Lindsoy & eor,der=t,o , , ono ....
r:a!Z :r 3,L-terWrqtror.a l.0
Ln
H
J
H
1 :^: l= :X ciczrotto FspOrs m
~ irz m 4:^0
. g . or 4S$a" LLO ;spa ctiL as o3 gLLTOL •a tocncco I s cut . (n
m
m
Ln
~

• ;; L~ 1 (coat'd )

Tobacco Tar Qnsr.tity fcg./3.00


Aathor TWO Polvc~elie Radrom rt~on _ -,,, Clr : r_ tt_ c_s_ . n M* .

Cosrlns, saoke anthracer)e ' 10 .2 21


Cooper & oondonsate Fyrone 9 .0
Li..~ a o-y

Cooper & smoke accaapht:Vlor.e ©


Lindaey •oondensata ant.tirao~

3,l,-bon: yyroae 08
1,12,-beasoperylea .

CesPbell ' m '' 3,4••boasqyreas sccs as tkAt preseat 19


& Cooper in a.-.ake condoasate
trcm equal veight of
cigazettea

Uright & smokn 3,S-bonzp7rsn@ 3-53


, -rxor ccrdersato

Seelkog eroke nathtr.alor.e


oondensat. ozitt~.rroone
3,L••tox .zpyrsne 1.<5-2.50
'.+right & swso anthracoafl 215
kyader oandensate P7rone
po=; lene
.°-.,:..^ ra rit'@2a ©
C}. ~ De:f3
3,t.,-tor.agyrea0
Lottre & "SJ=, a ntr.racor:o
Ja2m

Lettre,
Jahn &
IRM"

'=oke
c.or,deasat.e
;r~ror.o
1, 2.bon.,aztt-xaaene
1, : •benzpyrons
3,L-bonspyrece

3,lrtenzpyrer.@
) 26.7 65

?avabeck

lqo0«s BT.Co@ L' 2 uZoAo 6p ^~ v^


Cot7C~ eASate I, 2-ben:ant .1= cerA .6
3, :.-ten: r3: ec@ :. :

"> '"hose suw.ora eat :.:3 tod c,..., :.ntitj aa 1pa-rt ;c: :illlca ci v : o :o cc:.,; c:rsta.
Cae huadrod cicarettos giv@ 3 to 5 g . of vhols ooador.:ate.
4'ihis qt:aatlty roprevents tho total of t: e 5 hydrocarbons latod pc : 1^.0
oigar hutts .
13

• fw .~T^ ! ~ . .. . ..~tAl

Totacco Zhr c ur-ntit7 } C•11~~


~qlvr_e
i' .. ftt. .
Al': rer
.~.., . .. .~. ..=c7elle ,!':rg,.,,,,
c1_r,tga .
Cardon & awke 3*lr-benzwrans 2205 H~
Alvord ooadeasatA

Dickey & encka r.arht .~.ycro ~ 32


"'oz;ay o*..,am •.a _ :: t'rr-cwcc .....
.m"cnr..~t~roao .,.,.
Fyreno ©
flt:or••.nthor.o ©
3,4_beazFyroao
1,?2••?:en:.c;rot 7le~e ©

RodCran s=odo ace =;.hth;,lc3as tra ^19


oondaasat. raFhtt•.~alono5 16YOd7
ontl^.raccaos 7. Z-7. Pi 38.Lb
~!e
~ ..~..~~'~-eae
~.~.• .. . xCQ
ta`~
L"•^.'DS:EY v`
O
S'luorant-h one5 10.5-11 .2•Ti 13 .6~
^ ., . ., .. w . ... ..
(y .~
C.15-^ .<27
c -L ; ~J 1 ~} ~
3,G-~caz~ ; .~ . .i~ ~•f .~+•

1,~ .2_bonzoporylsne 0.147


anthanttrsno tr: ao6
3•c:ethylp-jrorre trsce

Ln
m
m
5 :3o1:t©d, :--leati ::x ar.d c ::•:ractcrSzod (seo ExrrriWor.t,al) . ~
6 % t'~.a t=sa cf_
7 Ca tt:o ba.9i3 of 314,00 C:."x' .. .L c :S-- .-ctt,e3 . Zn 3 scrica of ex ; cr:~ca•,a on
the protreat-oat of C.''r'L blend tobacco, 3500 C :1 :7L ciC.:r ottas wcr a
a=okod as controls and the polMol3o hyCrocsrtons eatiratcd afLo,r ccn-
cont;;ation by thiouroa aad tr'.r1trof'icurenoAe c=-eloz forr.ation and
orarvrostoarn~ (81) .
8 Ca tho br,eim of 1L,,11C0. . .CAbEL c{ ._rottes . In a sor_os of exxri .o^ts on
a4 a~ . n . • • .•- . ~i
n ^~ .. n . .
wt~ j
: . ri ~.. . . .. wa: . . r i . i. .r :: . .~ . ..~'.~. ..i~, ~ i'.1/ vr.a• . :.L H~~, : : £.` Mtv3 iif? ::t
..~

a=olCed ys cC-
.,l"ol .3 . -,,;rrQ^.o u~d
tiero with t: o corroarc n.Adir.s .' : rci~iors :`rrc~ t,ho 1C, .̀C0
c±prette run .
9 ^-- the be ef,s of 13 9 OC0 'C ~ ;
4%- i, c ±-?tte3 , in L2:
Z5<.0 CA : rL c_p..~ttas were s, .Mcked . ':'t:©
ir.C aFrrox :=te1,7 = pCe of 3,C•ben:,-g-rcr.e, ua.s c=bi:cd vith t:a 3,4-
ben: pqrar.e fraot3on lron the 1C, 500 C : YEL al.Za.wette r~.m .

0
f

. 4

:7o reaoarcb doacritcd in this report rorreseat3 a ccncertod ofrort to


• 1
2eterr.ino Wr.othcr or not tho poi;-c~,~c1So arcratic hyc:rocarhora rr o proccnt
in cip;r,.rotte aaoko oomdcncato. Cr.o of tho sa3cr obJoctions oftored to Fr :-
vioua imroatigations io .th,;.t t2•.o idozti:' :c:ticn of rpocitio ccnrour.@o colol7
on the hssio of ultraviolet ah+sorption etisdioo Is not 'dgri'riitive : `Sincv tho
preaont reaearch descrihos the actual isolotion . idcntification and c:~.,araoter• .
i:ation of soverai pol7cyclia ar=atic 2ydrocerbonep inoluciing the hi~+.2y
cc.-ci:o,-eaic 3,4-`Arzryreaej t:e rayor critic : .:ra of yaat rosca.Mch r.ro ncl
CU2L' : iod .

12:o z81or stePa er,.plojed in thia h.boratoz7 in the Ssol.z t:on of tho
Yol„7oyclio arcratio }Lydrocsrr.ons 1`rom C.%•iL cigarette =aoo cc:don^rato wrore
ac followas Col2ection of tho cnoko co :der.aato un'Jer aroking crr.3itior.3
.. h,. ra .: s--css.Z lh ..`_-ita ; c: e -. :c:.l 1:rct :cn:.tica of tho vhole ccndc r.-
••. ' -g
. ... . . .,s,:
s3teo to give a hoxar,e-soluble , neutml t`ractioaf ropeatod cr.ror.atogm#.7 of
the hoxane-eoluble, noutral fracticn !,n ordor to conccntrate '+.':e po17c;,•coio
arosstSc h7drocarbons f chrcratoC=pb7 of this arc=tio lqdrowrbon concent :ate
to soparate the ir.dividual 27drocsrtror.sj charactors.«ation of t': e in3ivid=l
polyc7olio aromatic tqdrocarconsf estiratioa of tbe =or=t of tho ir.dividul .:'
rydrocartaas in tr.e amoke corwona.zta on the w:sis of ul:.:.vic.:at ahsor-eti :a
d.zta.

.'a acmo iaa :,:~r.caas t.:iaurea,* picri : ac:,a ax


formation was utSliaod in the isolation and ideatificatioa of apecific aro¢a
t7droQarbons . ~

Ln
m
m
CO
15

. •... .
. .
. . T

1• ~`n`~r+a'+q arj Y^t~^"ao


~1~' ' ~r.r~~..

3•..C.:.f :r:- tIPIL


: trr.dzu%d C'r'EL ciprottcsp diroct iroa tba production li:o, wore
er.ployod in this stt:d,y.
..~ ~ ..i .~,, . .w

%•ll solvCrt3 '.iOPe di.'.ti11Cd .w.L : :t ;'O_-rrcr Ic -Csc'.I : © prior to tlr.C Ln


or:cr to =::.-IWizo t : 3 4iQ!cr t of n or.-vo :~:tao r.-tv'rial cc ntJincd tte2`C ; .^.•
^:o sciven' : c :.=.loyed wcr oI:exrxe, e;c1oh=nej. bonronol, e'cr,, ehloro :cr:
ar.d r e t~er.cl . "1!rsvi olot absorrtion at•:aies irdicated the sb; on..^c3 of
poi7c, ci :c s :c-. ..^ t : ch7 :~roca .wbor.s f-& :~• t-te o'istil1,¢d solven+,s .

( ;'otebook pages : 2?1?01t2?902)

Tt:o c p-pa rst un em plo,?ed for tre eol,lect c::


n of t IM C•+ :%:L ci4a-
m tte c = ck o Ma:er.3a•.,a :•as ecoc n t i.c~~ •e c..., ....o
. as •t •w ~ d .,L ~
v r...
..w `
. .•. . : od t;
W;µder, Craha.: ar.d Crcr.S~,rer (113, =0) . ; r.ascr di ::cr_rces were that
A +t 4 • • .
.

, ,- ~- r
1. ` :oked 60 cie-arettoe Lt a tir.o vhOroas in tho r.osorrt
st•.xd:r 30 c:j!` ret-tea Voa s=eked o :,.,.-ultar.oousl,^, and

2. :'nc?rcd t2:cir ci*s•••~+.tpe in a ve :-tica res :ticn :..crorc


in tlzis atud•j t?:o cib :..wet•„os vere swoxed i n a : cricc ntal
poaition.

"~ir ty V,121. ciC:.rottc3 werfl rlacod in a'mLtc,; of 3 s?- c-.ino c: r-;,,


. . . n .~ .~w }~ Ii vn '"S . ..~aiV~.v =. .w.w~
Vr. I 1CV~ . . .~.~/ ` Y• .Y.Q -lwr
\rrV• v . .Y~ . . vr

i
~'i 9 V O i. .C r.o
c!+-,_r ct.tcs as coon 3s a45- r :• to :;-~.... :e.ogt_h had 'ccon ccr.a4:..oc . :::o
s.. w^, A, ; :o.-V J!aced in p3 :t:on cn an Claca car.:eL:::::-:14 ::c
rocoSver on tho smkinQ i:ait. 'gais rccoivor s as conr.setr.d to a serieo c£
t•.ro 2_liter flacksi .E1, y„1
t connecting tut .on• "L•oc© fl .lnko s:ero i:d crzed
in Cry Ice contzinod in a etainloso stool tar.iss Co ir.wulatcd s:i W ccr'-,
sroetir.g, D . "Y:o rcecivirs £l,as ::s were ccr.rcctac : to the vz.c= FLr' p, `,
.. ..• ..w .+ .w .'~
/r • :. H
~••

~. glass tu :c ccntaiwc ; =,,^z~„x e~s .co3, G .

"':e vacu= vas orcated ty a s: a11, electricsll, dr :ccn r..w p, K(1.3


cu . : t . d _s^3.: ce-3 ::t of ::•eo air s cr rr n::t3 at a vnm= of C7 in . c .' w a r-
v

t}:-Oe r . r• :.. =o tcr , N, K-'s c.ut,. :tica1,].7 oponcd S'cr a 2-coccad irt :.•^mA1.
al:ov+.ng the vwc•, :,"n t:-= t; o ai .- ~ to be applied to tba co: ~
•. :i+iri .-1 ~ir 0:7 to +i. : O ., .:...ci,~:.Me ~•
... ... .. .3 ~+f~~^' .~a •1 . .~ w. . .v• .: .• .~
L.
0 0 0

~~ ®

\
l $

C r

I /, 11 "-\ /, il,\ P
`NI/ II a\/ II .\II:'. F

H I \ I I" "~\" Ar

FIG • 1 SCHmiA`PI C DIAGRAM OF SLt UKING APPARATlT :3

0T0S OTLTS
17

".'bo =ksr.g tS : o rcr ciC-Arotte avorarad 9 to 11 uinutes or fr= 28


to 33 put`:3 per ciCarotte at a rate of t,r co 12-soccnd puffs por ;.j .~,:to .
:Y~.e cisrsottes vc .-o szokod so thut Ar--czSra ;el7 45 to 50 = . of the
length was cons=od leaving a butt of 20 to 25 =.

One da7's onoldng uoumlly cowi3tcd of 1100 to 1,L00 C% :-SL ciVrottca .


: .e vholo condoncate was rirsod 15roM the variovs piocos of Clas3~ .aro into
the first receiving f2aok (uhic.3 goacra13,7 contained the na j cr rorticn of
L3 i .,. .C l 6111
:3LM

. .. nC 1.. .
.. w .. ! •
4 ~+ n
. ti to C "
~~{~i = ..~ . C
P

rVV~A•MVJ woro Mu • ~~i .^. i V ..Y • V• c :1'


. .1,@+y{~ . y.~~/v.1l of
the tar r f M•Y VYe sYrV~ •

cp;.urat•, :s * n e -.ot. :: o1.±o nolu•,;Son of tho C+ .MIL ciga.Motte =cko conden..


oato vas t ::on nub4 *ect..~d to a ckowial fractionation to be doscribed Sn a
ez:beec,uoat port of this report .

:.• s6C jz l~iz


o ,;

Fcur hLmdred C .'. : rI. cigarottos vere stored at 25° C . in a stsialo3s


steel 6-ire soch tnsbet in a dcsiccatcr containing a solution of 750 g . of
95 pcrcont elgoorol and 250 g . of vater . This solution r ..,iinta:..^od the
woist•.:.-ro ccntoct cf t .a c3ccrottos at 1^ .,:.4 perccnt . :I,.e contact t!=
in t-he desicc .ztcr was at least 6 hotzs pr'•or to s=oking .
..e" _ Cr .~t Ca .,«CO C ~t+3 O' ~'.:.^!1Cw_a""'" ''u~. . C .,
~• .. .~.
_Ce~tAr_o~ thgyiotal "~~ sP ?y,iP~s~r~C,~&arQtto T ::otobook
Pa~;os 27~02-2?903)

:r-o arcld .DZ " .^.: :old ( ::~aa 1) was arrar.ged as shc~a in i'i2 .

ao t.%ore cculd cOaceivab.Ty te a di:'feroncfl in the total n=tor of


pUr!'s per cigarot•.o t;a:ecn c!wa :rott.^a 1 a^~,~. 5, 6 a.w:d 10 cn :1
1:, 16 c-A 20 on 'rm Bs 21 ard . : 5, 26 c nd 30 on 'r- Ct di :o to t::c
1~ ..Jnw .. *4I~ pAtIi. .= q«1~~.' W .S~ w . ...S
. .••J ..y.y ..~.. y.~~V.~:~•~~ Vr M .V JLb V•VM C1 . .Ib~r• .t7,r
W,~
flr ~
.rD .. ~.eV~
. J~ W :~
. .~+Wwre~ tA i .. .w .Iw .L wL~~ tr • .~rt•~rw11VI~ n~
C2
+$r . . :f7 A~r(3 .~.r i~
.~~• . .~ ~ L .. iN ,~ P • Cw ei.Cil ~ V~.LO
• W i}+e ;r7i ..~ibr$
.. • w

on Arms A, B ari3 C . :5b1.e 11 srovs the resul•,,o ottai^.od . T"..o avoroce


nLWbor of p,v.*'fa per cigarot'.o tcr tr.o ovar•aU eystcn uus 30 .3 puff3 por
oigarstte .

P.o ossontial diff0renco vas found between the puff rates at di .°:orent
unifo :,d positior.a .
11 12 13 14 15

rm

Arm A Arm C

To Suction Centre

FIa . 2 3tANIFOLD ABRANGFLiSDiT

ZTOS OTLtS
19

^ TT

, .?riy"•'R C? Ir i .:.1',!ti'
:..~ .:~~. ~. .. ... .~~ .~ ..~.~ ~.~ ,. . .~.

A M1a A nu , _,a
A 1) C
Fuffa por PuFfs per Fuffa par
`oy C, i,rm, ,~„~ .tt3 ~wA. l;;o& Ci rc t .,~~
° &. ras i~ro
w .~ .. • w ^
wl .
/1 ~fl
1 ~'~ ) tr :
.l ~~ .i
.~.r
~
~ 4
~4
3~3 i II∎`.:
∎`.: 3 '.:1 . GiV

2 2?.-.~"9-3Y 29 .3 12 32r-.29-30 30.0 22 31--29-31 30 .3

3 31-31-32 31.3 13 29-2 .• .30 29 .3 23 29-<"9 -29 29 .0


4 32=3i-::9 30 .7 24 3y-30-30 30.3 24 3 "Low 3c-30 :c .3
5 31 -3 229 30 .3 15 32-a9-3o 30.3 25 30-31-29 30 .0
6 2 9 .30-31 30.0 16 31.•32-31 31 .3 26 31-3C-31 30 .7
7 33-32-31 32 .0 17 29-~''9-31 29 .7 27 32-32-<"9 31•0
.. .. . .~ ., .. ....
Ce 3 ~ -3., . .,1 . .,
.3 1 .0 ls 3~ -3 ~
1 .~ .~
31 ,~. 0-,
2-0 n
?-C .3
9 31 -22-31 30 .0 19 33r-30-31 30.7 29 29-31-31 30 .3
10 29-•~"9••29 ~`-'r 20 32-29-31 , 20.7 30 30-31-30
~ Av+erago 30 .3 Avoraga 30 .4 Avcraee .30.2

Over•a11 Av©ragg 30.3 puf:3/cigazbtte .

ZI. Tao1 ;.ttom of thl ;;Lgutzal ~:c ;_,m (`.otobocY


PaCes 27905, 2F.436)

Tho zct.hanolio solution of the vbolo condenoata obtai .Mod by s: olking 1'_Co
to 1L^O CP.2!F.L ci,r.:rottes (end aon ;„ainir.r 45 to 55 g, of whole con:cns:to) w:.3
nc•a, :' :cd v :th A4,n -3 . of 0 .2 N h ;drochlo::c acid . :^ho re~,:lt :: ;~cidic
t:on •aa.o estrr, .c~„od vit.h a total of 1500 r1L diotillEd he=e in s :x <5C-C-.1 .
;.crtlozs .

. The '.-. Q .1r .^. e Gx t, .. .^ir+Mi Yor e C c .•~.vrn ii(i .. .1 d eX w M c+vC d with a v C rJ .rt r .i c va. 2! .+ N i: .3

nP /.'/r1 ~ .O n .. tt s.'.d1 .w+ 5 . ..'~ . .wJa ..1


.. . .. .~• . . . . . . ., . ..~ .. .~ •y . . . . . .~ . . .r.w'~
.~ ~ . ^r'. ... ..
w1 ~ . . -r .
.~~ 1•~C`
~~

rc: y_ors . :he :ot~~al vrs ccded to !»' :o d,'.1;:?.e al~r:l: to : ec~:^o t?:c :ar rtics
of o :r.ulsione and sntsoqr.ent loso of polyc ; clia aror.atic Y7d .-ocar ho na . iho
I:cxzao ext .-act vns then sxtz•actod •.+IW% 1 ;0 =lL of an aqceou sol•.:wtcn of
..~ .L. .w \ : . • .~7. • !A 7=1~~ n e~ wF ..A .... l . ...
Rt7 w .. r! ~ .. .r . .Or ia V• I "1 r . . ~ ~ .C4 r~•W .g ...•~/ b . v .~. .~. . .~.

iJ .".G CGLCO :.w"'s'•n?C '~'. 9 .^.L`12 aZi .~'.v`r 1i. Tro 9170 'C:.a L'.CY.^. .w.^•• .^.CS
20

'• tol=3 of 10,5~,'YJ C'~TL ciC~arottes vcro s'r :osod yiolding a total of 430 u .
of vholo condea=te (kaccd on tho detar .:.Sa;.tioa of tbo voi;k.t of condor.oa'„o in
an aliquot) . Chorical t`ractionatioa of this vhole oondonaato aa rccc : acd nbcvo
gave 77.594 g, of the hr.=r.c-colublap uont.zl :tactica (0 .7:2 g, pcr 100
rottos) . Tr.o c.6.= :cal fftatioaatioa 3s au=arizod in Flovahoet I .

In an initial oxploratory run, a total of 25C0 C.' : :L ci Pb--r* ttrc 'jrro ~ c::cd
ti ~~?? 2 t .a..1! C f 11.0 E . ~ f -.1 Ola C^ :.Ae ".
~"~ ; :'7C3°_uCG' •.3 .r .. . .w

; eldcd +6 .0 g . ( 0 . c4 0 g. per 3•.^>0 cisarettea', of t:.e hcx: r.o-ao1u::a, r.e•,:•sal


!ractioa.

In a cuL~soc;z:er.t caoking rur : in vr3ch the protreat=c::t of C,c'EL ciga .rotton


z-aa boirx investicated (F31), 35C0 C'IY?L citarottes yio] .Zed 23 .365 g . (0 .E63 g .
per 3...O c :r~~.~ottcs) of tco ~cx ;.::o-solu :.le, r.outral f:action . At v:~or.a pointa
in the e• ;r-,.eri.,.ental vork to te doscrited .. certa :n fractions fron each of t .cse
t.~soe ruaa Were eitNer comb ' ined or iavvo3tigatod for spocifio polycpclie r .ro- ..atie
Wrccartons . Fovever, the bulk of the work •.4 be doccribcd in thio report
concorr.s the hezane-aolub3o, neutral t~mction from the I0*5G0 C12GIL cigaretto
r%M .

a•.. Z'21jr-,4,n= (notebook Fagoa 3t07C;3=C73t 2E437)

Tho p.aterial comprisina tho"hox ::no-solublet no•stral fraction fr=



owo dm7lo scokirle ( Table III) was chr-omtogr pl :od on al=i.-a ( a 1Lwir.ti~
Cxido Kerck) L: i.-.g a colurn, 45 nn. in diazeter . :be hci£ht of the
co1== a : ter t=,^.i:.g vaa 250 = . V.e he^.rar.o-solu'r,le, neutral -Craction
vaa di3solved in 60 r.l. of ho=..^a, placed on tbo eoluz-a and eluted with
600 =l . of hewro, IOCO nl . of 15 porcoat bonzene in hox,r.ne, lOCO r.l. of
tc.=ero axd r..o of :'bo velchto of t..a 4 S~cVrv .s rse
ia 7S bl o . .a .

Fraetiofl 1( oluted by hoxars ) con ..istcd of aaturatod, in :.^atu : ated


and arcr.atio hydrocartons ; fraction 2(eluted by 15 porcont toncene-roxaae)
cor.s istod of ur.saturated and arocztic h;,Tdrocsrbons ; 2`: action 3 (eluted Ly
benrEno) ccoraiated of the hi,-% rolccuiar voight carborql cozPoLndsl and
fraction 4(oluted tV tnet:.aaol) vso the residue a3 shown in Florasheet 2 .
:`raction 1 was slightly fluerescontf whereas fraction 2 was higb .'~y rluo-
rescont in uitriviolot ligr,t .

r raction 2from Rti:r.s 1, 2 and 4 vero ccnbL~.od ; fraction 1 from R=


3t 6 ar.d 7 were ocuhinod ; and fraction 1 from P.urs 4t 8 and 9 were cc :.,-
bi nod for aubsocusat c~romato~ra ., .

I7raotion 2 i .-om eaah of the ni ne r•.aa vao corhazed . Ln


~
~
~
m
Ln
m

~
~
r;n+`'s~ :•:T

;°r'LS'pI^!?
~rr. : ..
C» 'f '

1215 C~* ="L CTC0


-
?r'T'"='S
r .~.. .. .~

k'FL LF C^':'J''!'+r 7F

f*r= gl :.ac .-are with zothanol.


I 2 . hdd 650 r,1 . of C.2 :7 L-.,drechlot'lo acic: .
3. Extract with 6 x 250 rlL of ho=r.e

Aqi:ooua ¢eth.:aol lam F+cxa: ti 1,ayer


.~.

l. 'c5ttrsct with a ooZLt3oa


conai3tir.g of 6C0 cl. of
C.2 :1 eod' :: tVc:-a:-.+Co
cr.d 75 .^.1 . of mt.'-.:.-:cl .
2. :xt,-,,.ct with a sol::'! =
of rot~.a^.ol :•aatcr, 1s 1J
,.,cC ,:1 . .

~q~ot:o ret:a.-:ol layer l.a7er

ACZDIC T'R , .".•••.; , L F?'.Ml""T

6 .94o c.

Ln
m
~
cn
Tf FiI iy III

CfiRfTA'i'')f:nfFi:Y rF

T?"rF 15% E'enzone•-


g . 100 Aexane- hexano- 1'.enzene- Z'sthanol- Total
Qien- ellite'_1 03111.04 el ut.e elut nd 01 tate4
Ftun CiEaretto
l1o . flO . ~+ . re ttcs ~_ ~ --~- -- -% _ ---L -- ~ E_.

6.940 0.571 ' 2.2105 31..8 0.358 5.2 0.750 10.8 2 .888 :t.7 6.241 E8.5
1 1215

2 1:70 9.087 0.716 2.283 25 .1 0.302 3.3 0 .542 6.0 3 .805 41 .9 6.932 76.3

3 1150 8.61.0 0.751 2.157 R4 .9 0.451 5.2 0.514 6.0 4 .653 53 .8 7.775 89.9

d, 1320 10.719 0.812 1 .362 12 .7 0.454 4 .2 0.134 1 .3 1.957' 18 .2 3.90? 36 .4

12C0 0 .463 1 .313 23 .6 0 .326 7.0 0.100 1.8 2.915 57.6 4 .7]4 P5.0
5 5 .5562

6 1200 8.807 0.734 1.4'37 20.9 0.468 5.3 0.290 3.3 3.599 40.8 6.194 70.3

7 1250 9.447 0.756 1.947 20.6 0.453 1..8 0 .527 5.6 3 .990 42.2 6.917 73.2

8 1200 11.235 0.936 2.947 36 .1 o.646 5 .8 0 .1322 7 .3 5.9s1 9.3 10.396 92 .5

7.463 1 .080 1.667 2:.2 0.343 4 .6 0 .357 4.8 4 .061 51. .6 6.428 e6.2
05

10500 77.f!94 0.742 17 .71i3 22 .7 3 .P61 5.0 !, .(?36 5.2 33 . P49 43 .6 *59 .404 76.3

*j'ortion loct on uatrr unpirator .

910S OZLTS
23

~ ..' •.r
. :.~ .y I L `' = ~ C T T ^ ~ ~

grYe~~ . 7i~;iT7R' L FPlC"'ICa


= ;vnL tTc~LF.
6.940 g.
;
CLr^~,...Mtoira~ on alz~i .~xs (45 s~ . x 250 ~. )
~`------- -
~,~ ~eazonc~•• conzene r.otr.ar,ol
~~ao 100o a1. ~ zaoo r.i.
2000 r1l .
y u
ro,
FRO- 2
,
: n .35`?g . 2 .8F3 g .

~ G» CL'1~tiQ ~ chxlz kotoixs,


~ ~; ~ car Vos, ' etc .
1 eato rs

I I I

~~ C;abS: o vit5 s-» h=ct:or.a 2`r= eiG-.t additioaal cr.ro=tosra=}


I , I I

%.V
77 . 1 . . . .c :.J~ 04
~
i .
:,.. . .w g• 3 . 2 61 g . 4 .C3.5 6- . 33 . "
-"-1. 9 g o
~ total tota3 tot al total
i
w
To FLCdSFIZ:,T 3 To FLGSr=T 4
I`~ . .. ..+ .1 . .~w b <<+
P[!n v.w .. i~.
`
r•'j~rfn~w'w•~
I, .~ ct_cw. I _ cY ,, .-~_o
D"'"-.I'-:a (Notabc>ok Fagoo 32G7:o6s, =4:3)

: ..cticn l ;17.117 g. ) fcon tho prcocdi.-ig ch.=toC= vaa chrc .:: tc-
Era,pbed on ah:rins (Alucintm C~cids ::orck) uning a oolucn 45 == . ian d3ssitar,
250 t3a . in 2en'gth. Thrco scri.rato c..a ztograas varo r= wL^g 5 .63a g.,
5. :.E2 ;. e-- : 5.920 g . of this ='.3rSs?.

Tvc'_va .A.=wc:.3 v:rc takon in s.ll (1:0 e2utoci uit~ l vith 90


poroc=t bo=oaosowcne p e : d 1 ti,r ;_th u3 •^ ^cl) . Those ft-ac r :.cns, in t,.-.n,
uora ccbir,cd on t: a Yzz :o of im-'r^.,rod at:ro:p+„icn spcct.Ma to zivo 4 .^
olanaas o° c=;)curds sg follows s
1. :atuMtod h,drocarpons (oolorlsss molid), 2 .4:.7 g.
2. Tt:o unsatvrztod hqdrocarbon oompotimd A2-2a (pal,o 741la+
=i -0olZd), 5 .6 1 64 g.

U^ t*=l,ad h;-d:ocarr,ora ot : er ttstn compcurd A2.2


(3ro31ov oil), 5 .908 g.
;. ..i. a*~d ss`~ =« „_ c h~ocar o ...s
4. '

`ar ..va VdV~uL W`i~WW~MYiV~t ~~~'~i1Y, \ adVr .wl JV~~~ .

?hS.s rsyrrssc-its a total of 16 .51,.8 g. or 96.6 percant recovery.

?Y:o Iatt,:r i:rct.cn ( .tt . 2.4C9 g1) L4s ccW~`^cd ;'r-ctivm 2


(elutcd bJ 15 percent ton : or.a in hc=r.o, vt . 3 .E61 g . ) fzrcr. the proccd"-
:r.g chrcr.:.',a" .W. to elvo w o ; oI-,rcyc :.: a arc:.wtic hrcl .Mc~.~ :An ca::cc :~ ts
`~vt . 6 .350 30) as ohcra :l i_^. F1crwsL•.eat 3 . Ztis :ratcsrS.al, in bonzo:^.o aolu-
t:.cn, hcd a docp ti ::a :':~ rcccc:..^s .n •.1~Qiolot lieht w! :er o;.a '.:.z
vntori^ , not in soluticnp tluoroscod bluo-pnon in ultravio :.ot Iicht .

a VV4 .~Wlij AZ L is an W A+ .W M+irVa h7 ra V = r cn w h


ycM • = 4
V o^_

c M{.rfM c +W. ! in thio


YGrY 7
Mivi W1I t 8i r q 'S."3 W
M bVr . -- of tK .~ Cr.wr gt

2 S c P :cnfl =0 :ac ,41 OC 1 :::.•cd 2:czd to t :=1 t"o =c1r .Tuio h--3
double bonda . : edLct :cn elvoa a sa =-V+.od b7+d.Moc.:.~tcn •.ritu fo- .,!a
o f t=1-9 5t.~ .:ctL."`9 0f C~..~*'^OL4d A22 i v = be
described in a cubsoquont r"S .R.
I
.r~*°"±~a'^^'' ;, ~ ?~y ~~ q;;? :-"'~c ~, • _~L~, .. C •
• w wr~~
.~L . ,r = ' ~
; ~ ~.; ~ ! ( Fi: r. C^I'~7 1)
r . y ~ ~-^• .. ..~^?
(~i'FS'-
~ . .Jtir1 ~
6 . .~t: ~.~ .~. :~.. ..~. .':1 ~

:~ ; ; • ~ . ., ., . . . ~ ..

5.9.:C ~•

Cr.r^=togrzph on alumfna (45 ~ . z 250 ~. )

i:e.xa~e

w w
., . .^ . .~~
_ • .~ L2

! O .PC7 r%
V
0 .949s. ;1 .731g. t1 .211g.
, osttnrstod
3 ' Cocrourd ~ ua: aturat,ed ~ t:.^.aat..-~tad t:
A i- 2 b:rc'.rocarboas ~ ar-C Vwt io rvcao-
I Ca:•~Cr.3, e~t0."~
t
I I
S Cc=b :med with oir! Za- i`rac t3or. s ~ to BJ d r•viN 2, v f

~ 41
W `Y
~.• ? =.12

2.48.7 g• 5 .6C4 go 2 .439 go


total total total

~ .•C .~ a :
..~ 4 ..•
VC .~ ~ ii
w i•
..6

g._C! 7.-.,-,etZ=a2hZ
DJ'sc:~~y1tS

Cr.romtography of the polfcyalia cro=tic rydrorarbn cor.centrato


( 5 . 390 g. ) on al%=ir.a ( A 1=in'.~ W-do 1•:erck) in e coltsn 45 x . x 250 trz.
=ploying hcxane and tenzor.o-hexano eolutions as eluting solvente gave
t.r.a !a1.:rtii:_a -min fractiors ( seo Flcvaheot 4 )t

1L iiT:BL` tL .^"tltcd h,Jd : cca :'to.^`8 ., 1 . 2g0 e .


2. Pr=tio IWdrocarbens ( qery ,a1s b1Lo .°lucrescexo),
0.426e .
--ar-1-L4.alono-t7Pe of
arc=atio bydrocrr':cn.
3. Aroc$tio lqdrocartrona ( intense blue-vY~..ita fluoreacence) s
0 .1.23 g .
'!'yo vrricus fraot :o" . aonotitutir.g thia rain fraction
Cavg u1•.:-z7io:.: t aI,0or ;.*Aon 3zcctra (F:ec...~:un DR, 1.0-=.
s_lica cc7.lc, abcclute otr.ar.o2, 25" C . ) vit.': abcoration
at 3A^C, 3 ; 5, 355 and 374 t-p c .h.rro.ct.oristia of the
s +!^~sco~e-,r, .~-er.e~•:"rono-tppc~ of nrcT..;.tic hxrocarben .
4. A rozbtic b7drocarbons (deep purplo-t11ue riuorosconce )j,
1.11.6 g.
The varioue frrctior.a constituting this cain fraction

g.: .o ul+a~aviclct ahco Ytrcn spcct :z (1'oc'=n DR, 1.0-=.
ailiea cel:s, atsoluto eth:. .^.ol, 25° C . ) taith at3crpticn
tax4mci at 256p 2F.4, 342, 362, 379, 3C6 and 4^4 rJ .t
aw : acteristio of tho p7rer.o, %l,•bon: r~: e ::o an d 1,Lu•
hQ.^.co ;eryle= g.^cup of escmtio h7drocarbans .
5. aosidls (1.9(C6 g . )wha ;,b wi1.1 b4 == .',.i:cd •Ji•,a tho
tenzono•ol•atcd :aterial f:om the initial cr..^=tcgr=
(Flavsbeet 2) .

FractSon 1 abm (1 :2E0 g. ) s:a rccr.roratographod on alumira (25 =* z


2&5 = .) wing hexane as the oluti ::g aolvont to givo 0 .433 g. of
=saturated h7drocarbons a .nd 0.716 g. of naphttalor.o.-t7e-o t:y3roca rbocs
adn.:r.ad xit5 nnsaturated 2qdrocarbona . Zhis lattor tractSon vae
conanod vit5 Praotion 2(0 .426 g.) and 2»vooty~i,eci as dcscribcd in ~
Flavahoet 5. `' N
m
Ln
m
N
m
27

.
U :Rt P 4'lY.GRA M Y C E :^ ..:.:...,.~...

FR . 2 . F'if ;•'Fi ; . '? 2

5.330 C.

Chroratog=Fh on alumim

, r C=.no t 5 '"2C I .rNJII:.8T.13 ~ :~At .~'~ol


I 3' Lon:.eae . o:;.$t ore•• I
~ h= ne hex:4%O

;
~rLi 7 7 1, .i
C

1 .28 G' . 0 .426 Q . 0.123 g. 2.146 g . L9E6 g.


1;:.t'iut.LT^.. tC,i e3ter8 r7.ath . YCene, 3,,G-bcr.:.-
2 :7:rocarton, :.arht; d14T08 yhonant,:.z/enos, Y:j': C .^•C tj j.e
ostcrs, ostora
ra;btba]er.oa

i
c• r
on a.l1...r..a \ _
I
1 . 1 _

5~ .z . S
To e LC'ti:ar~r;:T 6 To s IlWS ME"T 7

i: '(.= .^.9 i F C.3 :a .^.e


I
. ..'K ~
:R , _
z • F,
'
~

.~urOQ3S{~7 'L8 (

~
.. . r. . v
• . . :- ..Iw
•V
.. WIL .Lra• ~
ma ° ."Lti m, 7 t;~J i^ . , ., . C1'M~`y cF t~l Fr'~f~~ ir!Tg

T! r
7 .I ~ ~+~7A~ ..

l.CEb g.

~ Ctsxstoeraph cn nhwmi :-z (25 c3?. s 1X


I Elute vSth hasaae .

Fv . z- ~~s,- 10
I
o . 9e~
~ Yo3~? .
e atera ~ ra,.ht..a.e
.er. ~
,4A ~ o9tE7T9
b ydPOQarb0B8

ChrcmatograFh on ahcias
I
~

7me . 12rg .
" . p . 69-790 Ctt
nltrav~.olot atsorp.•
tlcn cpectr . inCicates
mpkthalera uith trsces
Ot ~^nnlt`~7t~"`flf;^~l

~ubl4.-od

~ .
Residtze t*i: LY ^' .~ L'.~ L

5 ",g• n. p. 79 . 5-80. 5° C.
29

rJ . ? ;-nlct!^r: w,j '^P-ti''1ca'ic' : c'' tho -^d+•TS~ ::rl Foi^c--c11c

g, t'apttlP3cro
':?:o napt :t.~alono fracticn (1 . C°6 g. ) vas chrcr=:to , 4-1-od on ai
.....irs
(Alunia= Oxi,4o Merck) in a colacn 25 = . = 250 rs* u .ing hox:.no aa t.ho
olutinF oolvont . A total of tan fractions (L50 c.l, of aolvont) vere
collec±ed . Ccr»':,:tiono vero rcco on t»s t~sia of atoccr ;,t:ea
t* c' :e :~ ctioac ~ctioa (C .C2q g . ) t~ s»a.n .' ..w.
r lovehoot 5 . +

Z;ai3 mator iai vaa rec ~ rcr.ztorrs,r.»od on al=-i na as before to e-vo a


flracticn, vhich on evaporation contained 7 srC o of a colorlo3s, cry3talli .:o
.0 j==aea of .,: "ti'1 ~'.a .2"@ . ws.~ '' `"`C :+Ms:
0014d L•3 t!! t1 :' .f"
.+ t19 C_C:'
'? A w j a'~r~ +.
69 - 75° C . rltr-ar'.olot atccrj tion str.dias (Eeck : an DK,y1 .C+-cw. si2ioa
cellst, r.et»anol, 25° C . ) ir.dicatcd tho -Ixeaer.ce of napht?~.alor.o contar.inatod
with a_a_h_t .~,.:1, c_ (r.nx.4m* at 324 and 339 ay) .

CtU'
.~ :::.ti - of twa cater :a1l gave a coic:iecs cryo 11^ ao .14d, vt.
ZO o s t '6 - V . ..• ~_ : .~.. .a . L.~ .~
/C ~"
: ^
.. . . d . .a ~
.• ca
r. „
~y, ~. ... . .a•"
...u
, . V. . ..~ ;:. .._ ._oaa r

and iafl~-~ared ataorption spectm of t: is cater~'..a1 wcro ia3entical with those


of an aLt : er.tia sampls of ^ac»+.,»ale,:o .

?he rrx!= obtained in the ultraviolot ubsor ;.t:on spcctr= (icc:Waa


silica collo, ~et,'-.aziol, 250 C . ) of the sn»1i :..ed c~an; Io were
at 2 ;6, :66, 273, 276, 2F~, 2,1-.6, 2;7, 301 .0 3C6 and 311 r)a (cf .(41)) .
Calcu:.ation b:.3ed on oovorrl of t»oce i :dicatod the ;reaenco of
1.67 r-G, of ;ure na,^,ht.".alcne in the suhL• ..~xd raWple.

A mie. L:"a C pC :^t of tr0 = te r!az (y . r . 79 .5 + CC . ~° C . )


wh th an aut .*.octSc sa;.plo of r.zr»t.»alor.o (r. .p, 81,0 - P„1 .5° 00) gave no
dc ,. e3s .. .II
n ~ : . j . of M:.~~.W O, ct^i . .7 • G~1.C-0 C . ~ .

b• ~nt~ ~. ~Ms
1. CcT.C .A Z"'~•GIVFIR

Tt:e c:Mor.,atoCra,p~,~, identification and c .u.aractori=tion of


an•,,: racer.e are o .arized Sn Flovs»aot 6 . Cr.e t:-action of tho init!a1
chrcr..3tot:-= Cave ar, ultraviolet absorpt4on s~.ect: ~ i:.dies°,~:.
:.:.Z
.Z,~ L`:o
.
fi+re .9p. .7ce of
^~"Anf`w+{•rqwn•

2. CF o .tS
CC, IV F'um

An authentic aw.rle of acid cc rlex wa3 r:ro- iLn


~
,.~ .red according to tho zothcd
"" O;:•',..'w
_..ad by r ieaor (4C ) irca~
1. 0,, . ~
. C ;v U
~r.^.IL'3 ) o f a7:.̀. .:. Cc^A L :: :. N
. C~ C . C~Jj z O. I ts ) of f+^"~
.. . ~ m
Ln
boa : or.o ga4o the snthra,cer.o-;:c.-.c acid cc._^ ^, .1~, ~. p. 1: :. -1.:3° C . m
N
W
30

:~, j7, Ct'"Tw ~ p .*~n? .+t.*~!T~ .


~ Z~~Is^hTT ~.

~ ~ r . .

1
T

0.3:3 E•
-x
; ., . ..;.. C n c.l•=! :-.a ( 25 -~ .

Z: toaaeno-hoxanc~ 1N ceazoaa-hex= .^`o


Eoccaas ' ~
Fu F~-7
~ .
._ i
i
31r.C1ar
3 76 ~' .t:•sr:c3^s?
L.L.nnnw+1 .w
Cst e^3 C t•A

Cr,rcr;to..= ; ,h on aaicic acid


. (25 z~ . x 100 r~ . ) .

:oxsce 1~ ~onza :.o-c~ ~ ^


~
rt~. 2..b
23 r..3 0
45 ry• esters?
ant ~=acor.ep
estore

Treat vith F.icz'io


acid in tea :eme.

- ~ .~,T .) r~•• ;~
. .,

( ~..~~ c cl•~ = :.a (25 .~» s1:0-_.)•


`1,,

fi CT{ C % Ca a

42 =g .
Ch.~^.,s•„o~r:= ; h ca
1.r~

~ 25 = . : : 1s0 M .1 .

r
r?, t
:~.. .--
7. ~ .
.=,=
1 32 . =,-;
`Y
?IC:iC ACID

6 .5 =- .
Z..., n. . ^v-1..1
~~~ . 50
I. A
= .r . . ; : .W .~ .

Crr -. :-zta--cr.
~. cc
(4-5 = . x 1C0 =a.) .
T
Pierio N cid , A • 4' r. T
~. ..~.`..._ ~ .~.. ..._s.
. ..
r .p. 196-21r:0 C.
Crys ^ "co : rcr: =oLl=.:a2,
t. p. .^.L`6-21i o C . ; L.a . p . 212-213° C . '
4 .103 _:-,' :? s-oct .- -

Chra:.ic acid in r.cctio acid

~.~..~.

~I~.. wn . ..
~
~M A A
. . .p . /./irR. .C.G~ N . ; r
.. .M .p . C.
31

R h i.- t,_tvo tai11l rra= of t::o cr.t~~ccc ::c-cstc: Li- c aL.~o (coo
h
:1c43 Cet 6 ) ~'Jv0 6.5 arr . o r the SC i d ccL'^-'=
orploying the aL•ove prccodure (40) . I"= zolt :.nv ;.fliat of the c=-
pl= ti:0 21.:} •. 24211 C . a.^.d a risak e roltinv point with t2%.o aut%xntio
c=plo gave r.o doa*nro3sioa (140 . 241950 C .)•

Cecc==cssticz: of the cntrrrccnc-p :crio acid cc-lr.: rj c!^ro=tc•


, :ar+~7 V .^. .~.r,'..i.:a. fl.^) c-:_:r?csa sol ..d, r . ;;• 1%b - :1;)° C .,
1n1~1 ..~ .0 ~.
S. - Y :1 a ~+3. . .~ t w .r .n. .~ .:v . C. . .. C.. ~ .I Y. ...rrr ..
1/ /~lr

t :o :1 riva`~
.. = t+S"..Z :1o.L Cava t
w: w..1-w'. : c1.-nC) m .p• 2C6 • F:. ..ro C. A L..LZLw -0
t^oltir.g point vit/ an autlhontio a=plo (r.aot..n Y.odsk) # z .p. '216 -
21?° C .i =a1tod at 213 - 213° C .

:to abovo sEn rlo of onth~ ccno uaa disaolvcd in 2 .0 /rl, of


acot_o acid . Cno r.i2l .~tor of this colut :.cC «V.x r c:w":od :cr 1L
. of crr c^3c me-co in a colut_cn of 0 .75 r3 . of acotic aci.-vith4cC :
^ .15 =i . of Lr,a„~: cccc-d{m .^, to tho sctrr.3 of Craoro a:3 L+orc-. ::a
i .'i .,
;~ ~ ~,f~~ . .
. ...:ot .. .~
.m t .~CM of w 4 L .0~~.
rp . .in .~ ....0
.r ...~•~ A" Y .. ,• .~
~~ ~..R' Q~ r .. ~@.~'V ftrzl .-.-0~

ty e:;~ ct! cn with a total of 10 r] .. cf Y.cn: ono, g`.o rr ~rquf.:ar.o-


9, :,^ .
7bis rat,or3c1 trra Isrif'.od by c:~sc=ao~r : 7 ca a1t..:- Lml ar.d
cr7~ t.:3~: a! oa f5r= mothnnol to g.vo 1on; 7ol1c~.r noc,dloo of ar.t.~ ~~
~- 42W C. A .ri:c t•.:ro =oltinc I:c :.z:t with an
F:u+..y fl ::+.. ! c + :. .'.'~j. 1o S .'".. .p• "MS . 2t CO Ci of EuCo n o C 0 "r"C :+C 1 C .^. ( .". . -e • Z I cJ ~
..n . .. ~
. f.o i»O= '~ a Ln• .~ ..•^. 3 t c0~
. .aJn of t~
J ... J
Ic . .l~
.l ~ l . . . o ..+
: j . ~ 7 w~nt C ..Jn
. ..1 Lr..'..9
!dect.ral v:th that of an auth.entic sarrlo.

G EP-C ;^s

"'^ ~' L- v3olot ::ccL~..n M,,( 1 .C-cr. ailica, ccl:.op, absciL+.,3


1 ..0 1..~ ~ •M ,

e tM~Mcl, ~.5^ C. ) and r ! p-


rn-}}}rMr VM V YJ C jlY cn s octrM of ;t:.V Yr.t.. .' f.cV.re

vor o idcntica71 with thoso of an authontSc =plo .

^.Y:o L:1L:mviolot atoorpticn =::rica Lcro at 253, =46~ 310, 32d,


342, 3 .`, 5, 370 and 373 :p (c :. (!«2) ) . Calcj'.,:.ticn b.:ccd cn the
x-..nq at 34 .?0 35s and 3?3 L-p ita3cated tho proser.cs of 4.03 r.C . of
c:: tM--ccenc in thA s~lA ; rior to c~^.,:ractmi .-,ticn as tho aa~.-~^....
qta.~c:.or3~ : ^ . Ln
~
~

Ln
~
N
pro_:C C :'.."": ::t^` "' .. 1.. .~ ta, ..J.Jna . ..^. ti cn °'
and C4 :' :: c:' a e. i ^.t:o'.1 o f
3,G•be.w,-j : or.o aro out,1 'i::,d :: cct::.1 in 'r'2ovobcct 7 .
32

... . . _ . ~ .~ . .. . . . . . .. .. .. . .., .. .- ., .. , . .., .,~.. .,

. ..-V7r.•
B7 7 . .

~. ...~~. .. .~ :+.~ G

i. 146 €.
Chr = LC cm~yh Oii J33'^ m (c5 ~.x1?5

' S' =L!:e:• . ~ 4,'• ?'er :a^o-- :


:Qy`w . .w
w-
.. . .Q
~r ~ r41

: cza-s ~ r :oxa«e ~erxs:a

~ . .. . ~~=u F? .
'IV
0. 3220 E . 0. 074 Z. 0 .055 0 . ; 40 ~,+ .
03 t8r 8 7 1r,:-0 ::0 ) 3,1.-ben:.. 1,12 ..1,e czo-
t'h:or~,.at,*:or.e pm TO pery1@Do I
A w M.YM Yr .1Mo ra

4 V`r~CYY ;:h n
YCLi r M

r QT3@ amd
a O F'j oilioia ccSd
tl= raat: e:e (25= . z?.0= .)x
iaolatioa

N . QlII g. C . OIS

C Vb.V1VN - i {N• 3,Y'VV .wir~V^0 1f~Y .~ C L~C .1 Q\•~S~.VV

I
c a p io V+VQ.g { i^ "v ~
..• , b27 con iwA .'i n.+rn(= J . ^i.W r'L• W

3,4-banzFyrezo ) .

i C:-r:.1t O,r-^ rh C .^. ca: A (15w .


Y y
.. . .
"'
_ . • 1-2 .~~~ . .3

3 m c^.
I C}rcra tcrr =b oa :.2 :: i=
~
.. .~. .~.
v .I ,' - i .^ij° .^i .

+ J v : . .n.«
.~ .. .4. :a :.oi •
^+1a~..r±C+ 3 ,G - .1~~.. .. ..~
.~ ? IM
.- . ~.
:: . . .,

(m.p. 172•1'?'S° C .
Crystsllize !`roc mett~.aaol.
~
^_-_ . +r I 4_^r . .. . _..r. _. . .~
s., .~

~ C.620 rC.
I = . p. 175•179° C .

, - ...-.,...... .
,
1. 296 ag. in rixtti:re

~ :resL vith picr .c acid in


L ~bca^.eno .

~~~H+~~lf0
;- . .~L-z _ .
.T', 'liT

Cr :'r ~;2 Cl~ . r _z'2

c.p. 17E-1~3 m .p. 155-1?0

Cr,rstallize frx
bonzor.o
y I
DT CO T r !(; r,
_
pTC--TC ~~CTn
. •Ci
~i~ . . .,i~ . .r~j'`'`'4.%'

w.p.19C-5°om
.= .p. no
doprossioa

Co--b-ir©
I
Lrr ^ .,., . .. ., .-~.
..a. ..w~
~ : .. . . om a1•,.:..i:s
r--
-

ricri c A^id
\ ;/

~ . ..i .~~~ ~

~ M /~
l. .L.V = v.

= .p . 1? .^-1%7' C . ; =.Zi.p*
r.o ae ; r ossicn
L'V aad "m srcc :. .-a agrco .
3

.. ,.~ .. . ,, .. . ... _ ., , . ~ „ C .
*.• ~. : . . .. ~r . . .'.1 .. . ~ . .~ --
3~~ :.~ . .r .~l . . . .
, . --. .. .
r i. :j ~ ~L . . .rL::.G~ .~~
FIC=IC ACID C•' ~:: .._..
_ :.Y '
of
~ w w . .iS .
• .. .. . . . .~ ::~+w
.. . .. ww~
. ......w~w
~ i ~ .. «rw.j.~ . r. :.r
- . r ..
j.- . .. ~ .w. ..wrj~: iri^-1~'.x vt..

prepcrad accordine to the motbod of Fiener ( 40) . Z'ni3 cs torial


¢eltod at 195 - 1980 C .

x o outlined in ?lc•,r : boet 78 the 3il.-bon :,pyrono ccr.car.trate fr cm


t}:e 10 # 5CO CtiN.rL ciE^sctte r = vt s co=hir.ed vith a sirilar 2`rsc tion
,rw
!'r a ci Ctr.:tte r .--. cVntai .wi. in- y ZL~~ L' ~ . of
3,4-:n .^. .t.;:cro. :l:o co .:tined ccr.ccntratas were`rxL`'icd ~f !o ;rsticn
of tho ric: i o ac:d ccr.plox . ::da complex r.altod ct 190 - 195° C . ar.d
Cavve ;:o dcFr oraicn of the irelt3 :.~; poi nt vith tto authentic sa_-.pl.o
,.~: sparsd a !:ovo .

.7hr~to~,, .~j of t~o 33~-ye••~,; or.o-picri0 :.a: cc_~lax Cavo


a s=71e of 3#4-ber.c ;,yr eaei ic . p . 170 - 1750 C ., vhicW ravo no reltir.e
;oint deFroo3ion with an authontie caaplo`(a .p. 178 - 18^^ C.) .

3 . Ap!'CF:PT2Gtl "r7PrEC':F.A

:"1:e L'_tmviclat a:A iz .flta.Mcd ab3orption r;:ct ra cf t : :is sao


rlo
were identical vit? : thoce o .° an aut*entic s=r1e of

I :2:e ultraviolet ab3orytion caxt= (Locl=uan riC, 1 .C-= . silica


colls, abflclute ethanol, 250 C . ) vor e at 255p 2E8, 275, 2:7, 297,
34°, 3E.G, 3?7 and 403 z~if z -^ at 253, 2731 ::9-1, 295, 371 w.d 397
cp ; aI:culdor at 330 m in a~ccreat vi .h the pi:blS,16-ed ul:.- .:v'.clot
atrc :rtion cpectr= (L7) and tho opectr= of Eun aut~o :.tic cr.~ple
( rnst=n Xcda ;c Chomica13,, Distillation Products Ir.dustrieo ) .
~
Ca : c'.:: .aticn tascd on UMo u1t .-avio? Et a :cc: rticn at 31,9,
r
^w7 ~ ..,~ 4~,n3
I'~ .r.. .. .t~ ..wa
rp . ~
.. w .. .r ..,•
.r~f:
r~f:
d•
•S "
w .ojv`~ .~ of~1 .a7
..o ..~0
.
^ of 3,4.tE
rr':`B :0 :~ ~«3 8"OICB L`C .^. .^.~Zlratii ::^ :w 131 CLV C~. .`•z 3.

.^~ . ..i{li",n
..*- i.a;'i~`~a' .•i1e

1. Cf' :1CY.1TCCRr. F~:Y

The fltoranther.e-ric*a f-*-ct.cr.3 S:ro~ the 1C, `^C.` C' ::?.iL ci C:.: rtte
( C . :.41 G . ) and a3 ;,,C aiCa,-etto run .( 0 . %70 g . ) kGrfl cc,:,-
i b4

Chr=-to ; ra j"7 of thin raterial on al=ira did : ot rcrr..it iool : -


t:.on ot' c«;-3talL:o .l::cranthe: o duo to an oay ccnt,A::rnar.t.
. ~
!. , C . ... . .a- .~`1 CF wrLi.'if-?
~ ..~... ~.
~F n .~; :..~:,J!a rl..:C.: . . . .: .s...~ . ... ..1 . ~~
FL::CmE:CCly3= cn
~
J
vr. 3 pr.~,T.a :"Lil: W t ho

= t .", oc o: ::ckey 03) rs :oL'C• ; o. m


Ln
m
N
~

'71^e fluora .^.thono-r;chu frcction (0 .4C0 g .) vas dinsolvrd in 1.5
r.1. of varW (60° C .) Flacial acotic acid . 1, solution of- l,0 cC . of
2,49?-tr:r.itrofluorenone ia 3 .5 E1. of boiling glacial acot:c acid
vaa nddor3 and the resultinQ eolution vaa a13.oWOd to cool apont:.•u*-
ously to 25° C .

Finci ?eLl.aw-orr.r.Ce ncc.~c2es Frecipitsted aftor 2 hov+-s . Tnose


wc :ro rcccvoz•ed ~ ;~ ..:.d uer a :~s'~cd vit, ~2 :' . of cold
(0° C . ) haa::r.o to ~-ire z:.terial •lith an ir.definite r-olti .*.C Fcin t.
Chxror.atogmpby, on aliw,.i:.a deecWiosed the eoe,^.3.ez and Eavo !"racticna
with ultraviolet a : sorption apoctra cP.c.ractcrLstio of r- ; ~eno, f3.t:or•
ant3ser.e and :'ae flucrant::or.e3-r'..ch fr actions
vere ccrt_.xd, coaccnt: rt : d and zCain troatod with 2,4,7-trinit .-•o-
fr•,:oreacae in g1acS.a3. .acot3c acid aa before to eive ye13oW need3ca,
~. p. 201 - 210° C . ' A risture r.el tirg point ot the fluor : nttbor.o-trL-
nitroflucrenone coQplooc with an authentic aacpls (75), c .F . 214 -
215° C . ,,rsve no dopr ocs ion .

^ecc- :csiti cn of •.tc f?i:cr ~+.rono. .t.~ir.i ~ of'! »o .~a_no ccw^lex on


(25 =, x 1C0 .. - )Cave fhar^,.nthor.o, :. p . 103 - 1:E° C . A
cixtL,.•-,o -altinC point with an authentic -^le, V-.p. 1L'7 - 1C9° C .,
Zt7a no ae ;--assicr .

3 . A-EFORPTieN CFECIMA •
4ho first fraction Sr= the '_a ttor cr.rcratoCra.: gavo an ul *..ra-
vio :ct c :ccrytion Epoctr=vith =:= at <62, 274, 3G0, 328 and 3G3
r7i . ;'hooo r,acSr..a coir.cide with t .':o; e for the hydrocarbcn,
.r~r.~ (45)•
V1V• ~ •r •dV IYW~~V .i CM MrvGL•w.I V •~ ~r •~~ "

the ^yr6Sfl~~0 of 2 .95 «.c . of fNL'Cr:::.t::C ::3 in ;WMo =Cf'a CC» .': .^+r«.a :9 ~
, +e ult:aviolot abaorpticn r-& :r'.= were at
14 , 0,00 C1'/ZIM ci ga:•otte3 . "Y
2b1, 2'17, 22?, 3C°, 322, 341 and 358 =,p ( cf.(43),10
Ln
~
4•_ -4
N
m
. . "S iSYSz i J.TRIr:I :?~FLLCP.i'
' : A F-3 C~r?.ILA'*IC:1 0? 'r'YRE.M -E
cn
C ..~ .. LE x m
w
m
"1:e r* ;: vno-r:c.ti f:actiocs :~ the 10, 50^ cica:^ette :n:r
nnd th.e 3 ;Ca V : CL o:C--:ot',a uaro coWbinc; , C .ccclved !:. 1.0 wl4
of glac :r.l acotic acid Mr.d tr cYtcd wi t» 02.0 r.3, of
f.uorer.c :.3-9 in 0.5 r.1. of bo!' w E.'.ncio .lZ acz.t:C acid. A rod
c:iata2l:co solid p .-rocip:tatod ca cooling r clid a :`tcr ti.;.c;:-
inL with c.'•.illed bozane (1 .0 «,1., C° C . ) and drjinC, coltsd at
35

C : :t w_th an aut: cntSo s:r; ?o (?5), r .p.


2.:2 - .^.43° C., waa 235 - 23?° C . Me inflcarod ahso :ption oroctrs~
of thia ~tcr :al wa3 idc :~tic :1 with that of an aut::ontio o=p1o of
pyrone..triaitrofluorenono eocplmc.

The eocp,lox uaa dcc=pooed oa a1=,trs to obtain pyreno for


ultraviolet 8tsorption ottt3ivs . . • .
2. A wCRI:"T07 ^ PE C TA °Jl

Clt,.~violot abscrYtSon atudios (Pocl=n EX, 1 .C-.^-- . aiLcs co].3c,


abooluto eUanol, 250 C . ) on tho pyror.o obtained ty deco=,position of
',l:o co--plex ind icated a rir.3.n= of 1.36 c;,. of pyrcr.o in the ocrYlw-
oat• i'rco 24,000 C':mL cigarettes .

- :Y6 ultravio2et abcc:rticn =x:m wero at 262, 2?<^, 293, 31d, 334
ead 3?2 a}3 in aCreezont witb trcae of an authantie aarp1o (cS . (44))•

. . .0 1~ . _e~...,ct,,.
., did ..,,,
_ ... .. . ..
., ..., .., . ~ ..r.v,+ . . . . .,
..»,..~.~
ter.:; 3thr, cono for ico?atica or cr ::ractori :.ation . :he ultrasiolot ah3o rp-
ti^.a (Iccl=sn DK, 1 . ,~ . ailica co11a, ab3o?ute etY~.: no1, 25° C . )
wero a t L6,0_ , ~~ 2 C9 j 3'.'..~ 3 2 70 i~~..~r, 357] M z.+.d. 3.:v -.-,u a.: a '='c.:c.^. :i ~..~.
z t i '

published data (46) . ?Y:o eat:=ted quantity of 1#2•ben :8athrace'ne vas 0 .16
to 0 . :2 A. por 1Co cig^...rcttos .

:Y:o iaforration on t2hws L .atie hydrocarbon was obtained L7 !11.-action•


at_ :` t!~c r.c4+..rrl fmctia :: obtained fmn t ::o 3`.C' ' :r:7
cil-
.-r otto :^.m. :l:e ultr aviolot absorption rr ..-inn ('.Ec~:n CX, 1 . Cti-= .
3•f»~ reL`s, cyclchcw.3, 25° C.) were at 291, 303,0 331, '~.4-°, 3tx, 3E3
a:d G :..° n,u (c . . %"4C)) .

The evidence for this aroratio rqdrocarbcn was tho ultraviolet atzorp-'
tion naaiira at 408 ond 432 rp (of . (49)) .

()1
m
W
t-A
3d


Z2:e r.ain ir.tcroat in tbe 1=esonce of tho Fo37cyc3 :c arc.:,: tSc byd:ro~.r'rons
in ci,^arotte ccrwvr.3=Yo .'„^- t.':..t r...^; cf ': vrc cr::ra~.::.3a ~ro ~c:ra to ho
carcinoConio (53) to variouo sFEciao of aai .,~.aU. She cur: ont cer.trovoray con-
ccrr.ir.b the ir.fluonce oP cigarotto smo ::i::g on t,' :e incrotoir.e ihciCCr.co of =naor
o_: the 1:.^:C in t.`:e ~:~..a.^. r..-3o ilg, 3L, 35 . 36, 51, 52, 60, E6, 6?, 71, 72, ?4a
j n ~ 4 ~" , ! 17 , 11^ l ~~S = ~ ,~et ~'nern c n++1A~
. L . .I ~. ..~ .Y. . ~.. ~'C' C'ri~
br~
V C'ri~ :'r
:'r V Vr
V .(~ . A

ar'
./. .. ~1 data iwd .caj„e t'~
.M t t:•:^e is a a:.~ V~
- '^^~onSc
'^^~on
..VL in c .•-cro•to
Sc factor '^ C V ./ ;: :r~
densato (119, 120) . ihis c:..rcscreaic . ..cto : rosSdc3 {: the ^.cut:: 2
fraction of -the cwoke casden°ate (121 ; arA 13 producod p : iza.-i1,7 by p;:'ol"si :
of the tobacco durriw„ the e='r.i^g yrocoas (121) .

In vi :r.~ Qf t fd;,ta, :: is loCica to accc; o that L : e c:: c .:c~,cac aca :: ,


of cit rstta sr oko condca:ate ia due to the precor.ce of or.o or =cre carcinoceaic
gol;cqclio aroratio rydrocMr bons . 4l:o presenco of aeverhl of tho pollc-clio
2r-drocart':.r,s in c_Lc~rotto cnoko tzs boen des :cns+,ratcd by t,x.o .-,wc:o korlxre in the
•.ritsc: cta+.e9 r.nd a}.road, r.rir.circllf trj moano of ult~wiolct cxct .-~cF:cto~ot . .
!j..rc9 vcry iitt?o actua.l i: clsticts n4 cua :ratoriration work haa bevn rercrtod
in tho P:ct, this con3titutos twe ra :.a oi;3ect of the ;xcse--t recc :~.rc:.

7'h= 14 ;rl^-clic arc-*rtic r:,M'..rres~r.3 vhrc'~ have ei+w'^.er heon S :.c2;.t,-d ar


identified in the noutral fraetion of eie.~rette scoke . cc n:ona:.to are as fou~ ~ :
Acor.a;h•,~yle-:o (3C ?9), nntrsacono (2I, 30, 31, E2, 849 99), artranthrcr.o
a~uler.e (6, 54, 703, 1,2•ben :,anthracer.o (61, 70, 79), l,L^••boazorerilor.e (30, ,
'79) 3,G•bon: r,~ : ore (6, 20, 30, 33, 32, 65t ?0, 79, 99, 114, ]35), 3-=t1 :-~l~rer.c
("~
, , ::rhw'^s~
1 cct^s~~-so
.^.e :32r 79, 9'9~ :o (115N
~ ^„rfh:orant .: erA ~~ti1'_5`~r
•,~r /
. . .^ (^1 '1Cr '~lr '!^
..
.? ..~.l e..~ 11 .~
. . ( . .., . ._ . ._. ..,.+4
..~ .i ~-.1+nnw . . . .. .+...
. ..
.0 ~'!^
.-~^^~,
~+/w~ n ..rl .w.....
. : ...., ,.of . .,_ ..
79, 115) .
.'cr.o, 1,12•Lea^ope:~,lo ::o :^A
Cf the iacntir :a_d , cc~.~.'cr.o,
.i c aetiT.t7 in e~e :
rJ•: oro u_nce not .ean testo• S'or c.: ..rc~-~w~e.^.ic
to 1951 ( 53)• Cf tt'~e ro :,oir.dcr uh:c:: r.tve been tested for car ci .mcric
activ'.tj, Fart-well (53) 2sts r.arht..alcno, acor.arhttyloao, an th .~acene, Fha
threno, fluor.--thene, per•fleno and anthantr.reno aa boir,g r.or.c:..-c3noCoaic .
?Eccnt77 hovevor, L`ruaIc :y acd ~ cx ..-x~hl (37) describad the c^:rcinogenic :.ctivity
of antr.raceno in rats which developod t=orc on Wection with th :.s hydroc:.-hon,

:'Me 4 rowa'.rulr.3 i:JdrocrrL'onc, 1,2.benconthracor.o (10, 22, 103), chrj ccr.e


/!! !) !A 1r~ ~. . . .r1^ 1nG% . .w .i .. ..« . . . .n O1f"N . ..p~.A4 .ii M+ .~ .-inwr~e
.., ., ~a, •~~ •. ._, b . .. . .. ..~v . . . . ... . .~~ v ~

c.rc~nic zct :v ; ;;t whereas 3,4'2zn.~r^M-cro s hiC :a, ~ca rci .~oc cr,ic ( ceo ~ .~I
fcr ro'7 refcrencca to the c .zrcinor-.er.ic activ4_t7 of ",.:ao com-rour.d in ',»e Wousse
( 41 st rai-w ), rrt (9 otrcSns)r cui= pi6, h:ster, rabb.it, rigcon, fcu3 a-•d
Dcvti•

'.a ::'Scr.tad !_n t2 :o :x ;:er=.::nta1 :'ection of thin reYort, 5&o+ ; c;clic


.^•_~c t...'
...: ..r. .. : .. r . 4 ^ ' ..+~_ . :-... .:,»
....,.or ~.^
..e,; "o ;~
!-:vo teen _so?ntodt iCent :.fied ied ard -c:::..-actericed d in th ; cr_e l..io~.~t..^ .~-; in t~;
h~ r.e-soluble, r:eL•', ..rcl', rc.l i`: -atian of C"1-L c .~:.retto cccko ccr.dcnsato . ':hr~
of t*":oco h~ :McarVcr~ -_c= ::c• ^'rr^ro• ~ .G-tQrc-Rr.^^o> ~"r ~, :c^ect
: nn ofa.- as c=ca. :ogenio r.et:vit7 13 ccncnrned .

51710 5032
:7

It b~ L~ocn ~:a. ..~


~ c d that
w^t•MYn`• C C c " Yh C C
t .~e
Y
. -
~~^+M^~~+
. V~ . .VL V
r `j s{+•
~I~I
' .~YJ 0 t• .V ~n .F ~V ~
.~•.
V .I~

don.^.nto, or. the box.-no•aolublc, aoutr^..1 fsaction, ia a rarc:tl7 r.uah g•reator


tha.n th: t dco to tro
. i.^.divsc:;:a: cL.~^~^
v•r. . orcnic rzr~roc w
-..~i
~o-:a,
~. • c.r.:''^~
•w ..~ Ccr. , T;" .oco,

Ch- r,7E0 :O~~ &.^.3 3 G•bQ« :r~1"lJ=0 ..'3JC^t (J~« 4 , ._.~..~.~ . . i:a`fA
o~cplar.atsor~a of thin apparont a:oza~y appoar p?ausiblo at procent .

1. "Mo o.:.Mci,~o~r.ic . ic activity o!' t~e hexno•solublo, r.eutral fr~ction


(or vhole ccn3onscte~ ic de:e rz! r.ly to soco hitherto ta,.k=ova povortul :,,~
csrci ::oConic pcl ;, c .-c13c crar.:tic hydroc .:r:.ca .

2. ,1 a ;-r:orgiotio ef!'"t is ottai^od .pr cc tbe uict.m hJdreear vcr.o .


:2iis pr:eno=er.on has bccn coseribe8 ty ct ..~::erois vorlscrs (102, 103) in the
=so of the po1,7o7c2io a.-or:atic kydrocarbons .

0 1 r . .. - ~c =d :-rec c .t- in 4a4 O nCUt :"'r I .l.icL3 e .^i Ci• C.t V :w ttB .' = t.9 Y

. cc tcr.:vir.` as a cocaro inc e (l


l .4r .wYte •8 1 23 4t E , N .., " ., ' M .( , w^' j'.ni,

l<, =W eit: er for ocmo c :zi.ou.•.d in cigtu-oLto onoko or :or 30=o ccm,^-ound
preaent as a ; ol.:ut^..nt in air .

I nce i t i 0
o{J w BiZ o Jti"
r.. . wBi : ~ tr~..~~.t riiii r eHtB e zCjCV LcE s Civ=,4- iC.vCir~r.i
.4 ~.i .w
~w.1d .~.~~...c~aQ~iw - «~0 ~tC~~,~1
•i.L
~w .~ ~•wr
r1i. • ~ . .` W r M Vri
a Y . .w ~r~r vw+~

cir.c-cnio activ:ty of a n=ber of tiio3o ccc-,o•,a.d3, a rothod of either corgete .


. . .C'Jal Or a l= ct cc c-, ::oto of t}7or0 coW p ct nd 3 t`Y'ca c i G..r9tt8 3= :{fl 143
rC"
T£q., :: .-GG a

thia probl,ou : aa tbree ta .ia crFt•oachea .

1. : cr.o cc-,;.•,:: d or Croup of cc;oi..^:~n, e ., the a.3i~:-:tic r,; dr e..


esrbr.s, -. escnt in the tot:cco =y be prcc,.asora . - to t.`:o Fo :7cyclic
cror..atio b73rocn rbon3 presont ia the tobacco =oloa . Zt:ua, a 2ctiror=: g-, of
wo r -~i 1 •,r .. . .
.~..~~~r . , .
..~ew~i. r.r
~~ .~ .r.1. .~ .. ~~ . .
~ wi_~t ~.~o .r~~wt•~ ~ •

eithcr c .^•as.lBtA or ;,:...~-ti .a : rr:val cf this Fr c=ocr S :•cn tto tor,:cro .

L. .~
..Q i .S .~...~,.~.t Cw ~ .~.e ..r ~~v irf

to ;..p.r~Y:i :r.o (~ ^
r,r...,. . ^rDc C .) r;M
eat
.;,-ciaof
o° r.;1 orgw^«•
~ c ~tor ia
iol ;~^~
. ,,..o?
f1ho tob.:cco. :h •, :a p tre co ntcnt of tr.o po1,7c; clio b y droc* r. bc = i n •,yo
smoke r-I ght be l..Mjerec3 17 o: ther lo•.reriag t !:o cozi.-u3tioa to =,-crat•.rc of
the tobacco bclcv 5L"J° C . or by raising tho ccub=tion tc..rc =t.ao atove
E50' C . t7 tte addi tion of suitable Tb eco ca A itives wuot Le
osre^ti=?. L^ ec? .• :'1Csfl , t4?f..C l o30, a :.d ncnt emic , lt t the t.'^e;
=jz t cot to t.'-.o toxcca sc.ci :o cr alteratica
ef wo 093G M +.. : :: 1I f,14-mr2 . ..':+..3 .

,. ~.~•~.e F.c t :.M of cQ:•+iw ia .,n 1 .~.Cir c=!c .wi't orwaJ ~ e * go p fr eC J u.tl Ir`~ wn
cer+t :.in ozr-rtic ecr roz :nas sucb es t: o ste:rols, at r.ic-h terrcr_-tz,•.Me eou:4
w .' i / a
. C3 :r .r .»Z %wfl
. ..w... l
. > . . ..rr~~i
w
t i7.• o :yf~j '
~ .~ v. ~ .. i
w
crr~i
..r .r v ..v
~~,
rriw ::
.'`j1.
'

r~.w
.. o`ai of +v~e ~
.~• eo o .~uii a' u .~ iv.~.. towCrc . 77 rr ~ .7 r to fiJ .~w-iCi .:virr n i .:v 0 Ci= zc,- .

:-ettea vc-•Y?,d off oet auch a reaction .


.., . .. .. ..` . ..~ a~. . .
. ... ...... .. .....•
..+t-~ . ?r ,i
.. . . ~_ . . . 1 . --~..C :2T .) l1
.~T ,.., ..V
r~C .. ::: :± r;=~= :=!3 3~
F.Y' . . of U:o r.iSph.,^.t_e L-yd.-oc:..M:~ora ort :-:cted .^rcm tol-occco CSvea
an t.'-.raceno, p7rer.o, 3,4-bonaFyran e a :d 1#lWconrr-yr oao . :^ oaaorvatic na
38

wero =do IC-7 :•:r ir.l-.t ar.3 ry:•.c3er (I15) vit': : ccr.ect . to arn aiir!::tic h~Cromrlcr.o
cixture (90 pcrcont of vh4ch vas pxeat :.a,i.7 l:entriacontaao, a-C31H~) ot,tui .^. : d
b7 tbo extraction of tob~icco . Pyrol3rois of tbia wi :tture in an os~-ca-freo
at~ocFhcre ;iolc3od r~nt~.rscor.o# pyrene~ fluorant2:enes cr.ryaona and 3,4-bor.c;yroro
in the pqrolssato .

In 11~42, roi'fo (94) ncted thct t2 :e extrrciior: of tobacco with o••ch orEc..z io
L. ...-
.i\Y.'r~tt~
J ~~ ..n{•~'1~
.. . . . .-, .. . .i Y':.` . . .. .,
:. f rr^.
. tv :•.:9+j, e^' . ~
:C . ~ .. . ,
ro :.-a.lted i.^m a ro:^w' :cn of t,ho cr.rri.^oCcnio ccti•rity of '.ho t.s ott,,:'•:od ty
c°.catr :otive diotil2ation oY' : the oxttMsctod tot;.cco ao cc ;_p~-r cd vith the tar
ottained ty t} :o destz-uotive diati2l .ation of Uh:o nonoxtractod tot.ccco . Roffo
cu~. Featcd that the cxtraction would removo t ::3 FY;7tostcr oia, a nor : =1 con: 'i-
•. . ^,~ :;ccc. ^c w^. ~O C : .,» ..«< » ::9.53Q
._en.,0 . ~ r t .,.~r,.rCC ;. ,t
- 0 .7 o~ .~'+,..v^Y`4~ 4buEOd
.~;'t.o
on dry ueiCht r.u co .r.rxred Vith other ph,.nts, e .g., Fotsto, 0 .15 For contj
csbtaL-ev 0 .12 parcent ; oats, 0 .20 pcreent ; sqti;ach, 0 .16 pcr cent .

:. = c:M•. x a u V. .V rs r :.vo dcr.c ::J t.a


r :. ted t.',.:..•t the p7rolysia of ctcrola or sterol

e : tors, e .F., ch olc ;,tercl, 7n1II, R" = Ii . or choleoteryl paL-!t a to,


~'2 ; ,•,.~,^. ., in t,Y :o °cr- ... .•C^ of polyCyc? :c c: ~;.tic
( 39, 1G7 )I o : g ., c~-;•soao and 3'~othylc~clopcntonophonsnth.Mc:.e, :VIiI, of ~ :h'_c.h_ch
a t Icaat one, clx •, cc^o, is carcino ~_? auic ( E, 9, I^, 17, "' , I.:, 103, 105) . I.o
.yM~la! t~ . .
o r,.... ...'
._,r_....J .. w n .. • . 1
.. 1- ~e . .7 ...,.+ 3 t .+r.ti- G`.~
.s rv e •., •1 .~ ^V ..w-rf il ..
.....,._r .. of c ddn'~J
.= _„iormV 1
e M-
•-
rti ~

e?c13c nc=c«,:.tie ccw ;.ounds, severa3 o: which are earciacgonio and ti•hich woL
cp, ;e:.r in the noutr :.l fraction of toL•:cco =ace, e .g., c}oiestMd_enc-3,5, X717,
(39, 105), cl:olcsteacno-4, XX (390 107), dickolestoryl ether, XXI (39), cr .oles-
tai:o, XXII (3~), and coF.rostame, XXIII (39) . Cbolootadieno-3,5 (107, 109) and
c::ol.a3tenoMe-L (16) are carei .^,oCeaie . In Ceneral, the prytootaroln differ
2: on choloctcrol in t;:e otructure of tho side chain at C17•

Y7II XvZiI X :t

:. -`G\/-

XZ XXI XXII
x = -..'n(Cx)3•( % )3•ca(ctg)2 in
fo= :2ao XVII, XLt, XX, XT.I, 17CII
zzd
.1./1i.~~ . . .

•f.~1 J.
Co:s:4crst:cn ef tn i3 cata cc ::car^.:^g t.':o stcrols ar.d 11-h o cLi,',.w;,ic byd ro-
e:.r lm r.a aiu- rcst3 tha t tt o Frec•: -aor theor~ of eiga.rotte 3Cc6o C017C j C . C
i3 a loCical =e . At ;,resEn ts tt:e i3
to:r.g isvost :C•sted in thin 1abcratcr7 (81) .

With raaFcct to 2 . atove, °e :.r.::ay (55, 56p 57) and Yo :ma•.m- .1 and Ear.:3on
(5C-) deccn3tratyd thzt the p7ro?yaia of cuch or ;au! o =teri; 3s as
;rcact ( :b), crol:atcrrl (56, 58), c^.a7. (56) 57), ;etr ol~.r ( 5 :,)
~ i ip acet~ :.cno (56, 57 .1 . 81:d i.".o~`mo (55) at te--peratu: as ra :.Ci: C f: = iGC°
to 92C° C . (s to that ottsSr.od in t.o L=a ;:g cjC:.-ottca (3~, L9)) b=e
tr.rs vr_c!: vcro carci:o :erlc to r.curo sz_r. . T'hese tsrs ocn+„a•.r.cc a t~.iph ccr.-
ccat .-r.tion of pol7cyclio r.rro=t:c hydroc: rbor.a .

lir± ]rar accrcr :.•ao :ts r.rse toon carricd ou t t7 othor i .:t oc ti rntcrs vi!, :
recroct to hc .:ted f;c:ct•,;.^ :a, vUch aro ~•:.::ci~.r.lly ~,
a: .. .~c ra,,~^
..r_..ls, e .g.,
ta:cted t`cad (1^6), ror.stod coffee (76, S5, £t3), toa r90)~ fat3 (62, F7, 93i,
re,:to {iC4, 113) i a .^.d gr~in (69) . A ror e dctriled descriptioa of these
exror±=oat3 ~s boon Froaeat~ ~rev!oi :s~,,^ (S0) . In rcst in,tc.nces, ~ :~ci~c~~u^±c
tars voro ottai :cd b7 bcatina t : o!ccdot.:: f .

Far:-.LC,7 ( ;7) ot..er: Ed t_...t a Y twa ta ...,.c.•a V W e at ~ .h.c


.m oco=•rod, tho carcinoeonic uctivity of tho rcsulting tar also tc a- e aj, ^ .cront.
TMo g"eater tho te=Ceraturo of r,,•rol~-sis, tho groater the : ro.;.3ti : at.ica aad
caroinoeonic acti :vity over the te .-.Feratura ran€e 450 to 850° C .

It io possible that such a =ecb :r.i= is oporative in tt :o casa of tho L~ Ln


i:.g of totacco di:rir.g t.~o nor:.-sl rmolking r.roceca . In order to ryd ;:oo t!:3 ~
J
ccntent of .: e po1yt-Icae ara..~.:t :o tqdroca rtors in the sro :.-e, tho tc :'per zt ;w a ~
m
of ccrbu3tn cn e2xuad oi whcr ta lcs~orcd tolcv 5CC' C . er raisod a y;, : a 9r'C° C . Ln
:~j t2:e addition of sti :aa"1o re : Cewts . ':hin apr,roach vi11 ta wvactiumt3d in m
this laloratory in the tuture . w
Ln
a . . ,. . . ,,. .~ t .
b *- 3 MV . . s A~•
V.

t'. cc ..t i ., t.1 .Q ;-Wdu + i ci: of


o a. W c w.ti C C M.r • •~ Ma . . c- V t~ C ~. K.. . .v . .. . .. .r «i l :ei .ir

kn cvn (77) . th 0 j1Qrr.^ rvu-atio r:~•o-!


. .al,
, 'on bcati.~a with oit.ew . .e••:1Pti
. ...- or. .•~ole .._
w~ =
Ga to &-C° ~, C~ 7Q9 :. .^. ' ~C C• . . .. - :r A ~"',jC: CLC .^. C :' } . . .: ='-~'II _

`~~ ~ ., .
' ( .^ ~j ~^ ~ . . ~} w .. . . ..J ..n~•~ ~~~ ~ ~ - yw1
.• •Crj .~ .C+V~_1Q, ~~ ly ` .~J V~F.1 ~.CbVM ./W•. .r{•y xr--iY t~V .icc .7 : at ,v ..• ./Vy

to,z,:ccos does conta=.n froo sn1R,, .•w on tho lsaf (7) . Presi=bly t::o :r ce oulftr
r.: :ces e3 a eontar11r_:r.t durinv t .*.a arMi:b of txo tobacco vith certaia ouL L-~ .
containing Snaocticidos .
40

zxpcr'_s.enta v111 ho ccr--:uctod at acme tir.o in tho Putin•e to dotor ri.~.o the
offoct of tho suL^.:- content of tobacco on the pol7c; clic arc:.,at:.c,h9droca- --•: on
contont of the =ok,e oonde=to .

;be !ol i cyc~± c cr^nativ h„^-drccartoa ...c, scc .-:ri a.:t:rM^..-


oaro, phenanth-rene, ryrer.o, 3-rcth7l ;.qrcr.o, fluor :.ntr.ono, 1,2-tonzantlzracone,
3,4-`.oncp; rcae, 1, i : -tenzeFer; leno and znt!'-.cnthrene hrvo been identif iod as
co: •':it•,:ohts of tho szoko cor-,4cnsato troc V2SL blend ciCa : ettos .

It has boon Qut,,;ested that :ho contont of the pol7cyrlic aror.stio t7dro-
ca.Mbcr«3 in the siroko condensatA w,;.y te reducod t .y cno of the Pollcsdng uathodso

1. ^ e :•e..-vval of sFeci .ic precursors :rcm the tobacco .

2. "as ad'iti:.n of cc~.in acr*rcunrs to t .':e tobacco vr.ica wiil


either reduce below $Cd° C . or elevate ahovo 900° C . tho
c't~: .: :• :cn a.AtLj.i3r4'L'Sre of tC ba cco .

0:e renoval of free sulf'ur from the surfaco of tr.e tobacco . •

',.It ia rocc=urr_'ed t :^at invooti .:tion3 on the re4uction of tho content of


t. ;.O~ ~:~dT:C:S" .C~3 in SS c .~ : ."9t t O E:..^.Sfl :A

Aa out +^ed F .-cviously, such an invostiCaticn would involve one or wora


of the following proceduros1

l. ".ho recovar of cpecifio precursar3 L7 r.,ot2:ods such aa


ext.-.ction of the tot.:.cco with a sui•,ablo solvent, o . Cpi
pentan o, diethyl et .her, ota. ( T: is ir.7catigation has
been cor;~letod L-i the csao of the rsntano E4tracticn of
C' ~'r :. ~ :.on: to :.~cco (~1) vi t: S4: or:. ; le result3 . )

2. ".',,;e i--.^eotiLat.cn o :t s ;at : 1-'o aCCiLives uh{ch vill alter


tr.n =h•st_cn tc r~rst•~•o of `:aL tlo n: tobacco vithoU4.
u.x ;ua e : f ect on tho f:.+vcr of tho

3. :%e irve~ti~at- :n of the of°ect o .° cc:,-plete rc=ovn]l o:'


t.oa of

o=ok.o ccr.dcnsato .
1.
•,a tacco on t.s .. c~it
c ....W~ .. . the

. v ~ .~ 4- t.o = onCBo
I'cc .^. w«. z L«O s NC. .1C L .^.CJcco t'r','r'c .'1, e .~ . ~ flu^r-cL."• .^• ..l
ttal.oy, :'1r 3ciah, etc ., Le incostintcd with rsoFoct to the Fo2,yc4-cLo r .ror: ~:.c
41

h;drccar, to n cc^tcat of t .",ci: c :.,bo to dete :-.- :.:.e wh_ch toc.:cco tJro, iP a .^.y, in
C' ?•+ L bler.d tobacco Ss tho Frir.oiral offe : •dor • :his gr aject viil a23o sorve to
r.r.ticipate t`o resi:l.t: of ox-por :.-snra vhich aro teina cor.duted b.-, .t4'yr.dor (116)
an the c:roinogenic activity of tbo =oke condcn .ato from ciiarottca fahr ic .ztod
from tt:e individ=l tobacco tyFes aoatiomod ebooo . "

,F,rl,.r Y

vcrk in th:a labc;•atc7 vi11 acn.^.ist cf the 3avcct3~'icn of tho

~e arccifio ccnyo .dc in tot :cco vhi•ch rsb procur3ora of


the pc7;, cy ciic arozatio .hydrocarbons in the ctmoke ccac:easata
(aoe (81)) .

2• :•e addi trvoa required for the altorr.ticn of t: o cc::;;,:s tioa


ter.; cratura o .° C`+'ZL blend tot.:cco .

The ±n:'2uonco of tMo free sulfur contont of tobacco cn the


pol,ycyclio aromtic hydroca.Mbon coLteat of the s : oke .

4• Tho polycyolio a:•cr.at3o hyr:rocarhon content of tho s :cYo


eo- :dennate frcc eiC--rettea :ah: ieatcd frcn different tot,:eco
.. ~t . • .J ~ . • . ~
t j ~C'J, e+ ..,~
. ..I'si .y . . s @ .... - ti . .~.3{: ^ .
r "C~G . .}.
is aov in progress in the caao of tr.e fluo-cured to*acco .)

:°Y:e ir.fl•,ier.co of C-iR on tho Folycyclio arc=tio hydrocarbon


ccnter.t of t.ho --oke cordenonto lrom WZN: TCa c3.Carottes•
project s nov Sn proEreas . )

:.n 1 . and 3 . t~r:ec» ::ecc.:-ar, .^aticrs, th3 r=c^al cf c ;~,eci=ic


Fr ccurscra ar.3/or si:lf= Ly solvont oxt~~actSon of tobacco ri,g» : bo a Fa tenta :.le
;mccd=e• . ;nveatigctions o::, the aolvont ori..-acticn of C• tC-L bler.d tobacco ravo
been cc©pleted vith favarable rOYulta and vill be reported in tt•.e r.eas
(F1) .

~.~.~..
' c
A1.1n FxCo .:Zl i

Xr . r . F:oovsr
. .,, :, . ._ .. : . ..a
~ .•
~ •XLir:ay
Dr. Alan °odZ=r.n
L^ : .^ s7 ( 2 ~.
1>SG
T'.,~ds £eptczber. <S, 1950
FroW r.zr.tscr #tt jb ~,
lp;rcredt IL%~VLC,~~u/ : ~
-J
r_r,~ ."~- .: ;-^y
-

i• A flo nymou$ , CalK!±noCf!'.".Z in C, i'i! - Rlt t o /': ri? -• Mu 1• i'fi.Y• J• 9 12L/v i ...y -
1••G,jj((•rr
• '

Ai1o~ •r'1 ."'.ALTl~,.rr~rr•r.


C3~rCtfO P,~.C^T SITlf~
ri..~.~.~r._,~r.~~ - .
F` • ~ L3`0
(1954) .
'~ !^ f+I ..n . .r;i1~• . .C A•i!.+a' L~ LI M4I
)
.'.w. .+ . ..w .. , Aw {!-
l~. .wwtw f.CT ~ .~
. .+ V .r . .
~'.~ . i

Ar.o^,7rous, C' .-r"•te ^rtr„r_`;' =8«c~norc~ns . TCE;CrC (D• C• ) i Mp LU

(195L ) .

!noruroi:a, Frcc+•_cration ^4' Zblacco :ar. rC:r-M . EM . REWS, Z1,, ??,42


(1956)•
Ano-mccts, `'r^vinp ^~-•~ .:••~+uro rn+_3o to AffAct Clhf~-ic:is . .CI . TO' ;
60 232

, ^ot ::cco . R. J .
•~n . ~ . . . ., _ .. . , . . r•-• - . ..
. ~ ` .

s• Pi.Cti'W'.'l^.a, W• '•s CGo~L, J• W . 9 T..^.71al! e~ . , G~e kC2"'9, C• C . ~~., N~ :f1eL10 .


G. :'evettv C . I»0aad Robirsca. A• 2f• . ~•''~,~,__ :::__ ,• .
tv F+ . F Jc?rcc~r*~+r~ . IV . P}ICC . °CY . SCC . { LC::B~~1) ~ ;s 343-3uC
(1937) .

9. ::.:':"7 , G ., a -4 Caoy, J. Li, 9 S(' ...- . . ..1`±,^C*1 r f f't " ~ct l 0 .^. 4r .°C"'r3 Fo? :=
t .~ ^~n .a . ..d . ~ ".3 1.
.~' Z: C.'7Q A f 1 x .. .. .~~.+
r~
.1•

I0• D..rry, G ., Cook, J, W. 9 ?oclevocd, G . A . . D . 9 F.evott, C• D• p F.iej:er, L,


aP.L Y.C^.-aUGy! r.• Tn~ Irrcluctlc'1 rf C'.nC •1" tvcUr 'FYdr"a :'2'cr9 . ?T7 .
FRC:• Rt,T . £CC . 31C-351 (1935)•
11. Loreab :=, I. , Jr
"}~. r."c~-rc{^^re~ic
. ra
r, o~ .roP ~, rtcn
0 rt 1 M o .r
pc~ ~ . Ca1'Cr~
44-43 (1:1,.1) .
.. .~_ .r . .1 . . . ~a . . .a .r _n a~.~, PI ... ...J .71
~r . . .. . . . . . ..~ .....! _ .I

c1
~ 607

1 ! ~~~ . ..~r . . .~.:~~..~.. . ......~.i.r....


/~
~ 1147
:r•

7:. Ior-a r.wi•.~, . ., a:.d =^'o cr ,rrr,ton ^i2


a!'1 .. ..~~


:...Jr,iiw~
. ~.. . Aa A

of „c=n+s F :• :n . .1 .V ;::'Cr.?, =I$ 379-3S2 (-9L?)•

51710 5038
43

4 ~d)
. s.
15. ZO:•BZl b lw, I ., and P . ~! t-. ..~ ~ . . . .1 . a . ~t ~.A t ..-.,. .. . _

c _ .. .•.. ..
; ..av of Crret ...r n " 41 ft t .Q, •' • J.
C f NCEIR , 30~-39 1947 .
16. slachoP!', F., and F.up, J. d., 7et., ~:ry.g~inn~of~a C.:rc~~ ~n±c A_ t
4n thA ^nrr;:ar+,io~ e£ C!:^Ioetnr^1 to Prorectoror.e..e C' ~JCF.•3 F. .F.ai.C~i,
.C~i ,ai
6 y 4C'3-4G'9 (1946) .
27. i c t to .^1C^,l, A . C. , and Ncrt, -C. C . # 7%l ~., .. .. v ~ ..,..,... ..a_ :. °.._° , .~
M =":_~
er.r? nlete he!c?• AM . J . C't'C-11.?, ?;?, 'TF1-WG (1934) .

18 . L•res2ov, Z., Aoac3,S.n, L., P.aar.useen, 0 ,, •«.3 lta'.=~


, A• 7 •,
.
rrC•J^~•{Of3
. . . . . .1 r . . : , .~. . .
n^A ~t . . .. ..~ .~q r . ..• .~ .. .R ^ . .w1 ...4 •n t . .. ^ . .nr.pw
~. .~ : ~ . ' •
t,• V . ~ V r .~ ...V j ..~ : r . . .'
. ~

jj~t
COOl~~p~.
19• Ca~•+:xsll J . A• !and"r 1 R• I. , a r-r.~er:Gr.
'^:o~ i '.Z
: . .~.i~r~...
yit~ e Fiyfi ?^Ci~c^G~~:
~r. rr.~S•~.r
of Cr.^.er.r,
'rr
.•'~~ I ::D.,
.
. ~ ..~ r r .

20. F., a!" AlVOTd , B. T. o


.t
! M
r:_r.er_ ' r« . ~ ,reoc: rresaated st c :
+' a . of~~ ~
: C1 ~8 :.C0p 1.. ..+zTiL..,
,°.,,^... . .3 .. .7L' . .: ~ C .. .02' f:.9 ~aP:. :.Cfa:LCSlt C$ . ,
:.bc . -6-•3i, 1955 . Abstr . in : 0iF.•1. E::G . .'.E+3, 14, 225 (1956) ; 'CI .
L:1 ^ r?, l9, 4 (1956) .

21 . "c :r_ i .^.s, P. T., Coo,rer, R . 1.., ri^'a L.^A8e7, R . J.,


.ccrl,r-r, r3 :1TCt•tA w'+ o!n • `R i : • J• , IS. 2~jCr3 0 L ( .L9 r!• ) . .

, 22 . J• •1•, Pr^ .~r^+t .. .. r.f C:.•'• . .. ..


: t ~... ~. . .!• ! .7 .iw Cnw:. .+ .. .~• P~1^
~i . N•

::Cv" . C : `•^l:.A C.'.IiCIEM V( :~.~~'TD1, ~a 373-3 0 (1933 ) .

23• C L'OL, J• Wpt flk or3 g`'T'7 I :!;d :?


.o l:-ri ^_a Z p:"o^^rtio m Of th: e " rR l ;^.C^^': :O
^
s lai t .^.21et^!? • ~:~ :GL .~i • r • v1 J : ::Ii, . - u• li*~. .r.: ". .vF ~..: :. CK3 ., ~ i.i -+c.SJ (1, 139) .

24. Cooror, R. L., ::ret%r oP ±hs L :,^- iFAlrt!n o oTaGGo . ~Zi. ~.'rI?-^.
Ca :,C~ C+?~PA ICRi A~^ :.

25 . Coc-cr, a• l» p
13:4••i .'65.

CiC.Ci, pert :~• lw, ~'i ~. .~


:~
. a'' r nn
a. . ~+ l=" T, :~o, 573-579 t 1~j ;4 3 .
-cc-» r, =. . ..• . ~ , v 't•tcrt,
~ . A . ..
and U=~re,;;,
,~re " . ,i .,
-
w:^•~ro tn Ci~«nttA ~~c•~s •e Car.tr~r!_ut±o_tLc± t! :o mrr.r. E:.I : . J•
,~... . ,. . ....~?f ?, ,~~ 5 (1955) .
. • .
23. ~ .
- . .~
.. .
o 7 •l .. .i . .w
and
M .w. r...w., .. .VJ
L rai . .
c a
.N
.. ••~T rs • 117i-,1-MR .

51710 5039
( Ccnt' d)

29 . Ccop@1', Re L. j w,.d Und .^.cy , ~~C• , - '- -

: .«r~ .
•~:.i, V
., cr*cl! c
30. Coo;r.er, R . L ., and Lir.dcey, A ..^J., 1 .1 .."+~~,~rr~•~ro '+r :'. e!!'Par rfl f] ~
:r ..+n .4- .. /!f .. ..«nfa -~ r«^~ .1 . {•i+•'~vt~it ~ 3~.~i-3C9 / 1~.75J) .
~'e+f~rnf~^ .r7 . rnSi .

.. . " ~' "1 ~ r ..,. ..~„ ro


.'~ ► 0;' 1 . u . , ~ :. . d . , .~ " 214m
i. . L~ . and 0
.
~nn, .Mr+r+wr~ ~ . ~rRr`~rf ~aC ~• .r+4= . Ct «a~: . ~. .v~ .:.r .~ ~C~ 1 :+

d TCt,my , G . rpoo . pr C. coT1Ll.' d t o


3 ~ . r.!@J~ ~ • aw~ .' 17 . ~^ *~~~irwwn~~

, _r"•o;lr.o3.d-1 io~,.cco Ccw~.~, Wited b7


the ? eoGarch reP. .rt4cnt, lR. J.
cdA ., 1' . 1 :ar . R. .i . P.c?noids roaearca I11= .::7 i=F:'.let

,~ ., ~o v
f, .
3~ . uSCze~ , v. P . . I1' i•T te cO2TW' u 1cJt :^vn . ~~' :'~ ~, .7

.^'~~ ~^r^• ^
LV . +d
ro~ , n ot _ ,. ~ . .l~r,C~1 ~~
~. 7 tn4c' s-b iy!T= ' `
f..~:~!/!t~r . ^r ;'^'='"
. . ~~
1 ►Cii~ r,
. .Vr . .

-50 (1955) .
f ~ I`+• . . ..~^ ..!.aO p
.l . . .7
of.J ~,i~ if..9 :a1~If'4'•
/7• :
. . p a ::v K . L:
t~.~ •~ ~.rr.a•T .... .T~
. . 2 ..:--~-
• :.~'..; ~ • lF : ~ 1+~.%.~.. .
.~ rs~
0
36. ^oll R . ar.d F. . A . L . T+cc•a~ !n "el~•ticn t o
~. ~'-~T~nn
..~.~ ..:~~ rnr~i:~t =r l~~
'
;+wi 2"p R E`.TO'.'~ . Lgl To t`.R
.'.L . i.# ~~ (Z )$
~ t^ ~• t
.1 . ..-...~5
. a !S+Arn ,+en»
. { and :'c l-_-a rl, D . ~ ; ^ --
w. s't!rRl y' "~!LI!~ p L'C1
37 . ^Z'L :C :.:-8?, ..~F.~. -
t~ w ;~~r
•r~ r P
`1-360
~
~9 (1955) . •
iLA ~wC nnr,.,qwai7 .-n~ `
► n ~P~•~nn~ .~
is . •?. , ~.nd l .ol.^i ti
..~ R
~
lw
. rw
..: • -- -
.., ..A n;.r; -/ 94lr~~~) •
• .~ .i•;vri
s.. t ~ 1~9Cw'4 \

39. ~Ci ~ ., o.r.cl :toinor,~ P.


F . L., Co :y° --- = ^:
~ . , ••.~^'3
~.~.~~
,' ^s t~C nt 4 nr, , o C; . Qm "l'f 3" ,r.rZSLtc!!t +0
b33-l.4.? (1949 ) .

40. :3cscr, L. F.r


. 2nd : cition, p . ,'41.,
~• , •• • w ~ • .•^~ . fy r .rt+~l ~Q/
: :Cti :`n . ~ . J J . C . r Ci,t . .. . .C 1+E~

41 . ocel ~• A . and `•i C"1r.7 ~ . p V .L4~wS vifl~t rr P+Cti Ci


•,r..

Cc=;ci~:d3,' Cui~ve 195, Nev~Yor?t, No ? . s J. 'A' :lsr/ and Scra, Ir.c. , 1>5+.
w { ~,., n ~„w. ~; r4A
C" 21 . .i. .v ., vw is /GG .

tJ1

L~/ • • ..~ .w . , V W . 8 hI / • ~
~ .1

.G:. . Tu+3 . , CL..-vo 472.

1r6 . T. .' :#m . p r ..""~0 1+ W .


45

~i w '*7 ~ 1~Zt. I C:)

47. IbiB. , Cr."Vo 55L .

lw°. Ibid ., Curvo 567.

49 . Ihid., Curvo 569 .


r, "^^..,
,,, ., • lm p uo LT`:S'.T., . C ., ~~`^r awthw+L.nwr~n~++ .pntn,
b
50 . Cr .~..^ , C. VC3

~ .. .
., 5 «,.,
(2 . •)
+ .

51. Ccw. .{ w ....a . .wn ^'


t O. p
r .".(3,.~..~. 'S
0 .. m ^Ci~a31 .
ur:Tr}..~..
ir
o i~n Gif:A.
.r...~ .iri~_
:A. f
(hi5:) .
A

53. Psart.reL, J. L ., ^''nzwoy of Cc~oi :ndn '.;hich Pavo Econ ^ostcd for
~ w .~r+ 4 i :.LJ," 2.wd ai:,+
/~ + .A+wA .. .. w
A
N .~ Y.- . . V' ;~ ~r .4.r1. . . .~C. ::~ ..~a~..ti:C., . .~...., ~~.:.
V r• ~
.e
['.Ca1ia:
Ca1ia: : QC Y -~VGi , 1~i 5 1 •

.. . . ci r••,
. . . ,' 7
55. Z. L. p :,jo 7, .^. .r^-~.tion
.. cf C:;
:r rur `z ..w,.c h• ...r
P? :i'. ..~ . .,"
. ~'C : .~ , ., ~33-,,~~0 (1'>~G) . -

56. :.O ::r.::. =7, :.• iA , ''Yrnnji-


^
A
ow
nl n ~ FTM :~.~
.~~.~.. . ;..._:
..~.. : . .Lr~•.~.~r.. : ::I ~: .
~ 2~D . J., '~~ . ( .~), 1•L . .
57• iref:Sy :wy, :.• 1..,
~~r, t ! / . .. .r .
Ir•~

58 . (1c {V .G.:.Mf, 7 . MA' and \ W. .i V o Y, Y , n:Z =


i l w ~~' f rld :/1 Arj C,^~w, ~~
*'*1 F•R'O~Q^~9L3 F!`?'~t1s1` ~~. ~. .! .~~i.̀^.~~')li . .7 . : r~'l~i . «•iai ; .! ~~ .
607-632 (11028) .
.nwI~t ..y Oi~
59 . rc :t.^.kv .1 . : ., `wineP:rt, J . v ., !'.5. ."~ ~'abEr, D ., St-e~(~?
• ~ «~:~.. .~ ~
~.. ..A .. •'ww(~(1= .7rf . .C . ~.'+ 1A
o t l ~~w t r uL b.j.0

.i+.'i {r :: T• :r.• _-1 I,QQ b ; .:C of {.~`:e fLL . .i : i bMY C : --i eaa f Oc i Y ty , C1 n C Ln«.ati ,

60• lCw1~JCey.'
,.- . .. ~/
:-• ' ww
d V LL.wr
!~w .
: :^7 ..e1 2' .~.{M~'.1• 's I
C?~ R•. .ri li+ CT C ~~!

02:5:-<60 (1953) .
~~ ~~ ., I~ ~',1 "~,
V. . . ~r..i. J r~J ..^C!AqN!1
.wL ..
:7 .i :',= .^.=~ * .•,. : ~C .
~ .~
,F-~
-1
FCT-4 Y , .. Z i-+

62 . L::.e . D., a .^d Sv!, A . C ., '"r^


:+{''^
- - . (~ii. . .Ci ..: , ~
~ 1~.
W+~wiv j~
all

?=T--L?rG^`"'Kt (Ccr.tld)
T r .. .twC'
r rna+.e
63 . . .~i1 ~«•~ . • D ~• r-
C :..~l
Nr raZ .• .,t.n
. , Cnrt
, •"~«~n/f
t- t~ : :a.a~l
'~ w+
prt.zo ` ~a :~At
.a.Cd wC~t
~~
. e .
:',;et!.^.g of . the ~tir.ericaa Ct:ez.3ca1 : ociotyt- r-ir`w' .~Cj•~s Cct
21, 1954 . • -
.;1i / . T'/.•.tC. . .'.-r•r ~;~iL~'~ .'l>.
~~ r .`~^ Mwr1 T~!. ." ^n aJe.rt D~• /N'tr
l.+:a ., ... .. .. . .+ .r. :~ ./ .I ~ . • ~ J
t . ,~~ .S . .. t . . . . . . . • .« i

t'i• t -^n{ .n l 4 CO1


..

....N 14% .a^ n . (G), ?.? :-~.13 t17 :G)•

U V• :: : :• l. G ~.~d : vC' j:, . .i p a :.`~


.. r.E'ri"rilrt~~ . o
.t,~ t,ri"l~ t,

.. ..+ .{ ~_. . /, ~r«"tn± AM • : .'D • a .r. : 336-332


.. . ... .~~-.~

.^~ tces," L~rc~ce•^..,,rc~e•


67 . Licki:ti ='•,''tt•t olorie W- ;! 'r crIn;1.a:2o des L ;:r.eera
^ .• ..w -4 . . . : te ~.
~^:rcr•f, 1?53 .
C' :. ..
...G.t .rl •r ..p I` . . ...ai~.
..
' . /e.rn tn., .rt .,{t~r .t Of ~O~'*f:CD r
:~• Ni, . .n . . . . • .. `
. . . ; • . . t
• rFV - n~J . .
~ . .+ . .d . . . . ..~~ n~~.. w: .L.V :,~'. . i C
.~ivc ..r2~~ {~ir

19 55 . nt3~. . .•n: 6 9
r ::a;rt.~l cr.~s3 t a , a3 n. • «r r •w ~ {
uZ~'•a! " Fn~
^ (1 55 ~

• ti.rnwlwn'1f11 C~r".f~ttniit.^ CP n, .'.C=~n t'' ^,~«9


69 `~• l t?.S`.d KU C• n
~ O.
.f•~i~fLl•~ ;i~ .trt!!n n T' ~:fX?^ . ^t'. (i• :~ CC• : Ya : : ., rI.'L .
_

~ ^ ,.
:(1942)•
5 .44 ~

Ci . . . .Nn .!n r ..C t :C'• m 63


t•-
y Ct q37. y (1 .0) • 91
Jc :c3, , .. .
71 .~
:''cr.. C •~r:o.1,
~ ^
^ . .,^
. art:
P:. . ~ .
Go:cc :,C , t ..n
. . .•.{,^
• 'nw L.wnl 'Iw •1+A = t SD Ie;^7 D~ C',rA ; ^~ .'1 of + 1 jnl' . .V .:
_

.
¢ ...r. ;.l .. .. i7 .-• . ; ,+D C^!~ C~'?CP^1 rJ=
7 2 . ~ , IllsA
C• ., 'aAd zcrtor, :'~• Cf . p ` ~ - ,~. .
t
73%• ~ ~Z .5Q) .
f '` e te,.. 11 .`. : . ._ t .'. ..;
:,~~
t~ A '.11 L'
. .r - .__ t rr.d rAe
.~Iw•• r~> • C• ~ \

73 . . .~ :•
'/Crtw"•1 :•Ctw"1 {
n

I7)
.7r• !7, :: :i r :Ca .'4a:•,
i4•

.-?, 57,"5 {1033')) .


^ .; .. ~ ~w
1.• L . --
I S• . . . . ., ~. ..G •r. ~. , • t . .^ n.
_,+Mci'L^~~,«^^e• J . A :'. .

n6, '~C .
'_sIAI~ 7•2- .•

..wA !:1n~•i .. . . .w
.w . .{Jt~ .•a11w. •• :l•r.w{ . .. .~ .•
~AF!.!i'mwr!!fnett{l
77. . : :,'i
~i
..sw
. t. . . P. /~ ., . '~ {.. . yr, ~t .. .. I `
t- Il..• ~ Cra t. ;'c~ . C
+T .~
..J OS
.~ VV
C'
.~M•V

~. :~ahli~ ;.e:~, 1948 .


Che .~~t:~J," 3 :o~r York, '7. Y .~ I~tzrccic~cc
IMV .,
47

-T"iTCG'nFrT (Cont'd)
.,~. . . .
.. .. . . ....^ .~w,., ..
78 . 3C5-313 .n
k :9 :4 .

79. P.odg=a, Ag g Zhia P.eportt RB:?, "36p No . 9.


80. °ode=, A . # Poodatu£fs . Spccial P.eporto 1156 ~
~ov. 19.

Gr . ''Oa :..ir A• ~~'~ snnlwnle~ nr ~, • r " -wAtt$ T 7 • q''! 'fj


of •ri :'I'i. C 3 n'n d ' ?V` a 1c n o • FDi7y :'.(j sc Jiti.i . . :opo : *
i. to bo .

tjd .Y

82. fiof°o, A . 'R•..q ; 1 a rtz?~io !'o",3c _ j,!„_nc,. ECL. I'JC: . :~ . EtP.


~_...r, . .,~ ., ]~ .C
•, ,,,i, ,

.~~ , . ',',
, rn.~ . . . :13
. .:t~ ;~r a. DL'T:. .~!'.•
. •!'
L3 • r.of:o1 A . rS . 1 i
A~-
.~i.~i.. . :r ..~i
1269•=71 (1937)0
...,,,3
Pof :o, AA lcs 111nLi!r^.r .n :) ,: 3vnrcf,a 7r

8 3• AoPfo1 A• r .1 rr-- c,off eseg• -1 CL . I` : ' T• .'TU . ~ .~ .


. . ~ _I1I_w ~ ..Lr.. .~ n , f

.. : . .rY . C . . .wY. .~ ~ ll.Yll~ . ~~%i7/j v ..~ ..•~ . . . .. . . . .1 2L/!

86. ^otfol A. A . q e a llcer r.P Z :?o -c?Rl s I,;1,i±m .; co1


ECL . 7McT . M- . .ir{P . ::::TuT . C .% ::CLRI I§s 1-38, (1939) .

8'7 . Rotfol A . F . , ;~~1{ "i-R;+r,P.n ~?^4 ` 3ch ru±•t~rt:nv, rit


~ ~F,itrnrr.-.?iorton rotten, L•ULL . AC: CC . 'r?1! tX . L• TLDr-. CP% ;:C-'l'R1 ;, a~ 55u
(19~9) .
: ~nrPo ~ :. ~q~.f!Jwpr .,~ . .f .. ^ :=^ .q R~ lw?• Lf' :~• /~
G7K . L~ .. , s .
! 1
~ 1322-13Ed (1939 ) s 91,19? (1939 ) .

V7 . rr.^t!1 -at ;J 'np1,j,,,lrt Z.


fiP. "'FGP.: CR ., ~ 5~~-5y7 (1y39) .
~,^ i~..r .r7 . .! .w? h,..r Tf`!1 .
90 . Roffo, A . 1T .1 C~^w lrArnn+.~ .+ E^L.
,~? "b6lwc)3 (1 ;4C) f CIE ::..y.~AL :,i .p lrj 37C92 (1941) .
9+ . PAf .o~oo~ .1 . :-: .1~• ~ .G+i~ . : . . ._ . lr_~i . . . .-t f'. . ., . . .
^1~3
ltr' r~lny.i.~ ! i . ... .. ..ne . .J . .. ..
._
.~r r1(•~1 .
. .~~

tcrol . L-CL . TNVT . :::~..


,~ 'r:~ :'0 . C,'. ...• C.?f a'- 927-943 (1941) f
A L~ ~~ "^ 8 (1942) .

..t ..w =. l A' (". .. .. .~^i ~ .n w ..Z.


92s rof^DI i.
. S: * 1 (..';1'~rY~:;,"',_

~I' L,
;F~., 2133 (191.2) . ~ ~
m
. .•w . .
• . .~i . . • . . ` . . . . .. , .v . . . .~~ ..• :~ ...•
N
G~A I ~~ • .. ~ 1Q/ `
~ I•.7~ 7~ 1~':. 5
.~)j .1 ::.rJ1 .1 ~ +4h (i ;/ n42 ~

aP: io: to 1940, 3,LL•r.on..~ryron.a was !c:ovn as 1 .2.cenztrvrane .


48

PZzLTM.--f .`7PY (Cor.ttd) ,



94. ::o::o, .~• It.,
, ^ • JN .~ n ^ 3„n n .y w .'1LwL . .. nA '~ r • ~r1~ - ~ -rt•.•
~ ~~.
:,~~
n ! ~ '' :' 5 . .~ . t_ .`t ) . iu:i.
E:LP•
:L L . .lvri• i .•.'i1CrG ., .~i', •
P•,p .. (1,~j .
. ~1-5VM
.G~jA G~j (~iALX• ALrT.p .f.:,

63355 (19b3) .
95. ~ '~ 1
.3C: •CSd.S~~~• L . n CJ11f .. .
t ~~ ..~~...
4 t A•
C•
s•
w .^a
. ... .. C Ql.r
'"..P1rii3
.. T J•
t r tTat R,. n.r+~C
. a 1• r : "•D
C :..
.^t.
- • v . :~. . .L. (.
.•e.n
, . ~ .,_ . . . ~_
~.~ . . .. ..i . ~l ..w ' .w
.. C~ .• .f
. t j ~
•~.~..~ "_. ._wwn~o
p,
~.. .
t~+ -
'= -!
.--
~

1; 37-1252 t1953)•
T .t!+.~P~U_1'~~9~t~~ tF3?!VCrFT~t.n~7 . Z•
96. Z ., .^^w.a. ~ :. . ,
X?Zi;:~AFCR : C:t•, 261..2E9 (19G3) .~

9 7 . rC.^.2Y96, P• p :!i«:cr ,, 1.. 2 °' . :`dq C . . P•


:. . p ..+.^ p Zl.^.(: Dolgo:+ y :.• . # GY:1 .^.
Cs^c^M• CA2.CLR
F.L ~' ;:A rCIi, 10, 49-55 (1950) .

9F• : c:urcb, C•, asd Wlnter3toia, A,,


Lti . .,..~
. . ^ .t 1
.i •..-ri
. Y«~a~
3• 7•r!••P'?Hr',p^•`r^St•~
.+. .. «~ . v . .L . . .~7 ~~ lV - 7~G (1935?•

.Zt.A..A
99• eC^
'.
~I ., a ~p~p :'•tC f-7C a i 9 r :r, . . 7iP ;lP?~i

1C(:. :otal,a, K40 u,"ot::a, i;., aad S:olsti : P ., A ,_:,;.=_.r:ico_, clcr4.cal1-r * .


Wi^ed f'rcuo of Tarir•rr^r.ctina rc'ocarci•^.orcniol Arcnw for

101 . `1•,ubik, P. i{n~+ c^ tr+A ~c-6t!rQ P~a~e ih the Star-++a of Ccr~'r .o-
• ~ r... .r..wrr~rr~:rY. - ~
. .n .^. .~
~

.\
c+c r ~G{o
.~
•... .~.~/~ir. V ! C~.1 • ri:n . !i
!:w, . •~
. rn `^ .. ., • C
• • .'.L~

1%-./ (3')/w)•

i C1G.• r`Z ~.. ...;~:•w-.:.:


FtaL^or, P• i. ! i:.l'.r Cii'~~r IA 1! :•,

Z, 242 7-2:4 (1953)•

2030 ::toi n er, P• E ., and Fa2Y, A . L ., ;u R AttcrL er•d Ir. t 11 it3o n. r !'!'acte oF
~'~AC~~
~ . '~r~
~ ''~rC C ••wwlw .. ..~«j~.
t ~.'~
C1••+•K'r•,rn . s.._.._. . .. . •_ --2C=•Ath^lci :ola^.thrrr.©. , : .,C
c^^9-and
RT'=TA ::~"~.. 11, 50-G3 (1951) •
. ' ..'^ . . . .. _ _ :.
Ivl.• =+.Ai.^.L
.L' :, :. Z . v C La C lO o ~'
: .• # a .'. CC» v
«:.Y+ ' r• • •
.,^.t•f`'~lpntmreli 'crnl^< .,~C . ..~ '=tv~
._. . ~.. . . .f . ^ ~ y
~ ~ • . .. :. :. .~...~~'r"Ll ' ••.. ..~ .•. .
• . ... . ., i~~ .•. •

...~ ,,, . .cn cr .:A .-~ Cc,. ... .,~_


1C5. °ti ;or t, J . u•, ar.d ^.,o: t, C• C ., ~ .. ...~..., .~ r ,`+
Y
.~~
V •J ~ ~

i J i. (1939)o
• VC~V~
~V~

.IVV•
:~^_y r
./~ .v~ rVI
C f A ..wnlwn~.A
.. .^lr C .wLrt n nnneJ 1 n ^t'Y -n n
4
.5 .1: ::A ::' 46 • B.`l :•
li s L+1 , 10,28 .

51710 5044
49

(Cor.ted)

107. Vold3t . :a, A., .-


,C~ n l•
1. ~

.r .to
F„r .l Fr . ~ ;y, i'ri :s 1 .1 : 246-247 (1939) .

1C8 . ttc3oink # '-f. Fs o r; voor kt! M. .~l.1^,~r.C, r fC,-%re:~{f~


fnr tro ~c+velc+n~ .+~t oP ~L~r~) . a~..DE~iL i W: a:~itt . ~ G£:.M l K, ~
-,~3732-3747 (1948) .
1 ..9 . ' ;lit8z'=mn,: ;,, ~T^rT'+!'C .^t~ iorz of Ca :~c,l r.c-a •_~ n
}3 .in C i 1 C'. t:C 2 CL':G •~
P j 375•3ES
Z ( 293b) ; aLo ci rcd t7 Voldct.ra,
11. ceo (1C7) .

110. '.'stson, W . 1.9 and Conte, A. J, ;'_,rg_,Mn y -Ayn d Lu^R Car.cor., C.'t7CER,
?j 2G5-249 (19 ;L) .
111 . W;.Loon, :J. L, aad Cccto, A . J., ~ .c~r a: r~;,fr y+rn, AN:, J,
:V~C~t, f4, ~,47«45b (1955) . ,~._- .
312 . :.edCe•.ocd, F,, erc .' Coopcr, R . L,, ;K^n T?~t~ctio~ or,~ rMn ;--i_-~_,_t.ion
of ~ c .d ..^•r_, . .....,..1~:..;•
7 ..w n r
~
in rc?u
wi ., ..r j a1 ~'~ w~ nta a *d
I'I'

! :+aLYCT, Z 17G-173 (1953)•

C4 !1f:C:2' ..^nd Lw
o .P C~U ~ 9~*. .^ .^,fl'.3 i n
Fc2.strd Fc+od, tIA :'':E, " 9 64 (1939) .

114 . '•3r1Fht, G . F .o and `.,lync'er, E . L., C1 .rwrnjto 1`'


- ---- --=;r,
F^~C . A:l . AS;.CC . Ct, .;4M '::,','MF.C:~ip ? (1), 55 (1955) .
115. W: i,,r::t, C . Fp p and 'iyujer, E . L., a`u-~+hor Mrric^1 ,°t.•,:.ASna_ e*
. -`t ~.:
r: :v C• A .• j'•:r.~ i . C~•
(2)# 159 (195b)
.der, Z. L ., .26ekyr
Speech proacntod at t}:o ~ym-rooi•.r ca Tot .:cco coruluctcd bj tl:Q
Kot:ropolitan Long Ialand ~-utzoction of tho ft-mrican Croc .ic:1
Scciety, Erookl?n, 9. Y., Feb . 24i =6.

117 . i:qndor, E. L., and Co .i'iold, J,, ..n .+


..~...._. ....n. . L, . t
o P_ ~•~+n
tr _n !~
L1._ ..ic
~ i_..
n~ . .~ .
~~ Y' E'. .'G . J . %'"=D
._. ., 2l...Ps l.41-l+1.L (1,~ ~

• 'i j t:vP. :' , E. L . A rA ~ I' • A , p *rAl" .^.f!f!0 • rr }11• 5 r n a :1 •',1 I n^S ! r !2


, ^
C
..
" L
Cates . J . AIX . ~::.~ . .l: scc ., 32~33b ~(1950) .

119 . „~'
f
.....0 .~w ... L., C ..,...._.,
.,-, 4 .q1w .w
,.. Ap p a.r.d Croni.r:ge
: w
. s .t, i a e.t..l
_.rl•,_tr,r of ^srair.c^a v3th_ .Cir_rott., Ta.. . CArjCc'»i
S55-364 (1953)0

i
'T;•LT(C%C'?"rr"'m, . (Co.^.tld)

120, i ?yndor , E. 1.9 B.. A . , ar.fi Cro : ;^ ,,:or, A ., :.w


ndne- .
tZr`r1 A~ ~:^~'C~^f~"'1 ~J{i`tii r ~="':2'rl+t !^. w• i T . Te+Sa,t ,,rr 'w,~
'AL't!'A '~ .. .
. -T::.,
I C t.~r.P.
irs . v. .:.c..r .~Cii,
. 445-~44 : (1955) .
I?1.. Wyr.dor, E . 1.., a `I« .i vrI' ii ght, Ci. P., iftl~in!~ Af1 * ! "n
Carc ir.^ mm z in Ci r cra ttc Thr. PROC . AM . AC::CC . C:::::.::
•--_-----
(2), 159 (1956) .

1
July 25, 1962

Mr . Kenneth H . Hoover :

August 3, 1962 is the deadline for submission of


abstracts of papers to be presented at the 16th Tobacco Chemists'
Research Conference in Richmond, Virginia, September 26-28, 1962 .

May we please have your approval to present the paper


entitled "The Composition of Cigarette Smoke . XI . Heterocyclic
Nitrogen Compounds from Turkish Tobacco Smoke" by A . Rodgman and
L . C . Cook at this meeting, and may we submit the manuscript to
TOBACCO SCIENCE for publication? If approved, only the abstract
has to be submitted at this time for the conference . The talk
would be based on the attached manuscript .

The findings presented in this manuscript have been


described in RDR, 1962, No . 14 . The discussion given in this RDR
• of the testing of indoles and carbazoles for carcinogenic activity
has, of course, been deleted from the manuscript even though all
of these tests gave negative results . The review of other hetero-
cyclic nitrogen compounds identified in tobacco smoke, e .g .,
9H-pyrido[3,4-b]indole (norharmane), 1-methyl-9H-pyrido[3,4-b]
indole (harmane) dibenz[a,h]acridine (1,2,5,6-dbenzacridine,
dibenz[a,i]acridine (1,2,7,8-dibenzacridine), and 7H-dibenz[c .g]
carbazole(3,4,5,6-dibenzcarbazole) was'omitted from our manuscript
because of the reported carcinogenicity of the latter three compounds
(cf . RDR, 1962, No . 14) .

Alan Ro n

AR :has

Attachment ~_j
~
B
Ln
m
~
~
~ Author : Alan Rodgman
Division : Chemical Research Notebook pages : non
RPI1, 1961, No. . IV Previous Reports :
RDiyl, 19j4, No . 31
RD,J", 19j5, No . 13
RDR, 1956, No . 10
RDR, 1959, No . 1
RDM , 21962, No . ~_.
N o . o f pabe ;: : . . :

THL SinOI' .I1TG AND...~


HEALTH PROBLEM --
.,,,., ..,._ . _

A CRITICAL AND OBJECTIVE APPRAISAL OF


The cigarette smoke-~h alTf7'problem is discussed in detail,
and it is related to the potential iinvolvement of the members of
the Company's Research Department .•Arguments and conclusions by
those claiming cigarette smoke as a health higrareggn4gdl as
counter-arguments and conclusions by those not in'~accord with
such views . The weight of the arguments and counter&arguments
is discussed in some detail . An attempt has been made to present
the argu :nents and conclusions as objectively as possible . Based
• on theAarguments and conclusions .,lazzaafteft several recommendations
are made .
Thii~w .em.t report is an extension of a companion memorandum
(7?) which presented my position as briefly and as concisely as Ln
N
possible . The two memoranda have identical schematic organizations . _J
F,
m
As mentioned before (77), if requested, a thorough, fully documented
Ln
exposition of the ideas will be prepared . m
~
OD

MEMORANDUM
Although the majDr part of the sales of this Company consists
of cigarettes, what the Company sells is cigarette smoke . To maintain
our first-place position a,ainst any eventual ity, we should be first
in :3csu :.si vio :l of 1 .'"ifo=mati on concerning the co! :?no-,z_L ;1. n
~ v-l 4n~..

ef=ects of cisareLte smoke .


. larin ~ t+1r~, pt;3t ~ :J o d °Ca~ .`2 : , c :. ;~are ~ :@ 5'!Or:° 11Ei s b CC :: ~ :" e. tc::'` !r r~
~: f a i,^ :a of studi es relating it to ill-health and par.ticular=y to
_u :' : carc := ."_'f2 e :Aa~',t;_ 1 vy of v :?8? Ztud i Bs ? ::~:=i i1rFiLr? c i

• , ,
J :.~i_ .? •. .1^ o~. G a`~ e all;h v l ei -iPoi lali .
-2-
~ . The Evidence - Pro and Con
~~ The cigarette smoke-lung cancer problem has been investiga ted
epidemiologically, pathologically, biologically, and chemically .
Each discipline has yielded pertinent information . The -rpidemiological
studies have also suggested a relationship between cigarette smoking
and other diseases .

a . Epidemiological Data_
It has been shown in thirty retrospective (27*, 38, 10,4, 118)
and in four prospective statistical studies (15, 27*) that the
1incidence of ]lung cancer is low in nonsmokers, proportional to
ci arette consumption, greater in ci .garette smokers than in cigar
or in pipesinokers (who show a higher incidence of oral cancer
than do cigarette smokers), greater in cigarette smokers who
inhale than in those who do not inhale, greater in cigarette
smokers continuing the habit than in ex-cigarette smokers, and
comparable in male and female cigarette smokers when smoking
duration, amount, and tumor type are considered (39, 1'•7) .
1'hese "findirigs'-indicate that cigarette'.smck3.pg inci•eases~:the . .sisk
of, .d'eve] :oping lung cancer .- Many-authorities : be~ieve •the . .relation-
ship to be one of cause-and-effect .
Contradictory data have been provided by statisticaL studies
which suggest that smoking habits (and possibly lung cancer) are
linked to a constitutional factor . The twin studies of Friberg et
al ., (36), Fisher (34, 3j), and Raaschou-Nielsen (65) indicatedd
a greater concordance of smoking habits between identical twins
than between fraternal twins . These studies, however, fall in the

*This author reviews 27 different retrospective studies


by Breslow,et al ., Denoix and Schwartz, Doll and Hill,
Haenszel et al .,' Koulumies, Levin et al ., Lombard
et =:1 . , McCor.nel= e t al . , ~,a11 : Gnd eortzr, ;:u11er,
= Otter and Tuli ;', S .ad4 :'JS ky at al ., Orhzirer and Sch on=nger,
./:3chrer, et ai ., :ci :'.VaL'tZ e ~ al . , ..~.tl7cks, o t ot;i.$ and CG .a~vc?_' ,

:assins., .atSOn cind Conte, ~,rync;er


' and v0=` ;:fir'1 1, '.,r~t,4er
• and
,_ .. ..a :-;, , a;;-nher and _Qmor. .
• * : hi8 :~Ut :'lOr r? /? e .JS the w rQS p ectltT2 Stie8 ~ ;~ 17oi1 and ?:i 11,

~ a 1+'K Horn, and Do r:: .


i

-3-
same category as some retrospective lung cancer-smoking
studies, i .e ., careful but limited . The Seventh Day Adventist
study of Wynder et al . (120) provides serious argument for
the constitutional hypothesis . Other contradi'ctory data were
provided by th,i immigration (and also retrospective) studies
of Eastcott 431~ in New Zealand and Dean (28, 29) in South
Africa . These studies compared national averages of cigarette
consumption with lung cancer mortality data for immigrants and
nonimmigrants . I .e ., in the lung cancer victims the actual
smoking habits of immigrants to Ne ealand and New Zealand-born
persons were not known ; similarly or the South African study .
To validate his findings, Dean (29) obtained smoking data .on
his sample by questionnaires addressed to the next of kin, a
practice decried in several of the retrospective lung cancer-
s ;.,oking studies . Nevettheless, the results of these studies. ~,
. `c,r..d
(28, 29, 31) can account for only a saall fraction of the ;lung `~^^
cancer incidence observed between smokers and nonsmo%ers .
The statistical data from the lung caacer-sToking .studies
are almost universally acc pted . The majority of scientists accept
these data as indicative of degree of association or a
cause-and-effect relationship between lung cancer and smoking .
Controversy is provided by Fis4er (34, 35), Berkson (14), Little
(j3A), Greene (37), and others . More will be said about their
comments in a subsequent section .
After more than ten years of argument oen ~D o methodology,
sampling bias, retrospective vs . prospective study, inhalation vs .
noninhalation, real vs . apparent increase in lung cancer incidence,
short butt-length vs . long-butt length, etc ., criticism of these
studies has been reduced to the dictum A statistical study cannot Ln
r iv. ~ r
orove a cause-2 ::d-e.f~nc~ ~ ea_tionshio be i.v ..~. e?n s~wo ~a C+- .-
LOr.tJ. N
J
m
b. a_ho_ogicRl_,ata m
Ln
he fo_lowing observ ;tions have been made : m
(a) Ci s FlrettP, s"1ciCeT_`s' lungs showprofound celli; l ar chc Isxe s
( s .~~.; a '"'" . ;sia , '^ ~
meLav== `" .~asl-ce= p Pr:~_1 a :' i~.
~ ^, ;? . . .. ~=•~'
~ :vrr
~ .us :1°"

atV 'p : .as ) w :' :s c :. Gre pr o7o~"`ul.~7nal t0 ci ~are ' te consu"'i~ ~1 .on
(c ; , ; ::ese c : .ang e s :Fcre .z,e i1~W_rrs :ive? -- _ .n t:,e _-
or proportion to the time inter- ;a1
-': -
between cessation of smoking and death (5), and similar
changes developrin= the? lungs of mice exposed to ci ;;arette
smoke (50-52) .
(b) Fluorescent constituents of cigarette smoke are absorbed
into respiratory tract cells of ,::an and experimental
animals (59, 60) . However, fluorescence and carcinogenicity
are not synonymous (17) . Carcinogenic polycyclic hydrocarbon
(benzoCalpyrene, dibenz [a,h3 anthracene) and noncarcinogenic
polycyclic hydrocarbons (anthracene, phenanthrene) are
highly fluorescent ; carcinogens like urethane, p-benzo-
quirione, and P-naphthylamine exhibit little or no fluores-
cence .
(c) 'rlhole cigarette smoke (46) and some of its constituents
(phenols, fatty acids) (33, 119) cause ciliary paralysis .
(d) Cigarette smoke collects at cilia-free areasnand at areas
of paralyzed cilia (33, 41) .
Contradictory evidence indicates the following :
(a) The above-described cellular changes can be caused by
previous respiratory diseases :-•:like. : influenza (2),
pneumonia °~
(107), Asiatic influenza (30),Apul~ :onary infarcts
(6) .,and by illnesses like uremia (105, 107) . ana vitamin
,7 deficiency .
These changes are )bserved to a degree in ir .fants (3), in
~ Aor3s :nokers (43), and in resid-~nts of areas of extreme
\ air pollution (106, 110) .
W These changes are observed in the tracheas (windpipes) of
~ smokers, but anceri60#40 tracheaIjis extremely rare
~ (43-45, 10,09 115) .
(d) Ciliary paralysis can be caused by air pollutants like
i::dust-i a? gases --2) and au' ;on,obi le e :{ :.aust ,7.,ases (=
~e) T:zere is no evi lencz t these c :_ar.;;ed ces ls ever beco^e
cancerous .
fl Y1F'ci-,",t e £ :;2a v be s', . . . :':r ::i z e ~1 a s =0_ ", ciVs . - 1. ::ce _U= ar
-5-

chanEes in the lung ng and ciliary paralysis can be caused by


factors other than c ;garette smoke, since these changes occur
in nonsmokers' lungs and in the cancer-free trachea of smokers,
and since it is not known whether these changed cells become
cancerous~ ci~arette smoke, therefore, is not'1'ne only factor to
be blamed in lung cancer causation .
c . Biological_Data
Cigarette smoke condensate is carcinogenic to mouse skin (27*) .
Much is made of the fact that the dosage leve], used exceeds that
of the human exposure . Other investigators like Passey, Orr, Moore
and Miller (27**) did not obtain positive results with nominal
dosage levels ; Softe interpret this an indication that cigarette
smoke is not carcinogenic . It should be noted, however, that
many attempts were made to induce cancer in animals with coal tar
prior to the first success with highly unrealistic dosages (121) .
Kennaway ~44 .) :nommented on these negative findings as follows :
"The emphasis laid upon the collected negative results
of painting experiments from various laboratories, .and the

1 nders~resultsplicit•sugs~st
~Y •
r ~ suggest that these disoeesmokin
. . . . ., wher g
is concerned, the comparison of evidence from man and .from
animals may not .always be conducted with complete impartiality .
.~(.Positive results, if obtained by legitimate means, ~
must take precedence of negative results ."
Cigarette smoke condensate is a powerful ;romot6ng (or
rcinogenic) agent for polycyclic hydrocarbons (102) .
Inhalation studies with cigarette smoke have yielded an
increased incidence of adknomas in adenoma-susceptiblW~~~~ains
(32, 61) . No human-type carcinomas have been produced although
cellular changes and bronchitic conditions have (50-52) .
It is interesting to consider the studies of Campbell (see (108))
}f_' :_1S author reviews the swudies by Croninger and SuntZ?ff,
Guerin a'n d Cuzin, Koprowska, I- :oore and Bock, vrris et a? .,
: uSi,ara, 'Jynuer et al . ~
**M, his author reviews t'r.e studies by Pas ::ey, Orr, I'TocrE° and iilll@Y` . v
~
~

. . 1AA O .`Lt
\
i

, . . r.• .t , . . . .-- . l

. . . • -
i ..~ . . . . ~ . ~-` -
-6-
who obtained no increased .lung tumor incidence in mice inhaling
either autoinobmle exhaust gases or cigarette smoke . Subsequent
stud,y by others has shown that inhalation of exhaust gases and
at :. =osp'r.eric dusts incrd eased the adenoma incidence . Campbell's
negative findings with cigarette smoke are often quoted as
demonstration of the noncarcinogenicity of cigarette smoke ; seldom
is his evidence quoted to indicate the noncarcinogenicity of
air pollutants!
These negative inhalation results are interpretdd by some
as an indication that cigarette smoke is not a carcinogen for
human lung tissue . Two facts offset such thinking . First, mice
are not men, hence carcinomas should not be expected in a host
resistant to the induction of carcinoma of the lung, and whose
usual lung cancer is the adenoma (108) . Also, asbestos and sodium
arsenite, recognized industrial carcinogens, have not been shown
to be carcinogenic in animals (16) . Secondly, the ratio, lung
cancer deaths :total ci;arette smokers in the United States
. . .. ~ is approximately 1 :1700, hence an inhalation
experiment involving Tice would require 1700 animals for the
production of one carcinoma, assuming thsit the response of mouse
and human lung tissue wafhe same . No such number has been
used in any single experiment . T"ne 'biological :-findings are dismissed
by some with the statements Nice are not men ~.:nd Mouse skin is
not human lungL tissue, statements to which even the proponents
of the cigarette smoke-lung cancer proposition agree (116) .
d . Chemical Data
Cigarette smoke contains fourteen polycyclic hydrocarbons
(27*) and three heterocyclic nitrogen compounds (1-13) knourn to PIN
be carcinogenic to mouse skin . The hydrocarbons include nenzral
an thrace ne, benzo ~si,i~ per~~lPne, :~enzo~aj .~;rrene, benzo ~e3p .-ren, ,y
chrysene, dibenz [!j,h3anthracene, 1-metry lpyrene, cho_a :ahrane !84 ; ,
aibe ::zc pyrene, dibenzo Ca, llpyrene , di ;=:n.:cCa, i3 pyren :, ,
? , ~.-uih ;; Ctro-lH _ - b enzc Ca3 t°,~' clopen t~hlant :~=acer.e , ' C , ? _-ii :L ;;"k= o- ~
Ii
N

I (J~
cho_an ;?-irene . m
Ln
w
-7-
9H-benzoCa3cyclopent[i,anthracene, and benzCe3acepizer.a~ ~hrylene .
The heterocyclic nitrogen compounds are ?u-dibenzocarbazole,
dibenz~M,acridine, and dibenz La,Z3acridine .
Cigarette smoke also contains various promoting (or cocarcino-
Ezelnic) agents like the phenols and the fatty acids .
These findings, at dirst impugned, are now accepted but
dismissed as unimportant because none of the compounds has been*
shown to be carcinogenic or cocarcinogenic to h ruman lung tissue .
It is unlikely that such experiments will ever be carried out .

e . The Evidence to Date


Obviously the amount of evidence accumulated to indict
cigarette smoke as a health hazard is overwhelming . The evidence
challenging snch an indictment is scant . : :owever-, the evidence
from epidemiological, pathological, biological, and chemical
studies supporting the proposition that lung cancer is caused by
or associated with cigarette smoke is paralleled by similar
evidence supporting the proposition that lung cancer is caused
by or associated with air pollutants . In some instances, the
evidence seems to be stronger in sun-)ort of cigarette smoke
as Pcausative or associated factor ; in other instances, the
evidence ^seeas :: to be stronger in support of air pollutants as
a causative or associated factor .
Any criticism levelled at the lung cancer-cigarette smoke
proposition, e .g ., statistical studies annot prove cause-and-
effect relations in between two factors (a criticism of the
epidemiology) ; mice are not men (a criticism of the biological
evidence ) ; metaplasia and hyperplasia do not become cancerous
(Jcriticism of the pathological evidence) ; and no experimental
evidence exists to show that any cigarette smoke constituent is
carcinogenic to human =ur_& tiss .:e at `-ze 1?vel := t =r
ci ;'"%lreti,Pe ss^.:oke (a Cri tic].sT! of th+° chemical ev1 .d?ncc" , is
eq*ua'_'_y applica~ble to the l-ur:g cancer-ai= po :.lutc :. .t _= pcsit_on .

Ln
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1Pb
-a-
~ . Interoretation of the E ,cidence (healt
After reviewing this evidence, many governmental~ag ncies
and medical societies throughout the world have concluded that
ty* i:t=.was ..sufficient to establish a cause-and-eff ct relationshin
between ci arette smoking and cancer of the lung .J~ ?ior.e stated that
:
smoke was the cause, the only~ cause, etc ., and many
acknowledged the role of air pollutants in the increased incidence
of lung cancer . None suggested that research on all other factors
be dropped in favor of a concerted study of cigarette smoke .
Theae agencies inuluded the American College of Chest Physicians (1),
the British Ministry of Health (27*), the British Medical Research
Council (27*), the Danish Joint Committee of the Danish National
Health Service, Dh Cancer Society, and the Danisr. :•:edical
Association (26), ~Tational Cancer Institute of Canada(27*), the
~
Netherlands Ministry of Social Affairs and Public Health (27*),
the Royal College of Physicians (Gt . Britain) (103), the United
States Study Grouf on Smoking and Health 1957 (27*), the United
States Public Health Service (27*), the World Health Organization
(27*), etc .
Com,aenting on such pronouncements, Little (~6), Scientific
irector, TIRC, said
"-Se will not find out from over-simplified and
perhaps superficial concl~}hi' .ons .on s as to causation .
Such an attitude would only stifle or delay needed
research to find the basic origins of lung cancer and
cardiovascular diseases, which are most powerful,
diversified and deadly enemies to our well-being . Nor
will they be solved by resolutions or by review
committees that cobcern themselves solely with
sugz,estive or incomplete data ."
At present in the Unite-EStates, this evidence is under
review b ;;r t wo 'r r ::upS, ti. e~Sur ;eorn ser.era l ' s r".C: vi a, . .r y Co ." - ; ''c? e on
" _huUts :or su :,1+::arizas :.ese o ;;inions .
• Smoking and Health and by a special committee of the American
Medical Association . It,wi11 be very surprising if their
conclusions differ substantially from those o .£ other groups cited .
It has been repeatedly stated tiiat some scientists discount
the cigarette smoke-lung cancer theory . This is true . But it should
be noted that many of those quoted in this regard are on record with
contrasting views . Scientists in this category include, among
others, Arkin, Berkson, Dean, Eastcott, Fisher, Hueper, Little,
Macdonald, Passey, Rigdon, and Rosenblatt .
Berkson is repeatedly quoted as one of the statisticians
disagreeing with the cigarette smoke-lung cancer data . However
Berkson's considered opinion is illustrated by his statement (13) :
" . . . . .the definitive important findingA these prospective
statistical studies is not that there is an association
between smoking and lung cancer, but that there is an
association between sir.oking and deaths from all causes
~ generally . . . . ."
The thesis that cigar6tte smoking was statistically associated
with a shortened life span was advanced almost a quarter of a
century ago (64) .
The statistical studies by Dean (28, 29) in South Africa
and Eastcott (31) in New Zealand cannot carry the weight ascribed
to them . Eastcott's study (31) did not compare immigrant and
nonimmigrant lung cancer victims with respect to their individual
smozing habits but with the yearly per capita consumpti n in
~obac o
New Zealand and the United Kingdom . Since the per capita . sumption

was greater in New Zealand than in the United Ifingdom and since
t:°:e number of i"1migrant lung c .: ;ncer victims ':la ;, ;_ea':er tflan the
n umbzr o c noz .immi grant lung cancer victims in New Zea,
and,
c snc -u d e d t, .".c:?: s .". :or.i2lg` ~:111 d
. n OV cGn r-OL : = 1S

arl;> >oan. (2c) d4.d not comnare i nd=vidua= : :'oa :1. :1 s h'c bi ts . ~Ln'
~
2 G ) ascertained j: :c
:a•t~-?!`, .:e ( the C :: :1=Sr ~

V ?O?=-=rI~~SS c7~ .c=TO~ . . . .. vJ .__t? 'i`,i :iS' :1 e a : Oi cn

~ a~rocedure cr :.ticitied pre v ioUS l ;y by re v iC w ?_r 8r8 of + l :°

,,, _ . .
-10-

::otin, member of the Scientific Advisory Committee, TIRC,


~ recently commented (40) on the conclusions of the 195! U . S .
Study group on Smoking and Health :
"The statement . . . . . .to the effect that 'The sum
total of scientific evidence establishes beyond reasonable
doubt that cigarette smoke is a causal factor in the
rapidly increasing incidence of human epidermoid cancer
of the lung' tepresents a view wi ;h which we concur ."
Little, Scientific Director, TIRC, stated in 1947 (5j, cf .
55) :
"Although no definitive evidence exists concerning
the relation between the use of tobacco in the instance
of lung cancer, it would seem unwise to fill the lungs
repeatedly with the suspension of fine particles of
tobacco products of which smoke consists . It is difficult
to .see .how such particles can be prevented from becoming
lodged in the walls of the lungs, and when so located,
how they can avoid producing a certain amount of irritation .
One might also question the ultimate results of continued
inhalation of the type of atmosphere which characterizes
the lower levels of city streets . Experimental work
with animals involving these matters is still inconclusive,
but it seems probable that the lung as an organ is not
immune to the ef'Lect of chronic irritation and that it
will in this resnect resemble the other organs of the
body . Such being the case, wisdom in avoiding unnecessary
lung irritation seems to be establ'ished ."
and more recently (58) :
" . . . . .in the first place we don't criticize the statistical
findings . We believe that they were honestly obtained and
that they show, under the conditions that they were collected,
a strong correlation which is suspicious enough to make it
imperative that further research be carried on . . . . . . "-
Hueper, long a proponent of the lung cancer-air pollutant
proposition, noted (42) :
"A~, .definite amount of reservation is indicated in accepting
the claims advanced by some parties concerning the role of
cigarette sr.:olcin ; as a direct or indirect factor in the
caU :a tiCli Gf lun z cancer . :`Te 'i r•rt ;leiZsS the type° :$nd a ;-, lount
of evi3enee on ti :is mat cer on :^.and J ustifies the conciusi on
uaa t ci~arettF .-r ;.;ci:in~ ,, ha . ~ co ::tY`i au ted to or a s cr a v ate d the
a ctiCi :: of oL :~er c •-. r Cl n o`eali .-I Zre :7~p ii a 4iir y p (i~•11•: tw n t~ J~7
~rC ::i;;ci?iy i~S_'U~?c :a~i ;;' fUnCt :i .O : :?i dl :•~i~r - c ~~eS sn in :, r 0 . :: h:i _~i
-:uc~sa . . . . . . .I t be .:,ost u::arise ., or. the ot :_-= hand ._~ _
t::r-,u~%j .x: r~ ;~.ar.,~era ted = .p?: ..si : P_ .:,cA•~. : :. ` : . s ~ ~ --=' ::: ~: ~ _
of cigarette smoking, the studly . . . .of air pollutants would
be impaired and neglected . The available evidence raLher
definitely assigns to these factors an important ro ;e as
human respiratory carcinogens ."
And Passey (63), who does not believe that lung cancer results
from the action of carcinogens ; sai5 :
"I do not belittle the important part which smoking
plays [in lung cancer causation,] . My aim is to sug`est
its mode of action . In fact, I would say that- .-it is
dan ;erou s to smoke . "
Additio(Vl citations could be given but these few suffice
for now .

III . The Tobacco Industry's Contribution


To investigatre the cigarette smoke-health situation
The Tobacco Industry (except for ift Liggett and Myers Tobacco
Company) has given about five million dollars to TIRC since 1954
~~-- for research . According to Little,(54), its Scientific
Director, the purpose of TIRC is
~ " . . . .to encourage and support qualified research
scientists in their efforts to learn more about these
complex problems [cancer and heart diseasz'' ."
Through December 1961, TIRC grantees publ ished 197 papers
(56,", 57) . Of these, 36 were concerned with the chemistry od
toooacco and its. smoke ; 47 with cancer research ; 13 with human
lung studies ; 78 with heart and circulation studies ; 4 with
gastrointestinal tract studies ; 5 with psycho-physiologiL\-cl
studies ; and 14 miscellaneous studies (lung cancer reviews,
tobacco-health textbook) .
I believe that much of this research, particularly that
on the chemical, biochemical, and biological study of tobac-co Ln
~
~,nd its smok e could have and .:shoul . ' :zave ~-~e :r. ou ; ;n _Q
~
m
, . : e : .`~ a e :.z .- c h d ..t~'~artalents of the tobacco co'a p aa_es* .
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*1'2:e ^I : l1 i~rantBP isGlate4'~ and characterized C-'- ;,'C.''O r ;,- ::1C'~t? r_° 0°
Gri'~'.~ su :'7sef,uently UuyJli sl?ed hi . _°i :?!lin'c';s : A 3_m 1=P. '_' S1.url,;," 'tira :
out in t ._i s Ccmr.~r%n ;;-' s~ C. i'._ .._.
. . . ~ = , . ~. . ,.. . ._y.y -: , t~"' ~ ,v ._
~
. L 4
. i 'e~. +.
~, , :, ~l, y~
~ .. . ': ~. ~~ •~ . .. 'r,

. .'J,J . ._ .ac . C7'a n. . :r_ . .~J , s cl.~l~?v1 :1, a ^T .s`_


.: A . .~ _Il ~' . :a.CCV .::
n o:. oi. P
-12-

"'he meml:ers of this CompGny's Research Department are as


qualified,as objective, and as interested in learning
~ " . . . .more about these complex problems . . ." (to quote Little (541))
as scientists not employed by abobacco-rnanufacturer .

Concerning qualification of research persons, it is interesting

to note the criticism of cigarette smoke inhalation studies (pre-

sumably those of Essenberg) by Little in 1957 (55) :

"These poor beasts are usually put in practically an

air tight container, and smoke is pumped in and pumped


in in such quantities that the white rats become yellow

or yellowish brown . . .
.'1 Acvl~~
and to relate this criticism to observations made (51) inAcigarette
smoke inhalation studies (50-52) conducted by a TIRC grantee :

"Depending on the time of exposure, the fur of the

exposed mice gradually changed from white to yellow


to darkish brown . . . ."

This smoke inhalation project was activated on September 1, 1957,


over a month after Littlefs criticism of such techniques .

If a coordinated chemical, biochemical, and biological research

program on the tobacco-health problem were undertaken by the members

of this Companyts Research Department, the findings made could not


have any more adverse effect on the Tobacco Industry in general or

on this Company in particular than those reported JW* (56,57) OW


OW by ~ TIRC grantees or associates, Kotin and Falk (parA,lysis
S
~ ~ .

of cilia with cigarette smoke and components),


Leuchtenberger (cellular changes produced in the lungs of mice

exposed to cigarette smoke), Bock, Moore, and Homburger (tumor

production with cigarette smoke), Kosak (isolation of carcinogenic


0
-13-

compounds compounds from :cigarette smoke), etc . It may be advantageous in


the future for our Research Department personnel to have experi-

ence in studies involving test mammals, particularly if govern-


mental restrictions are imposed because of conclusions reached

by the recently appointed Surgeon General's Advisory Committee

on Smoking and Health . One of the five observers at the first


meeting of this Committee was a Division Director of the Food

" ~ and Drug AdministrationAMembers of this Research Department

have studied in detail cigarette smoke composition (8, 9, 1$-24,

47-49, 68-77, 79-101, 114) . Some of the findings have been pub-
lished (19, 22, 24, 74, $0, $2, $9A, 91, 94, 96, 9$, 100) . How-
ever, much data remain unpublished because they are concerned with

carcinogenic or cocarcinogeniccompounds (23, 47, 4$A, 6$-72, 75,

_ 76, 78, 84-86, $$-, 92, 101, 114.) or with patentable material

(83, 89) . This raises an interesting question about the former


compounds . If a tobacco company plead "Not guilty" or "Not proven"*
to the charge that cigarette smoke (or one of its constituents)

is an etiological factor in the causation of lung cancer or some


other disease, can the company justifiably assume the position

that publication of data pertaining to cigarette smoke composition

or physiological properties should be withheld beeause such data


might affect adversely the companyts economic status when the

company has already implied in its plea that no such etiologic

effect exists?
It is not my intent to suggest that this Company accept the

E .g ., Lartigue vs . Reynolds Tobacco Co . and Liggett and Myers


Tobacco Co ., Greene vs . American Tobacco Co ., and Pritchard
vs . Liggett and Myers Tobacco Co .
-14-

cigarette cigarette smoke-health data at fAce value, but I do suggest that

this Company, through its Research Department, actively partici-

pate in'cigarette smoke-health studies . Other Companies (General

Motors Corporation (7), Imperial Tobacco Company (Great Britain)

(10-12)) have reported their findings on the air pollution-


health problem and cigarette smoke-health problem, respectively,

without apparent loss of prestige (or income) .


IV . Recommendations
After consideration of the evidence available on the cigarette

smoke-health problem and the Company's obligation* to its customers,


stockholders, and employees, it is recommended that facilities,

animals, and personnel (where necessary) be acquired to study

biologically cigarette smoke, tobacco, tobacco .and additives .


This recommendation has been made kv*aw by Teague (111)

in 1953, by Rodgman in 1954 (66), in 1955 (67), in 1956 (68A),


in 1959 (72), and in 1962 by Nielson (62) and Rodgman (77) .

Data from such studies may be invaluable if governmental restric-

tions are imposed as a result of the conclusions of the Surgeon

Generalts Committee on Smoking and Health . It is, I believe, moEe


urgent than ever that we acquire dexterity in biological tech-

niques .
* It is nterest ng to note remar s like y on t t eyt do
something about the liquor industry? After all, there are an
estimated four million Americans classified as alcoholics . Alco-
holism •im not only is a health hazard to the drinker but also
causes untold anguish to his family ." or "What about the meat-
packing industry and the supposed relationship of stturated ani-
mal fat to cholesterol-caused circu&atory disorders and heat.YC :
disease? After all, many more persons die of heart disease than
lung cancer ." These remarks may have some justification, but
~ attempts to minimixe our obligations by pointing an accusing
finger at others is no solution to the cigarette smoke-health
problemi
-15-

It is recommended that data already available on physiological3r

~ active cigarette'smoke components, e .g ., polycyclic hydrocarbons,

phenols, be published . It is also recommended that analytical


procedures concerning such compQnents be published .~
_. ....,
These recommendations are made because I believe they repre-
sent the best answer to the questions : What effect would immedi-

ate publication of these data have on this Company's economic


would be the
. status? What/effect on this Company of not publishing these

data now, but being required at some future date to disclose


such data, possibly in the unfavorable atmosphere of a lawsuit?

It is recommended that the Company'is supervisory personnel


be provided with reports like the Royal College of Physicianst

report Smoking and Health, the Annual Report of the Scientific

~, Director (TIRC), and other pertinent review articles just as


~ they were provided with Northrupts book Science Looks at Smoking,

the pamplets Tobacco and Health, and "favorable" articles such


as the one from Life entitled New Evidence That Cancer May Be

Infectious . In this way, the Companyts supervisory personnel


will be better informed about the cigarette smoke-health problem

than they would be if their main informat ion sources were the

daily newspaper, Readerts Digest, etc .


And finally, it is recommended that the Company's manage-

ment recognize that many members of its Research Department are ~


~~,,
A~
intensely concerned about the cigarette smoke-health~prmSand
.%,
eager to participate in ' study and solution . A
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., . . ~
• L,
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. ~. . •
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• 1 . American College of Chest Physicians, Statement on


Cigarette Smoking . DIS . CHEST, 42, 233(2 .

2 . Andrial, M ., Tracheal and Bronchial S ;:uamous Metan?asia


-a M:.A . AR H . _z'
in Influenza .. ., 68o, 94- 2 5° •

3 . Auerbach, 0 ., Stout, A . P ., Hammond, E . C ., and Garfinkel,


Microscovic Examination of the Bronchial Epithelium in
Children . . .1ll'Ll{• . A a I ! J 40-64 e 60
4 . Auerbach, 0 ., Stout, A . P ., Hammond, E . C ., and Garfinkel, L . 0
Changes in Bronchial Epithelium in Relation to Ci arette
Smokin and in Relation to Lun Cancer . NEW ENG . J . MED .,
265, 253-267 (1961) .

5 . Auerbach, 0 ., Stout, A . P ., Hammond, E . C ., and Garfinkel, L . I


Bronchial E ithelium in Former Samol :ers . iTE .J ENG . J . MIE : .,
267, 119-125 (1962) .

6 . Balo, J ., Juhasz, E ., and Temes, J ., Pulmonar- Infarcts and


Pialmonar,y Carcinoma . CANCER, 2, 918-922 (1956) .

7 . Begeman, C . R•, Carcino•genic Aromatic Hydrocarbons in


Automobile_E_ffluents . Paper presented at 1962 Automotive
Engineering Con~;ress, Detroit, Mich ., Jan . 8-12 (1 ;62) .

8 . ~ellin, S . A ., Hi her :att Acids in the Smoke Cor.densate


of Burley and Flue-cured Tobaccos ._ A actori'a~~7e ~n
Exuer? ment Showing the Effect of Variation of' Ci arette
Pioisture~ ~J~ht and Tobacco Type . RDR, 1~_,~~ No . 8 (Feb . 6) .

9 . jBellin, S . r1 . ,Tftentification of C and C Saturated


#:~ Fatty Acids and, C16, C1? Unsa ;;rated ~'?atty Aci ds in
Tobacco and in Smoke . RDR, 1962, No . 5 (Jan . 29) .
10 . Bentley, H . R ., and Burgan, J• G ., Polybuclear Hydrocarbons
in_Tabaac~.ancLTQb~tccSL~rioke, I• 3,4-3e_ neDrene . AN .4LYS^,
8~, 442-447 (1958) .
11 . Bentley, H . R ., and Burgan, J . G ., Polynuclear H`drocatbons
in Tobacco and Tobacco Smoke . TI . The of . ..
3.en, ;;-~re :~e Fourid _ in ...r'~4 :'~~ unu__m9oac-g ~sr ;or:a- .i:?'ALYa'f,
~~ ?23-727 ~1q60)• -
12 . 3entley, H . R ., and 3urgan, j . :, Po1~-~uclear _:iy:~~,ncan ~ :ns
in Tona.cc .^o and '^o ;- cco
• ~-.- -E
r,v ,~-
F q r,a :•~,ion cf 3,4 -~a "- r~ z c:~ _~~ • • ~ cne in r_~ 9 rx:e
~.

{ 1': r)0 ) .

Un
m
ON
w
13 . Berkson, J . The Statisticel Investi tion o Smoki nM a na ance
Lung . J, 0
• • 1

].1,. . Berkson, J ., Smokin and Cancer of the Lun . PR.OC . STAFF . MPG., MAYO CLIN .,
a, 367-3g5 (1960) .

]5 . Best, E . W . R ., Josie, G. H ., and Walker, C . B ., A Canadian Study of Mortality


in Relation to Smokin Habits . A Preliminar Re ort . CAN. J. PUB . HEALTH, L2t
99-1041961)0

16 . Boqland, E., The Biolo ical Examination of Carcino enic Substances . BFtIT . 2~D ;
BULL ., 11 (2 ) , 93-9 (1958) .

17. Bruce, W. F ., Carcino dr e s V A C ence


Intensit of Cholant e and Certa n o I Hom J . AM. CHEM. S6C ., ,,,,2,
304-305 (1941) .
18 . Cook, L. C ., and Rodgman, A ., Th®_ Analysis of Cigarette Smoke Condensate . XXIII .
a- and -Isv nt no id om Turk h To ~ . RDR,~ , No . 21 pr . .

19 . Cook, L . 0 ., and Rodgman, A ., ..The Com osition of Ci ar tt Smoke . VIII - and


R-Levantenolide from Turkish Tobacco Smoke . TOBACCO SCIENCE, 1, 32-33 (1962) .

20. Cook, L. C ., and Rodgman, A .,_ The Analysis 'of Cig,arettQ Smokg Co„Dd,gnsate . ~V.
12a-?i dro -- =..- RDR, _1261, No . l,l+
Sept . 22 .

• 21 . Cook, L : C :, Rodgman, A ., and Ypung, G. W., The Analysis o Ci rett Smok


. Condensate . RVI . Normal Lone-chained Primary Alcohols . RDR, ,1260, No . 22 (July 1) .

22 . Cook, L : C ., Rodgman, A ., and Young, G . W ., The Com osition of Ci arette Snoke .


VII. Normal Lon :chained Prima Alcohols . TOBACCO SCIENCE, 1, 6-10 ?91 .

23 . Cur*_diff, R. H., Gross Se aration and Determination of the Phenolic Fr ction from
Toba cco Smoke Condensa tes . RDR, ", No . 9 Feb . ]4

24 . Cundiffp R . H ., Sensabaugh, A . J., Jr ., and Vlarkunas, P. C ., -Ti_tXetric


Determination of Acid Fract e . TOBACCO SCIENCE, _6, 25-27
1962 .

25 . Dalhamn, T ., Studie8_~n, .t1~ FffACt of &,1 f,rr D


Ra bbit Tra chea in Vivo a nd in Vitr~o ,ra r4 on the Res or, ., ~t,~on_al CaP,a o~ the
P~as~l Cavity, AM. REV. RESPIRAT . DISEASES,'~ 566-567 ~].9611T.

26 . Danish Joint Committe,,Tobacco and Lung Cancers Deliberations of the


Danish Joint Committee with Particular Attention to Cisa ette Smdsing .
DANISH ?dCD . BULL ., 2, 99-11 (1962)0 -

27 . Davies, D . F ., A Review of the Evidence on the Relationshi between Smoking


and Lun~ Cancer . . Cn.'~ONIC DIS ., U1,, 579 14 19 0 .

• 28 . Dean, G., Lur.,, Cancer Among ;v,aite South Africans . &RI'i'. i-M) . J ., 1M (ii),
552-557 .
c$
29. Dean, G ., Lun Cancer Amon White South Africans . Re ort on a Further Stud .
BRIT. I4ED . J ., 1s61 ii , 1599-1605 .

30 . de Baan, P ., Lon afwi kin en bi Aziatische Influenza . NED : TIJDSCHR . CEiTy' SK.,
19L 721-726 1959 .

31 . Eastcott, D . F., The Epidemioloay of Luna Cancer in New Zealand . LANCET,


1~6_ (i ), 37-39 .
32 . Essenberg, J. 24., Ci arette Smoke and the Inc idence of Prima Neo 0 lasm
. of the Lung in the Albino Mouse . SCIENCE, 1,1 561-56-2 1952 .

33 . Falk, H . L., Tremer, H. M., and Kotin, P ., Effect of Ci arette Smoke and Its
t n Ci ate cus-seoretin h ithe ium . J . NAT . .,
~, 999-1012 4959) .

34 . Fisher, R . A ., Lung Cancer and Cigarettes? NATURE, 182 . 108 (1958) .

35 . Fisher, R . A ., Cancer and Smokin . NATURE, 182, 596 (1958) .

36 . Friberg, L ., Ka~.J, L ., Deneker, S . J ., and Jonsson, E . ; Smoking Habits of


Monozyr~otic and Dizygotic Twins . BRIT . MED . J., = ~i), 1090-1092 .

37 . (hreene, H . S . N., Introduction to "Science Looks at Smoking, ' by E . Northrup,


New York, N . Y ., Coa~ard-MeCann, Inc ., ~. '

38 . Haenszel, W., Loveland, D . B ., and Sirken, P?.. G., Lung Cancer I3ortaiity as Related
to Re ' n e and Snokin Histories . I . White Males . J. NATL . ~.aNCr'~ LWST .,
2, 947-1000 (1962) .

39 . Haenszel, W., Shimkin, :~I. B ., and Mantel, N ., A Retrospective Stud of Lun


Cancer in Women . J. NATL . CANCER INST ., ~, 825-842 1958 .

40 . Hamilton, J . D ., Sepp, A ., Brown, T . C ., and 2~cDonald, F . W ., I•3or holo cal


Changes in S~nokers' Lungs . CAi1. i~D : ASSOC .,J ., ~ 177-181 (1957) .

41 . Hilding, A . C ., Cigarette Smoke and Physiolo~ic Drainage of the Bronchial Tree .


DIS . CILST, ~, - 2 .

42 . Hueper, W . C ., Kotin, P ., Taber, E . C ., Payne, W. W ., Falk, H . L ., and Sawicki, E .,


Carcino enic Bioassa s on Air Pollutants . Paper presented at 53rd Ann . I~ftg ., Air
ollution Control Assoc ., Ci~icinnati, Ohio, Diay 25 (1960) .

43 . Ide, G., S~ntzeff, 'y ., and Cowdry, E . V., A Com arison of th- Fistoaatholo of
Tracheal and Bronchial Epithelium of Sinokers a s onsmokers . C~~~r~i., 12,
473-4 4 1959 .
44 . Kennaway, B . L ., ' Some uestions on Cancer of the Lun ., Ler~nx and Urinary Tra ct .
BRIT . i•~D : J ., 1~7 i, 299-306 .

45 . Iinudtson, K . P ., The P,.tnologic Effects of S~~okinT Tobacco on the Tra_c'aea and


Bronchial 1•~ .icosa . ~i ;ri. J . CLZ•I . PdT ;zOL ., ~, 310-317 9 0 .

46 . Kotin, P., and Filk, '~I . L•., The Role and Action of Envi_ronmental Aents in
the PFthogenesis
.. . . . . .. .
of. . Jung
. .
Cancer . _II . Ciarstte
. . . ..~ . . ~. . .~. :r'
5mo :ce... CaIC•.~, ~ 250-262 (1960) .
~

51710 5065
A

47 . Latimer, P . H ., Thd Determination of Phenol in Ci rette Smoke . RDR~


1961, No . 37 (July 25 .

48 . Laurene, A . H ., The Com °sotion of the Vapor Phase of Cigarette Snoke .


RDR, =, No . (Oct . 17) .

!,.$A . Laurene, A . H ., and Young, G . W ., The Develo, pmen,t of a t~ss Suectrometric


Analvsis of Phenols in Tobacco Saaoke . RDR, 1961, ,No . 38 July 25 .

49 . Laurene, A . H ., Young, G. W ., and Ch•eene, G. H ., The Quantitative Analysis


of Cigarette Snoke . Part I . RDR, 1, No . 20 (Sept ; 4 .

5 0 . Leuchtenberger, C ., Leuchtenberger, R ., and Doolin, P . F ., A Correlated


Hiatolo~ical, Cttological and Cytochemical Studp of the Tracheobrenchial Tree
of Lungs of 2dce Eacposed to Cigarette Sinoke . I . Bronchitis with Atypical
1958) ~a ~ - h~go~,in 2- i ce Ex~osed to Ci~arette Snoke . CANCER, 7 , 490~06
.

51. Leuchtenberger, C ., Leuchtenberger, R ., Zebrun, W ., and .Shaffer, P.,


A Correlated Histolo ical C tolo cal and C tochemioal Stud of the,
r~eo eeobro+ ncTi a ee o ce ose to~~aret e Smoke . IT. Varying
~esnses of t~a or Bronc~ii~o Ci arette Smoke Absence of Broncho enic
Carcinoma After olo osure and sa earance of Bronchial Lesions
._ er s sa on o ,_~,osure . C A ,12, 21-7 2 (1960) .

52 . Leuchtenberger, R ., Leuchtenberger, C ., Zebrun, W ., and Shaffer, •P .,


A Cor e H ca C a nd C Stu of the
Tr e ial Tr of Mice ed to Ci rette Smoke . III . Unaltered
Incidenc of Grossl Adenomatous Lun Tumors in Fema e ce After
Prolonged Exnosure to Cigarette Smoke . CANCER, Ia. 95 -95 (1960) .

53 . Little, C . C ., "Cancer, A Stlzdy for Laymen", Aw .¢Y~ta~ Caca~Y ,

53A . Little$ C . C ., Smokinu and Lung Cancer . CANCER RESEARCH, ]6, 183-184 (1956) .

54 . Little, C . C ., 1956 Re ort of the Scientific Director . TOBACCO IdDUSTRY


RESEARCH C02-II , .

55 . Little, C . C ., Statement in "False and `,&sleading Advertising (Filter-Tip N


Cigarettes)"9 Hearings before a Subcommittee of the Committee on ~
Government Qoeratiens, House of Representatives, 85th Congress, July 18-26 ~
(1957), 34-61 . ~
~
56 . Little, C . C ., 1960 Report of the Scientific Director . TOB4CO rJDLS711 0
RISLAH,CH C0nr'II'M'Ezr,-116b . w °i

57 . Little, C . C ., 1961 3eport of the Scientific Rirector . TOB :CCO Ti'TDTZ3RY .


. msEA:wa C0: t•f-TTTy, 9 ,_b~. F r'

58 . Little, C . C ., Tn„terview, CBS~.


Re,vorts ..~ ae Smoker . Text of a televis ion
- The Teen-a
.~...;......_.
program, Columbia Broadcasting System, Sept . 12, ,]a2 .
.10

59 . MeTlors, R . C ., Cellular Localization of Fluorescent Products Derived


from Cigarette Smoke : ._Studies_ in Ncnerimen aimals and in bi~n
~luorescence ~Scrosco
. . . ~.. W. Y... r. _.... Y.. _......,.. .~dP~ J.^PATIiOL ., -1957, 611 .

60. Nlallors, ft . C ., M~,co~onic Localization of Tobacco Smoke Products ian


the 4.esniratow
... vnsw.- .+.. .
r~,~Tracts
~..wwn..
of Animals E7cnosed to~ Ci .rette Smote . rR OC . AI4.
e .w
ASSOC . CAi•1CER ;fSARCH, 2_`U, 325 (1958) .

61 . Muhlbock, 0 ., Carcinogene Werkina van Si arettenrook -ihiizen


bi . ?`MD.
TUDSCHR. GENEESK ., c)2, 22?-2278 (1955) .

62 . Nielson, E . D., A Pronosed Research Program of Biolo i~Testing . RDId,


19.66z,, No . 113 (NOV . 19 .

63 . Passey, R . D ., Some Problems of Lung,Canoer . LANCET, , 1,2 (i),, 10?-112 .


.yy.~F ~.yYMM/10 .aY~a.
M/Y Yi iM

64 . Pearl, R ., Tobacco Smoke and Longevity . SCIr,'•JCE, 87, 216-217 (1938) .


.. .. ._...,~._
,
65 . R.saschou-2lielson, E ., .._,t
Smokina_Habits
---. .....,...,in ... .__.. . DA:dISH rED . BULL . p _, 82-
Twins.
._ . .w...~
88 (1960) .

66 . Rodg*nan, A ., The Synthesis of Various Substituted Phenols for Use as


Flavorants in o cco o uc s . , , No . E . .

67 . Rodgman, A ., The Fractionation of Ci. .~ret~te


. "" __
Smoke
______r _. . . ... Tars . RDId,
._ .... and,~
=, No . 13 (AP .

68 . Rodgman, A . The Analysis of Cigarette Smoke Condensate . I. The


lation and or dentificati~on o~f PolXc~clic Aromatic drocarbons in
.~
""CANLEL Cia2rette Smoke Con nsate . ~RDR, ]„ .16b, No . 9 SEPP . 28) .
4 rw . ~wi

68A . Rodgman, A ., The Pre ration of Some Phenolic Flavorants . RDR, 12~6,
No . 10 (OCT . 1 .

69 . Rodgman, .A . , _s_iE_o_f__Cin__ette_ Smoke Condens-Q,te . II . The Pr_e-


t r°9~m,gnt QfC4,'Z, L QPnd Tobacco . RDR, 195 6_ No . 12 (NOV . 1 . ~

70 . Rodgman) A ., The Ana;ysis_ of Ci,a,arette Smoke Condensate . III. Flue-


cured Tob,;cco .=D. v y ~

71 . Rodgman, A ., The Analysis of Ci rette Smo e Condensate . IV . 3,4,g,9


Dibenzv ene in CAMEL Cigarette Smoke Condensate . RDR, ,_o .
OCT . 17 .

72 . B,od,,~n, A ., The Analysis of Ci,sratte &-aoke Ccndensete . VI . The


Influence of anl'c ve`n~ .. .._ ... . r..r .e.. ...treatr.tent
. .•..u.. o`ib~ia cco and { %,-her F i~ c ~or s on the
..
Pol* c clic H,-droc~rbon
. . .
.......r,. ~. .• .,..., .. . Con~ont . c=
...,: ,~ricqa~yCo:irens=te
.. . .~.. .. . . :~Dd", 1 ;5a,~i1o . ~l
JA .~d. 29 :

73 . Ro%,grmn, A .,
aDa, 1 7 Q, No . 11 ( : I:lY 1~ ) .
N1

• 74 . Rodgman, A ., The Com osition of Ci arette Smoke . III. Ph adienes .


J. ORG . CHE:•i., 2,~1. , 191 -1924 (1959) .

75 . Rodgman, A ., The Analysis c .f Cigar.ette Smoke C-ndensate . X. The


Effect of PoxNous Paper and or Filter Tip IJaterials or Aluminized
Pauer anaior ~ .umina aaca.zive t!te*
b~r~,r' nolas
etalst•ll1 . .. ....._...._..
i on
uom an
~"~~"`MiY'lb `rotal
.,
76 . Rodgman, A ., The Analysis of Cigarette Smoke Condensate . SIC . The
De,ter~,-n.~in,ation ,of Pol c.....clic
.,.... . Aromat
... . . c drocarbons
.-..~...,.._. . +~'~; 6f; i13" . 1
JAN .

'111R
~ cjg% n~., t
H 1 ~: A ~ a
h sittW96 on .o~~ C_i6~~ rett~' Smo e, Smo~cipg, ~pnd
H;~I, 2, ~1+To .

77. Rodgman, A ., The Smoking and Health Problem - A Critical and Ob ective
.Appr~ a~ i 1. RV1i, 1 , No . ! .

78 . Rodgman, A ., and Cook, L . C ., The Arialsis of CiAarette Smcke Condensate .


V . The Pol c olic H drocarbon Precursors in Tobacco . RDR, IM, No . 1
DEC . .

79 . Rodgman, A ., and Cook, L . C ., The Analsis of Ci arette Smoke Condensate .


VII . Solanesol and Solanes 1 Ace eta
r.... .
. RDR, IM, o . 22 DECOMM~_

80. Rodgman, A ., and Cook, L . C ., e mnosition of Ci r~ret~e Saoke .......I.


~ u,.w.. ..
SolaneUl Acetate .
.t~e TOBACCO SCIFNCE, I, 86-88 (1959) .

81 . Rodgman, A ., and Cook, L . C ., The Anal sis of Ci rotte Smoke Ccndensate .


7~Iq :aUoZjL,a,rol . RDR, IM, No . 23 (SEPT . 29 .

82 . Rodgman, A ., and Cook, L . C ., ~,no t o Ci arette Smoke . IV.


Toco herol . TOBACCO SCIENCE, /~, 7-8 1960) .

83 . Rodgman, A ., and Cook, L . C ., The A al sis of Ci arette .Smoke CondPnsate .


XIIIy Sclareolide from Turkish Tobacco Smoke . RDR, =0, No .8 (M 1 .

84 . Rodgman, A ., and Cook, L. C ., The :ln 1 si of Ci arette Smoke Condensate' .


i Aroiaatic H drocarbons . RDR, 19 , No . 20 AMY 2 .

85 . Rodgwn, A ., and Cook, L . C ., T'h_e_AnglYs.Ls ..°f Oi arette Smoke Condensate .


e ect of Alumi !S "no d Catal sts on Total c
H d ca bo s Total Solide and Nicotine . RDR, 10c60, No . 36 DEC . 2 .

86 . Rodgman, A ., and Cook, L . C ., Th~ysis of CiL7r, rstte S .7oke Condensate .


XVIII . Chloranil and 2r7-'s~initrofluorenone
.,_. _. a s Fi? torViip
.. ~aditives .
RDB,, 1,~~0, ido . 3S7T~~C. 7) .

a7 . R.odg.nan, A ., and Coo :c, L . C ., The Anal sis >.


~ ....M..~ of Ci~arotto
.. . . ..:? : ..r- . Smc'a
. ..~ CondQns .te .
XX. 1,,~,tote on the Normal Long-caained F3riria_ry ~?cono•lsi~ .. :~n ddrendtua.to
.

8£i . Rodg.nan, A ., and Cook, L . C ., The Anal sis of Ci ar,?tte Smoke


~, ; JOCI .
Phenols ; RDR, 12.61, No . 10 (FEB . 23 .

89 . Rodgman, A ., and Cook, L . C ., The Analvsis of Ci~,arette Smoke Condensate .


' . ~h va e ,.
T h obacco S~noke . RDR, ~, No . 42 (ATJG . 18) .

S9 .A. Rodgman, A ., and Cook, L . C .p The Com osition of Ci rette Smoke . X.


12ac-HydroL i ovl . Oxid e fr m Turkish Toba cco mo . TO ACCO
SCIENCE, 6, 123-124 (1962) .

90 . Rodgman, A ., and Cook, L . C .•, The Anal sis of Ci rette Smoke Condens :ite .
p c ic Nitro en Com ounds n Tur ish obacco Smo
E o . 14 JUI~ 21 .

91 . Rodgman, A ., a nd Cook, L . C ., The Composition of Ci arette Smoke . ~ XI.


Heteroc clic Nitro en Comoounds in Turkish Tobacco Smoke . TOBdCCO
SCIENCE, §~, ~174-177 (1962) .

92 . Rodgman, A ., and Cook, L . C ., The .An?l sis of Ci arette Smo e Condensate .


KXVII . Eu enol and Isoe enol . R, 1_962_, No . 15 ITNE 21 .

93 . Rodgman, A ., and Cook, L . C ., Bellin, S . A ., Mims, S . S ., and Young, G . W.,


The Anal sis of Ci aratte Smoke
. ., ..,.,,. . .,, .. , ~Condensate
.. ..,~.w ........ ∎...... ,.
..~. XXII.
. .,..... ~., ,....The
,. Comnosition of an
Aliph~,#y~ o~st~~r k~a ction fr om Toba cco and Toba~+. eco Snoke
.~. . ..~r.+ .-
. RDR, 1961 , No . 15
( Mr1R . 27 .

• 94 . Rodgman, A ., Cook, L . C ., Bellin, S . A ., Mims, S . S ., and Young, G . W ., The


Comnosition of Ci arstte Smoke . IX An A,linhatic Ester Fractio ,from ~
Tobacco and Tobacco oke . T0 CCO SCIENtCE;~"k, 4(1962)': -`r `

95 . Rodgman, A ., Cook, L . C ., and Chappell, C . K ., The Analvsis f Ci~ratte


Smoke Condensate . XV . Compa•rison of Different ~`obacco Types . nR, 11,60,
Mo . 21 JUP1E 30 .

96 . Rodgroanp A ., Co .ok, L . C ., and Chappell, C . K ., The Comos


~ ition of Ci . ar
~ ett,e
S~oXe.,,.,,,_VI_k n rison of Different Tobacco Types . TOBACCO C NCJ 0
1-5 (1961) .

97 . Rodgtnan, A ., Cook, L . C ., and Latiner, P. H ., The Anai"rsis og Cigarette


Smoke Condensate . VIII . Solanes 1 Esters and Phytosteryl Esters . RDR,

98 . Rodgman, A ., Cook, L . C ., and Latimer, P . H ., The C.:,.voosition of_Ci~~~retz9


. Smoke . II
.. ........_,.,~~_ ..., ..._:aqsXl ana ._Pnytostorll,Estors . TOBACCO SCI^?TC3, 1, 125-12C
. Sola
..,,..~_

99 . Rodgman , A . , Coo :, L . C ., and ?fi;.s, S . S ., The Ana]~,y_sis of


,.....,•...,. . . ...
Cigarette
. n .. ~ ...
+. m.- .
Smoke
Condensate . :{II. Scualenes and Solanesenes . RDR, b0-, No . Ln
~"~.wM...-a..wvr..w,.ns.c.:wtw-ssv..css .r`+Aw.na.-iR.r ∎w~.rrt~f.•_w+..a. . N
v
F-+
100 . Rodgman, I ., Cook, L . C ., rnc '•Iims, S . S ., Tne_ C e~mDositir.+n . o_t Cihr_,v 4- ,e m
'. . V
.S ~1{P
..ws.ww . SolanFSenes
..n .s.n..
.
... . .u.. . . . .,. ....,r .w.. ..
J.
0?G
. . C"1
s~. ., 2o : I, 97-501
• CJ1
m
Ch
l0
1 3
101 . Rodgman, A ., and t•1ims, S . S ., The Anal sis of Ci . arette Smolse Condensate .
XXIIIII ._Possi,ble__Precu_rsors in Tobacco of enols n o acco !ao e . -""
W/VMdR'ILIAIYI~Y/. . .

RDR in preparation .

102 . Roe, F . J . C ., Salamin, 14 . H ., and Cohen, J., I om-?lete Carcino ens :in
Ci ga-r-e-tte Smoke Condensates Tumour Promotion a Fhenolic Fraction .3cIT.
J: CANC~ 33 .

103 . Royal College of Physficians, "Smoking and Health" . New York, N. Y ., Pitman
Publishing Corp ., 1.~,62 .

104 . Saboux, M. S ., Osman, L . M., Glem, J ., Fahy, T ., and ILamb, P ., C4c


of the Lungs .R vi~ew of J09ses,: DIS . CHEST, Al, 530~'j46 (1962) .

1% . Sanderud, K., Squamous ithelial Meta lasia in the Respirato.ry rTiact in


Ur,~nmj.e,~,. BRIT. J . C.ANCER, ~, 2 -

106 . Sanderud, K ., aamous NTetulasia of the Respiratory Tract Epithelium . An


Autons Stud~y of 21/~ Cases . . a oriT'o`To~iacco '~moT cua "
.. .~~~ on,and
~
~,es ~de ce BCA ~'

107 . Sanderud, K., uamous bista le sia of the Re s irator Tra ct Foitheliu~~a.
An Autopsv Stud of 214 Cases . , . e a on o"'TTseas~"e:"°'~'~le PtT~L:
OBIO WS .,

108 . Shin,ikin, td. B ., Pulmonar T ors in Ex^oerimental Animals . ADiI. C :1CER


R='SE~IRCH, I, 223-26? (1955) .

109 . Spain, D . t•i., The Distinction Between Re eneration and Atyaical Alterations
. ip he Bronchia lMucosa . ANf. REV. TDffaC . , 7, 5''1- ?09 .

110 . Szolomajer, J ., Mor holo ic31 Chanaes in the Tracheobronchial :•iucosa of


Residents of Cincinnati and va.rons . n: CTO OF SCIMCE DISS ., V•dIMMSITY
OF CIi•TCIPIi'Te1T , , 04 pp .

111 . Teague, C . E ., Si :rv v of Cancer Research with Emphasis uaon Possible


Csrcino ens from Tobacco . SPECIAL REPORT, FEB . 2 .

112 . Tremer, H . 2•I., Falk, . H. L ., and Kotin, P ., Efc .Air Pollutants on Cili-
ated Mucus-secretin Enitheliu .*n. J. NATL . CA?TCER I'TST ., a, 9-9 : 1cn9 .

113 . Van Duuren, B . L ., 3ilbao, J . A ., and Joseph, C . A ., Tho Carcino enic


Nitro•en Heteroc clics in Ciaarette-Smoke Condensate . J. NbTL . CH~.
I ~ :, ;~~
114 . Walker, W. E ., Phosrimtric Deter.mination o R Polyn 1'egrA=oic
iivCrocarbons . MR, I``?bl, 's•to.~~(qj .t'? . 2'7).

115 . '.leller, Z . W . , M°tanla sis of Bronchial Epitheliira


+.. .....~r (A. POst- :iortel"Al Stud ) .
.,, .... . . .,r. - . . . . ...r«..., .. ..+ ..r.....,. ... ..~..
:,:d. J . CLT.•' . PA!.? 2i, 7,~~=~l77.

116 . :Iynder, 73 . L ., L•aborntor• I COn~:r


~ 'i
y bL̀ltion t o _ t ~Re T~o.- bacco-~.~iaacer ~"ob: .il .
1'~Vl .~ ' . ^JLT~ . '.:C~~ it.~ .
/,p'1' , 17~ .~t-lU 1 ;~l~i~/v`/
f Nq

117 . Wynder, E . L ., Bross, I . J ., Cornfield, J ., and 0'Donnell, W . E ., ;!Ms


Cancer in Women : A Stud of Environr~ental Factors . 1dEW ENG .
0
255,, 1111-1121 1 .

118 . 4ionder, E . L ., Ferrari, E ., and Frrti, E ., Lung Cancer in Venice . An-


Evidemiolo ical Stud . LIITCLT, 1961 (ii), 1347-13 9 .

.
119 . Wynder, E . L ., and Hoffmann,. .DStudies with the Gaseous a nd Particul,,ite
Pha se of Toba
.... ~. cco Smoke . PROC . Ai 1. A ., . CI` rI. MT,ti . C, W, 373
U '2-.

120 . Wynder, E . L ., and Lemon, F . R ., and Bross, I. J., Cancer~and Coronary


Arter Disea se 9monrz Seventh . L1a-v Adventistr .

121 . Yamagiwa, K ., and Ichikawa, K ., Uber die Kunstliche Erzeumng von


II . - .,
ll ~ ~ a„I/,fJY

,
' Author : Alan Rodgman

Division : Chemical Research Notebook pages : none


1 q6 3
r
RDM, 1962, No . V Previous Reports :
t RDI4, 1954) No. 31
No . of pages : RDM, 1955 , No . ]3
t RDK, 1956, No . 10
RDR, 1959, No . 1

TIZ SMOKa1G A_IiEALTH_ PBOBLEM,--


.. CRITICAL
A AND OBJECTIVE
_....-.. .. ...... .~..~......APPRAISAL
... ...~.......

The cigarette smoke-health problem is discussed, and it is related to

the potential involvement of the members of the Company's Research Department .

Special emphasis is placed on the lung cancer problem . Arguments by those

claiming cigarette smoke as a health hazard are prese~tedp as well as the


i
oounter-arguments of those not in accord with such views . The weight of the arguments

and counter-arguments is discus ed . An attempt has been made to present the

o arguments objectively . the rguments,

are 4iade .
v

u
several recommendations

This memorandum presents my position as briefly and as concisely as possible .

Id a companion memorandum with V& identical schematic organization, the same

thoughts are presented in more detail . If requested, a thorough, fully documented

exposition of the ideas will be prepared .

=fORANDUI~ u,
. . N
Alt0ough the major part of the sales of this Company consists of cigarettes, N
m
what the Company As se,i}V se113" is arette smoke . This Company, therafore, Ln

should be posfty concerned with the physiological ppperties and composition of N

cigarette smoke . The benefits antbio* from such '.cr.owledg3 are obvious, particularly

if it anticipates possible future governmental regulation . During16 past two decades,

cipgarette smoke has been it :1e target of a host of studies relating it to ill nealth

i I and particularly to lung cancer . The majority of these studies incriminate cigarette

smoke from a health viewpoint .


-2-

_I. The Evidence - Pro and Con

The cigarette smoke-lung cancer problem has been investigated

epidemiologically, pathologically, biologically, and chemically .

Each discipline has yielded pertinent information .

L- NP1d44o1oZiaa1 Rata_ •
~ The results of 34 different statistical studies show that cigarette

smoking increases the risk of developIng lung cancer . Mbny authorities

,;; :_believe the relationship to be one of cause-and-effect,

Contradictory data have been provided by limited statistical studies

which suggest that cigarette smoking is linked to a constitutional factor .

The results of these studies can, however, account for only a small

fraction of the difference in lung cancer incidence observed between

smokers and nonsmokers .

The statistical data from the smoking-health studies are almost

universally accepted . After more than ten years, criticisms of the studies

have been reduced to the dictum A st~at~istioal sjW,y ctannol „nrove a c~gsQ ;

and-ef o,C rel,ationsl•Ip~b_2tXeen two factors .

k. _Patho_lggi_cLl. Dg,tL

qIt has been observed that cigarette smokers' lungs show profound cellular

changes which are proportional to cigarette consumption, that fluorescent

const3ituents of cigarette smoke are absorbed into respiratory tract cells

(although fluorescence dnd . :cercinogenicity are not synonymous), that cigarette

smoke and some of its constituents cause ciliary paralysis, and that

cigarette smoke collects in the lungs at cilia-free areas and at areas

with paralyzed cilia . cn


~
~
N

• m
Contradictory evidence indicates that the above-described cellular

changes can be caused by respiratory diseases and other illnesses, that

these changes occur to a degree in infants, in nonsmokers, in the windpipes

of smokers (although cancer of the windpipe is rare), and in residents of

areas of extreme air pollution, and that ciliary paral,ysis can be caused by

air po].hutants like industrial and automobile exhaust gases . Also it is

not known whether such changed cells ever become cancerous .

These findings may be summarized as follows : Si1ce cellular changes in

ttM Vtst.<=ar_J f L il Y r_a M. a f or"th_e t ff~n &M re_t

s si s occur in m s' 1 s a the ncer• ee

3LU U ee 7iV a $an t-i 0 !liOA".LO ether_ theae _ch lungm d

re k ot_th a_c_tor__to be

blamga , in lung, q,ancer caqs_ation .

_c. P.i412g&CL1.Pg.tL

Cigarette smoke condensate is carcinogenic to mouse skin . Mch is made of

the fact that the dosage level used exceeds that of the human exposure . Other

investigators, using nominal dsage levels, did not obtain positive results .

Some interpret this as an indication that cigarette smoke is not carcinogenic .

It should be noted, however, that many attempts were made to induce cancer i~z

animals with .coal tar prior to the first success with unrealistic dosages .

Inhalation studies with cigarette smoke have yielded an increased incidence

of adenomas in adenoma-susceptible mouse strains . No hAman-type carcinomas have

been produced although the previously mentioned cellular changes and bronchitic

conditions have .

These findings are interproted by sone as an indication that cigarette

smoke is not carcinogenic to human lung tissue . Two facts offset such thinking . Ln
~
J
Fir,st, mice are not men, hence carcinomas should not be expected in a host ~
m
Ln
m
~
~
resistant to the #nduction of carcinoma of the lung and whose usual lung

cancer is the adenoma . Secondly, the ratio, lung cancer deathsstotal cigarette

smokers in the United Statds, is approximately 1 :1700, hence an inhalation

experiment would require about 1700 mice for the production of one lung caroinoma,

assuming the response of mousd and human lung tissue was the same . The biological

dindings are often dismissed with the statements Dfice are not men and bfoM

4413,1g,,no hji.man lung tisr,sue.

.4• 2hjnjc"&'tL
Cigarette smoke contains at least 17 compounds carcinogenic to mouse skin .

Cigarette smoke also contains promoting (or cocaroinogenic) agents . These findings,

at first impugned, are now accepted but dismissed as unimpoe3tant because none of

the compounds has been shown iZ X&M to be carcinogenic or cocaroinogenio to

human lung tissue . It is unlikely that such experiments will ever be carried out .

e_ . Thg XvIdgnge to_ D_ate_


Obviously, the amount of evidenoe accumulated to indict cigarette smoke as

a health hazard is overwhelming . The evidence challenging this indictment is scant .

Attempts to shift the blame to Ither faotors, e .g., air pollutants, necessitates

acceptance of data similar to those denied in the cigarette smoke case .

IIt Igtgruret_ ;Ltjqpy of the Evidence


After reviewing this evidenoe, goversmental health agencies and medical Ln

societies throug9 world have concluded that a cause-and-effect relationship G

e.-dsts between cigarette smoke and lung cancer . It is predicted that the recently m
J

appointed Surgeon General's Advisory Committee on Smokinp and Health will reach the "'

same conclusion.
It has been repeatedly stated that some scientists discount the cigarette smoke-

lung cancer theory . This is true . But it should be noted that many of those quoted in

this regard are on record with contra\ np views, e .g ., Berkson,the statistician, has sqc

stated " . . .t:Ze definitive important finding of th3se statistical studies is not that
tiier3 is an a3sociation between smo :cing and lua?, cancer, but that there is an
association between amoking and deaths from all causes generally . . . . .", and Kotin, '

member of the Scientific Advisory Board, TIRC, stated "The statemeiti . . .to the effect

that 'The sum total of scientific evidence establishes beyond reasonable doubt that

cigarette smoke is a causal factor in the rapid]y increasing incidence of human

epidermoid cancer of the lung' represents a view with which we concur .~

M. The T_, b,g,_aaco Indus_t_,ry, !s Cont ibu ion

To investigate the tobacco smoke-health situation the Tobacco Industry has given

about five million dollars to TIftC since 1954 for research . According to Little, its

Scientific Director ., the puppose of TIRC is " . . .to encourage and support qualified

research scientists in their efforts to learn more about these complex problems ~Cancer

and heart disease .'' Through December 1961, TIRC grantees published 197 papers ; 36

on the chemistry of tobacco an~tLts smoke, 47 on cancer research, 13 on human lung

studies, 78 on heart and circulation studies, 4 on gastrointestinal tra ct studies,

5 on psycho-physiolo4ol studies, and 14 miscella neous studies (lung cancer reviews,

tobacco-health textbook) .

I believe that much ofi^this research, particularly that on the chemical, biochemica]

and biological study of tobacco and its smoke, could have and should have been carried

out in the research departments of the tobacco companies . The members of this Company's

Research Department are as qualified, as ob3ective, and g,s_ Inter~ _e tqd in learning " . .~

more about these complex problems . . . . .'as scientists not employed by a tobacco manufac-
no
turer . Any findings made byt us could'iave any more adverse effect on the Tobacco Industry~

than those reported by TIRC grantees~~


.

This Company is studying in detail the composition of cigarette smoke, but much

data remain unptblished because they are concerned with carcinogenic or cocarcinogenic

compounds or with patentable material . This raises an

cn
P.
~
~
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Ln
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~
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interesting question about the former yioNqUO compoundsS If ab0tom company

plead "Not guilty" or Not proven" to the charge that dig,•rette smoke (or one of

its constituents) is a~~ factor in the causation of lung cancer or

some other disease, can the company justifiably take the position that publication

of data pertaining to cigar.ette smoke composition or properties should be

withheld because such data might affect adversely the company's economic status

when the company has already implW in its plea that no such etiologic effect

extsts?

It ls not my intent to suggest that this Company accept the cigarette smoke-
KV--.
health data at face value, but I do auggest that active participate

in cigarette smoke-health studies .

B . RECOP MNIDAT IONS

10
After consideration of the evidence available on the cigarette smoke health

problem and the Company's obligotion to its customers, stockholders, and •employees,
i

it is recommended that :

1. Facilities, animals, and personnel (where necessary) be a•cquired *s soon as

t possible to study biologically cigarette smoke, tobacco, and tobacco additives .

Data from such stddies ma y be invaluable if gover an ~ 1 restrictions are

imposed as a result of the conclusions of the Surgeon 14eneral's Advisory


Ln
Committee on Smoking and Health .. N
~
~
2 . W14- ~ata ahm..ig available 6n cigarette smoke constituents with adverse m
~
m
physiological effects be published . ~
~
3 . Data on analyt.ical pnocedues concerning such constituents be published .

4 . The Compan7's supervisory personnel be provided with reports like the

Royal College of Physicians' 4_mwoft Smoking and He9lth and the AnauAl Renort

of the Scientific Director (TIs1C) just as they were provided with Science

Looi:s at -mokina 0?orthruv),


. ._._ and iiealth pamphlets, anr:.
Tobacoo
"favorable" articles from tI~ .

5 . This Company's management recognize that many members of its Research

Department are intensely concerned about the cigarette smoke-health problem and eager to rarticipate in h4m study and solution

!
• January 10, 1963
Mr. Kenneth H . Hoover
Re: RDM, 1963, No . 1 and RDM, 1963, No . 4
It is my understanding that if I sign and
approve these reports I am subscribing to gl] of the
opinions, conclusions, recommendations, and the like contained
therein . I believe that these reports are factually
correct, and I agree, in general, with the interpretations and
conclusions presented . I-further believe that these_
reports are useful and timely, and should be allowed
to see the light of day . I do not, however, agree
fully with all of the statements, particularly certain
of the recommendations, made therein, and on this basis
probably should not "approve" these reports under the

• existing definition of "approval ."


The health question has no easy answer and
generates many points of view . It would be remarkable
indeed, if my views on this complex and controversial
question coincided exactly with those of Dr . Rodgman.
I believe he has a right to be heard despite my
honest disagreement with him on certain minor points .
Accordingly, I recommend that the reports be accepted
and distributed . I might also suggest that copies
be made available to members of our Legal Department .

C.E. Teague, Jr.


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L : :o_ : r.lan Rodg:::an February 12, 196 4

Divisio :.: Chemical Research Aotebool: pages :


See Appendix I

RDR, 1964, No . 1 0 Previous reports :


See Appendix I I

No . of Pages : 70

THE ANALYSIS OF CIGARETTE SMOKE CONDE' XSATE . MV .


A SUMMARY OF AN EIGHT-YEAR STUDY

OBJECT :

To summarize without experiment detail the results of a study of ciga-


rette smoke conducted in this laboratory from August 1955 to date .

SUMMARY :

During the past .eight years an intensive investigation in our laboratory


on the composition of cigarette smoke from various tobacco types and blends
has permitted identification of many compounds and classes of compounds .
These include the following :

1 . Saturated hydrocarbon fraction

Very little work was done on this fraction in our study since this
material had been investigated extensively by others . This fraction
was isolated from thecigarette smoke of a11•types and blends of
tobacco studied .

2 . Phytadienes and neophytadien e

Neophytadiene was identified unequivocally as the majc .:- phytadiene


in the cigarette smoke :--om WINSTON blend, CAMEL bler._, Turkish
blend, flue-cured and i. .•.ley tobacc . The remainder of the
phytadiene fraction, also present i . =he smoke from these tobacco
types and blends, consisted of at least three and possibly a s
many as 12 phytadienes .

3 . Squalene and isosqualenes

The squalene-isosqualene fraction isolated from WINSTON blend


tobacco smoke consisted of at least two, and possibly three isomeric
hydrocarbons .

4 . Solanesene t

The exper : .:ental data indicated the presence of'at least two
solanesenes . These were present in th . smoke from WINSTON blend,
Turkish blend, flue-cured and burley zobaccos .
:. . Polycyclic arosatic hydrocarbons

To date, 43 polycyclic hydrocarbons have been identified in kI.;STON


cigarette smoke . 0! these, 14 iaere '__~antified unequivocally . Those
were as follows : naphthalene, 1-methylnaphthalene, 2-mcthylnaphthele .^.e,
acenaphthene, acenaphthylene, fluorene, pizenanthrene, anthracena,
pyrene, fluoranthene, benz[a)anthracene (1,2-benzanthracene),
benzo[a)py~ene (3,4-benzpyrene), and dibenz[a,h)anthracene (1,2,5,6-
dibenzanthracene) . The remaining 29 hydrocarbons were identified
solely on the basis of ultraviolet absorption data . Included were
the following : 1-methyl-3,4-dihydronaphthalene, 2-phenylnaphthalene,
9-methylanthracene, 9-methylphenanthrene, 1-methylpyTMene (3-methyl-
pyrene), 2-methylpyrene (4-methylpyrene), 4-methylpyrene (1-methyl-
pyrene), 3-methylbenz[a]anthracene (3-methyl-l,2-benzanthracene),
benzo[ghiJfluoranthene, benzo[j]fluoranthene, benzo[k]fluoranthene,
benzo[c]phenanthrene (3,4-benzphenanthrene), perylene, benzo[e]pyrene
(1,2-ben .-yrene), benzo[jh_i]perylene (1,12-benzperylene), cholanthrene,
naphtho[2,3-e)pyrene (2!,3'-naphtho-l,2-pyrene), naphtho[2,3-a]pyrene
(2',3'-napht,ho-3,4-pyrene), dibenzo[a,l)pyrene (1,2,3,4-dibenzpyrene),
dibenzo[a,h]pyrene (3,4,8,9-dibenzpyrene), dibenzo[a,i]pyrene (3,4,9,10-
dibenzpyrene), dibenzo[df, mno]chrysene (anthanthrene), coronene,
2,3-dihydro-1_A-benzoja)pent[h]anthracene (5,6-cyclopenteno-l,2-
benzanthracene), 10,11-dihydro-9_H-benzo[a]cyclopent[i)anthracene
(6,7-cyclopenteno-l,2-benzanthracene), dimethylphenanthrenes, methyl-
fluoranthene, methylchrysene, and a methylbenzo[a]pyrene (methyl-3,4-
benzpyrene) .

In a limited study of CAMEL cigarette smoke, the following 12 polycyclic


hydrocarbons were identified : naphthalene, phenanthrene, anthracene, pyrene,
1-methylpyrene (3-methylpyrene), fluoranthene, acenaphthylene, benzo[a)pyrene
(3,4-benzpyrene), benz[a]anthracene (1,2-benzanthracene), benzo[~lperylene
(1,12-benzperylene), anthanthrene, and dibenzo[a,h]pyrene (3,4,8,9-dibenzpyrene) .
Of these 12, five were identified unequivocally - naphthalene, anthracene,
pyrene, fluoranthene, and benzo[a]pyrene (3,4-benzpyrene) .

It has also been demonstrated that the cigarette smoke from Turkish blend,
WINSTON- and CAMEL-type flue-cured, WINSTON-type . . .ri2v, SALEM blend, Kent
blend, Parliament blend, Lark blend, and G-7X tobaccos contain the following
five polycyclic hydrocarbons : anthraeene, pyrene, fluoranthene, chrysene,
and benzo[,g]pyrene (3,4-benzpyrene) . It is highly probable that all of the
polycyclic hydrocarbons isolated from WINTSTON cigarette smoke could be found
in the smoke from any tobacco type or blend.

The effect of various factors on the polycyclic hydrocarbon content of


tobacco smoke was studied . Such factors as (a) the use of additives on the
tobacco, the`eigarette paper or the filter tip material, (b) more efficient
filter tip materials, (c) the use of porous cigarette papers, (d) the use of
tobacco ieaf selected from specific areas of the plar.i ., and (e) solvent
extraction of the tobacco prior to smoking produced a reduction in the `n ~
polycyclic hydrocarbon content of the tobacco smoke . ~
m
Ln
m
OD
N
At least three of the precursors in tobacco of the polycyclic hydro-
carbons in the smoke,have been defined . These were as follows : the
phytosterols, e .g ., 15-sitosterol ; :the terpenes, e .g ., solanesol ; and the
saturated hydrocarbon fraction .

6 . Aliphatic ester fraction

Degradation of an aliphatic ester fraction isolated from the


smoke of WINSTON blend and Turkish blend tobaccos yielded 16
normal long-chained primary alcohols ranging from dodecyl
alcohol to 1-heptacosanol, inclusive, and 17 known acids
ranging from myristic to octacosanoic acid, inclusive, plus
oleic and linolenic acid . Thus, the ester fraction could con-
ceivably consist of a total of 272 different esters . This ester
fraction was similar to that isolated from extracts of .flue-cured,
burley, and Turkish blend tobaccos .

7 . Solanesyl esters

Degradation of a solanesyl ester fraction yielded solanesol and


five known long-chained aliphatic acids indicating that the
solanesyl ester fraction consisted of at least five different
solanesyl esters . This fraction was present in WINSTON blend,
Turkish blend, flue-cured, and burley tobacco smoke . Solanesyl
acetate has been identified in the smoke of WINSTON blend, Turkish,
f lue-cured, and burley tobaccos .

6 . Phytosteryl ester fraction



Degradation of a phytosteryl ester fraction yielded stigmasterol
and 13-sitosterol plus six known long-chained aliphatic acids .
Thus, the phytosteryl ester fraction could consist of as many as
12 different phytosteryl esters or as few as six . This fraction
was .present in WINSTON blend, Turkish blend, flue-cured, and
burley tobacco smoke .

9 . Lactones

Turkish tobacco smoke has yielded the lactones sclareolide,


cx- and p-levantenolide . ;

10 . Alcohols and Hydroxyethers

The following alcohols from the tobacco smokes indicated have been
identified unequivocally ; solanesol (WINS=Z blend, CAMEL blend,
Turkish, f lue-cured, burley) ; stigmasterol .:nd A-sitosterol
(WINSTON blend, CAMEL blend, Turkish, flue-cured, burley) ;
12cX-hydroxy-13-epimanoyl oxide (Turkish) ; and phytol (Turkish) .
4

WINSTON blend tobacco smoke has also yielded a normal, long-


chained, primary alcohol fraction containing eight alcohols,
1-heptadecanol to 1-tetracosanol, ir.clusive .

Turkish tobacco smoke has yielded an isoprenoid alcohol fraction


containing phytol and other acyclic unsaturated isoprenoid
alcohols in the C15, CIO, C25 and C30 series . Also isolated were
the macrocyclic hydroxyethers, cx-5,8-oxido-3,9(17),13-duvatrien-l-ol
and Cx-5,8-oxido-3,9,13-duvatrien-l-ol .

11 . Phenols

The follow~ng phenols from tobacco smoke have been characterized :


CX-tocopherctl (WINSTON blend, Turkish, flue-cured, burley) ; phenol,
o- and p-ckesol (WINSTON blend, CAMEL b lend, SALEM blend, Turkish,
flue-cured ; burley, G-7X) ; hydroquinone, 1-naphthol, eugenol, and
isoeugenol (Turkish) .

It was also shown that the amount of phenols in tobacco smoke


exceeded that in the tobacco smoked . An attempt to define the
precursors in tobacco of the simple phenols in tobacco smoke,
e .g ., phenol, o-, m-, and g-cresol, indicated that these pre-
cursors are not extractable from tobacco by the most efficient
tobacco extractant, methanol . Pyrolysis studies indicated that
the known major tobacco constituents, cellulose, pectin, lignin,
and glucose plus fructose (as invert sugar),*yield phenol and
p-cresol on pyrolysis . Similar studies indicated that various
tobacco types, under controlled pyrolytic conditions, also yield
phenol and P-cresol .

12 . Aldehydes and Ketones

CAMEL cigarette smoke has yielded the following aldehydes and


ketones : acetaldehyde, acetone, propionaldehyde, 2-furaldehyde,
glyoxal, pyruvaldehyde, 2,3-butanedione, 3-heptanone, and 2,3-
pentanedione .

13 . Heterocyclic Nitrogen Compounds

Turkish tobacco smoke has yielded the following heterocyclic


nitrogen compounds : pyrocoll, indole, 3-methylindole (skatole),
dimethylindoles, trimethylindoles, carbazole, and methylcarbazoles .

14 . Miscellaneous compounds

The following miscellaneous compounds from tobacco smoke have been


characterized : 6-acetyl-2,3,4-tris-d-p-methylvaleryl-S-D-gluco-
pyranoside (Turkish) ; furan (CAMEL blend) ; benzene (CAMEL blend) ;
and the 4-(2-butenylidene)-isophorones (Turkish) .
5

^ ~ :LE OF CO\TENTS
Pafie

OBJ :.CT . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . 1

SU*L 1AP.Y . . . . . . ., _ . . . . . . . . . . . . . . . . . . . . . 1

LIST OF TABLES . . . . . . . . . . . . . . . . . . . . . . . . .

A . INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . 10

I . Hydrocarbons . . . . . . . . . . . . . . . . . . . . . 10

a . Aliphatic Hydrocarbons . . . . . . . . . . . . . . 10

1. Saturared Hydrocar.bon Fraction . . . . . . . 10

2 . Phytadienes . . . . . . . . . . . . . . . , , 10

3 . Squalene and Isosqualenes . . . . . . . . . . 12

4. Solanesenes . . . . . . . . . . . . . . . . . 13

b . Polycyclic Aromatic Hydrocarbons . . . . . . . . . 14

1 . Isolation of Polycyclic Hydrocarbons from


Cigarette Smoke . . . . . . . . . . . . . . . 14

2 . Reduction of the Amount of Polycyclic Hydro-


carbons in Cigarette Smoke . . . . . . . . . 22

i . By Use of More Effective Filtering


Agents (15) . . . . .. . . . . . . . . . 22

ii . By Use of Porous or Aluminized


Paper (15, 18) . . . . . . . . . . . . . . 22

iii . By Addition of Certain Compounds to


the Tobacco, to the Filter Tip Material,
or to the Cigarette Paper (15, 18, 19,
22, 29, 30) . . . . . . . . . . . . . . 22

iv, By Choice of Tobacco Leaves (15) . . . . 22

v . By Solvent Extraction of Tobacco


(12, 13, 15) . . . . . . . . . . . . . . 30

3 . Precursors of Polycyclic Hydrocarbons . . . . 34

II . Esters . . . . . . . . . . . . . . . . . . . . . . . . 37

a. Aliphatic Ester Fraction . . . . . . . . . . . . . 37

b. Solanesyl Esters . . . . . . . . . . . . . . . . . 40

1 . Solanesyl Acetate . . . . . . . . . . . . . . 40

2 . Solanesy2 Ester Fraction . . , , . . . . , . 40


_ . :~? CC : ;_:;`;TS (Cont` d)
?a e

c . Phytosteryl Ester Fraction . . . . . . . . . . . . 41

d . 6-Acety 1-2, 3, 4-tr :.s-_d-A-methylvaleryl=


p-D-glucopyranoside . . . . . . . . . . . . . . . 42

III . Lactones . . . . . . . . . . . . . . . . . . . . . . . 42

a. Sclareolide . . . . . . . . . . . . . . . . . . . 42

a- and A-Levantenolide : . . . . . . . . . . . . . 43

IV . Alcohols . . . . . . . . . . . . . . . . . . . . . . . 43

a . Solanesol . . . . . . . . . . . . . . . . . . . . 43

b . Normal Long-chained Primary Alcohols . . . . . . . 43

c . Phytosterols . . . . - . . . . . . . . . . . . . . . 44

'd . 12cx-Hydroxy-l3-epimanoyl Oxide . . . . . . . . . . 44

e . Unsaturated Acyclic Isoprenoid Alcohols . . . . . 44

f . Macrocyclic Hydroxyethers . . . . . . . . . . . . 45

V. Pheno l s . . . . . . . . . . . . . . . . . . . . . . . . 46

a . Isolation of Phenols from Cigarette Smoke . . . . 46

1. cx-Tocopherol . . . . . . . . . . . . . . . . 46

2. Eugenol and Isoeugenol . . . . . . . . . . . 46

3 . Other Phenols . . . . . . . . . . . . . . . . 47

. Analysis for Phenols in Cigarette Smoke . . . . . 47

c . Precursors in Tobacco of Phenols in Tobacco


Smoke . . . . . . . . . . . . . . . . . . . . . . 48

VI. Acids . . . . . . . . . ' . . . . . . . . . . . . . . . . 50

VII . Aldehydes and Ketones . . . . . . . . . . . . . . . . . 50

VIII . Heterocyclic Nitrogen Compounds . . . . . . . . . . . . 51

, IX . Miscellaneous Compounds . . . . . . . . . . . . . . . . 51

X . Comparison of Different Tobacco Types . . . . . . . . . 52

XI . Summary . . . . . . . . . . . .~. . . . . . . . . . . . 54

B . E};PERIMEhTAL . . . . . . . . . . . . . . . . . . . . . . . . 55
7 „

TA.Bi.E OF CONTENTS (Cont' d)


Pafie

C. DISCUSSIO,\` . . . . . . . . . . . . . . . . . . . . . . . . 5 6

D . CO\CLUSIONS . . . . . . . . . . . . . ,. . . . . . . . . . 61

E. RECOP^WN'AATIO\S . . . . . . . . . . . . . . . . . . . . 6 2

I. Future Work . . . . . . . . . . . . . . . . . 6

II . Patentability . . . . . . . . . . . . . . . . . . . . 63

BIBLIOGRAPHY . . . . . . . . . . . . . . . . . . . . . . . . . . 64

APPE\'D?X I - Notebook Pages . . . . . . . . . . . . . . . . . 69

APPENDIX II - Previous Reports . . . . . . . . . . . . . . . . . 70

0
;._S^ 0 :' :r, :LES

Table No . Ti .le Paae

I Polycyclic Hydrocarbons in Cigarette


Smoke . . . . . . . . . . . . . . . . . . . 19

II Filter Tip Materials : Effect or. Nicotine,


Total Solids, Tota~ Polycyclic Hydrocarbons
and Benzo[a]pyrene in WINSTON Blend
Tobacco2 Smoke (15) . . . . . . . . . . . . 4

III Effect of Porous or Aluminized Paper on


Nicotine, Total Solids, and Total Polycyclic
Hydrocarbons in WINSTON Blend Tobacc lo
Smoke (18) . . . . . . . . . . . . . . . . . 5

IV Effect of Additives to the Tobacco, to the


Paper, and to the Filter Tip Materials on
Nicotine, Total Solids, Total Polycyclic
Hydrocarbons, and Benzo(a]pyrenel in
Cigarette Smoke . . . . . . . . . . . . . . 6

V Position of Leaf on Stalk : Effect on Fats


and Waxes, Flavorants, and Nicotine in
Tobacco and on Nicotine, Total Solids,
Total Polycyclfc Hydrocarbons, and2
Benzo[a]pyrene in Cigarette Smoke (15) . . 9

VI Solvent Pretreatment of Individual Tobacco


Types and Tobacco Blends : Effect on Total
Polycyclic Hydrocarbons and Benzo(a]pyrenel
in Cigarette Smoke (12, 13, 15) . . . . . . 1

VII Effect of Tobacco Constituents and Other


Orgsr.ic Compounds on the Total Polycyclic
Hydrocarbons and Benzo[a]pyrenel in
Cigarette Smoke (22) . . . . . . . . . . . . 5

VIII Known Constituents Obtained by Degradation


of Aliphatic Ester Fraction (LXVIII) from
Tobacco Smoke (45-47) . . . . . . . . . . . 39

IX Known Constituents Obtained by Degradation


of Solanesyl Ester Fraction (LXXTC) from
Tobacco Smoke . . . . . . . . . . . . . . . 40

Known Constituents Obtained by Degradation ~


of Phytosteryl Ester Fraction from Tobacco _,
Smoke . . . . . . . . . . . . . . . . . . . 41 ~
6
Ln
XI Phenol Content of Cigarette Smoke from m
Various Tobacco Types, Tobacco Blends, co
co
and Cellulose (32) . . . : . . . . . . . . . 8

XII Pyrolysis of Tobacco and Tobacco


Constituents : Phenol Content of
Pyrolysate (50) . . . . . . . . . . . . . . 50
LIST OF TArL ~S (Cor.t' d)

Table No . Title Paee

}:III Conroarison of the Smoke Condensates


from Different Tobacco Types . . . . . . . . 53

0
10

:~ . T' ;i:07L'C^IOiy

At present, the R . J . Reynolds Tobacco Cr. . .pany is recognized as the


ioading company in the Tobacco Industry of the United States . The Company's
s ::olcin ; products constitute over one-third of those sold througnout this
country . Since the major part of the domestic sales of this Company consists
o .: smoking products, e .g ., cigarettes and pipe tobacco, it should be reme :r.bered
that the customer's main interest is not in the cigarettes and/or pipe tobacco
Der se but in the smoke derived therefrom . For this reason alone, the recog-
r.ized sales'leader of the Tobacco Industry should also be the recognized
leader of the Tobacco Industry in its contribution to scientific knowledge
concerning the composition of tobacco smoke .

Tobacco smoke is a mixture whose precise composition has never been


defined . During the past eight years, we have conducted an intensive investi-
gation of the composition of tobacco smoke - particularly cigarette smoke .
The results of this study of cigarette smoke together with the pertinent
experimental data have appeared in a series of Research Department reports
and memoranda dating from 1955 to the present . In addition, selected portions
of these results have been published from this Research Department . The present
report will summarize for ready reference, omitting the experimental detail,
the results presented in the various publications, reports and memoranda .
References pertinent to each topic will be found in the original reports,
publications, and memoranda .

The following sections describe briefly the various compounds or series


of compounds isolated and/or identified in our study of cigarette smoke :

I . Hydrocarbons

a._ Al.jphatic Hydrocarbons

1 . SATURATED HYDROCARBON FRACTION

A saturated hydrocarbon fraction, m .p . 62 .5-64 .5°, was isolated


from the smoke of cigarettes fabricated from flue-cured, Turkish,
burley or blended tobaccos (16, 17, 48-50) . Presumably, this
fraction was similar to that represented by I (n L 20 to 34) and
II (n - 17 to 30) .

u,
CH3(CH2)nCH3 ~3(~2)n~(~3)2 ~
N
m
II cn
m

2 . PHYTADIENES

A series of phytadienes consisting of hydrocarbons with molecular


formula C20H38 and whose structures may be represented by III, IV, V,
11

-and VI was identified as constituents of cigarette smoke (16, 17) .


Only neophytadiene (III, n - 3),

11~'`
H[CH2CH(C'H3)CH2CH2]nCH2CCH=CH[CH2CH(CH3)CH2CH2]3-nH

III

H[ CH2CH( CH3) CH2CH2] nCH-C(CH3) CH-CH[ CH2CH ;(CH3) CH2CH2 ] 3-nH

H[ CH2CH(CH3) CH2 ]mCH2CH(CH3) CH2CfiaCHCH(CH3) _CHCH2[ CH2CH(CH3) CH2CH2] 2-mH

V
fIH2
H[CH2CH(CH3)CH2CH2]mCH2CH(CH3)CH2CH=CHCCH2CH2[CH2CH(

VI

the most polar phytadiene, could be isolated in pure form from


this series . Neophytadiene was the major component of the phyta-
diene fraction . The presence in cigarette smoke of at least one
representative of each of the structures III, IV, V, and VI was
demonstrated by the reaction sequence shown below . This involved
the Diels-Alder reaction of the phytadiene fraction :or subfraction
with 1,4-naphthoquinone (VII), air oxidation of the adducts (VIII,
IX, X, XI), followed by oxidation of the resulting mono- (XII),
di- (XIII, XIV), or trialkyl substituted anthraquinone (XV) to
the correspondingly substituted anthraquinone mono- (XVI), di-
(XVII, XVIII), or tricarboxylic acid (XIX) . Anthraquinone-2-
carboxylic (XVI), 1,2-dicarboxylic (XVII),
Na2cr2o~ .
III (n = 3)
000 02
112504 ~

VIII XII XVI

IV = 3) R 1iN03
02 _ -------y i

XIII XVII

OQ 0
III (n = 0, 1 and/or 2)` 02
VII I
VI (m = 0, 1 and/or 2)
I

x XIV XVIII

C0011
R 02
~)
11NU 3 `
C- il
If ~( ()U( I

X]}:
Z60S 0t Lti5 xi XV
12

1,3-dicarboxylic (XVIII), and 1,2,4-tricarboxylic (XIX) acids were


obtained .
.
No evidence was obtained for the phytadienes XX (m = 0,1,2)
and XXI (m @ 0,1,2) since these will not yield anthraquinone-
carboxylic acids in the reaction sequence shown .

H[ CH2CH(CH3) CH2 CH(CH3) CH-CiiCH=C(CH3) CH2CH2[ CH2CH(CH3) CH2CH'2l2_mH

H[ CH2CH(CH3) CH2CH2]mCH2C(CH3) sCHCH-CHCH(CH3) CH2CH2[ CH2CH(CH3) CH2CH2 ]2-mH

XXI

Discounting the optical isomers and the ais, trans, cis-cis,


.trans-trans, cis-trans, and trans-cis isomers, nineteen phytadienes
are possible . It should be noted that III (n - 0) and IV (n s 0)
are identical .

The evidence indicated that at least four of the isomeric 0


phytadienes were present in cigarette smoke . These were as
follows : neophytadiene (III, n- 3) ; 3,7,11,15-tetramethyl-1,3-
hexadecadiene (IV, n - 3) ; 2,6,10,14-tetramethyl-1,3-hexadecadiene
(III, n - 0 or IV, n - 0) ; and a 1,2,4-trialkyl-l,3-butadiene . As
many as thirteen of the nineteen isomers may be present ; namely,
III (n - 0,1,2,3), IV (n - 1,2,3), V (m - 0,1,2) and VI (m - 0,1,2) .
The phytadienes, other than neophytadiene (III, n - 3), are present
in the smoke condensate in relatively small quantities compared to
the amount of neophytadiene .

The phytadiene series was obtained from the cigarette smoke


condensate from Turkish, flue-cured, and burley tobaccos and from
several different commercial blends of tobacco (WINSTON, CAMEL,
SALEM, Kent, Parliament) (16, 17, 48-50) .
Ln
3 . SQUALENE AND ISOSQUALENES
~
A series of hydrocarbons, C30H50, consisting of squalene m
(XXII) and isosqualenes, presumably XXIII and XXIV, was isolated ~„
from WINSTON cigarette smoke (53=55) . . The amount of squalenes ~
in the smoke was 2 .4 mg . per 1000 cigarettes . w
13

H[ CH`,C(CH3)=C'dCHi ] 3[ CH,)CHaC(CH3) C~:2] 3H

}OaI

CH2-C ( CH3) C'd2 CH2 [ CH2C (CH3) -CHCH2 ] 2[ CH2 CHaC ( CH3) CH2 ]

XXIII

CH2=C(CH3)CH2CH2[CH2C(CH3)=CHCH2]2[CH2CH=C(CH3)CH2]2CH2CH2C(CH3)=CH2

XXIV

Treatment of this fraction with hydrogen chloride yielded a sample


of squalene hexahydrochloride which was identical with an authentic
sample prepared from squalene . '

4 . SOLANESENES

A series of solanesenes, C45H72, the major portion of which


appeared to consist of XXV and XVI, was isolated from WINSTON
cigarette smoke (53-55) . .

~2
H[CH2C(CH3)=CHCH2]8CH2CCHgCH2

XXV

H[CH2C(CH3)-CHCH2jgCH-C(CH3)C=CH2

XXVI

Similar series of hydrocarbons were obtained by the dehy-


dration of solanesol (XXVII) at 70° using potassium hydrogen
sulfate and by the pyrolysis of solanesyl acetate (XXVIII) at
400° .

H[ CH2C(CH3)=CHCH2] 90H

XxVII
14
0

~H[CH2C(CH3)=CHCH2J90C H3

}:XVIII

Ozonization of the solanesenes obtained either from ci ;a-


:ette smoke or by dehydration of solanesol, followed by reductive
cleavage of the ozonide, yielded formaldehyde,-acetone, levulin-
aldehyde, and methylglyoxal . These cleavage products were identi-
fied as their 2,4-dinitrophenylhydrazones . ,

b ._ Pol,ycyclic Aromatic Hydrocarbons

1 . ISOLATION OF POLYCYCLIC HYDROCARBONS FROM


CIGARETTE SMOKE

Fractionation of the smoke condensate from 20,000 WINSTON


blend cigarettes permitted the identification of 43 polycyclic
hydrocarbons (28) . Of these, 14 were characterized by chemical
and physical properties in addition to ultraviolet absorption
spectra . These 14 .included the following : naphthalene (XX]X),
1-methylnaphthalene (XXX), 2-methylnaphthalene (XXXI),

acenaphthene (}IXXII), acenaphthylene (30CXIII), f luorene (XCXIV),

XXXII MIII XXXIV


pher. ::nthraze (:=,V) , anthracene (} :}:.1VY) , pyrene (:ti}:}TII) ,

C / \ \
\ ~ / /

XXxV XXXVI ??:.1VII

fluoranthene (XXXVIII), benz[aJanthracene (1,2-benzanthracene)


(XXXIX), chrysene (XL), benz[aJpyrene (3,4-benzpyrene) (XLI),

XXXVIII XL XLI

and dibenz(a,h)anthracene (1,2,5,6-dibenzanthracene) (XLII) . The


remaining 29 polycyclic hydrocarbons were identified solely on
the basis of ultraviolet absorption . These 29 included 1-methyl-
3,4-dihydronaphthalene (XLIII), 2-phenylnaphthalene (XLIV),

XLII XLIII }.ZIV

~
m
..• . .~ . ' • .fl
9thylanthracene (} :LV), 9-rwzhylpne :.anthrene (}:LVI),

CH3

XLV XLVI

1-methylpyrene (3-methylpyrene) (XLVII), 2-methylpyrene (4-


methylpyrene) (XLVIII), 4-methyipyrene (1-methylpyrene) (XLIX),

% ~% / / (

H ~' . . ~
\

XLVII XLVIII XLIX

5-methylbenz[a]anthracene (3-methyl-l,2-benzanthracene) (L),


benzo[A.h.Li]fluoranthene (LI), benzojj]fluoranthene (LII),

/ \ \
ri
\' / / C:'.

L LI LII

benzo[k]fluoranthene (LIII), benzo[c]phenanthrene (3,4-benzphen-


anthrene) (LIV), perylene (LV),

LIII LIV LV
:7

benza[ aJpyrene (1,3-aen zpyreze) (LVI), benzo[ cc : :jper}•iene (1, _2-


benzperylene) ( :.VII), cholanthrene (W-III), naphtho[2,3-e]pyrer.e

/I

/ \\
\ II
/ /

LVI LVII LVIII

(2',3'-naphtho-l,2-pyrene) (LIC), naphtho[2,3-a]pyrene (2',3'-naphtho-


3,4-pyrene) (IX), dibenzo[a,l]pyrene (1,2,3,4-dibenzpyrene) (IXI),

m
L]X LXI

dibenzo[a,]I]pyr.ene (3,4,8,9-dibenzpyrene) (IXII), dibenzo[a,i]pyrene


(3,4,9,10-dibenzpyrene) (LKIII), dibenzo[def,mno]chrysene
(anthanthrene) (IXIV) ,

// \
I
/ / ( \ /
\ \ /

LXII LXIII LXIV


is

coroner.c : =~:V), 2,3-diZydro-'_;i-banzo[_ ;cyclope .,t[h]Enthracene (5,6-


cycloper. :.a :io-1,2-benzanthraczne) (iXVI), and 10,11-dihydro-9H-
benzo[ a]cyclopent[ ijar. ;.hracene (6,7-c .•clopenteno-l,2-benzanthra- ,
cene) (LXVII) . In addition, ultraviolet spectral evidence was

I
.
I
LXV LXVI LXVII

obtained for dimethylphenanthrenes, a methylfluoranthene, methyl-


chrysene(s), and a methylbenzo[a]pyrene (methyl-3,4-benzpyrene) .

The polycyclic hydrocarbons found in our study, but not


reported elsewhere, include 1-methyl-3,4-dihydronaphthalene (XLIII),
2-phenylnaphthalene (XLIAV), cholanthrene (LVIII), and naphtho[2,3-e]-
pyrene (2',3'-naphtho-l,2-pyrene) (LIX) . Of these, cholanthrene
(LVIII) is known to be carcinogenic to mouse epidermis .
.
Fractionation of the smoke condensate from 10,500 CAMEL blend .
cigarettes permitted the identification of 12 polycyclic hydrocarbons
(11) . Of these, five were characterized by chemical and physical
properties in addition to ultraviolet absorption spectra . These
five were naphthalene (lQCIX), anthracene ()3 :XVI), pyrene (XXXVII),
fluoranthene (XXXVIII), and benzo(a]pyrene (3,4-benzpyrene) (XLI) .
The remaining seven hydrocarbons, identified solely on the basis
of ultraviolet absorption spectra included acenaphthylene (XXXIII),
phenanthrene (XXXV), 1-methylpyrene (3-methylpyrene) (XLVII),
benz[a]anthracene (1,2-benzanthracene) (XXXIX), benzo[phi]perylene
(1,12-benzperylene) (LVII), dibenzo[ def,mno] chrysene (anthanthrene)
(LXIV), and dibenzo[ a,h]pyrene (3,4,8,9-dibenzpyrene) (LXII) .

Table I lists the polycyclic aromatic hydrocarbons identified


in cigarette smoke to date in this laboratory and the approximate
amounts of these compounds found in the cigarette smoke from
various tobacco ble,nds and tobacco types .
TABLE I

POLYCYCLIC AYUROCARL'ONS IN CIGAIti';.rJ'B SMOKE

~antity, Micrograms pcr Y.i_lol ;ram of Tobacco Smokcc h i .n thc Ci.~arrt_t c Su,r .kc tr,~n,
CAi31 :T.- WINSTON-
Type Type WINS''ON-
WINSTON CAMEL SALEM Flue- Fluc- Type Turki.sit
Polycyclic ilydrocarbon Blend Blend B lend Cured Cured BurlSy hle„d
_ G-7X l:ent: Lriri:
(28) (11,14) (15) (15) (15) (15) (15) (15) (21.)
1. Anthracene (XXXVI) 275 104 178 257 212 269 299 126 246 •i-

2. Pyrene (XXXVII) 60 95 34 53 53 55 86 26 52 -I-

3. FluoranL•hene (XXXVIII) 260 152 190 247 205 266 330 1i,0 205 208

4. Benzo(a]pyrene (XLI) 64 84 65 67 63 77 119 33 60 82


,. .
.c,
5. Chrysene (XL) 44 + 10 31 23 19 18 6 30 •t•

6. Benzja]anthracene (XXXIX) 17 2 .5

7. Benzoj hi]perylene (LVII) 17 +

8. Dibenzoja,h]pyrene (LXII) trace 0 .9

9. 1-Methylpyrene (XLVII) 3 trace

10 . Dibenzojdef,mno]chrysene (IXIV) 7 trace

11 . Acenapht-hylene (XXXIII) 500 +

12 . Pltenanthrene (XXXV) 140 +

13 . Naphthalene (XXIX) 2280 +

14 . 1-i`ic thy 1naph tha lcne (XXX) 360

15 . 2-i•icthylnahiithalene (XXXI) 1000 00TS OTLZS


TABLE I (Cont'd)

Quantity, Micrograms per Kilogram of Tobacco Smoked, in the Cx_f;arrt:er Smolsr Frol :1
CAMEL- WINSTON-
Type Type WINSTON-
WINSTON CAMEL SALMi F lue- F lue- Type Turkish
Polycyclic llydrocarbon Blend Blend Blend Cured Cured Burley Blend G-7Y. Kent.- Lark

16 . Acenaphthene (XXXII) 1720

17 . Fluorene (XXXIV) 230

18 . 9-Methylphenanthrene (XLVI) 43

19 . Dibenz[a,h]anthracene (XLII) 15

20 . 1-Methyl-3,4-dihydronaphthalene 250
(XLIII) ,.,
V

21 . 2-Phenylnaphthalene (XLIV) 140

22 . 9-Methylanthracene(XLV) 60

23 . 4-Methylpyrene (XLIX) 62

24 . 2-Methylpyrene (XLVIII) 51

25 . 5-Methylbenz[a]anthracene (L) 3

26 . Benzo[ ii]fluoranthene (LI) trace

27 . Benzo[j]fluoranthene (LII) trace

28 . Benzo[k]fluoranthene (LIII) trace

29 . Benzo[c]phenanthrene (LIV) trace

30 . Perylene (1.V) 14
tOtS OtLtS
31 . B~o[ e]pyrene (LVI) 44

32 . Q . ..mnthrena (T,17III) 6
S
TAT,LF I (Cont'd)

Quantity, Micrograms per Kiloram of Tobacco Smoked, in thc Cigayecrr_ ;;u~l ;•:•
CAr1F L- WINSTON- - --
Type Type WINSTON-
WINSTON CAMEL SALEM Flue- Flue- Type Tur.ki.sh
Polycyclic 1lydrocarbon . Blend Blend Blend Cured Cured Burley lslcnd G-7X I :c•ul

33 . Naphtho[2,3-e]pyrene (LIX) trace

34 . Naphtho[2,3-a]pyrene (IX) trace

35 . Dibenr.o[a,l]pyrene (LxI) trace

36 . Dibenzo[a,i]pyrene (LXIII) trace

37 . Coronene (IXV) 3

38 . 2,3-Dihydro-lii-benzo[a]cyclopent- c-~
[h]anthracene (?XNI) trace

39 . 10,11-Dihydro-911-benzo[a]cyclopent-
[i]anthracene (IXVII) trace

40 . Dimethylphenanthrenc(s) 140

41 . Methylfluoranthene 43

42 . Methylchrysene(s) 22

43 . Methylbenzo[a]pyrene 6

ZOTS OILTS
2 . REDUCTION OF TFI r*!XNT OF POLYCYCLIC Hl'OROCai.EONS
IN CIGARETTE S"'•OI:E

It has been demonstrated in this laboratory that the amount


of the total polycyclic hydrocarbons in cigarette smoke can be
reduced by the following methods :

(a) by use of r.:ore effective filtering agents

(b) by use of porous or s .iuminized paper`

(c) by addition of certain compounds to the tobacco, to the


filter tip material, or to the cigarette paper

(d) by choice of tobacco leaves

(e) by solvent extraction of tobacco

i . By Use of Ilore Effective Filtering Agents (15)

Table II illustrates the results obtained in studies to


determine the effect of various filter tip mate=iels on the
amounts of nicotine, total solids, total polycyclic hydro-
carbons, and benzo[a]pyrene (3,4-benzpyrene) in WINSTON blend
tobacco smoke .

ii . By Use of Porous or Aluminized Paper (15, 18)

Tab le III illustrates the results obtained in studies to


determine the effect of porous or aluminized paper on the
nicotine, total solids, and total polycyclic hydrocarbons in
WINSTON blend tobacco smoke . The aluminized paper had very
little effect on the quantities of these in the cigarette
smoke .

iii . By Addition of Certain Compounds to the Tobacco,


to the Filter Tip Material, or to the Cigarette
Paper (15, 18, 19, 22, 29, 30)

Table IV shows the results obtained in studies designed


to find suitable additives (usually inorganic compounds) which
could be placed on the tobacco to reduce the amount of the
polycyclic aromatic hydrocarbons, particularly benzo[alpyrene
(3,4-benzpyrene), in cigarette smoke . It should be noted that
alumina (29), hydrated alumina (18, 22), catalytic rhodium,
palladium, and platinum supported on alumina (29), magnesium
nitrate hexahydrate (22) and aluminum nitrate nonahydrate (22)
were quite efficient . Hydrogen peroxide (22), am .~nonium
O:• :EL'a . ..2 ) , C` . _ .:i: ( 22 ) ~ m et :1J^. i ^i: t= 2), , . . ~ .. :: i :1L•~:: ;)Cr-
~7 ~•
chio_,. ;: e ^.or.ahydr_t„ ~--i , and a :.ur., :nu ... a c ;;tcta tet :ahycrate
'22 ) ve i . --C-~e c :.a::ft: . :Cle ''••4 ..• 4- 10'
n o~ sL'1~L• r
Ll:v4-r~•.•6•- .• n.i . r r . . ..in total p
.•. .iJe olyYyc l- rc y r J ca r ./ o ^s and
i{ .-

c.c^.cc'_ ;pyrene (3,'+-bencpyreze) in the smoke (22) .

The use a s filter t :.p additives of agents such as chlor a r.il


G':. 2 ,=:, 7 -t r i ::it :c t 1L'o :e :.one (1 10 , 30) which are known to co mp leX
with the polycycac : ydrocarbo :a ciC not result in any marked
decrease in the total polycyclic aydrocarbons at nominal levels
of the comple: : :.: g agent (0 .6 or 0 .> .:.o . per filter tip in the
case of the tr :n_ :_ofiuorenone) . At a high level, chloranil
(6 .0 mg . per filter tip) produced a 23 percent reduction in
total polycyclic hydrocarbons . However, chloranil is a mucous
membrane irritant in the human .

Mixtures of sodium and potassium salts of citric acid


applied to cigarette paper resulted in a decrease in the total
polycyclic hydrocarbons in WINSTON cigarette smoke (15) .

iv . By Choice of Tobacco Leaves (15)

Table V shows the effect of position of the tobacco leaf


on the stalk on the amount of the po7rcyclic hydrocarbons in
the cigarette smoke derived therefrom . Although there may
be a discrepancy in the results obtained in the case of the
burley tobacco samples due to a possible interchange of
samples, it is obvious from the data obtained that tobacco
leaves can be chosen to give low values of total solids and
polycyclic hydrocarbons in the smoke derived therefrom .
TAP,LE I I

FILTER TIP MATERIALS : EFFECT ON NICOTINE, TOTAL SOLIDS, TOTAL POLYCYCLIC


HYDROCARBONS AND BENZO[a)PYRENE 1- IN WINSTON BLEND TOBACCO SrIOKE (15 )

Nicotine3 Total Solids 3


Filter Tip in Smoke in Smoke Total Benzo[aJp)'renc l
Length, Mg . / Red' n Mg . / Red' n Mg . /kg. Red'n y/kg . Red' n
Materia l men. Ci . % Ci . % Smoked % Smoked %

Nil. -- 1 .97 -- 26 .0 58.3 81

Estron 8/70 17 1 .48 25 20 .7 20 50 .5 13 77 5

Estron 8/70 17 50 .5 13

Estron 8/70 17 _ 46 .2 2 1

Estron 8/7 0 17 1 .43 2 7 20 .5 21 51 .6 11


Estron 8/70 plus
17 1 .44 27 20 .7 20 50 .2 12
2% DOW ET 358
Estron 8/70 17 1 .44 27 19 .7 24 50 .2 12

Estron 3 .3/66 17 1 .22 38 16 .0 38 33 .5 4 3

Dico 230 17 30.9 47

Dico 240 17 -- -- 32 .3 45
Ecusta TOD 705 10 1 .19 40 16 .4 37 39 .4 32 63 29

Ecusta TOD 705 17 0 .94 52 13 .6 48 26 .8 54 52 36

Ecv -t:a TOD 705 24 0 .65 67 9 .6 63 23 .3 60 43 4 7

Nil -- 1 .60 -- 22.2 -- 58 .3 -- 81 --

Ecusta TOD 17 0 .88 45 13 .5 39 26 .5 55 52 3 6

Ecusta TOD plus 207. 13 .5 39 22 .8 61 48 4 1


17 0 .83 4 8
polyethylene

13, 4-Ben'l.pyrene 3Analyses conducted by Analytical Division

268-Ien . WINSTON tobacco rod ; Type 543 paper 4Analyses conducted by Chemi.cal. Dixi.si.c~n
(See Tab1e IV, Footnote 21 for description )

• S0T5 OTLIS
23

EF73"T OF

. .• :r1C

Total
coti:: a- Total So1ids Polycyclic 3
; ~ ~ in Smoke Hvdrocarbons
P .:per Filter Tip *s ./ ReG'n ::g . / Red' n Mg . /kg . Red' n
T%-,e Materi al Cic
-._ ...: % Cia . 9. Sr•^.oked °G

543 Estron 8/70 1.44 -- 19 .7 50.2

552 Estron 8/70 1.17 19 15.7 20 32 .4 35

543 Estron 3 .3/66 1 .22 -(15) 4 16 .0 -(19)4 33.5 -(33)4

552 Estron 3 .3/66 0 .76 38(47)4 13 .1 18(33)4 25 .4 24(50)4

543 Estron 8/70 1 .58 -- 18 .7 -- 48 .1

Alumi-
nized Estron 8/70 1.50 5 19 .4 -4 49 .5

168-mm . tobacco rod ; 17-mm. filter tip .


2Analyses conducted by Analytical Division .
3Analyses conducted by Chemical Division .
4Values in parentheses represent percent reduction from that obtained for
WIl`STO\ cigarette smoke [type 543 paper (see Table IV, Footnote 21 for
description) ; 68-m . tobacco rod ; 17-mm. Estron 8/70 filter tip) .
.

TABLE IV

EFFECT OF ADDITIVES TO TllE TOBACCO, TO 17IE PAPER, AND TO THE FILTER IP i•i~T F,RIALS
ON NICCYrINE, TOTTAL SOLIDS, TOTAL POLYCYCLIC HYROC.ARBONS, ANI) BEN2O[1]RENE: IN C :IC.Aitl•:7:1'i: Si :`)i :l:

Nicotine 2 Total Sol } ds Polycyclic Ilyd rocrirbo ns3


Additive in Smokc in Smoke Total 13enzo[ a ] py rcttc r _

Mg. /g . Mg . / Red' n Mg . / Red' n Mg . /kg . Red' n y/kp, . Red' n


Material Tobacco Cit; . % Ci . % Smoked % Smoked

To WINSTON Blend Tobacco :

Nil (29 ~ --4 1 .17 -- 15 .2 -- 39 .0 -- 10


Alumina s6 (29) 20 .0 1 .00 15 '13 .6 11 36 .5 6 ~~
11)
5% Rhodium on alumina5 ~29) 20 .04 0 .78 33 11 .6 24 29 .7 24 '
57. Palladium on alumina (29) 20 .04 0 .90 23 10 .5 31 •27 .1 30 ?1
5% Platinum on alumina5 (29) 20 .04 1 .04 11 10 .2 33 26 .0 33

Nil (22) -- 7 -- -- -- -- 51 .1 -- 83 --
Sulfur (22) 0 .107 -- -- -- -- 61 .1 -20 90 -9
Sulfur (22) 0 .257 - -- -- -- 65 .9 -29 101 -22

Nil (22) , --8 -- -- -- -- 48 .8 -- 81 --


Hydrated alumina9 (22) 3908 -- -- -- -- 35.6 28 70 14
8
Nil (22) 47 .3 -- 90
Hydrogen peroxide (22) --8,10 46 .6 1 --
Magnesium nitrate hexahydrate
(22) 50 .0 8 37 .6 20 26 68
Ammonium oxalate (22) 45 .1 4 -- --
2 1. 08,11 51 .0 -8 -- --
Cystine (22)
Methionine (22) 1 .258,11 50 .2 -6 --

Nil (22) -- '1 .37 -- 19 .4 -- !e . o 50 .6 -- 82


Magnesium nitrate hexahydrate
(22) 20 .0 1 .23 10 19 .8 -2 17 h 44 .0 13 51 38
Aluminum perchlorate J
nonahydrate (22) 20 .0 1 .36 1 19 .8 -2 '' 49 .8 2 82 0
Aluminum nitrate
nonahydrate (22) 20 .0 1 .28 7 19 .7 -2 43 .1 15 45 45
Alu m acetate tetra-
hydo (22) 20.0 1 .49 -9 1819 .7 -2 48 .9 3 78 5 9-
TABLE IV (Cont'd)

Polycyclic llydr.ocarhou ::3 _


Nicotine Total Solids
Additive in Smoke2 in Smoke2 Total P.en•r,o[aJpyr.i•nr.l
T18 . / Red' n Mg . / Red'n Mg . /k8 . Red' n y/kp. . ILcd' n
M ter ia 1 Tobacco _.~ %~ Cir % Smoked % Siwl:cd 7,

Nil (182 -- 1 .58 18.7 -- 48.1 --


Alumina (18) 250 1 .15 27 14 .3 24 39. 5 18
. ;
To CArU:L Blend Tobaccol2 i?

Nil (182 -- 2 .27 -- 25 .7 -- ?"f 31 .3


Alumina (18) 250 1 .63 27 21 .3 1P?"`I'' : 26 .0 17
.' ^
To Flue-Cured Tobaccol3
.rh'! 4
Nil - 1.91 -- 24 .4 -- 7).l --
Aluminum nitrate nonahydrate 20 .0 1 .83 5 25 . 0 -2 1191 .5 31 „-

To Filter Tip Mater.ia116 (30) :

Filter Tip Additives Triacetin


Mg . / mg• /
Material Filter Tip Filter Tip

Nil -- 12 43 .0
Chloranil 6 .0 12 33.0 23

Nil 12 • 1 .10 -- 15 .9 43.8


Trinitrofluorenone 0 .6 12 1 .11 0 15 .9 0 40 . 3

Nil -- 18 1 .11 -- 15 .3 41 .6
Trinitrofluorenone 0 .9 18 1 .06 5 15 .2 0 38 .9 7

g0Z5 OtLtiS
}

TABLE IV (Cont'd)

Total So l ids polycyclic llych-oc arO


_honc3
To Cigarctte Paper (15) : Nicotine
in Smoke2 in Snpke2 _ Total J:enza[ a] pyi-cnr. 1
Mg . / Red' n Mg . / Red' n Pig. /k8 . Rcd' n y/lcg . l.ncl' n
Paper Tvne Ci . % Cis%~ Smokcd % - Sitwked %

A17,18 65 .3 --
AAA 17,19 55 .2 15
A17,18 71 .3 --
AAA 17,19 63 .7 11

A 17, 18 65.3 --
AAA 17,19 51 .1 22
M17, 20 51 .3 22

54321,22 50 .5
r~

13 , 4-Benzpyrene . 1368-mm. tobacco rod .

2 Analyses conducted by Analytical Division . 14The Analytical Division, ti s .inf; an entirel.y di .ffc•r,'i,t-
analyti•cal procedure, reportrd 73 y/kg . of t•c+b :,c,•„
3 Analyses conducted by Chemical Division . smoked .
468-mm. tobacco rod ; 17-mm. Estron 3 .3/66 filter 15The Analytical Division reported 58 Y/kl ; . of t,+boccc,
tip ; type 556 paper . •smoked, for a reduction of 21 percent .
50bt:ained from Engelhard Industries, Inc ., 16WINSTON blend tobacco ; 68-nxn . tobacco rod ; 17-nnn .
ir',twark 2, N . J . Estron 3 .3/66 filter tip .
6The alumina employed was that used as catalyst 17WINSTON blend tobacco ; 70-mm . tobacco rod ; 15-nn,r .
support in the experiments involving rho d ium, Estron 8/70 filter tip .
palladium and platinum .
18Type A paper contains no citric acid ,s :rlts .
7 70-nun . tobacco rod ; 15-mm. Estron 8/70 filter
tip ; type AAA paper (see footnote 19) . 19Type AAA paper contains 1 .4 percent of citric acid
equivalent (1 :1 sodium:potassium) .
8 68-mm . t-blcco rod ; 17-mm . Estron 8/70 filter
tip ; type AAA paper (see footnote 19) . 20Type AA paper contains 2 .0 percent of citric acid
equivalent (1 :1 sodium :potassium) .
9 0bt a in.•cl from Reynolds Metals Co .
10 5% of a 357~ solution of hydrogen peroxide, v/w . 21Type 543 paper contains 0 .87 of citric acid equi . va lc•nr
(3 : a1 sodium : potassium) .
11Equoent to 0 .25 mg . of sulfur per g . of tobacco . 22t•IItiSTON blend tobacco ; 68-mm . tobacco rod ;
1270-mm . Ynhnrrn rnfi .
TABLE V

POSITION OF LEAF ON STALK : EFFECr ON FATS AND WAXES,


FLAVORANTS, AND NICOTINE IN T013ACCO AND ON NICOTINE, TOTAL
SOLIDS, TOTAL POLYCYCLIC IYI)1tOCA12130NS, AND BENZOfa]1'Y121 :NTIN CI(:Ar.r.~rrl~: Sri01 :1:/- (15)

~ Tobacco
?~ ~ o
Smoke .~ ,~
01
Ether-Solubl.c Platcri n 1 :;3
Total Polycyclic Benzo[a]- Fats
Position of Nicotine3 Solids3 Hydrocarbons4 pyreneT94 and
Leaf on mg :/ mg•/ mg ./kg . y/kg . Nicotine3 Total Waxes F lavoran t :s
Stalk ci3; . cig . Smoked , Smoked Y

Flue-cured Tobacco :
b,~ ~~~ 1,) - ., . . g~ f. •

Upper Quarter
Lower Quarter
2 .34
1 .56
29 .0 ti '
23 .1 1t' ~
40 .2 l
31 .7
.
: •. . • .
69
54
2 .06
1 .54
7 .93 6 .ti4 „
5 .63 ~: .51 1
:, 1 .39
1 .12
.• .
./

Burley : •

Upper Quarter5 5 .14 32 .2 ~2t 60 .0 I , ~gi, 85 3.60 8 .03 6 .65

Lower Quarter5 2 .82 ~ 21:4 / t•~{ 43 .6 ' 63 3.91 6 .90 5 .44


f
13,4-Benzpyrene
eb
2Type AAA paper (see Table IV, footnote 19, for description) ; 68 mm . tobacco rod .
3Analyses conducted by Analytical Division .
4Analyses conducted by Chemical Division .
5It is possible that these samples were interchanged with respect to designation during srnne hhase c,L tatc
several analyses . However, the important fact is that thpre is considerable difference betwc:ru the
amounts of the total polycyclic hydrocai k ~leaves situated differently on the tobacco
plant .

OtZS OZLIS
30

v . Ey Solvent Exz :act ;on of' =o ::acco (12, 13, 15)

The results of t : e of =^a e-__ect of solvent


e}:trac; ion of tobacco on the poly cyciic hydrocarbon of the
smoke condensate are su=Gr_ced in Table VI . The following
conclusions ^ay be drau~r, fro ., these data :

(a) Solvent extraction using ?entane, hexane, or ether


of a particular tobacco t~pe reduced the polycyclic
hydrocarbon content of t :L smoke .

(b) Solvent extraction of a blend of tobaccos, e .g .,


CAMEL or WINSTON blend, resulted in a decrease in
the total polycyclic hydrocarbons in the smoke
condensate .

(c) Solvent extraction of the constituent of a blended


tobacco type, e .g ., the Turkish blend, flue-cured
blend, or burley blend, in WINSTON blend, followed
by incorporatiorn of the extracted tobacco with the
other two components (non-extracted) still yielded
a reduction in total polycyclic hydrocarbons in the
smoke . In this respect, extraction of the Turkish
blend portion of the WINSTON blend produced greater
reduction in total polycyclic hydrocarbons than did
.similar extraction of the flue-cured blend . Extrac- ~
tion of the burley blend yielded the lowest reduction .

(d) Hexane extraction of a tobacco type or a tobacco


blend followed by partition of the hexane extract'
with aqueous alcohol permitted separation of the
generally nonpolar and nonflavorful tobacco com-
ponents from the generally polar and flavorful
components . When the polar, flavorful fraction
was returned to the hexane-extracted tobacco and
the resulting tobacco was smoked, a pronounced
reduction both in the amount of the total poly-
cyclic hydrocarbons and in the amount of benzo[ .Rj- Ln
pyrene in the smoke was observed (1) . These values )-A
were not too different from those obtained with the m
smoke from the hexane-extracted tobacco itself . It v,
was concluded from these findings that the polar, ~_A
flavorful fraction from tobacco did not contribute ~'
markedly to the polycyclic hydrocarbon content of
the smoke (See also Section A .I .b .3 .) .

In every experiment in which solvent extraction was carried


out, either on the whole or on a portion of the tobacco consti-
tuting the cigarette, a reduction in polycyclic hydrocarbon and
benzo(aJpyrene (3,4-benzpyrene) content of the smoke was observed .
A patent on the extraction procedure plus the partitioning of the ~
extract has been issued to the Company (1) .
TABLE VI

SoLVENT PnE'rICFATi`IENT OF INDIVInUAL TOBACCM TYPI :S AND TOBACCO BU.NDS : ErTI:("r ON T(r'rA) .
POLYCYCLIC ItYDROCAR1i0NS ANl) BENZOI a]PYRENEI IN CICARETl'1 : St101C1: (12, 13, 15)

Polycycl.i.c IydYorarban :: in Siaolu_ -


Extraction Tota 1 - - L cnvc, a] l! >_rV
-n
Tobacco State of Time, Temp . Ng . /kg . P,ed' n y/icf ; . tted' n
Extracted Subdivision Solvent hr . °C . Smoked % Smo_kcd _ _ry.
_ _

CAMEL Blend Tobacco (70-mm . tobacco rod, type A2 paper) : ~- - ~

Nil cut --- --- -- 23 .5 -- 81, --


CAMEL Blend cut pentane 4 .0 25 14 .3 39 21 7 5,

CAtiEL-type Flue-cured Tobacco (70-mm . tobacco rod, type A2 paper) :

Nil cut --- --- -- 18 .0 -- 67 -


Flue-cured cut pentane 4 .0 25 14 .2 21 47 30 c,_.~. .
Flue-cured cut ether 4 .0 25 6 .3 65 7 90

Turkish Blend Tobacco (70-mm . tobacco rod, type A2 paper) :

Nil cut --- --- -- 55 .8 -- 11.9


Turkish Blend cut pentane 4 .0 25 21 .9 61 3/ 73
Turkish Blend cut ether 4 .0 25 5 .5 91 4 96

Turkish Blend Tobacco (68-mm . tobacco rod, type AAA3 paper) :

Nil leaf --- --- -- 56 .5 -- --


Turkish B lend leaf 9:1 hexane : 2 .0 60 36 .4 35 --
isopropyl
alcohol

ZZZS OILTS
TA13LE VI (Cont'd)

Polycyclic liydrocarbons iii :n, kr


_

Extraction Total _ Ben :•.o( a]hyrrr1r L _

Tobacco State of Time, Temp . ri£ . /kg . Red' n y/kF ; . Rc•d' n


Extracted Subdivision Solvent hr . °C . Smoked % Smc~l :cd %.

WINSTON Blend Tobacco (70-asn . tobacco rod, 15-mm . Estron 8/70 filter tip, type AAA3 p :+.p('i) :

Nil cut --- --- --- 52 .7 -- 75 --


Turkish Blend4 cut ether 4 .0 25 37 .1 30 36 5?
Turkish B1end5 cut ether 4 .0 25 50 .8 4 75 (1
Turkish Blend6 cut ether 4 .0 25 64 .7 -23 91 -2 ].

Nil strips --- --- -- 57 .1 -- 81


Turkish Blend leaf ether 24 .0 25 28 .2 51 11 . FSG
WINSTON B lend strip ether 24 .0 25 22 .0 61 10 89
WINSTON B lend strips hexane 24 .0 60 30 .2 47 12 .5 8/1

Turkish Blend leaf ether 24 .0 25 23 .77 56 9 .58 ."•°


F lue-cured strips ether 24 .0 25 34 .27 37 338 GC~
Burley strips ether 24 .0 25 47 .77 12 56 8 30

Nil . strips --- --- 56 .4 -- 76


WINSTON Blend strips hexane 7 .0 6 .5 28 .7 49 22 7].

Nil cut . 55 .1 -- 79 -
WINSTON Blend cut hexane 2 .0 60 20 .4 63 32 6U
WINSTON Blend cut heptane 2 .0 83 26 .4 52 45 43

Nil strips --- --- -- 53 .3 -- 83


Turkish Blend leaf hexane 2 .0 60 39 .6 26 --
Turkish Blend leaf hexane 24 .0 60 36 .7 31 --

£TTS OrLIS
TABLE VI (Cont'd)

poly cycli.c ]ly_drocarbon s i»


Extraction Tota 1 ~ ] 1>~ rc•lu .1
Tob ;!cco State of ' Time, Temp . Mg . /kg . Red' n Y/kf : . itrcl' n
rxt•ractcd Subdivision Solvent hr . °C . Smoked % SnK•krd 7.

WINS''ON Blend Tobacco (68-mm, tobacco rod, 17-mm . Estron 8/70 filter tip, type AAA3 pape r) :

Nil strips 47 .5 -- 87 --
Turkish Blend leaf 9 :1 hexane : 2 .0 60 30 .8 35 39 52
isopropyl
alcohol

Turkish Blend Tobacco (70-mn, tobacco rod, 15-mm . Estron 8/70 filter ti12, type AAA3 L1apcri :

Nil cut -- 49 .4 -- 11.9


Turkish Blend6 cut ether 4 .0 25 50 .3 -- 1.1.5
w
w
WINSTON-tYpe Burley Tobacco (70-mm, tobacco rod, 15-mm . Estron 8/70 f.ilter ti .p . ty pe _AAA3 raJ~~r

Nil strips 49 .4 -- 75
,
Burley strips ether 24 .0 25 23 .9 52 56 5

13,4-Benzpyrene ; data for other individual polycyclic 50ne equivalent of Turki sh b letxl tvbTc•co cxt rac : t:
hydrocarbons were obtained but are not reported here . was returned to the extracted Turkish blend .
2See Table IV, footnote 18, for description of Type A 6Pive-t-hirds equivalent of Turkish blend t-obacc :o .
cigarette paper . extract was returned to the extracted Ttirkish
blend .
3See Table IV, footnote 19, for description of Type AAA
cigarette paper . 7An average of 54 .0 mg . of polycyclic hS•dror.,n-botis
per kilogram of tobacco smoked was usccl as c.ontrol.
40ne-third equivalent of Turkish blend tobacco extract value .
was returned to the extracted Turkish blend .
8An average value of 83y bcinzC)( .-ijpyrr.ne (3,4-
benzpyrene) per kilogram off tobacco suwkec] wasc
used as control value .

~tit5 01 Lt5
3 . Pkr,CU :SORS 0:

On the .csis o_ .:':e : esu :ts o :.tc : ncd in the above-described


studies, the pri:cursv~s .. .n tob~,i:cco o-z :.e polycvciic ilydrocarbJns
in snloke were studied . Solve :a extraction studies indicated th : t
a considerable proportio :: of c : ase precursors ;:er e re : :ovable from
the tobacco by organic solver.ts (12, 13, 15) .

Addition o,: a pents ne e ::tract of CAMEL blend cabacco to non-


extracted CAN;:::" bland tobacco resulted in a 20 parce,t increase in
total poiycyclic nyd :-ocarbons and a 33 percent inc :•o ::se irn the
amount of benzo[ajpyrene (3,4-benzpyrene) in the sma, :e . Similar
increases were noted when an ether extract of Turkish tobacco was
added to nonextracted Turkish tobacco . Partition of a pentane
extract of CAr2EL blend tobacco between equal volumes of hexane
and 9 :1 ethanol :water followed by addition of the 9 :1 ethanol :watcr
concentrate to an equivalent amount of CAMEL blend tobacco indicated,
on the'basis of no increase in total polycyclic hydrocarbons or
benzo[aJpyrene (3,4-benzpyrene), that the bulk of the precursors
was in the hexane layer from the partiticn . This was confirmed by
the observation of a substantial increase (about 40 percent) in
total polycyclic hydrocarbons in the smoke when the hexano fraction
from the partition was added to an equivalent amount of CAML blend
tobacco prior to smoking .

The structures of the known components of a pentane extract


of tobacco, which, in turn, would appear in the hexane phase of a
hexane-alcohol :water partition were considered in an attempt to

define the precursors in tobacco of the polycyclic hydrocarbons
in the smoke (22) . At least three types of compounds were shown
to be involved . Additiorn of a saturated hydrocarbon fraction
(typified by n-hentriacontane), 0-sitosterol (as representative
of the tobacco sterols), and solanesol (as representative of v,
tobacco terpenes) to tobacco increased the amount of the poly- ~
cyclic hydrocarbons in the smoke therefrom . Sclareolide (a con- ~
stituent of Turkish tobacco) and the substituted malonic acids
appeared to make no or negligible contribution to the polycyclic Ln
hydrocarbon content of tobacco smoke . These results are shown N
in Table VII . It is possible that sclareolide would yield
dibenz[a,h]anthracene (1,2,5,6-dibenzanthracene) (XLII) on
pyrolysis during the smoking proces's .

XLII

Sclareolide
.! J

It is v er y ,: .Q .^.i.: :: ~ ,.s :. :a .`. o - i. ob .^. .•Co ot :itlr


than those studied :..: .' :, a p recursors oi the polycyclic
'r. y drocarbo ::s i n the tob a cco sr..o k e .

T ALB.T+:'+ M

EFFECT OF :"~ ~?CC0 CJXSTITuE~;_s r,'A o : ::Fi. 0?:G : •IC


CJ.:POJ\~S 0:' z :: T0' = ?O' 'C :'CLIC F:7i OC:. .'aOriS :`:D
EENZO ;a)?Y:E:iEI~?'X CiGAFW'!'= S ::DI:E (22)

?olvcvalic Hvdroca_ bons2


Additive Total Ber.zo[ajpyrene
Mg ./g . ag ./kg . increase y/kg . Increase
Nata_ ial Added Tobacco Sr..oked % S .:.ol:ed % r , . .~.

To WINSTON Blend Tobacco3 :

Ni1 -- 51 .1 -- 83 --
N+neral oil (TSC 350) 4 .0 57 .8 13 S7 5 ,
Solanesol 3 .2 58 .9 15 94 13
Solanesol 6 .4 63.3 24 94 13
Saturated hydrocarbons 2 .0 63.6 24 94 13 L. S
5 .0
Saturated hydrocarbons 4 .0 73.7 44 100 20
26 96 16 Y ,v
;.-Sitosterol 1 .9 64.3
r-Sitosterol 3 .8 72.1 41 106 28

Nil -- 48 .8 -- 81
Tripy:-istin 4 .0 51 .7 6 86 6 , ~

To G-7X4 :

Nil 26 .8 -- 33 .
Sclareolide 4 .5 28 .5 7 35 6
Disodium isopropyl- '
malonate 3 . 0 '~
Disodium sec-butyl- 26.5 -1 34 ~~ °~ ~ ~
malonate 4 .5 1
Saturated hydrocarbons 4 .0 40 .0 48 42 27 (,!1

13,4-Benzpyrene .
2Analyses conducted by Chemical"Division .
3Type A4A .paper (see Table IV, footnote 19, for description) ; 15-mm. Estron
8/70 filter tip ; 70-mm. tobacco rod .
4Type 543 paper (see'Table IV, footnote 21, for description) ; 68-r.im. tobacco
rod .
so

T :1a O-: ei . . : .: :.~y ~ .:S:~i: are t:•:0 ^^'`': me cG . ... . ._5~S i:rF:D~• :.a Ja c c o
components rz .• conve_ ced tr, polycyclic 'r.ydrocar bons du_ ing
z1tie si .'J+Li ::- ".:e : :.i :. :., and ^.~re obvious r. :icaa nis^,
involves ta .? _ .. : - . .~ po :yJ"c«c : ydrocarbO :.s from _ClaClveiV
_ .._'~e rr,oiecu :es structLrally _,, :atsd to the poivcyclic hrdro-
cw_oons by an essentially unir..oiecuiar reaction . E . g . , :~-
3:e,:triacon tar.e could be conve:-ced to ber.zo[ .g ;py_-ene (XLI) by
appropriate cyclizatioa, dehyd .oger.ation, :.nd fragnentation,
and ;-:-sitosterol could bz cor.verted to c:^.olar.threne (LVIII) by
a?propr :.ate cycl :.zation, dehyd. .~tion, dehydrogenation, and
f :war.u::~tation . The possible conversion of sclareolide to
dibanz[a,h]anthracene (1,2,5,b-dibenzanthracene) (XLII) has been
mentioned previously .

-H %

(CH2) g_n

n-hentriacontane XLI

2 2, -H20

HO

p-sitosterol LVIII

Indeed, individual pyrolysis of large molecular weight components


of tobacco does yield significant amounts of the polycyclic
hydrocarbons .

The second mechanism of polycyclic hydrocarbon formation


involves the degradation of tobacco components to small, highly
reactive entities which recombine at the elevated temperature
to form polycyclic hydrocarbons . E .g ., a tobacco component such
as n-hentriacontane at a temperature of 870° could yield acetylene
molecules, which in turn, could recombine to form benzo[a]pyrene
(3,4-benzpyrene) (XLI) ; terpenoid compounds such as neophytadiene
or solanesol eould yield isoprene, which in turn, could form

?o?ycyclic hydrocarbons . It has been known for four decades
that pyrolysis of acetylene or isoprene will produce polycyclic
hydrocarbons .
I t _s auite p_ob a :. le _ :.Ft : .:,:. : c-_c 1•• ;4 r OCc.•: b J .^.S
tobacco F. m JiCe a r ise b 4 bOL'.: f.lc c :+ : ::is .^.s ;` w C C .7nside r the fi r st
i^.'.c .^.a ::is :' descr i bed above t0 :. a t he :'J : e =-'p Jrt .: :lt of t *h e two .

TT T`sta i s

F- . - A1^o_a_ic tster ~:_ction

An aliphatic ester fractio :: was isolated from t:I\STO\,


Turkish, and bu:lay cigarette s-:oke (45-4?, 51, 52) . The constitution

CH3(C_'2)n+200CR

L?:VIII

of this ester fraction was elucidated as follows : Saponification of


the aliphatic ester fraction (LXVIT) yieldad a series of acids (LXTX)
and a series of norr.al lona-chained primary alcohols (T.}OC) . Treatment
of t ::e acids L}:IX with diazomethane, followed by vapor-phase-chromato-
grep : y and/or mass spectrometry of the methyl esters LXXI, indicated
the ::.ethyl esters of the follow :.ng acids : The saturated acids, myristic
to octacosanoic, inclusive ; the unsaturated acids, oleic and linolenic ;
several unidentifiable acids . Palmitic acid was the major constituent
of this acid fraction with myristic and/or stearic acid the next most
plentiful .

?e=manganate oxidation of the alcohols LXX, followed by treatment


of the resulting acids LXXII with diazomethane, yielded a series of
methyl esters LXXIII . Vapor-phase chromatography and/or mass spectro-
metry of LXXIII indicated the presence of the methyl esters of the
straight-chained acids varying in chain length from that of lauric
(C12) to that of heptacosanoic (C27) acid, inclusive . The alcohol
portion of the aliphatic ester fraction (LXVIII) must, therefore,
consist of the alcohols from dodecyl (lauryl) alcohol to 1-hepta-
cosanol, inclusive . 1-Docosanol comprised the major component of the
alcohol portion of the aliphatic ester fraction (LXVIII) .
1.. / . %~ : :I

RCOC:i - + C::%(CH~14-- , C:i20H

LXIX LX?:IV LXXV


l I

CH2N2/Et20 IKMn04/CSHSN CH2N2/Et20 KMn04/Me2C0

V V NY W
RCOOMe CH3(C"2)n+1C00H RCOOMe CH3(CH2)nC00H

LXXI LXXII LXXVI LXX VII

CH2N2/Et20 CHZ2/Et20

v v
CH3(CH 2)n+1C00Me CH 3(C"2)ri OOMe

LXXIII LXXVIII
P .• r oi ., sis of I:::VIII Et 4 75° in En iner : atmosphere yielded a series

o: :.cidS :: nd a s er ies of .. - El[Ce ::es " .. :1XV) . The co^:p osition of


. . :e : c~Gj . . . . 'Ali ::2 to be SiaJSiE:.tiEll•,i the Sam~e as ti: t of : ai3
acics C ::i_ction o : Ml'V y ielded a series of acids l ;nich
was converted to a series of me :.'r.y1 esters Lfi}:VIII . Vapor-phase chro-
m.atoo:-ap :.y ,::. ::!or mass spectrometry :.ncicated the pr esence of the methyl
esters of undecanoic (Cil) to 'r.exacasa :~oic (C2U) acid, inclusive . The
methyl ester found to be present in cile greatest amount was methyl
heneicosanoate indicating, on the basis of :he loss of one carbon from
the chain, that 1-docosanol comprised the major component of the alcohol
portion of the aliphatic ester fraction (LfiVIII) .

On the basis of these findings, the aliphatic ester fraction may


contain as many as 272 combinations of the acids LXIX and the alcohols
LXX since degradation yielded 16 known alcohols and 17 known acids .
Table VIII su=arizes these findings .

TABL:: VIII

MOk'\T CONSTITUENTS OBTAINED BX DEGRADATIOr


OF ALIPHATIC ESTER FRACTION' Ly :VIII
FROM TOBACCO SMOKE 4( 5-47 )

Alcohols Acids

1. Dodecyl alcohol (LXX, n=9) 1. Myristic


2. 1-Tridecanol (LXX, n-10) 2. Pentadecanoic
3. 1-Tetradecanol (L)M, n-11) 3. Palmitic
4. 1-Pentadecanol (LXX, n-12) 4. Heptadecanoic

5. 1-Hexadecanol (LXX, n=13) 5. Stearic


6. 1-Heptadecanol (Ly.', n-14) 6 .' Oleic (9-Octadecenoic)
7. 1-Octadecanol (LXX, n=15) 7. Linolenic (9,12,15-Octa-
decatrienoic)
8. 1-Nonadecanol (LXX, n-16)
8. Nonadecanoic
9. 1-Eicosanol (LXX, .n-17)
9. Eicosanoic
10. 1-Heneicosanol (LXF., n=18)
10 . Heneicosanoic
11 . 1-Docosanol (LXX, n-19)
11. Docosanoic
12 . 1-Tricosanol (LXX, n-20)
12 . Tricosanoic
13 . 1-Tetracosanol (LXX, n-21) Ln
13. Tetracosanoic ~
14. 1-Pentacosanol (LhM, n=22) J
F+
14 . Pentacosanoic m
15 . 1-Hexacosanol (LXX, n=23)
15 . HexacosanoiF Ln
16 . 1-Heptacosanol (LXX, n=24) ~
N
16 . Heptacosanoic m
17 . Octacosanoic
1. .~.V .~''..1GS~~T i~Ti :1 C.
iw .
.. :. T_
-`.

Solfinesyl acetate R G) was isolated from the

.-1 ~ Cra~ ..(Cii 3 )=l, :C.:-I J g00CR

"LY:iL.l'

cigarette smoke from WINSTON, Turkish, burley, and flue-cured


tobaccos (23, 24, 48-50) .

2 . SOLANESYL ESTER FRACTION

A solanesyl ester fraction (LXXIR, R~ Me) was isolated from


the cigarette smoke from WINSTON, Turkish, burley, and flue-cured
tobaccos (48-52) .

Saponification yielded solanesol (LR}IX) and a series of acids


which were converted to the corresponding series of methyl esters
by treatment with diazomethane . Vapor-phase chromatography of
these methyl esters yielded the acids listed in Table 7X .

H[ CH2C(CH3)-CHCH2190H

TABLE IX

KNOWN CONSTITUENTS OBTAINED BY DEGRADATION OF


SOLANESYL ESTER FRACTION LXXIX FROM TOBACCO SMOKE

Alcohol Acids

Solanesol (L~:) 1 . Lauric


cn
H
2 . Myristic N
H

3 . Palmitic

4 . Oleic (9-Octadecenoic)

5 . Linoleic (9,12-Octadecadienoic)
? 1

C.

? pizytostcr .'1 ester _raction t•:as ^_solated _ron the ciSarette


smoke -~o^ iUriCis : , :+'.: : ley, and I :Ue-CL : e d C3b'uCCOS (~~+5'-57) ..-57)

Saponification yieldad a :'aytosterol fraction plus a series


of acids . Conversion of the acids to the corresponding serias of
::a{~ :~y'i esters, :c.llowed by vapo .-p :-ase chromatoorapny of the r..ethyl
esters yielded acids listed in~Table X . Chronatographic fraction-
ation oi the phytosteryl f_action in3i cated the presence of stigmasterol
(L=I) and ;.-s :.tosterol (L?:,t:-xIl.) .

TABLE X

'sC~OW\ CO\STITiJJEETS DB I TED B :.' DEGRADATIO\


OF W'YTOSTERYL ESTER FRACTION FROM TOBACCO SMOKE

Alcohols Acids

Stig::zsterol (LXXXI) 1. Lauric


A-Sito£terol (LXXXII) 2. Myristic
3. Paimitic
4. Oleic (9-Octadecanoic)
5. Linoleic (9,12-Octa-
decadienoic)
Linolenic (9,12,15-Octa-
decatrienoic)

CH(CH3)CH=CHCH(C2H5)CH(CH3)2

HO

LM I
43

: :us, the phytostc_yl ester __,. .. :_ . . . - . :v contairn as r.cny as


12 co ::binations of the acids showri ? : :'ab'la X Er,d the phytosterols
<?. .\?:_XI ar.d ?-MN:Ii) since degr ;:cat :or. , :eicec six kr.oc::z acids and
two ? ::ytosterols .

d . h-Acetyl-2,3,4-tris-c-~.'-,- .:s_ :: .•livaleryl---D-alucopyr4noside

The sugar ester, c-scetyl-3,3,~:-t : :s-c-~- ::ath~*ivaleryl-,^.-D-


giucopyranoside was isolatec :_o^ Turkish tobacco cigarette
smoke and characterized on the basis of ir.frEred absorption, melting
point, and mixrure melting point studies (33) . Approximately 1 .4 g .
of this ester was isolated from the ss.oke for 20,560 Turkish tobacco
cigarettes (97 mg . per kg . of tobacco smoked) .

LXXXIII
0
MV s CH3CH2CH(CH3)CH2-C-

III . Lactones

a._ Sclareolide

Sclareolide (=IV) was isolated from the mainstream smoke of


cigarettes fabricated from Turkish tobacco grown in the Souyalissian

IXCXIV

region of Greece (27) . The sclareolide in the mainstream smoke


represented 28 .7 percent of that found in the tobacco, considered
on a^.oisture- and sand-free basis .

The sclareolide from the smoke (0 .736 g . from 20,560 Turkish


tobacco cigarettes ; 51 mg . per kg . of tbbacco smoked) was identified
on the basis of melting point and mixtu . :. melting point studies,
infrared spectra, . and elemental analyses of the isolated material
and its dimethylamide derivative .

:ZCJ
~ ~Gt

rrin l."h°.ric diter~,^ri:T:G :. ., .c::C :.o ::es, (L.~ XXV ) a .^.d


r.-leva: - e .^.olide trere i m
soia :.ed froti z 1:e c :. ;aret :.e smoke

'0~
~ ~._1 . . .

=V =VI

of Turkish tobacco grown in the Souyalissian region of Greece (2, 3) .


The identity of these lactor.es was confirmed on the basis of infrared
absorption data, optical rotation, and malting point studies . The
amount of cx-levantenolica ("'V) isolated reDresented 0 .0019 percent
of the tobacco smoked (19 mg . per kg . of tobacco smoked) ; the amount
of P-isomer (LXX}.'VI) represented 0 .00014 percent of the tobacco smoked
(1 .4 mg . per kg . of tobacco smoked) .

IV. Alcohols

a . Solanesol

The terpenoid alcohol solar .esol (=) has been isolated from
the cigarette smoke from WINST0\, Turkish, burley, and flue-cured
tobaccos (23, 24, 48-50) .

b._ rormal Long-chained P_rimary Alcohols

A series of normal long-chained primary alcohols (LXXXVII) was


isolated from WIhSTOh cigarette smoke (5, 6, 31) .

CH3(CH2)nOH

Oxidation of this series of alcohols yielded the corresponding


series of carboxylic acids . These acids, on treatment with diazomethane,
yielded a series of inethyl esters . Vapor-phase chromatography of the
esters indicated the presence of octadecanoic (C18) to tetracosanoic
(C24) acid, inclusive . Mass spectrometry of the acetates of LXXXVII
suggested the presence of 1-heptadecyl (C17) to 1-tetracosanyl (C24)
acetate, inclusive . These mass spectrometric and vapor phase chromato-
graphic results indicated that the series of alcohols contained 1-
heptadecanol to 1-tetracosanol, inclusive .
44-

c.

Cigcrette s .;.o :cc __;,rm burley, and ilue-cur ed


:.obacccs yiel4ru a series o' : nycostero_s, t'ae major Dart of which was
,_ .
. ..OS : Z o, . . . T ) (4S- 5 0)
.S{.-? .:r : .~i~..el .~l ~ : . . .. .1. - ) QnQ r-Fl i r l k 1+:1r~.. .l .

u . 12y-Hvcxoxv-l3-evirwnovi 0::idL

' 3w::iydro :;y-13-eDi manoyl o ::ide (=i1') was isolated from Turkish
tobacco smoke by - ; .o,uid-liquid pa:tirio : anc column chromatograp ;:y
(4, 34) . it was identified by its point, mixture melting

=IX

point, optical activity, infrared absorption, n .m.r . spectrum,,,and


mass spectrographic data . Approximately 0 .140 g . of LX}gCIX waa
obtained from the smoke from 20,560 Turkish tobacco cigarettes,(9 .7 gm.
per kg . of tobacco smoked) .

e .,_ Unsaturated Ao,yclic Isoprenoid Alcohols

Turkish tobacco smoke has yielded an acyclic isoprenoid alcohol


fraction (39, 41-43) . The presence of phytol in this fraction was
demonstrated as follows (39) : Acetylation of this fraction followed
by column chromatography gave phytol acetate (XC, R- Ac), saponi-
fication of which yielded phytol (XC, R- H), identified as its
3-nitrophthalic acid ester . No evidence for isophytol in this
fraction was obtained .

Ln
~
~
~
m
CH2OR

XC

~
p :es,: :ac ;, c_ .. : s :. .. . .~ :,-c C13, C^5, and C30 _sop :enoid
av_• . r ` :, - .ri 1 • " c
. s i e. s-o :. ::-de :•c ^ ~ ccr.c• ~ _ .~ . .__ ~• :: s :clo~ demoas~_ated-~_'-ated as
.c11o: ;s (41-43) : Cs.por -paasc: c :: .c :7_-tc~ : ;:-' .•ie : :;ed foar f_ac ;ao :.s .
_ :+e er..ar ;er.t ti:aes of the f_rsrt a : d secc ::d corresponded to those of
~arac:svl .:nC p7yto1, respect :vi: :y . . :0 .:, in_ : Fl: ed EbSOrpziOri and ttle
die ::crcr.ces between the cr..a : ;;on'. t: :-c s of gerr:r.iol, fwrncsol, and
ph .•tol, it was concluded .. . . ., t::e cr•d =ourth fractions from
t :.is c : .oaatograr.-. cor.cainedyC,)$ and 0,3 isa ; _a: oid alcohols,
respectively . 'So evidence for the CIO, C35, or C40 alcohols was
obtain ed .

r':cetylation of the smoke-derived alcohol fraction followed by


column and vapor phase chror,stography yielded four fractions whose
emergent times and mass, ultraviolet, and infrared spectra indicated
that (a) the -first fraction contained the acetates of the C15 alcohols
farnesol and a dehydrofarnesol with conjugated double bonds, (b) the
second fraction contained the acetates of the C2p alcohols phytol (XC,
R - ~) and dehydrophytols w'..th four and five double bonds (two of which
are conjugated), and (c) the third and fourth fractions contained
acetates of C25 and C30 isoprenoid alcohols, respectively . No evidence
for acetates of the C10, C35, or C40 alcohols was obtained . The ratio
of the amounts of the acetates of t :.e C15 :C20 :C25 :C30 alcohols was
appro ::i :nately 1 :2 .2 :1 .2 :0 .8 .

Chromic oxide-pyridine oxidation of the smoke-derived alcohol


fraction yielded a series of unsaturated aldehydes . Vapor-phase
chromatography of this aldehyde fraction yielded four fractions
whose infrared absorption and emergent times suggested the presence
of C15, C20, C25, and C30 isoprenoid aldehydes, respectively .

Catalytic hydrogenation of the smoke-derived alcohol fraction,


potassium permanganate oxidation of the perhydroalcohols to acids,
fo11owed by treatment of the acids with excess diazomethane yielded
a methyl ester fraction . Vapor-phase chromatography of this yielded
four fractions whose infrared absorption and emergent times suggested
the presence of the methyl esters of C15, C70, C25, and C30 isoprenoid
acids . The ratio of the amounts of the methyl esters of the C15 :C20 :C25 :C30
acids was approximately 1 :2 .5 :1 .5 :1 .

Thus the data on the smoke-derived alcohol fraction, its acetate,


its corresponding aldehyde fraction, and its corresponding saturated Ln
N
methyl ester fraction suggested the presence in Turkish tobacco smoke _J
of unsaturated isoprenoid C_5, C20, C25, and C3p alcohols ; no evidence ~
m
was obtained to indicate the presence of alcohols in the C10, C35, or
Ln
C40 series . ~
N
Ol
f ._ Macroc_vclic Aydroxvethers

The two macrocyclic diterpenoid alcohols cx-1,5-dimethy1-12-isopropyl-


9-met:.ylene-5,8-oxido-3,13-cyclotetradecadien-l-o1 (XCI) and cx-l2-isopropyl-
5,8-o::ido-1,5,9-trimethyl-3,9,13-cyclotetradecatrien-l-o1 (XCII) were
isolated from Turkish tobacco smoke by liquid-liquid partition and repeated
column chromatography in amounts of 15 .3 mg . and 6 .4 mg ., respectively, per
'T J

?.C I XCII

kg . of tobacco smoked (40, 60, 61) . \ .m .r . data for the dehydration


products from XCI and XCII permitted assignment of the structures
shown for XCI and XCII .

V. Phenols

a ._ _Isol_atio_n of Phenols_from C ;~_arette Smoke

1 . a-TOCOPHEROL

a-Tocopherol (Vitamin E) has been isolated from WINSTON


cigarette smoke (25, 26) . Confirmation of the identity of

HO

this compound was provided by infrared absorption studies of


the compound itself and by mixture melting point and infrared
absorption of its p-nitrophenylurethan . a-Tocopherol was also
detected in the smoke from flue-cured, burley,and Turkish
tobaccos .(48-50) .

2 . EUGENOL AND ISOEUGENOL

The two phenols eugenol (XCIII) and isoeugenol (XCIV) were


isolated from Turkish tobacco smoke (38) . The identity of XCIII
was established by vapor-phase chromatography and infrared

OH

CH2CH-CH2 CH-CHCH3

XCIII XCIV
F: .:sO"?tr0 : st,:i._i:S O~ : t: „$ :Li:l.z L`l :.raviolet
aosoipr :o n 5 ;., : ;.•: o= rL ^L : .h%.- e . . of •:CsV was
i:s t abi-F.:led w v ;:.p o r - ;, :asv a :: :.
s t udies Of th e isolated :.1ateria 1, by u•lzrav iol at absorption study
cf i ts meth}•1 ether, ar,d :.\• r.elt_^.g poi :~t, : ixture r..elting poin : :.
End infrared c.bsorpt :on scudies c_ its -nap :.ta y lureti:a:n derivative .
The amoun ::s of ea g :: ::o : ( :: ;,_I=) .:. ::d i soL .:aor.o'- (}:CIV) isolatod
were 5 .7 mg . and 21 :+g . , respact :vely, ?ar. ;:a . of tobacco smoked

3 . 0`HER ?iir.i;O:.S

A study conducted with Turkish tobacco smoke indicated the


presence of hydroquinone (XCV), 1-r.aphthol (XCVI), and a series
of xylenols (XCVII) . .

OH OE OH
I I

XCVI XCVII

b. :nalvsis for Phenols in Ci2arette Smoke

The quantities of the phenols, phenol (XCVIII), o-cresol (XCIX)


and a-cresol (C), have been determi :ad in the cigarette smoke from
WI\STO\, WWL, SALEM, C9 flue-cured, cased and uncased K4 burley,
Turkish blend, and special G7 tobaccos (32) . Tab1e .XI indicates the
results obtained in this study. Also included are the results of
the determir.ation of these three phenols in the smoke from cellulose
filter rods and from cigarettes containing methanol-extracted C9
flue-cured tobacco .

OH OH OH

CH3

XCVIII XCII: C

O1
F-~
N
Co
4S

?s.~r\..n T. ~. . . . .~- .~ } .~ n_ .
t _ ~ _ .;. ...nr.~-
S :..J: -

?'tii : = iC :1: C C y L 1 n--
C -- JJ T ^VLVJ .,~ (32)

M otal of phonol,
MTo bacco c-Cr,:sc_ o-Crzso_ o- and v-cresol
T .m e ,!C+{ . . . v / 1_ . Y / c' L• Y e. -~, //cii. . y /a. y/ciC . Y

C9 Flue-
cured 229 326 61 86 88 125 378 537

C9 Flue-
cured, 248 310 82 103 127 159 457 572
Methanol
Extracted

K4 Burley,`° `
Cased 134 196 59 86 116 170 309 452

K4 Burley,
Uncased 130 246 55 104 72 136 257 486

Turkish
Blend 192 278 41 60 77 111 310 449

Special •
G-7 45 87 17 32 31 59 93 178

Cellulose --- --- --- --- --- --- 9 23

ZdIIN STO\ 43 65 10 15 33 49 86 129

WINSTON,
no filter
tip 159 241 38 57 70 107 267 405

CArEL 183 269 57 84 81 119 321 472

SALEM 33 48 8 12 26 39 67 99 ~~
~

c ._ Precursors in Tobacco of Phenols in Tobacco Smoke

A study was conducteu cc ar.swer fcl'..owing questions (59) :

1 . Is the difference in amount of phenols in tobacco and tobacco


smoke as disparate as reported previously?

2 . Do the phenols in tobacco str.oke result from the thermal


decomposition of simple phenol derivatives like phenol glycosides,
salts or esters? If such derivatives are present in tobacco, are
they decomposable by chemical reaction?
3 . Do tobaccos contain a^y cor.stitua :rs wnich, on py~-olysis,
.•ieid paenols?

4 . Does robacco _ .. ..,.=f, orn py:alysis under the same conditions


as i :: 3, yield p : a : ols?

5 . Does any con stit : :L ::r added to tobacco during cigarette


:;a:vfactu.e yield phenols on py~ol .~s_s?

6 . Does spinach as rep :._ :.ad p :Lv :.ousiy : n smoke studies yield
less phenols on pyro=ysis does tobacco?

The answers to Questions 1 and 2 were obtained by an analysis for


the phenols phenol and,p-cresol in a steam distillate, in a chloroform
extract, in an alkaline hydrolysate, and i :n an acidic hydrolysate of
tobacco . Since none of these treatments yielded detectable quantities
of these two phenols, we concluded :

1 . The di fference in amounts of the ?henols phenol and P-cresol


in tobacco and tobacco smoke is as dispara :.e as reported previously .

2 . The concentration, of the glycosides, salts, or esters of


phenol and Q-cresol in tobacco must be negligible or zero since neither
alkaline nor acidic hydrolysis of tobacco released any appreciable
quantity of these two phenols .

The answers to Questions 3 to 5 were obtained by analysis for


the phenols phenol and u-cresol in pyrolysates of the tobacco con-
stituents cellulose, pectin, lignin, and glucose plus fructose (as
invert sugar) ; in a pyrolysate of the additive invert sugar (glucose
plus fructose) ; and in the pyrolysates of C9 flue-cured, K4 burley,
and Maryland burley tobaccos . Since appreciable quantities of phenol
and Q-cresol were obtained in each instance, we concluded :

3 . Tobacco constituents like cellulose, pectin, lignin, glucose,


and fructose may be precursors in tobacco of phenol and P-cresol in
cigarette smoke .

4 . The pyrolysis of C9 flue-cured, K4 burley, and Maryland burley


tobaccos does not proceed in a manner substantially different from the
pyrolysis of the individual tobacco constituents listed in 3 .

5 . The tobacco additive invert sugar (glucose plus fructose)


may be one source of phenol and 2-cresol in cigarette smoke .
Ln
~
The answer to Question 6 was obtained by analysis of phenol and ~
~
_v-cresol in a pyrolysate from powdered spinach . Per gram pyrolyzed, m
the spinach yielded approximately the same total quantity of phenol Ln
plus v_-cresol as did the Maryland tobacco in 4 and about 60 percent of r
w
the total quantity of these phenols obtained by pyrolysis of the C9 m
flue-cured and K4 burley tobaccos in 4 . We consider that our findings
agree substantially with previously reported data that spinach smoke
condensate contained about one-half the phenols found in the smoke
condensate from a cased commercial blend of tobaccos . Table XII
summarizes the findings from the pyrolysis studies .
~ . , --

- . .-Jw . .--

nn•. .,
~ ..~'. : ..Il .. .i
= . . .. .nT n . . .r.- .-..
.~ . '.~ ./ v .~ ..- .. ~-

Pheno 1,
. :croa=ams/c . vx*rolyzed
- - - i° C . ?''.L^oi u-Cresol
,-

Inai:': :ii:a1 const :tuents

Cel'_ulose* X2 550 460 215

Cellulose* N2 650 350 110

Pectin N2 550 310 130

LignN2 550 2370 2330

Lignin%rk Air 550 440 460

I nvert Su g ar N2 550 140 50

Tobaccos and spinach



C9 flue-cured N 2 550 730 310

K4 burley , cased N2 550 620 390

Maryland bur ley N2 550 470 150

Spinach N1) 550 360 280


~
~
V
~
srWhatman Cellulose Powder, W. and R . Balston Ltd ., England . m
**West Virginia Pulp and Paper Company . u,
~
w
~
VI . Acids

The smoke condensate from 20,560 Turkish cigarettes yielded in excess


of 20 g . of long-chained acids (45-47) . Infrared absorption data indicated
the possible presence of both saturated and unsaturated acids such as palmitic
acid, stearic acid, oleic acid, etc .

VII . Aldehvdes and Ketones

Examination of the smoke condensate from C .~ML cigarettes indicated


the presence of acetaldehyde, propionaldehyde, acetone, furfural (CI),
3-heptanone (CII), glyoxal (CIII), methyl glyoxal (CIV), biacetyl (CV),
and 2,3-pentanedione (CVI) (8) . Identification was based on infrared and
melting point studies of the 2,4-dinitrophenylhydrazones of these com-
pounds (7) .
Zi

0
C'r.3C: C : `C :~C H3 OC::CHO
~ Ci:O

C: CII CIII

XCIX C

C::3COCH0 CH3COCOCH3 CH3COCOCH2CH3

C :V CV CVI

VIII . Heterocvclic Nitro¢en Cor,roounds

The ::eterocyclic nitrogen compounds pyrocoll (CVII), indole (CVIII),


3-mazhyl :ndole (skatole)(CIX), dimethylindoles, trimethylindoles, carbazole

i~
0

CVII CVIII CIR CX

(CX), and methylcarbazoles have been isolated from Turkish tobacco smoke by
liquid-liquid partition and column chromatography (35-37) .

The separation of indole from its homologs and the carbazole from its
homologs was accomplished by vapor-phase chromatography . Identification of
pyrocoll (CVII), indole (CVIII), 3-methylindole (skatole) (CIX), and
carbazol ;. (CX) was made in each case on the basis of melting point, mixture
melting point, infrared and ultraviolet absorption spectra, nuclear mag-
netic resonance spectrum (except for carbazole (CX)), and mass spectrometric
data .

Per 1000 Turkish tobacco cigarettes, the amounts in milligrams of these


compounds in the smoke were as follows : pyrocoll, 1 .3 ; indole, 1 .4 ; 3-methyl-
indole (skatole), 4 .3 ; dimethylindoles, 0 .8 ; trimethylindoles, 0 .5 ; carbazole,
0 .7 ; and methylcarbazoles, 0 .15 .

IX . Miscellaneous Comnounds

The following miscellaneous compounds have been isolated : furan (CXI)


and benzene (CXII), from CAMEL cigarette smoke and the isomeric 4-(2-buteny-
lidene)isophorones (CXIII) (44) from Turkish tobacco smoke .
52

:i~Cr
.~C: iC

CXII X
C III

X . Cc :nnErison of Different Tobacco Tvwes

Since the smoke condensates from burley, flue-cured, Turkish, and


ZdINSTO\ blend tobaccos were available at various times during our 8-year
study, we considered that the determination of some of the major com-
ponants of the so-called neutral fraction from these condensates would
urovide useful information concerning the relative composition of these
smoi:e cor.ca^.sates (48-50) . Unfortunately, the findings were not strictly
comr;a=abi,e because of the differences in the filter tip length on the
tobacco rods . However, the findings are presented in Table XIII despite
the limitations imposed on the comparative aspects of the various smoke
condensates .


5:

C~_. .r~ . .~. . . ~ : .~_ ..

:L• c o Z(:C :^ s w t C r o^
o_ r Ir:_s :- .-cL :; ::r 1Lv tdl 'N STC :: b lend
.. ~8 c rv b ^c C o~ Lo ba ccoC

` L r ..r e G
S4~ .' ..• ~~J V 630 5;:0 735
570 580 683 600
\eophyta4iene`'' 235 180 200 165
Squalene and isosqualene ? ? ? 4
Solanesenes + + + 85
Polycyclic hydrocarbor.sr 49 26 50 53
Authracene 0 .29 0 .21 0 .27 0 .28
Pyrene 0 .09 0 .05 0 .06 0 .06
Fluora :.:: :e::e 0 .33 0 .21 0 .27 0.26
EenzoL : .- ; yrene 0 .12 0 .06 0 .08 0 .06
Chryse :a 0 .02 0 .03 0 .02 0.04
u-To :.opherol 95 233 305 109
Solanesyl acetate + + + 25

• Solanesyl esters
Lona-chained saturated esters
+
60
120
+
40
+
66
4
:hy~osteryl esters + 65 15 26
Solar.esol 1500 2450 2570 530
Phytostarols 315 200 330 225
Phenols
3' :.enol 278 326 246 65(241g)
o-Cresol 60 86 104 15(57g)
p-Cresol 111 125 136 49(107g)

a7'0-mm . tobacco rod, no filter tip .

b70-mn . tobacco rod, 15-mm. Estron 8/70 filter tip .

e68-r.Lm . tobacco rod, 17-nm. Estron 8/70 filter tip .

dlncludes neophytadiene .

e?:ateriul w:zose infrared absorption agreed with that of pure neophytadiene . ~

f(?ualities for individual polycyclic hydrocarbons represent average values G


for sever&l deterr.iinations . Ln
w
g6S-mm . tobacco, no filter tip . ~
• (S'C-aC) XL:zr
..:..'•0,7 0078Gt'O~T,, SpFO-uata`3 •i •2j aU,7z zO
ad -3 j o ssoc,: :v~ : :c pa=zT,uapr uaaq an V q 005 j ;.oc V ctoz ;;:•~~ .^_ `CO8 =^oqv
3 naZ_ T n i:cJt e?YO' :SS OJOLCo .'`i :2'} S au e ::OC'z- O o ?O
ST O a En O :
•'[L^Z a a .''. n:1 ticjG::O :
0 v ti?c n iSZ S ; c:TC'~S 0 --lj a .: v2 }O ! 2 :T z
° . .^~6aaxe at : . :? .._
. u ; s ;71 - ." : ^ ::ot,r :

~C
.. . .L ~ , urr . . ... . . .. .;._ ~ rJC .? :. .. .c5 .;:::a .. ..~: Gw~u ~ ..r .._ . .s . : _ . . • u . . . r . .ur~ ., :.
. .:C C'v'~ : ._ .- . :. Ca C :.~,^ :.-Etta? :&t'2 J :. .. . . .ii. : . .__
?i- :i ; Mea:o-ranGa pa . .:inen_ to these p :oco ;:ur~ ::
c~~~ i:wo z :sa b,:aa ?.cna_ed (9, 10, 1-9, .515-SS) .
56

the ✓ ^Jir 6 I.l


.G4i. a 6
:. 4• . a If, rV . . .i~•~.4eraJle SC1 e :1~rrr c L,
. rlil• : .~. 4

: :a :: becn presentcd which reiates tcbacco ,, o : ._ng, particularly ci ; c,rot :e


to specific diseases . This evrua::ca consists of four t ;,-pe ;. ;
na :~c1y,
. statistical, pathological, bs.o1c ;;=cc?, and clie ::ical . Our Studi4s
h .^.ve been co :l,^.l^r ned solely ttiit :l the ia : t .3_ C.S :.a - the cCe" ic,^ i
oi t ;Db .,cco f',^~+ :e . For a consistent pic=ure to be Daint6d of cilJ : .`b :iCCo
s ;.yoice-d :sease problem, the evidence from each discipline m, :st a,-reo u•itii
that from .. :1a other three . :it . . _espect to the co .:.position of tob ;icco
smoke, ciell' cEl Cy : ;.i:':CE and the che :'ical evidence r eA :lrti't! by
othc:-s consis ::ent with the reoo_ted statistical, nathological, and
bioloeical data? To answer this question, let us first review briefly
the statistical, pathological, and biological data available .

The statistical data consist of the following : The results of some


29 retrospective statistical studies based on clinical findings have
indicated that the risk of developing lung cancer, especially opidermoid
or squamous cell carcinoma, increases with the amount of tobacco smoked
as cigarettes . When the tobacco is smoked as cigars or in a pipe, the
risk is m.:ca less . Presumably very few pipe and cigar smokers inhale ;
most cigarette smokers do inhale . Of these 29 retrospective studios,
none by itself proves a significant association between cigarette smoking
and lung cancer, but the combined evidence from the 29 studies is highly
suggestive of a significant association . This suggestion is bolstere d
by the results from seven prospective statistical studies whose results
indicated a significant association not only between cigarette smoking
and .lung cancer but also between cigarette smoking and heart disease and

several oz:er diseases . Although the results from these thirty-odd
retrospective and prospective statistical studies cannot prove a cause-
and-effect relationship between cigarette smoking and specific diseases
and although these results are not considered to be extrapolatable t o
the smoking population as a whole, the statistical evidence itself, with-
out contradictorydata, is irrefutable . At least four of these studies
have shown that inhalation of the cigarette smoke increased the risk of
developing lung cancer . However, the interpretation of this evidence
from the thirty-odd studies may and does vary . In these studies, each
one dealing with a relatively small study group (compared with the total
number of smokers in the population), the evidence indicates that the
heavy cigarette smoker in each study group has a greater risk than the
moderate smoker, the moderate smoker has a greater risk than the light
smoker, and the light smoker has a greater risk than the nonsmoker of
developing certain specific diseases .

Pathological data indicate that the number of sites of hyperplasia


and metaplasia in human bronchi is proportional to the amount of tobacco
smoked as cigarettes . Similar pathological conditions have been produced
in e :;perimental animals by exposing them repeatedly to cigarette smoke
under conditions requiring the animals to inhale the smoke . It has also
been shown that inhalation of tobacco smoke results in absorption of
fluorescent tobacco smoke components by cellular components of the
respiratory tract . The exhaled cigarette smoke is less fluorescent tha n
the inhaled smoke ; microscopy in ultraviolet light of the intact respiratory

tract exposed to cigarette smoke reveals fluorescent areas in the cells .
Of course, fluorescence is not synonymous with carcinooenicity . It has
also been shown that exposure of extirpated respiratory tract tissue to
whole cigarette smoke reduces the ciliary beat frequency with a concomitant
slos•ing down of the outward and upward flow of mucus . Thus the protective
57

. . . . . . . . . v . Or w . .C'Z r`S :, rrMa.VrY r vz .NaVo .rV


liC:_, r . ._v ra:~ .r . .r ...V .: _ .: C.rr_ ..r b ::w1: rrL . . . . . rJ

rC.sJ_ _ .. . .. . . .r . . . . . rv .

.:a'~ . . . . .. v ~ "_ .•it4 C :


the C r_rG:ry a e Hr rr eV VLa\. y can Je r e CMV{: d :c ..~:r V . _ :.a
. . .,.\• iL: Lr .L• v ur ..r bl e . C.ieF..s or _Ja :/:.r ."i a C. C.-1 ;[4
::ral : rso + .is :a~~3.$t~C
:.a~~3.$t~ C E :14 ;:t
to 2.' r om any y y . a5 : . .. : in pr G g.essi0 n o-~ t . :C
so ;. :Ce .

".:Qt:3 DlaSt~C .. .: : tiC tissue to cancer . Ciliastasis is ?_ c :a:CCCi


:TOt C :=y L:• ..r . . s^o :Ce but S•.'a: ce_tain ciaa_Ctt .^, ,. . . . : ::L
r :act :Ga . Soma auz :Grities 5elieve that tize sec,uance, n :,r .-,1 tissue to
decil•'ated tiss~je to rk taplastic tissue to hyperplastic tissue ta cancer,
can be accox~plished by repeated exposure to an irritant . '

Biological studies involving skin pa :.nting have indicated that ciga-


rette smoke is carcinogenic to the skin of the mouse, rat, and rabbit .
Inhalation studies have indicated that exposure of lung cancer-susceptible
mice to cigarette smoke _esulted in an increased incidence of adenomas in
the exposed mice . Such experiments are criticited because no carcinomas
have been produced ; but the type of lung tumor cc.aracca :istic of the mouse
is the adeno :na, not the carcinoma . Other studies have i :Tdicated that both
whole cigarette smoke and certain cigarette smoke fractions are cocarcinogenic
(or promoters) for known carcinoger.s like the polycyclic hydrocarbons . Bio-
logical studies on the respiratory tract of an intact host have also shown,
as in the pathological studies described previously, that whole cigarette
smoke and certain of its subfractions are powerful ciliastats . Although
animal data on carcinogenesis or cocarcinogenesis are not extrapolatable
to humans, there are many instances where industrial ores, tars, and oils
(suspect on the basis of statistical data) have yielded biological data
comparable with those obtained with cigarette smoke . Institution of pre-
ventive measures based on these data concerning industrial materials
resulted in a decreased risk for the industrial population exposed . Thus,
precedents do,exist for the institution of preventives measures with
materials whose risk was first noted statistically and whose adverse
physiological action was then demonstrated biologically .

Irregardless of its interpretation, we have the following evidence :

(a) Statistics - both retrospective and prospective studies indicate


a significant association between cigarette smoking and certain
specific diseases .

(b) °athoioav - fluorescent cigarette smoke components are absorbed


by respiratory tract cellular components ; whole cigarette smoke
and certain of its subfractions . product metaplasia, hyperplasia,
and ciliastasis in experimental animals ; the extent of metaplasia ~
and hyperplasia in cigarette smokers is proportional to the ~
amount smoked . 6
Ln
~
w
00
58

carcino mES a_e 7rodL'C o d ~ :1 I'.ice,


and rabbits painted soht :.o-a o : ci ; ::rette s*:oi.e cor.densat4* ;
.^.a aCleaO r. .. .;.~8 ,L : 'vd u c e-
l i:i d in . .~c .°... -
rats,

c -__r .7 : :.e .°.L10iCe ; w11o1 e



Cla ar ette s~ :. ::e and ce rz C i , o= its S ::J :1LCti0 :S ,..1C p rol'otin g
agents and ci?iastats .

:i.uS , the answer to the G,i.es :~Jn


:.~' Jn ed p_eti
p os /',, ~ - :,,~~ e : u :- •
c~ ~ L ~• .~ . ..sxcal
ci~~
C vi Gf:nce
and L :+e ch ar..' c a ll evidence i. - o :.ae r s cJnsist en w :.th
thc _eoortad statistical . oatholo_ical, and biolotical data? may be
answored as follows :

The known composition of tobacco smoke is not inconsistent with the


statistical _inding that cigarette smoke may be associated with lung cancer,
heart disease, etc . Cigarette smoke contains polycyclic aromatic hydro-
carbons and asterocyclic nitrogern co :lpou nc:s - several of wnich are known
carcinogens ; phenols and fatty acids - several of which are known promoters ;
phenol, aldehydes and ketones, nitrogen oxides, hydrogen cyanide, ammonia -
all known ciliastats ; .nicotine and related alkaloids - many of which have
demonstrable effects on .the .cardiovascular system .

The known composition of tobacco smoke is not inconsistent with the


patizological .findings that fluorescent components of cigarette smoke are
absorbed .by respiratory tract,tissue, or that metaplasia and hyperplasia
are produced in the respiratory tract by cigarette smoke, or that ciliastasis
is produced by cigarette smoke . Cigarette smoke contains about a hundred
highly fluorescent components - the polycyclic hydrocarbons and the . hetero-
cyclic nitrogen compounds ; many of these will produce metaplasia and
hyperplasia and .even carcinoma`in experimental animals . Cigarette smoke

contains several known ciliastats .

The known composition of tobacco smoke is not inconsistent with the


biological findings that cigarette smoke is carcinogenic, cocarcinogenic,
and ciliastatic . Cigarette smoke contains at least a dozen polycyclic
hydrocarbons`known to be carcinogenic . It contains at least three
heterocyclic nitrogen compounds known to be carcinogenic . It contains
nitrogen oxides, which are known to be carcinogenic and emphysematogenic .
It contains arsenious oxide(As203), long suspected as a carcinogen ; it
contains polonium-210, and it very likely contains carcinogenic epoxides
and dialkylnitrosamines . Cigarette smoke also contains promoters like
phenol and many of its homologs and the saturated and unsaturated fatty
acids . It contains ciliastats like formaldehyde, acetaldehyde, acrolein,
ammonia, nitrogen dioxide, hydrogen cyanide, and the low molecular weight
carboxylic acids . N
w
~
A logical sequence for the activity of factors pertinent to the carcino-
genic risk accompanying the inhalation of 'carcinogenic aerosols and irritants
present in cigarette smoke and polluted air has been outlined . The ability
of the respiratory, tract to prevent the retention and accumulation of
foreign particulate matter,by means of ciliary action and mucus stream

*It has never been ascertained whether cigarette smoke condensate wDulL be
more or less carcinogenic if the volatile components (aldehydes, etc .),
lost during processing of the :. ;:zoke, were still present during the carcino-
genesis studies .
r ..Vl . _J _ ~ rrr . .r .. . . r. . .. rv . .rr .rr Vr . . . . .. . .rrr ._ ~ Vr Va. .rr . . .. ~~~inbs .

~G~ .1 : :~ _r . . ..s~ • ~ :~ . . .~ .rr ..~ . . . .. . .r~C1~~L . . ..~ . . r . . .:J11 .w~ . . . .._ C ..~1: ::J :: .. . .. .. . . .. : -, : :5

o : .rwrV.r ..V . .L :. ..v

\': ~r .Z irritants favors t .. c;-- r . .. . . .. .. o. C . . ..1. .: IZL .r.. . . Ll-: S pir .r..bVry
-
tr . :.V t . .

:.t crgaed that ..;:e c_ ben:;c[a ;pyrene or rs'~ :ious


;.
O :•. s mO::e is _ I:su : !'_ c :, eT.r :J LOc :+L`i.t - : Or the obSC r \'CL
..
ca .c i
r...dea
v ~.._ ~
, cr c~b~ e . -.
r•^~ ~~ ~~
s-o : :e . • _his,~oi cour
~c .e,. Ls • &.
t .ue : ~at ao

one has yat conducted the obvious e ::per : :::~a to determine waethcr the
amounts of t : e carcinogenic polycyclic hydrocarbons plus the amounts of
the carcinogenic heterocyclic nitrogen co,:aour.ds plus the amount of arsenious
oxide plus the amounts of the cocarc :.nogenic phe ::ols and fatty acids are
sufficient to account for the.observed biological results . Calculation
has indicated that the kr.oc•m carcinogens and cocarcinogens in cigarette
snoke can account for about 90 percent of the observed activity . Such a
nixture could behave synergistically, additively, or ir.hibitively . It
is obvious that concern with the relative concentration in cigarette
smoke of one, or at most, of a few of the components is ridiculous . As
an absolute criterion of safety insofar as health is concerned, chemical
analysis of cigarette smoke, while highly suggestive, is physiologically
meaningless . The scientific community only accepts biological data as a
criterion of the healthfulness or harmfulness of a particular material .
The pharmacological properties, whether good or bad, of cigarette smoke
cannot be deter :ai ned fro .:~ chemical data which indicate the smoke from
Cigarette A contains more or less Carcinogen X, more or less Proa ;oter Y,
and more or less Ciliastat Z than the smaRte from Ciaarette B . The only
meaningful assessment of the relative tor:icity of the smokers from
different cigarettes is a biological assay .

Although it has not been attributed directly to the mounting evidence


on the health question, a gradual change in cigarette smoke has occurred
during the past ten years . For the first five or six years of this period
the amount of particulate matter in cigarette smoke was reduced by the
use of more efficient filter tip materials . More recently, efforts have
been directed toward a search for methods of removing specific components
or types of components from cigarette smoke with particular attention
being directed at present to the removal of promoters and ciliastats . Of
interest is the fact that the most successful results in selective fil-
tration - the use of Carbowax-type compounds to remove the cocarcinogenic
phenols, the use of the Keith charcoal filter'or other types of charcoal-
impregnated filter tip to remove the ciliastatic aldehydes - have arisen
where cOr^.lementarv chemical and 'cioloaical data were available .

Our chemical studies have shown that the concentration of specific


u,
smo ::e com:onents can be altered by specific treatment of the tobacco . ~_A
_j
1'.e ::c ::e and ether extraction of tobacco decreases the total polycyclic H
hydrocarbon and the benzo[aJpyrene content of cigarette smoke ; alcohol m
extraction decreases the total polycyclic hydrocarbons and benzo[a)pyrene Ln
~
but increases the phenol content of the smoke ; increasing the porosity of ~
the paper decreases the polycyclic hydrocarbon content of the smoke . m
vr p '. . L .. c 41Gr '..a .er

o . i.•r :;4:reLLa E'mJ :1e CiO ::'~oS :Llor. .


ra z _ :c:n o ::t in 11 956 r. ::d . 1 ; 5 7,
e .s rsr rS L . a b ;' i e .~. ..

cr
.. Vr 4r c o . .J~

:c
t~ :. ..ra:b ..ra :1

. .,-a ~ .: .. .°i t:J .r :aZ : ..rOr: S ~ ' rrrF LL.C.~~ ~•,. .5


7 : :3ao l . -
VJ V
o

?,r
r

.• : ..~
LLI :)

L
L.~.
a co
c

S

or h z or.lv^'.: : .n ; a ;entS _in ci g ar et .., . .^.J z !> C3n stressed i :: L : ;a c .7 :1-
to :'.:7 or i:ry 1 :.t er i.ttL' Cs . The concc :._ :' .: : iC n of ..̀ :iC: c,^.rcinoacnic p11)'C\' c lic
hyC.r oc .'t, rbons, r : :~ :: :.cu 1 .1r ly -, n Cia.^, . rz e :t•C S1 .'.oi :c has b v Oa
t '.it,.
~ SUJ,~~.
~=O^ .. t of i :1•-
. ..C ::ra ~~l~ @ study S :. - ..- e 1 ^ .:J . ^•.'le i~
~ •e S :11L 5 .'
of
,~ ~
.•Ur
. • ~
t . .. ..~. l l~.a...
c h e :.wcal stuLies on caa e:: ::_act_on of t ;.bacco ::ou :c: have suggestad that
the tobacco :a .ce derived fror: e:;tr a c : .ed tobacco had be e n ir.zp roved
irom the 73a L i .: viewp o int since extraction of t'r.e tobacco result e d in
a r e :ilct ;on of t he concentrE. l .on C t z at _east SC': e of t : e c .lrcinoSCnic
polycyclic hydrocarbons in the smoke . This appeared to be confirmed by
biological data (reported by other workers) on the carcinogenic activity
of the cigarette smoke from extracted and nonextracted tobaccos . However,
the decrease in caicinoger.icity o° the sr..o : ;e was generally less than the
decrease in the benzo[aJpyrene content of the smoke . The results of later
chemical studies ihdicated this improvement may not be so marked tecause
alcohol extraction of tobacco resulted in an increase in the phenol contentt
of the smoke . Let us compare the exposure oi a host to the cigarette smokes
frorm extracted and nonextracted tobaccos . As mentioned previously, the
biological data on the activity (carcinogenic and sebaceous gland sup-
pression) of the smokes indicated the smoke from the extracted tobacco
was less carcinogenic . But is the smoke from the extracted tobacco less
cocarcinoeenic when the host is exposed to this smoke together with
carcinogens from some other source, e .g ., polluted air? Our chemical
data suggest it is not .

Any change of the tobacco or the cigarette (extraction, tobacco


additives, filter tip materials, t :,lter tip addit-:.ves, paper porosity,
tobacco blend) will necessarily a :.ter the relative composition of the
tobacco smoke . How do we relate this composition change to the change,
if any, in the pharmacological properties of the cigarette smoke? For
what components of the cigarette smoke do we routinely analyze? Do we
determine the concentration of the carcinogenic polycyclic hydrocarbons
(benzo[.k ;p ;.rene, dibenz[a,i]pyrer.e, and dibenz[a,hjanthracene), the
ca.cino~cr::c heterocyclic nitrogen compounds, the lactones, the cocarcino-
genic phenols, the cocarcinogenic fatty acids, the ciliastatic aldehydes
(formaldehyde, acetaldehyde, acrolein), or other pharmacologically active
smol:e components like carbon monoxide, hydrogen cyanide, hydrogen sulfide,
nitrogen oxides, arsenious oxide, nickel or nickel carbonyl, polonium-210,
dialkylnitrosamines, low molecular weight epoxides, and/or nicotine and
related alkaloids? A chemical analysis which indicates a decrease in the
concentration of each and every one of these components or groups of com-
ponents does not necessarily demonstrate, in any way, that the cigarette
is safer biologically to the host . Some smoke components not determined
may have increased in concentration to cause a totally unexpected effect .
At the risk of being repetitious - the only meaningful assessment ssmnt of the
relative toxicity of the smokes from different cigarettes is a biological
assay .
Ol

,,, . .
:/• .V. . .r .!

. i J .". . r .:S ,.~ s 0 r a r .ltI coii?OS«r .7 .: 0 ~ C2,ar, : .. ..t°, s^ode, ..ne


~iG : ~e .'.C .:c?i. :

~. 1. :.~G :.'e :.te S :iJ :it? is a very cofir, Ca-ri .:l (50, 57, 5S') .

2. C-_*a ~ : a tt a sLloiCr° fro .i. any t :JacC :. C\'; Z o: Co Da cco blend cont .nans
c :6* C .^.obea.7.c co^ :7on2nz s (be ;lZo [ _:jp :"` a :: :, 1JDyr o :1e,
di'De : :2[a,b ] a:a::.acei: a , a~ :.e*.Z j _,l 1 c :lollnth rene,
benz[aJar.thracene, Ci :. b er :S.[ a, SJacridi :3 P d .a?a :iL_ ,}1 lacridine,
7a-dibenzo c,gJcarbazole) (11, 12, 13, 14, 15,1n, 20, 35),
cocarcinogenic components (phenols, fatty acids) (32, 38, 59),
c :liastatic com?onents (aldehvdzs and ketones, ammonia, nitrogen
oxides, phenols, hydrogen cyanide) (7, 8, 32, 38, 59), and
irrizants %'aldehydes, nitrogen oxides) (7, 8) .

3 . ' :Ze composition of cigarette smoke can be altered by the following


:.r eatr„ents .

a .- Pretreatr:ent of tobacco by solvent extraction : Solvent


extraction of tobacco reduces the polycyclic hydrocarbons
content of the cigarette smoke ; the extraction increases
the phenol content of the smoke (1, 11, 12, 13, 15, 32) .

b . PretreEtrent of tobacco b,~ the use of additives : Addition


of inorganic compounds like cupric nitrate to tobacco decreases
the polycyclic hydrocarbon and benfo[aJpyrene content of the
smoke (1$, 22, 29) . Addition of sulfur to tobacco increases
the polycyclic hydrocarbon and benzo[a1pyrene of the smoke (22) .
Addition to tobacco of organic compounds like sclareolide and
the salts of substituted malonic esters improved the cigarette
smoke flavor by increasing the concentration of flavorful
components in the smoke . Addition to tobacco of organic
compounds like solanesol, the saturated hydrocarbons, or the
phytosterols does not alter substantially the cigarette smoke
flavor, but does increase the polycyclic hydrocarbon and
benzo[ajpyrene content of the smoke (22) .

c . The choice of filter tiu materials : The composition of ciga-


rette smoke can be altered by the choice of filter tip materials
(15, 18) . Cellulose acetate and cellulose have different
affinities for the particulate phase and its components ;
charcoal, alumina, and silica gel, have different affinities
for the vapor phase and its components .

d . Pretreatment of filter tias : Certain compounds added to filter


tip materials can alter the composition of cigarette smoke ;
e .g ., agents. like 2,4,7-trinitrofluorenone or chloranil which
form stable complexes with polycyclic hydrocarbons when added
to the filter tip material reduce the polycyclic hydrocarbon
content of cigarette smoke (19, 30) ; various Carbowaxes on
filter tip material reduce the phenol content of cigarette
smoke .
62

G• ' cC = _
r .:e
'iao :, :co
zo*_ . .ccc 7 : a .^. z .. c .G C'
leaves fro :ri
ea :CL t e

rVi.s, .~'rr .. .r1Mr ~\, G1Yrt?r~Ry
CObc^..cc0 %-,+G's and i: : ~ :,Cr Cr. : *- i: :1dS ~1 ~ LJ b a^.c o t\'pa s `'` eld
cigarette smokes with d :_fere :: ; coc:po :: .t :o n s (11, 13, 13, 15) .
:

i . ?wner *)o_cs'rtv and ^dCej-~• .es : of


ci ;arette smo ::e a_tered by alterir.g zize porosity of
the cigarette , " nd/or tae use of an a :;r.i ;:ive such as
sodium and po :.assi~- cit_ates on tze paper

. Tobacco contains compounds V :ich ::aven been demonstrated to be


precursors of carcinogens ir. smol;e . Solanesol, the saturated
hydrocarbons, and the p :.ytosterois in =obacco are precursors of
various polycyclic hydrocarbons in s:r.oke (11, 12, 13, 15) ; nico-
tine in tobacco is a precursor of carcinogenic heterocyclic
nitrogen compound in smoke (35) . Plausible mecnanisms for the
formation of these two classes of co .-apounds from their precursors
have been advanced .

5 .. Tobacco contains compounds which have been demonstrated to be


precursors of the cocarcinogens (or promoting agents) in smoke .
Pectin, cellulose, and lignin .in tobacco are precursors of the
cocarcinogenic phenols in smoke (59) .

6 . Tobacco contains compounds which have been demonstrated to be


precursors of the ..ciliastats .in smoke . Cellulose and glycerol in
tobacco are precursors of ciliastatic aldehydes and ketones in

smoke . Cellulose in tobacco is also a precursor of phenol, a
known ciliastat,• in smoke (7, 8) .

7 . None of the chemical data acquired in our studies or in studies


conducted elsewhere is inconsistenz with reported biological,
pathological, or statistical data indicting cigarette smoke as
a health hazard .

8 . Although considerable data are available on the chemical composition


of cigarette smoke, much more data are required to define completely
both the chemical and physical nature of cigarette smoke (59) .

E . Rr.COr~~k'DATIOAS Lnr

I . Future Work ~'

During the period June, 1954 to May, 1963 many recommendations con-
cerning the study of cigarette smoke were made . Many of these recommendations
ware followed up by research which was subsequently reported . Some recom- ~
mendations, stili pertinent, are as follows :

1 . A : .l additives to tobacco should be tested biologically for their


adverse effect, if any, on a host (11a) .
.. . : J:
.
. C_rLvr ~ .. r . . ~y . .~. `_ .'i'.~

G .::t . . i :3 . . : ve alrc .':.CV ECC,L :iri:C and those d .3ta t•:::ic .^.
.',cC : iliri3 j : : .. : 2~ .. : u :e wi!_ .7e :i$a :a .^.5~~12_ 4I they are
. . . _ . r_ . . Vt .: Yl :t . . Sicsoorc ;.._ aG . .a (V, _3, _S, 59) .

4. A of . . . . ;) f y siCo - C : e :ac3_ of aerosols as they


J, ., :C. y
.:o to~a ..co s ::o ::e and its 'i_t:ation would be valuable .
(T ::_s stc :c:y is in progress) .

5 . The study of the compos__'_on of cigarette smoke by the isolation


and characterization o .-' _ts components should be reactivated as
soon as possible .

II . Patentabilitv

The patentability of various ideas and findings has been discussed


in the appropriate sections of our earl_er reports .

~.
Alan Rodgman:

Distr ;bution•

Mr . Kenneth H . Hoover
Mr . E . H . Harwood
Dr . Murray Senkus
Dr . Claude E . Teague, Jr .
Dr . Alan Rodgman
Library (2)
Dr . Fred T . Williams

First Draft Submitted : October 24, 1963

Completed : February 14, 1964


From manuscript :ww :pws

Approved :
,
,
04

:i~'' :.=~~ : ;'~.Y

i. . :ai c711r .., ' ::d R:odL : . ..' :, F . A . 1 :C, : . J . ReynJlds Tobacco Co .) r
''rocede dc : E : :.ement d4 =aba :. . = RIXC :. ?A Ti:\T N0 . 1,206,210
(Feb. S, 1y60) .

2 . COo'.., L . C . , and Rodgr.;,n, r:• , T ::e An" lvsis of Citar ette S ::zo ;cC
Condensate . }:.l'II2 . a- ar~.d 6-Levantanolide Tu : ki sh Tobacco
Sn:o :ce . RDR, 1961, No . 12 (Apr . 28) . .

3 . Cook, L . C ., anr: Rodgman, A ., T:^.e Co,::osition of Cigarette Smoke .


VIII . o'- and S-Levantenolide from Tu_ :cish Tobacco Smoke . TOBACCO
SCIENCE, 6, 32-33 (1962) .

4 . Cook, L . C ., and Rodgman, A ., The Analysis of Cigarette Smoke


Condensate . XXV . 12a-Hvdroxv-13-evimanovl Oxide from Turkish
Tobacco Smoke . RDR, 1961, No . 44 (Sept . 22) .

5 . Cook, L . C ., Rodgman, A ., and'1'oung, G . W ., The Analysis of


Cigarette Smoke Condensate . XVI . Normal Lona-Chained Primar,y
Alcohols . RDR, 1960, No . 22 (July 1) .

6 . Cook, L . C ., Rodgman, A ., and Young, G . W ., The Comoosition of


Cigarette Smoke . VII . Normal LonR-Chained Primary Alcohols .
TOBACCO SCIENCE, 5, 6-10 (1961) .

7 . Fredrickson, J . D ., Chappell,C . K ., and Rodgman, A ., The Pre-


uaration of Reference 2,4-Dinitrovhenvlhydrazones for Ninety-one
Carbonyl Comoounds . RDR, 1956, No . 6 (Apr . 27) .

8 . Fredrickson, J . D ., Chappell, C . K ., and Rodgman, A ., The Analysis


of Cigarette Smoke Condensate . }LXX . Volatile Aldehvdic and
Ketonic Constituents . RDR, 1963, No . 12 (Feb . 8) .

9 . I'.od"man, A ., The Use of Potassium Bromate as an Oxidant to Convert


Carcinoeenic Hvdrocarbons to Noncarcinogenic Quinones . CIM, 1954,
No . 34 (Nov . 17) .

10 . Rodgman, A ., The Fractionation of Cigarette Smoke and Tar . RDM,


1955, No . 13 (Apr . 29) .
Ln
11 . Rodgman, A ., The Analysis of Cigarette Smoke Condensate . I . The ~
'l
Isolation and/or Identification of Polvcyclic Aromatic Hydrocarbons ~
in CAMEL Cigarette Smoke Condensate . RDR, 1956, No . 9 (Sept . 28) . m
~
~
lla . Rodgman, A ., The Prevaration of Some Phenolic Flavorants . RDR, Al
1956, No . 10 (Oct . 1) .

12 . Rodgman, A ., The Analysis of Ciaarette Smoke Condensate . II . The


Pretreatment of CA.*EL Blend Tobacco . RDR, 1956, No . 12 (Nov . 1) .

13 . Rodgman, A ., The Analysis of Ciearette Smoke Condensate . III .


Flue-Cured Tobacco . RDR,,1957, No . 4(A:arch 14) .

65

3-7 ~ :,0 . ..3 •


" JCL . ~~ - -

_: . aa,
.= :! :-'C`? o= .- " a
. . . .' :E_y-. .. : : ~ '~: ~-L : .~ S ._ .a7 ~. : . ~V . VI . Tll t~.
7~~n
-_ ^V
:IV 1Ve aL _ ~. .. "~ .- . F- Vr i .L Jiv~.o -.4• •~~ 1 ~+ ..CLV• on
.C! 171L

YCo`~ . .V : : :. i~ rWr., ~i5

iG . Rodsman, a ., _ :z r._ C__=_et- S-o; :e Cozder.satC'. . LC .


P'r.vtadienes . R3:-, ?jL, -i

17 . . Rcd ;r.an, A ., _he Con.oosit :on oi Cica_ette Smol:e . III . Phvtadienes .


w . OR3 . CHEM ., 24, 1916- :.;24 (_959) .

18 . R:.dor:.an, A ., The Analysis of Cigarette Smoke Condensate . X . The


r :: :ect of Porous Paoer and/or Filter TiD Materials or Aluminized
?sver and/or Alumina Additive fRevnolds Metals Cor .:oanv) on Total
Polvcvclic Hvdrocarbons . RDM, 1959, No . 80 (July 16) .

19 . P.odgman, A ., An Additive ::or Filter Tiv Materials . CIM, 1960,


No . 4 (July 13) .

20 . Rodgman, A ., The Analysis of Cigarette Smoke Condensate . }:I}C .


_::e Determination of Pol .•cvolic Aro, :atic Hvdrocarbons . RDR, 1961,
No . 1 (Jan . 6) .

21 . Rod ;rzn, A ., The Ar.alvsis of Cigarette Smoke Condensate . XXXIII .


P :.lvcvclic Hvdrocarboi:s in Lark Cigarette Smoke . RAM, 1963, No . 37
(=~'Y 1~)~ •

22 . Rodgman, A ., and Cook, L . C ., T'.:e Ar.alvsis of Cigarette Smoke


Condensate . V. The Polvcvclic Hydrocarbon Precursors in Tobacco .
RDR, 1958, No . 18 (Dec . 1) .

23 . Rodgman, A ., and Cook, L . C ., The Analysis of Ciearette Smoke


Condensate . VII . Solanesol and Solanesvl Acetate . RDR, 1958,
INo . 22 (Dec . 31) .

24 . Rodgman, A ., and Cook, L . C ., The Comoosition of Cigarette Smoke .


I . Solanesyl Acetate . T0MCC0 SCIEKCE, 3, 86-88 (1959) .

25 . Rodgman, A ., and Cook, L . C ., The Analvsis of Cigarette Smoke


Condensate . XI . a-TocoDherol . RDR, 1959, No . 23 (Sept . 29) .

26 . :;odgman, A ., and Cook, L . C ., The Cor:oosition of Cigarette Smoke .


_V . ^>.•.-Tocooherol . T03::CC0 SCIENCE, 4, 7-8 (1960) .
Ln
'27 . Rodgman , A . , and Cook , L . C ., The Analvsis of Cigarette Smoke ~
~
Condensate . XIII . Sclareolide from Turkish Tobacco Smo ::e . :.DR, N
m
1; 60, 'x o . 8 (Apr . 1) .
Ln
N
28 . Rodgman, A ., and Cook, L . C ., The Analysis of Cigarette Smoke ~
m
Con ::er.sa _e . XIV . Polvcvclic Aromatic Hydrocarbons . RDR, 1960,
No . 20 ( ::ay 26) .
L N

.. ^ ~ r .
d .:, . .
::J !~
, .. . . .. v vy . :y .. . ~. . , . . . Z n !
v_S'i = 'L ti SI? Jia?
Co da t
11 »Ci Q
• S E ~~ E. .^.t r~ • .a4 m .4- -u 'TiV r .: (j
` CtMb : l v s .. .•!

on :.'o .`^' E 0 .^ : bo ` _ J`ai Soi •Gs . a :^. :: .\I-Cotine .


RD.'t, =;u ;; . :;c . :,6 (Dec . 2) .

30 . Rodgma^., A ., and Cool: L . C . ,A^a l-sis o : C ; ^ .1re*te Sr.:oke


Condensate . ?.VIII . C ::?o_F ::i1 and 2 .4 .7-__•i~nitrofluorenone as
Filter Tia Additives . C7 R, '900, No . 58 (Dec . 7) .

31 . Rod3 .~,an, A ., and Coc : :, L . C . ,=ra'vsis of C ; care`te Smoke


Condensat }^ : . ? ;ote on i:he Lc .a.-Chained Pri~r~arv
Alcohols : • An Aadendu :; to ?.DR . 1960 . N ;, . 22 . RDR, 1961, No . 5
(Jan . 26) .

32 . Rodgx.s.n, A ., :::.d Cook, L . C ., The Analrsis of C!__arette Smoke


Condensate . }:: ;I . Phenols . RDR, 1961, No . 10 (Feb . 23) .

33. Rodgman, ak ., and Cook, L . C ., The Analysis of Cigarette Smoke


Condensate . XXIV . 6-Acetv_-2 .3 .4-tris-d-B-methvlvalervl-6-D-
elucoovranJside from Turkish Tobacco S .;.oke . RDR, 1961, No . 42
(Aug . 18) .

34 . Rodgman, A ., and Cook, L . C ., The Coroosition of Cigarette Smoke .


X . 12o:-Hydroxv-13-euiraanol+l Oxide from Turkish Tobacco Smoke .
TO?ACCO SCIENCE, 6, 123-124 (1962) .

35 . Rodoman, A ., and Cook, L . C ., The Analysis of Cigarette Smoke


Condensate . XA'ATI . Heterocvclic Nitroeen Comnounds from Turkish
Tobacco Smoke . RDR, 1962, No . 14 (June 21) .

36 . Rodgman, A ., and Cook, L . C ., The Comoosition of Cigarette Smoke


XI . Heterocyclic Nitro¢en Compounds from Turkish Tobacco Smoke .
Paper presented at 16th Tobacco Chemists' Research Conference,
Richmond, Virginia, September 26-28 (1962) .

37 . Rodgman, A ., and Cook, L . C ., The Comoosition of Cigarette Smoke .


XI . Heterocvclic Nitrogen Comoounds from Turkish Tobacco Smoke .
TOBACCO SCIENCE, 6, 174-177 (1962) .

38 . Rodgman, A ., and Cook, L . C ., The Analysis of Cigarette•Smoke


Condensate . )MVII . Phenols from Turkish Tobacco Smoke : Eugenol Ln
and Isoeugenol . RDR, 1962, No . 15 (June 21) . ~-A
~
~
39 . Rodgman, A ., and Cook, L . C ., The Analysis of Cigarette Smoke m
Condensate . }OZ1X . Phvtol (3,7,11,15-Tetramethvl-2-hexadecen-l-ol) . Ln
~
RDR, 1963, No . 9 (Feb . o) . ~
~
40 . Rodgman, A ., and Cook, L . C ., The Analysis of Ci¢arette Smoke
Condensate . Z}•OCI . (x-1,5-Dimethvl-l2-isouroovl-9-methvlene-5 .8-
oxido-3,13-cvclotetradecadien-l-o1 and o:-12-Isopropvl-5,8-o ::ido-
1 .5 .9-trimethvl-3,9,13-cvclotetradecatrien-1-o1 from Turkish
Tobacco Smoke . RDR, 1963, No . 24 (Nlar . 25) . •
41 . Rodgman, A ., and Cook, L . C ., The Analysis of Cigarette Smoke
Condensate . XX1:II . Isoorenoid Alcohols . RDR, 1963, No . 35 (May 8) .
. -

.
at ~7t : T ;;-acc ; ~ :._ . . ._ ~s' .~~sc~rch
_. -23 J
`_iVJ)

~:J . . . . . . ., . .. :a, .. , and Cooa, .. . C ., 2,.L t - o^ ~• C :'7•'~~La.'.~.1• : S


.• .
.7 .~e .

`i Ur.sa_ura_ed A :.cohc ;.s frc- ?';:r : 's ;. Teb; ccc.~Sn•a' ; o . TO!1.CC0


7, .i. 3 1- 1 :r 7 ( ~96 .i~ . . .

/. !.
-r-r . ri . , and CoO : :, L . C . , The A.nalVSi S o f Ci_"YCt -e S .,7i :~',
C J1C. .?nS : r e . de :1G' ) -iS .7 D h0Y0^ a S ' r o :* Tul- k :.S.1
:'o~ 4a cco S : :o : RDcR in p :-epaYa-io n .

45 . Rodgman, A ., :;ook, L . C ., asllin, S . A ., rlims, S . S ., and Young,


G . td . , Tae Ar. ..lvs ; s of Ciearette Smoke Condensate . XXII . The
ar. :;lio :^.a :ic Ester Fractiorn from Tobacco and
^Jbacco Sr :,ice . RDR, 1961, No . 15 (Mar . 27) .

46 . :; :,dg .nan, A ., Cook, L . C ., Bellin, S . A ., Mims, S . S ., and Young,


G . W ., The Comoosition of Cigarette Smoke . M The Comoosition
c : an Aliohatic Ester Fraction from Tobacco and Tobacco Smoke .
Paper presented at 15t'r. Tobacco Chemists' Research Conference,
P ::iladelphia, Pennsylvania, October 4-6 (1961) .

47 . Rodgman, A ., Cook, L . C ., Bellin, S . A ., Mims, S . S ., and Young,


G . W ., The Cor, .oosition of Cigarette Smoke . IX . The Comnosition
of an Aliv'.:atic Ester Fraction ::rom Tobacco and Tobacco Smoke .
TOBACCO SC-6ENCE, 6, 42-49 (1962) .

48 . ::odgman, A ., Cook, L . C ., and Chappell, C . R . , The Analysis of


Cigarette S-:oi:e Condensate . V . Comoarisorn of Different Tobacco
TS es . RDR, 1960, No . 21 (June 30) .

49 . :.odgr.%an, A ., Cook, L . C ., and Chappell, C . K ., The Comuosition of


CiQarette Smoke . VI . Carmarison of Different Tobacco Tvoes .
Paper presented at 14th Tobacco Chemists' Research Conference,
Winston-Salem, North Carolina, October 13-14 (1960) .

50 . i.odgman, A ., Cook, L . C ., and Chappell, C . K ., The Comoosition of


C=2arette Smoke . VI . Cor.marison of Different Tobacco Tvices .
TOBACCO SCIENCE, 5, 1-5 (1961) .

51 . Rodgtr.an, A ., Cook, L . C ., and Latimer, P . H ., The Analysis of


C_sarette Smoke Condensate . VIII . Solanesvl Esters and Phvtostervl
Esters . RDR, 1959, No . 2 (Feb . 10) .

52 . Rodgman, A ., Cook, L . C ., and Latimer, P . H ., The Co :noosition of


C : . .arette Smoke . ?I . Solanesvl and Phvtostervl Esters . TOB.=.CCO
SCIENCE, 3, 125-128 (1959) .

53. TJ ;; ;man, A ., Cook, L . C ., and 'Mins, S . S ., The Analysis of Cifiarette


Condensate . XII . Saualer.es and Solanesenes . RDR, 1960,
:io . 3 (F eb . 10) .
O :)

1
> :. . . . ~ .:i. :, t`. . , CoOn,

~' ' C~te S :"J


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1
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55 . :od^, ::ls:r., A ., Cook, L . C . , a ::d ._ . .s, S . S . , The Ca,::nosi zion o f


Ci •^arette S,:.oi:e . V . So :4 :lesr :zLs J . G RG . CHEM., 36, 497-501
(i;oi) . -

56 . Rodgman, A ., anc ?:e nz, W . i'] . , Co-~or.e^.ts ^•.evorted in Tobacco


Sra ::e . RJa., I c o0, No . 47 (May 27 ) .

57 . Rod ;man, A ., Aienz, W . W ., Huffr, .zn, F . E ., and Smith, E . N .


Co ;zonents Recorted in Tobacco Smoke . RDM, 1962, No . 43 (May 21) .

58 . Rodgman, A ., Menz, W . W ., and I:onstanti :.aia, G . A ., Comnonents


Reaorted in Tobacco Smoke . Suauiemer.t 's . Comoonents ReDorted
from May 1962 to S-)_ii 1963 . RDM, 1963, No . 32 (May 2) .

59 . Rodgman, A ., and Mims, S . S ., The Analvsis of Cigarette Smoke


Conaer:sate . )MVIII . Possible Precursors in Tobacco of Phenols
in Tobacco Smoke . RDR, 1963, No . 1 (Jan . 9) .

60 . Rowland, R . L ., Rodgman, A ., Schumacher, J . h ., Roberts, D . L .,


Cook, L . C ., and Walker, C,T . E ., Jr ., Macrocyclic Diterpenes .
Hvdroxvethers from Tobacco and Tobacco Smoke . Paper presented at
17th Tobacco Chemists' Research Conference, Montreal, P . Q .,
Canada, September 23-25 (1963) .

61 . Rowland, R . L ., Rodgman, A ., Schumacher, J . N ., Roberts, D . L .,
Cook, L . C ., and Walker, W . E ., Jr ., ~iacrocvclic Diterpene
Hydroxyethers from Tobacco and Cistarette Smoke . J . ORG . CHEM.,
?9, 16-21 (1964) .
ii96? `A7I Atsnzqa3

uEUBpog ualy

Aals ol SS6T `t isn£n y :PajgQ

`OOt-TSCiOt ` c c ~_- ~CC'c-TSGi?t `IS-tOt£?t `COC-I : ;^rCI `CS-I~LSCI


009-IS_OOt Cv : :59~ . CC :- :S065'0 ` i
-TS96S0 ~ `COb-ICS/3C OC9-i05SCC °0c CS~
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.
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.+J, . .J . i .~ . .

1 ; 55, Nos . 6, 9, a^d 12


*O:., : ; 57, \os . 4 and 13
:I.DR, 1. 95 B, \os . 18 and 22
RDi:, :. ; 39, \o . SO
: TJI., \os . ':., 2, 11, and 23
_950, \o . 47
RDR, :;00, Nos . 3, 8, 20, 21, 22, 36, and 38
Chi ; 1950, No . 4
RDR, 1961, Nos . 1, 5, 10, 15, 21, 42, and 44
RDDf, 1962, a\To . 42
RDR, 1962, Nos . 14 and _5
F,DM, 1963, Nos . 32 and 37
RDR, 1963, Nos . 9, 12, 15, 24, and 35


Alan Rodgman

February 14, 1964


, CONFIDENTIAL kj ()
f .
f

R !4 D LONG-RANGE PLANNING

SMOKING AND HEALTH: PROt1UCT AND St4OKE COMPONENTS

Dr. Alan Rodgman


FC Director of Research
October 8, 1976

. .;.r .. .~..__. ..
:.3' - . .C: . . .. .. . . .•V.~- . . . .1 . .. . . . . . .
. :~.:: :.:,•~• . . : s. :' . r : .~ ., .,~.. . .. . . . . •r . . : . . = .a . . ; ;
INTRODUCTORY NOTES

On the following pages is presented a discussion of Key Issues


for long-range planning in the area of Smoking and Health,~ :_ Product
and Smoke Components .
In reading this n:inuscript, the reader should be aware of the
following :
(1) The author does not necessarily agree with or accept
any or all of the data, claims, statements, allegations,
etc ., advanced by proponents of the smoking-health
theory with regard to the components considered .

ENO (2) For each product or smoke component, the bleakest


possible outlook has been presented•. In many •
instances there are substantial data to contradict
some or all of the claims advanced by proponents
, of the smoking-health theory .
(3) For most of the product and smoke components . I
have included in the discussion the use of such
~A"' as " . . .proponents claim . . .," " . . .proponents
c~ ~~+nn . . . . . " . . . Proponents allege . . .," " . . .proponents
• ~f~`#~ t . . . ." " . . .the alle9ed activities . . . ." " . . .the
• ;Xlaiiped properties . . .," etc. In parts of the
ssion where I may have inadvertently omitted
.'41M•qualtfying words or phrases, their presence
* be underbtood by the reader . •
(4) 1YR7references cited in each of the position
s should be considered as representative .
ome sc~oke or product components such as
nic0tine, "tar", or carbon monoxide there are
hundreds of references available .
(5) Several product or smoke components are-discussed
In the introductory text but do not appear in a
Position Paper or in the Key Issue tabulation .
These were included for the sake of completeness .

%o

V, , R2,236
/

R & D LONG-RANGE PLANNING


.

SMOKING AND NEALTfi : PRODUCT AND SM0KE COMPOtiENTS

MISSION STATEMENT
• To define those components in the Company's products and/or in the smoke
from the Company's products which will be implicated either positively or
negatively in the smoking-and-health controversy .
r, It is anticipated that past and present trends to indict various components
ojjtobacco products and/or their smoke as contributors to ill health will
ntinue till 1989 but at a highly enhanced level during the decade 1979-1989 .
~• Past and present indictments will continue .in the future to concern not only
direct exposure of the smoker to the components of the mainstream smoke
~ '" at wchih isnhaeut
ild) asoblhtenrectidiexposure of the nonsmoker or .
ker cohort to the components of environmental smoke . Environmental smoke •
defined as the sum of the sidestream smoke (the smoke liberated to the
sphere between puffs) plus that portion of the mainstream smoke exhaled
the smoker . •
Attacks will be mounted against proprietary and other flavorant systems,
sing formulat , .•'etc
. whose. components appear on the GRAS list which was
generated prima y to permit inclusion of various materials in edible or
~• osmetic produc, he GRAS list in general does not cover inhalation of
` se com?oundmor .eir decomposition products generated during the smpking
,~cess"
~ .•
also likely that certain product or smoke components*now
nera%ons ~ snfe, or at least not indicted as harmful, will eventually
considered l because of the acquisition of new information on their
hysiological pr :ties . .
4It is visuali2 d that claims concerning a given component may be viewed
s either an "opportunity" or a "threat" or in some cases, both an "opportunity"
nd a "threat" ; e. g ., some health authorities may claim (as some already have
one) that the nicotine level of the smoker should be increased to satisfy the
moker's physiological requirements and deter him from inereasing his consumption
f low-"tar" cigarettes . This presents an "opportunity" to the first company
hich attains a realistic goal of a"tar" :nicotine ratio substantially less than
0 . This concept may also be a "threat" since other health authorities may claim
hat both nicotine and "tar" should be reduced simultaneously to the eventual
__ eaninn aoint . . .
To combat the anticipated situation with regard to the components .of
Compa•iy products and•their smoke, R & 0 will need the following : '
1 . Increased awareness and intelligence on the activities .
of various governmental agencies (NCI), medical
societies (Americtn Cancer Society), and popular

~. . .:, ~
,
2

I
publications (READER'S DIGEST) devoted to the
curtailment and elimination of the smoking
habit .
2 . Logical anticipation of which components,
either product or smoke, will be indicted
and the sequence of their indictment .
3 . Increased staffing with highly competent
people, acquisition of appropriate instrumentation,
and generation of advanced technology to quickly
and accurately answer any or all claims against
a specific component . (It would be highly
desirable to have the necessary answers in hand
or to the time an attack is mounted against
griTven component) .

:4 . Alternative product components to replace those indicted and for which no satisfactory rebuttals
are available or forthcoming .

The numbe nown components (excluding propriEtary flavorants) in the


ou~pany's tobacn ~`oducts exceed 1200 while, that for smoke exceeds 2300 .
r~er f th se c ponents are cortmon to both tobacco and smoke . For smoke,
t is te the number of known components is less than 10% of those
ctu .a~,1 : ~r~, ese ,
Kher~ thes ers are considered, it is obvious that no detailed account
n be given of 'total known composition of smoke and/or tobacco in terms
f anticipated g=term indictment of all the specific smoke or tobacco

Jitherebesindic%ted or 5ebtheisub3ectiofsconsiderablenworkaandsadwhich versewill


iscussion between 1976 and,1989 .
A brief discussion of these areas and their status as ofOctober ' 1976
oltows .

~.
i
,

s
TABLE I
. ' PRCDUCT AND ShiOKE COMPONENTS

I . SMOKING AND HEALTH : PRODUCT CONPONENTS


A . Filler
1. Tobacco Types •
2. Processed Tobacco Products
3. Tobacco Substitutes
4. Nicotine
5. Casing Tlaterials'
a . Sugar
b . Licorice
c . Cocoa
d . Glycerol and Other Humectants
6. Flavorants
7 . Contaminants
a. Pesticides •
b. Dust and Sand

Materials .
Additives
!lasticizers
« lavorants

F5
C . Paper
~ 1 . Paper'AddStives : Dyes

~ SMOKING AND HEALTH : SMOKE COMPONENTS


.

.A . Mainstream vs Sidestream Smoke


B . Environmental Smoke
C . Smoke Phases and Their Components
1 . Particulate-Phase Components
a . FTC "Tar" I

b . Nicotine
c. Pesticides
d. Polycyclic Hydrocarbons

imw
.

. e. J•te tal l tc Components


i . Polonium-210
ii . Cadmium
f. Nitrosamines

2 . Gas-Phase Components
a. Carbon Monoxide
b. Nitrogen Oxides
c. Hydrogen Cyanide
d. Hydrogen Sulfide
e. Other

D. Smoke "Stran ers" Generated b Uni uel Processed TobaccoProducts


~Un gi- u~ eFil er an ter avorant ystemc, an , n que aper pye
S,ys tems
I . Tr~atco f;~MPG MYS I

Tobacco yyoe

8efore 1989 flue-cured'may be indicted as a smoking-health


hai.ord and recom~endations for its removal from tobacco products
be odvbnced .

8ecause of the high incidence of respiratory tract cancer at


no,,,,f nal per capita consumption of smoking products, it is alleged
tho't flue-cured tobacco (by far the major tobacco component of all
~U, r . Products) is a major contributor to respiratory tract cancer
in the U• K . These allegations are based on vital statistical ~>
~ Wa which are interpreted to show that the death rate frcm
O reoPirdtory tract cancer is much higher in the U . K, than in the
~ U, 5 . A . at essentially the same per cigarette consumption . Pro-
po,f,ants of the smoking-nealth theory claim that dilutiori of flue-
cur ed tobacco with burley, Maryland, Turkish, and G7-type' stem
shoet In the American brand lowers the smoke carcinogenicity and :. . .m. ;:. ::
~ thts dilution explains the lower incidence of respiratory tract
carir.er In the U . S. A . vs the U . K .
OVO
~ ~~~ponents of flue -cured tobacco alleged to be ~"
re4qoR`1for the activity of the smoke are the waxes
~(a1 e9 cursors of carcinogenic polycyclic hydrocarbons)
anil t~6 s ars . Also, flue-cured tobacco usually generates
~ ~ ~.On Ac raoke which is more readily inhalable than a more
;.ba4rc = e . Flue-cured differs markedly from burley in its ' :•;: ~`
~~~#iiuh ~~ ~bX} level of sugar vs a very low level (clx) in ~ .
b~rley~~~. I .A .S .a .) . The difference in wax content of the
tNn c toGa s is not particularly y pronounced . :
3, 2 . Pr ces~sed .Tobacco
. Products
F or more than a decade it has been known that inclusion
of stem materials (usually in sheet form) in a cigarette blend
~ dporea :es the alleged specific activity of smoke condensate in
~~ Moiise skin-painting experiments . . From 1950 to 1970 the percent
ini'lusion of stem materials in cigarette products throughout <k~ `
~ tht+ Affierican industry gradually increased, arod at the same time,
thh alleged specific activity and the benzo(aagyrene content of
th is S mo ke from such products gradually decreased .
~ :: L„
In additional experiments conducted by NCI from 1970 to•1973,
~ it was alleged that G7-typra sheet a :aterials (high stem content) ~
m,nufactured by Schweitzer and At•S&F showed some apparent advantage m
ovar CUt tobacco filler in specific carcinogenicity in mouse '• 3L,
sklii-Painting experiments . The Company has used G7 at a grccually Ln
iil, rea .ing level for over 25 years and thus provided products ~ .hose oD
sn,nkes . according to the thesis adti'Mnctai by some smoking-health pitipon6nfs, would alleqedly be lowor in
:iamr.ialian skin carcinogznicity o
than those of its competitors . Much of this alleged advantage has ~
bpan lost to the Company as each competitor developed and used its
a ~ n~ ~n proprietr.ry sheet m.aterial . ' "
«.

~
6

#4

4
The concern or "threat" here is the fact that G7-type sheet
materials in general generate higher levels of certain smoke
• gas-phase components than does cut tobacco filler . These gas-phase
components, because of their volatiiity, are not involved in mouse
skin-painting tests with smoke condensate . It probably will be
claimed before 1985 that excessive exposure of the respiratory
tract to such gas-phase components impairs the respiratory tract
defense mechanisms (ciliary and/or macrophage activity) against
"tar" elimination . Pres,:nt evidence suggests that at nominal
exposure levels, much of these indicted gas-phase,components
are "scrubbed" out of the smoke stream by upper respiratory tract
(mouth and throat) secretions . However, excessive levels of
these gas-phase components generated from high level inclusion
of stem material in the smoking product may saturate the
upper respiratory tract "scrubbers" thus permitting these
E no
components to reach the lower respiratory tract (lung) .
The results of experiments conducted by NCI on three
..types of expanded tobacco (RJR (expanded with Freon 11),
PP1 (expanded with ammonia/carbon dioxide), NCSU (expanded
by freeze-drying with water)) and the results of experiments
contracted to IBT by RJR on its G13-expanded tobacco
demonstrated in each case that the smokes from the expanded
toba ~ossessed slightly less specific activity (but
not ~~aA'°.`i••ficantly so) ir. mouse skin-painting than did the
smogisixon a control, nonexpanded tobacco . In a macrophage
actf~ity inhibition study, the RJR G13-expanded tob~+cco smoke
004 sh ed 1 s inhibitory effect presumably due to lower levels
of g ase components than did the control tobacco smoke .
•Thes 'logical findings are in accord with detailed smoke
co on studies conducted by RJR . .
'RJR proprietary expanded tobacco is the only one
of 'three wf .ich. introduces 'into the smoke an unnatural
componen or "stranger," .Freon 11 .' Although this is present
at very low levels, future indictments of Freon 11 in a
health and/or environmental situation may seriously compromise
our use of this expansion agent .

3. Tobacco Substitutes
Several tobacco substitutes are now available in the
market . The two most important are Celanese's Cytrel and
ICI's NSM . Within the projection period, a tobacco
substitute such as these will be used successfully in the
U. S. A . to control smoke composition as a health-related
measure . '
The development within the Company of the substitute
J10, a puffed grain, will permit rapid response by RJRT to
this situation when it occurs . J10 offers several advantages O

CO,
O
D

CA10
r

RJR24242 N
,
7

.
over Cytrel and NSNI ; namely, the original R & 0 costs of
J10 are less than 10% of those expended by Celanese and
,
ICI, no royalty payments are needed since J10 is an in-house
. developed and patented product, the raw material cost for
J10 and the cost of manufacture are much less than those
for Cytrel and NStd, J10 has an expanded structure and
volume-for-volume replacement of tobacco by J10 is about
a 1 :3 replacement on a weight-for-weight basis, J10 on
admixture with tobacco introduces no "strangers" into the
smoke, and the present status of a biolcgical study on J10
smoke condensate in a mouse skin-painting experiment
indicates no problem . (This study will be completed by
the end of the 3rd quarter, 1977) .
Should the situation arise in that the consumer
desires a tobacco substitute in his cigarette, the use
of J10 by RJRT presents a real "opportunity" from both
an economic and a smoking-health point of view . '

A ._ Nicotine ,
Nicotine in tobacco products may be subjected to two
s by proponents of the smoking-health theory :
Because of claims that nicotine is allegedly
involved in cardiovascular problems, to
decrease nicotine in the product so that
reduced levels of nicotine will appear in
the smoke. •
. . To increase nicotine in the smoking product
I so that increassd levels of nicotine will
appear in tht. smoke at a lowered "tar"
E delivery, thus satisfying the smoker's
physiological requirements at a lower
level of "tar" intake . Part of this
physiological satisfaction can be
accomplished by control of smoke pH but •
this approach has definite limitations .
Solution of a . is the simpler since "tar" and nicotine
usually parallel each other in the smoke since nicotine is a
particulate-phase or "tar" component . Systems such as blend,
filtration, air dilution, paper porosity employed to lower
"tar" delivery usually lower uicotine delivery by roughly the
same percentage .
Another facet of a . is the recent and consistent indication
in studies conducted by NCI on three series of experimental
cigarettes that the specific carcinogenicity of smoke condensate
in mouse skin painting is proportional to the nicotine content
of the condensates .

RJR24243
.I
8
I -

Solution of b . presents a real challenge : to increase


• the nicotine content of smoke while maintaining or lowering
the "tar" delivery . Possible ways to accomplish this include :
the use in the blend of high levels of high-nicotine tobacco
(usually not readily available in quantities needed), enhancement
of the nicotine content of the blend by addition of nicotine
salts, development of a unique air dilution-filtration system
to lower "tar" levels but not nicotine levels (a highly unlikely
concept) . .

. The use of added nicotine salts requires a suitable source'


U of nicotine in its natural configurationa . Possible sources ,
include : synthesis (problem here is that unless a stereo-

h specific synthesis is available, 60% of product is in the


unn2tural configuration, hence is unusable), extraction of
nicotine from specially grown, generally nonusable tobaccos

~ such as Rustica, genetic development (probably requiring 5


years •o gf eneM work) of high-nicotine . low-"tar" delivery
tobaccos, biosynthesis of nicotine by specific microorganisms,
recovery of nicotine at all process points involving heating
of tobacco throughout the Company . The latter presents the
bestt "op~ortunity" . Each drying operation in our tobacco
.g line decreases the nicotine content about 5%, 613
reduces nicotine content, etc . PH, in its new
n Richrr.ond, recovers all volatile effluents and
. ~. .,_---- them to recover both the tobacco flavorants and
which then are returned to the Pti products .

g Haterials
major casing materials (sugar, licorice, cocoa,
hw~ rits) have a long history of use in tobacco products .
Unticently, no serious question was raised or evidence
obtained on their involvement in the smoking-health issue .
However, within the past few years, health claims against sugar
and cocoa in the blend have appeared . It is, however, anticipated
that these claims may become more serious during the projection
period . As "tar" and nicotine numbers have been reduced by
blend adjustment, use of porous paper, use of improved filter
and air dilutfon systems, etc ., future attention will be
directed to those items previously considered minor in comparison
but which will eventually attain an important place tn thg
smoking-health issue .
.
These casing materials, presently acceptable according to•
the GRAS list for ingestion and/or cosmetic use, present '
diverse problems when their inhalation or inhalation of their
decomposition products is considered .

~
a Nicotine, as does menthol, exists in two isomeric forms . 0
0
In each case, one isomer occurs naturally, the other does not . a
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RJ R24244 a
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a . Sugar
As noted previously in I•A•1, the sugar content
of flue-cured tobacco is alleged to be in part the
tobacco component whose decomposition products are
responsible for the higher carcinogenicity of the
smoke from flue-cured cigarettes over that of the
smoke from a blended cigarette . The evidence for this
is primarily statistical, e . g ., higher 1ung .cancer
death rates in U . K. where wholly flue-cured cigarettes
are smoked vs lower lung cancer death rates in the
U. S . A. and elsewhere where blended cigarettes are
smoked.
This epidemiological evidence appears to be
confirmed by biological studies (mouse skin painting)
which show that the specific carcinogenicity of -
flue-cured smoke condensate is substantially greater
than that of the smoke condensate from Maryland or
burley dnd essentially the same as that of Turkish
.tobacco smoke condensate . Turkish, like flue-cured,'
has a high sugar content, averaging about 10% .
ver, an NCI study in the 3rd Series of cigarettes
icated that neither sugar nor humectant added to
experimental control blend affected the specific
cinogenicity of the smoke condensate, but sugar •
s hunectant did correlate with higher seecific •
cinogenicity . Sugar added at the 5x level also
reases the "tar" and nicotine delivery of a
en tobacco blend .
Results of studies conducted in-house indicate
t the sugar levels in Compar~y products could be
subistantially reduced without serious impairment
of smoking qual i ty .
b . Licorice
Licorice was originally used in chewing tobacco
and its use was transferred to pipe tobacco and
subsequently to cigarette tobacco . It imparts a
certain sweetness to the smoke . Its active ingredient
is glycyrrhizin, a salt of the triterpenoid glycoside,
glycy rrhizic acid . Neither of these has been detected
to date in smoke . It has been speculated that during
combustion glycyrrhizic acid can form carcinogenic
polycyclic hydrocarbons such as benzota) pyrene from
the triterpene moiety and phenols from the sugar
inoieties . To date, the only evidence in partial
support of this claim is that pipe tobacco containing
high levels of licorice (and thus glycyrrhizic acid)
yielded substaotially higher levels of oenzo[alpyrene
than did cigarette tobacco smoked under identTcal
conditions .

9's R2ak"
10

It is anticipated that at some time during the


. projection period governmental regulations may require
the listing on the label of the leyel of licorice
in the smoking product . This would necessitate
Company compliance, the use of an alternative to
licorice, abandonment of its use, or generation of
data to show that the premise for labelling is
invalid .

The labelling regulation is viewed as a""threat",


the discovery of a successful alternative as an
"opportunity" .
c. Cocoa
In a recent study by NC1, results in a mouse •
skin-painting experiment indicated that inclusion•of
1% cocoa in the experimental blend increased the
specific carcinogenicity of the smoke condensate
obtained therefrom .
Regulations to label for cocoa content of the
~ing product would result in compliance by the
,mpany, replacement of cocoa with a suitable
• rnative, abandonment, or generation of data to
rsho)y that the premise for labelling is invalid .-
;Glycerol and Humectants •

It is anticipated that during the projection od two events will occur


; namely, a smoking-health
m will be levelled at one or more humectants and/or
decomposition products in smoke, and a regulation
wil be proposed requiring the listing of such added
ingredients on the-label .
The NC1 study on the 3rd Series of cigarettes
demonstrated w':;.t glyccrol added to the control blend
had no effect on specific activity in'mouse skin-painting
of the smoke condensate but sugar plus glycerol did .
All other evidence from 1960 to date suggests that
humectantsdo not play a significant role in tobacco
smoke carcinogenesis .

6 ._ Flavorants
The use of additives to enhance tobacco flavor was criticized
more than ten years ago on the basis that possible prectirsors of
irritants and/or toxic substances were being introduced into the
smoking article . It was also pointed out that the pyrolysi :
a
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R J R24246
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11
4

products in the smoke from cigarettes containing such flavorants


are rarely tested in biological assays . From this, the question
was raised : Should not such flavorants be subject to regulation
by governmental health authorittes as are artificial food
fiavorants?
Within the projection period, the use of flavorants - even
proprietary flavorants - on tobacco products will be attacked
on a greater scale as contributors to the alleged adverse
properties of tobacco smoke . In general, proprietary and other
flavorants added to Company products fall into two classes :
They are known components of tobacco and are added to enhance a
specific flavor characteristic or they are on the GRAS list
which, as mentioned previously, is a list of compounds considered
safe for ingestion or use in cosmetics . The GRAS list in
general does not cover inhalation of the listed compounds or
their decomposition products produced during the smoking
9. process . '
Awareness of this situation ts already evident in that
NCI has already contracted a study on flavorants .to A . D: Little .
Proposals for future work by NCI include inhalation studies
on s e enerated from tobacco treated with a variety of
know • cco flavorants .
f the Company's proprietary and patented Turkish-type
flav 'rant have tremendous potential economic ad'vantage to the
ompa articularly as the cost of Tur'a sh tobacco continues
77to es• 1•e . One of these is a known component of Turkish
oba nd its use will probably present no serious'problem7 rhe , N13, is structurally similar to a sugar ester
isola rom Turkish tobacco but to date, N13 has not been
demo ted as a Turkish tobacco component. Demonstration of
thc*,,res~ce of M13 in Turkish tobacco is an "opportunity" to
protect the Company's right to use this flavorant in the face
of future regulations and to preserve the economic advantages
inherent in the use of M13 . '

7._ Contaminants

a . Pesticides
Various pesticides have been banned from use •
on tobacco plants over the past several years . .
Those permitted at the present time may, at seme '
time in the future, be banned on the basis of some ,
environmental or health-related hrzard such as •
occurred in the banning of DDT (concentration of
DDT in mammalian fatty depots and liver) . Usually
it requires years for soil once impregnated with a specific
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pesticide to become essentially depleted of the
pesticide . As a result the pesticide appears in
subsequent years' crops of tobacco even though the
banned pesticide is no longer in use . Post pesticides
are transferred intact to some degree from the
tobacco to the snooke during the combustion process .
This will probably present no problem with the
sale of the Company's domestic products but may
present a problem in international products
marketed in some European countries such as Hest
~Germany where pesticide residue regulations are
very strict .

b. Dust and Sand•


FRO This is not precisely a problem with the
Company's flroducts but is a health-related problem
in the work areas where Company raw materials are
processed (stemmery, blending, etc .) . The Company
has diligently followed OSitA regulations to control
sand and dust levels in the work areas, but it is
anticipated that these regulations will become even
Wk* demanding during the period 1976-1989 .

t~, •4 B . Fi 1 tet
l .- .~~ Materials
use of the traditional filtration material, cellulose
acet• , ill continue through the projection period . Nowever,
increa emphasis on gas-phase components such as aldehydes,
hydr eyanide, hydrogen sulfide, etc ., may result in the
design a d ~tilization of more efficient carbon filters .
Carbon, of course, does not absorb either carbon monoxide or
nitric oxide, the predominant (>98x) component of the nitrogen
oxides . . •
.
2._ Filter Additives

a . Plasticizers
Since every plasticizer•currently used on a
filter tip Is entrained to some•dEgree in the smoke
stream and thus appears in the mainstream smoke
inhaled by the smoker, claims concerning the
hazard of these components will appear during the
projection pericd . The plasticizer most commonly
used in the American tobacco industry is triacetin .
which, on exposure to smoke and entrainment in the
smoke stream, does react to form diacetins and
13
.

, monoacetins plus acetic acid, an alleged ciliastat and


inhibitor-of macrophage activity (impairment of
respiratory tract defense system) . The filter-tiN
suppliers will probably deal with this type of problem
and the development of alternate plasticizers .
However, the effects of alternate plasticizers on smoking
quality will require detailed evaluation within the
Company,
b . F1Avorants
Most flavorants added to filter-tip materials
are transferred unchanged to the smoke stream and
appear in the mainstream smoke . Decomposition
F=* products, such as are Inevitable with flavorants
added to the tobacco filler, are of little concern
here . The major concern is that most filter-tip •
flavorants, while on the GRAS list, have not been
cleared for inhalation . The work proposed by NCI
to examine In an Inhalation system the effects of
•tobacco flavorants•and their decomposition products
in test animals may eventually result in indictment
~~pnTy of some tobacco flavorants but also some
1; a
er-tip flavorants .
. ape~

jPaeer Additiv_es :_ Dyes


If the Company develops new smoking articles which
i~ude a dyed paper system, then detailed investigation
he effect of the dye system on smoke composition
be required to answer the question : Does the dye
system contribute "strangers" to the smoke? : Fortunately,
we are in an excellent position technologically to
perforni this type of comparison study . We can compare
the smoke composition from a control and a test cigarette for over 1800 smoke components to determine
the presence of "strangers" .
Two such studies have•already been carried out to
investigate the contribution of the WINCHESTER paper
dye system and several MORE paper dye systems to smoke
composition with a clear demonstration that no smoke
"strangers" were generated . At present, it is unlikely
that apy.other laboratory can perform this type of
study as rapidly or as accurately as we can . However,
the time may come .when technological advances elsewhere
will permit'others to duplicate this or to extend it
to a greater number of compounds present at very low
levels in the smoke . One research objective is to
assure that we can define smoke (or tobacco) composition
to a greater degree than anyone else .

, ~, I R2ao
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SMOKINC AND HEALTH : SMOKE COtiPONEtiTS ,

A . Mainstream and Sidestream Smoke

Mainstream smoke is that smoke generated during puffing and is


inhaled by the smoker . Sidestream smoke is that generated during the
nonpuffing or free-burning part of the smoking . Sidestream and
mainstream smoke are qualitatively the same but differ substantially
quantitatively ; e' g ., both smoke streams contain carbon monoxide,
nicotine, nitrogen oxides, ammonia, benzola) pyrene, etc ., but the
mainstream vs sidestream yield per cigarette varies widely depending
on the component . The levels of some components in the sidestrean
are a bou t th ree t imes the l eve l i n the ma i nstream smo k e ; for oth ers,
the ratio of sidestream:mainstream levels may be as high as 10 or 15 .
FOO, B . Environmental Smoke
Environmental smoke is that smoke to which a nonsmoker or a
nonsmoking smoker is exposed when in close proximity to a smoker in
the act of smoking It consists of the sidestream smoke evolved by
the smoking article between puffs plus that portion of the mainstream
smoke exh~~~y the smoker . Thus for a given room volume, environmental
smoke wil dependin ; on the number of smokers in the act of
smoking, ~ .'particular smoking habits such as puff volume, puff
frequency pu duration, nuqiber of puffs per cigarette, degree of
inh~latio~i, et . . clus the degree of ventilation in the given room .
he is on environmental*smoke will increase substantially
WMg th y part of the pro3ection period (from 1976 to 1980)
as propon f the smoking-health, theory continue their attenpts to
combat smok *by depicting it as a"dirty" habit which not only is
harmful e`participant in the smoking act but also has a harmful
(and annoyin effect on persons - whether smoker or nonsmoker -
in close proximity to the smoker.
This aspect of the smoking-health problem must be viewed as a
real "threat" to the tobacco industry in general and RJRT in
particular . Even the increase in market share of low-"tar" cigarettes
projected for the next decade will not detract from the attack on
environmental smoke . The quantity of sidestream smoke is not
substantially reduced by blend adjustment, unique filtration or air
dilution systems, paper porosity adjustment used specifically to
produce a 1ow-"tar" cigarette . . .
The claims will increase in magnitude by the smoking-health
proponents' stressing that the nonsmoker is involuntaril exposed•
to a host of allegedly hazardous compounds inOuding car on monoxide,
nicotine, benzota~pyrene, nitrogen oxides, hydrogen cyanide and
sulfide, aldehyd-es, acids . The health condition (such•as allergy,
cardiovascular strength or weakness, respiratory tract condition)
of the nonsmaker so exposed will be stressed as well as the effect 0
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R~R2425~
15
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on his particular condition of involuntary exposure to thc :se


~ allegedly harmful smoke components ; e . g ., a person with a chronic
cardiovascular condition, it will be claimed, may be pushed over
the brink of a cardiovascular incident by his involuntary exposure
to carbon monoxide and/or nicotine .

C. Smoke Phases and Their Components


Cigarette or pipe smoke is an aerosol consisting bf small liquid
spheres or droplets suspended in a gas stream . The spheres are the
~ particulate phase of smoke, the gas stream is the gas phase . At
present there are about 1950 parti :ulate-phase components known
and about 400 gas-phase components . The definition of the co~ osition
of the gas-phase is almost complete but it is estimated that the
Eno number of components known in the particulate-phase represents only
about 10% of the total present . About SO components are co ;nnon to
both smoke phases, water and phenol being two examples .
1 ._ Particulate:,Phase ComQonents
a . FTC "Tar"
While not a component er se but a complex
~€:i~A,#re, we will consider tFeFT "tar" as a
7component. The FTC "tar" from a cigarette .
ismok~d under standard conditions is defined ,
e weight of total particulate matter .
the weight of nicotine and water . Because
tar" contains many components (certain
cyclic hydrocarbons, their nitrogen analogs,
samines, metals, lactones, phenols) alleged'
b•e harmful to the smoker, the smoking-health
cla~ against "tar" will continue unabated during
the projection period despi te the fact that 1ow-
"tar" cigarettes will command an increasing share
of the market . tlany smoking-health proponents
will push inexorably for lower and lower "tar" .
values and the accompanying decrease in nicotine
until the smoking population in effect weans itself
from smoking . This must be considered a serious
"threat" .
b . Nicotine
The future controversy concerning nicotine in
smoke will involve two separate premises by
proporrents of the smoking-health theory : One group
of proponents will claim that nicotine in smoke •
together•with "tar" should be lowered progressively
if not immediately and thus wean smokers from the
smoking .habit . The second group of proponents will

R S R24251
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0

claim that, since people will continue to smoke


to obtain the nicotine physiological satisfaction,
the nicotine in smoke should be increased while
"tar" should remain stationary or be decreased,
thus decreasing the number of cigarettes per day
required to provide the smoker with his nicotine
requirement and lowering his daily "tar" intake .
Host previous evidence has not incriminated
nicotine as a health hazard although some authorities
considered nicotine to be harmful to the cardiovascular
system. As recently as 1964, the Surgeon General's
Report on Smoking and Health, which evaluated all
evidence to that date, gave nicotine a clean bill
of health . It is now alleged that recent evidence
demonstrates nicotine to indeed be involved in
cardiovascular problems
. Also, data collected byNCI on three sets of experimental cigarettes whose
smoke condensates were studied-in mouse skin-painting
experiments indicate in all three studies a correlation
*between specific carcinogenicity and nicotine content
P4 f . . .the enndensate_

The decision as to which of the two routes


~o 'llow with nicotine (simultaneous "tar" and
;nico~ine decrease or "tar" decrease, nicotine increase)
~ be a difficult one . Whichever route is selected,
preciable segment of the smoking-health proponent
ation in the other camp will be embittered and
bly deluge the press wit4 unfavorable comments .
To generate increased levels of nicotine in smoke
at -4duced or stationary "tar" levels requires a
source of nicotine. This has been discussed at some
• length under Tobacco Filler (Section I . A . 4 .) .
If one examines what is required of an ideal "
cigarette in terms of "tar", nicotine, and carbon
monoxide deliveries according to the low "tar"-increased
nicotine-low carbon monoxide delivery theory, it is
apparent that a real challenge and "opportunity" are
presented . In the following table, the deliveries
of several typical cigarettes are summarized together
with the corresponding ideal situation .

Ra R'Z4252
• 18

c. Pesticides

Over the oast decade, several pesticides


previously used on tobacco have been banned and
subsequently replaced with acceptable compounds .
It is anticipated that during the next decade some
of the currently acceptable pesticides will be
found to exert some health or environmental hazard
and they too will be banned . Soil impregnated with
a pesticide usually requires several years for complete
dissipation and the pesticide will appear in subsequent
years' crops but at a decreasing level . This might
be a problem with products exported to countries
such as West Germany whose•pesticide laws are very
strict . Most pesticides on tobacco are transferred
intact in some degree to the smoke stream ; the
balance appears as decomposition products in the .
smoke stream and butt .
d. Polycyclic Hydrocarbons
Concern with cigarette smoke polycyclic
ocarbons allegedly carcinogenic to man has
axed and waned for over 20 years . Some dozen
cyclic hydrocarbons, typified by benzo(alpyrene,
a inogenic to mouse skin, are present in
to~cco smoke . In addition, several carcinogenic
~ro9en analogs are aresent in•tobacco smoke .
It is anticipated that during the projection
od these polycyclic hydrocarbons will again be
~asized. With regard to mouse skin carcinogenicity,
~cco smoke is a unique mixture of .tumor inhibitors,
tumor initiators, and tumor promoters which may exert
their activity either additively or synergistically .
It is conceivable that some government or medical
agency will investigate in detail this additive
and/or synergistic effect, an experiment that has •
not been conducted to date .
Since the polycyclic hydrocarbons are "tar"
components, reduction in cigarette "tar" levels
effectively reducesthe levels of these allegedly
harmful polycyciic hydrocarbons . Selective removal
of polycyclic hydrocarbons from the "tar" by
fi l trati on is very unl i kely . However, a1 terati on
of the burning characteristics of the tobacco
rods to decrease polycyclic hydrocarbon formation
is a distinct possibility . Burning characteristicS .
can be changed by blend selection, paper porosity,
additives, air dilution, etc . Most additives
studied in this regard to date have imparted an
undesirable quality to the smoke .

RJR2425 4
19

e . Metallic Compounds
1 . Polonium-210

The concern over polonium-210 in smoke


as a causative factor in lung cancer first
surfaced in the early 60's, and effective
counterargument : and data were presented to
offset the original thesis and thd ensuing
publications . Recently this argument has
again been publicized, but to date no serious
concern appears warranted .

Because of the ease with which the public


can become concerned with things "radioactive"
the claim of the hazard of polonium-210 in smoke
will continue sporadically throughout the •
• projection period . • •
ii . Cadmium
Several dozen papers on the carcinogenicity
of cadmium and its presence in tobacco and smoke
have appeared during the past decade. The
publicity concerning the hazard to the smoker
has been relatively low level . However, this
material - as an item of concern to the industry -
might be emphasized extensively within the next
decade, probably near the end of it .
Nitrosamines
The presence of nitroeamines in tobacco and smoke
demonstrated, and claims concerning the hazard to
the smoker in terms of respiratory tract cancer were
advanced . Even the major proponents of the theory of
lung cancer causation by cigarette smoke are divided
in their estimate of the role of this class of
comAounds in respiratory tract cancer . Many nitrosamines,
including several present in tobacco smoke, are
carcinogen :c to laboratory animals, but the dosage
required to demonstrate activity is fairly high in
comparison .to other carcinogens ; e. g ., benzo(alpvrene .
Claims about the hazard from nitrosamines in smoke
will surface on and off during the pro3oction period . It
is also possible that similar claims will be levelled at
nitrosamines in chewing tobacco since at least one brand
(a European one) analyzed showed relatively high levels .
of several nitrosamines in comparison to the others . At
has been demonstrated in laboratory animals that ingcstion 0
of nitrosamines can initiate cancer not only in the digestive . a
No
tract but also at other sites .

R ~ R2,4255
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0

2 ._ Gas-Phase CoMponents
a . Carbon Monoxide

It is claimed that carbon monoxide in the mainstream


smoke from a smoking article has a harmful effect on the
cardiovascular system of the smoker . Carbon monoxide
combines with the blood hemoglobin to form carboxyhemoglobin,
and hemoglobin thus bound cannot transport oxygen . lhis
places a higher work demand on the heart to pump more
blood to provide the same oxygen level to the system . The
sidestream smoke also contains carbon monoxide at a
substantially higher level per cigarette than the main-
stream smoke . Thus, considerable publicity has appeared
with regard to the carbon monoxide levels in environmental
smoke and its effect on nonsmokers in close proximity to
the smoker in the act of smoking . Carbon monoxide and
nicotine are the two components in environmental smoke
which have received the most adverse publicity . '

At least one country (Sweden) has legalized the


labelling of cigarette packs with the per cigarette
on monoxide delivery (to be in effect 1-1-77) ;
eral other countries (West Germany, France, Finland)
~~ considering such legislation .
~ in the U . S. A., the FTC is conducting pieliminary
Ou )1k to devise a system for determination of i'TC "tar",
. tine, and carbon monoxide on the same smoking sample .
•is predicted that the FTC system will be in operation
.the end of 1978 if not before, and attempts to require
: on monoxide labelling will follow soon thereafter .
Carbon monoxide levels in smoke cannot be controlled
inex ensivel by any known filter system which does not
ncrAase the pressure drop across the cigarette . Claims
that certain filter systems do reduce the carbon monoxide
level have been found to be inaccurate because the
pressure drop a :ross the filter system and overall
cigarette was increased to such a value that all smoke
products were reduced . This is symptomatic of high
pressure drop systems . The same effect observed with
special filter additives (which markedly increase the
pressure drop) claimed to be effective against carbon
monoxide can be obtained with cellulose acetate filters
at the same high pressure drop . • •
The most effective way known to date to reduce
carbon monoxide levels in cigarette smoke is air dilution .
As noted in II .C .1 .6 ., this also substantially reduces
both the "tar" and nicotine in smoke . 0
0
a
The recent READER'S DICEST article on carbon o
• monoxide is a portent of things to,come with regard
N

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R J R24256
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to this compound . The public has been exposed to so


, many articles in the popular press on carbon monoxide
in automobile and truck exhausts that it probably
understands comments on this compound much better
than it does similar comnents on nicotine .
The concept of labelling for carbon monoxide is
fraught with dangers for the industry as it will
represent the first riedge (after the "tar" and nicotine
labelling regulations of several years ago) of a continuing
attack . It is predicted that once regulations on carbon
monoxide delivery are forthcoming, a systematic plan to
require labelling of other smoke components will be
proposed . The predicted sequences will be : carbon
r.anoxide, nitrogen oxides, hydrogen cyanide, hydrogen
sulfide, aldehydes . At the same time this is occurring
attempts will be made to require labelling for such
product additives as sugar, licorice, cocoa, etc .'
b. Nitrogen Oxides
As indicated in the previous section, it is
predicted that nitrogen oxides will follow carbon
boxide as the target for labelling regulations .
There are five nitrogen oxides in cigarette smoke,
nitric ixide accounts for more than 98%of the
s~~al (usudlly about 300 u9 ver cioarette) . Traces
nitrogen dioxide, nitrous oxide (laughing gas),
w . trogen trioxide, and nitrogen pentoxide are also
sent . The mafor concern with the nitrogen oxides
i the properties of nitrogen dioxide, which generates
trous and nitric acids with water . Nitric oxide in
~.tr or oxygen can-generate nitrogen dioxide .
Because of the methods of determination of
nitrogen oxides (usually the nitric oxide and nitrogen
dioxide), the oxides of nitrogen have historically,
been expressed as nitrogen dioxide . This is contrary
to the state of affairs existing in the smoke since
over 90% of the nitrogen oxides is nitric oxide .
Expressing the nitrogen oxides as nitric oxide will
serve two purposes : It more closely describes the
content of smoke in terms of the actual smoke component,
and it will reduce the value reported as nitric oxide
to 30/46 or 0 .65 of the value reported as nitrogen
dioxide . Thus a 300-pg delivery of nitrogen oxides
expressed as nitrogen dioxide would be a 195-Ug
delivery expressed as nitric oxide . •

c . Hydrogen Cyanide
The toxicity of hydrogen cyanidE is well-known .
In an industrial atnosphere, the permitted Threshold
Limit Value (TLV) for hydrogen cyanide is 10 ppm .
22

The TLY is defined as that average concentration to which


a worker may be exposed for 8 hours per day, 5 days per
week for his working career . 10 ppm of hydrogen cyanide
is equivalent to approximately 11 ng/ml .
The mainstream smoke from an average cigarette
contains from 200 to 400 ug of hydrogen cyanide ; if
a 10-puff cigarette is assumed with 35 ml/puff, then the
hydrogen cyanide concentration per ml is 5,0'to 1140 ng/ml .
The sidestream smoke contains higher levels per cigarette .

Early in the projection period, claims about the


hazard of hydrogen cyanide to the smoker and in environmental
smoke will increase . A publication already is imminent
in that the READER'S DIGEST plans an article on hydrogen
cyanide in cigarette smoke sometime in the very near
future . Hydrogen cyanide, like carbon monoxide, is a
compound that the general public is mere aware of than
say, nico tine .
Hydrogen cyanide in mainstream smoke is controllable
several methods : The use of air dilution, the use of
ic filter additives, and/or the use of carbon filters .
One of the classical treatments for hydrogen
nide exposure where distress is .observed is the
alation of nitrites such as a 1 nitr,ite . It
Id be argued (as a last resort) thet the hydrogen
nide in inhaled cigarette smoke is much less
2ardous ttan the same level of hydrogen cyanide in
because cigarette smoke contains substantial
uaantities of several nitrites (methyl nitrite, ethyl
n'~trite, etc .) whose simultaneous inhalation with the
cyanide may affect in part its toxicity . It is
predicted that before 1985 attempts to require labelling
of the cigarette pack for er cigarette hydrogen cyanide .
delivery will be implement~
d. Hydrogen Sulfide
The public generally identifies hydrogen sulfide
with the odor of rotten eggs . Most do not realize
that the toxicity of hydrogen sulfide, as in its TLY,
is the same (10 ppm) as hydrogen cyanide . 10 ppm of •
hydrogen sulfide Is about 14 ng/ml . Its level in
cigarette mainstream smoke is slightly less (50 -150 vg/cigarette
than that of hydrogen cyanide . If a 10-puff cigarette is
assumed with 35 ml/puff, then the hydrogen sulfide
is 140 to 280 rg/ml . The levels in sidestream smoke are
also higher than those in mainstream smoke .
u
The level of hydrogen sulfide in mainstream smoke 00
should be controllable by air dilution, basic filter a~
additives, carbon, and/or inclusion of nontoxic metallic
compounds able to form sulfidcs'in the filter . a
A
C10

RJ R2425g
23

0
It is predicted that attempts to require package
labelling for the Mrr ci arette delivery of hydrogen
sulfide wt11 follow the successful implementation of
such labelling with regard to hydrogen cyanide .
e . Other
Before the end of the projection period, the
aldehydes, ketones, and acids in•cigrrette mainstream
smoke will again be emphasize d as health hazards to the
smoker and those in the sidestream smoke wili .be claimed
as hazards to the nonsmoker exposed to environmental
smoke .

In the mainstream smoke of a cigarette delivering


about 15 mg of "tar", the acetaldehyde and acetone
contents are about 900-1000 and 450-500 ug, respectively .
The sidestream smoke levels are at least three times
these values . ,
It is alleged that the al-dehydes, ketones, and
acids interfere with the lower respiratory tract defense
mectranisms by ciliastasis and inhibition bf macrophage
~~~ vity . There is, however, evidence to suggest that
1ts obtained in in vitro systems with detached
tissue are not ent7apo ab,1e to an in vivo system . Pas-
~"sa - of acetaldehyde in smoke through t~ ora cavity .
:~ectively "scrubs" out much bf this aldehyde frn^~ the
A ke stream ; thus very little reacges the smokeres lungs
ntcrfere with the two defense*mechanisms noted above .
?~ has been demonstrated both in laboratory animals
humans .
€ Ten or twelve years ago the concern about aldehydes,
etc., and their interference with the lung defense
mechanisms was high and led to the surge of carbon
filter cigarettes in the mark~t . Subsequent studies
blunted many of the original claims . However, it ts
predicted that near the end of the projection period
(1985-1989), this theory will again be emphasized .
. Smoke "Stran ers" Generated b Uni uel Processed Tobacco Products
stems
Filler and Filter avorant ystems, an n que aper Dye Systems

As the complexity of RJRT pro4ucts increases in terms of the use of


uniquely processed tobacco materials, unique filler and filter flavorant
systems, and unique paper dye systems, the need for detailed smoke comparison :
studies to satisfy the Legal Department requirements that no smoke "strangers
be generated will increase . It is predicted that the marketability of a
new product involving one or more of these systems will ultimately depend on
such a demonstration even when consumer acceptability, esthetics of packaging :
design, etc ., are high .

.
R~Rz~2~9
. ., ,, : . .
.i
14

0
Five years ago such studies were run sporadicallx in our laboratory,
but since then, the number of analyses has substantially increased :

Fortunately, we are in an excellent posttion to conduct such comparison


studies to search for "strangers" in smoke . During the past folir years,
we have shortened the turn-around time from about nine months to less than
a month, increased the detail of the total analysis (1400 components vs
500 components), and improved the quanti•tation . It is anticipated that
improved technology and•increased staffing will permit such comparison
to be carried out with even shorter turn-around time, in greater detail,
and with improved quantitation .
To disprove our claims that such systems as those mentioned above
introduce no "strangers",in the smoke, other laboratories (government,
competitor, medical agencies) would have to be able to perform such
E no
analyses in at least the same detail as we . At present, no other
laboratory is in such a position to do so . Hopefully, we will maintain
our lead in analytical expertise for such comparison studies : With
this technology at our disposal, we will always be able to claim that
we expended more than a cursory effort in our search for "strangers"and were indeed diligent in our investigations
.

.~ R
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0

POSITION PAPER - fORMAL DOCUt•tENTATION

OING AND'HEALTHi PRt1DUCT AND'St10KE CO2_,4PONENTS


PRODUCT C0I4PONENTS : A. Filler 1 . Tobacco Tlpes

1 . TREND, ISSUE, OR EVENT IDENTIFIED DES/ CRIQED

Some investigators claim that the level of flue-cured tobacco in a smoking productt
is, through its smoke, related to respiratory tract cancer ; e. g ., in epidemiol.ogical
studies, the U . K., whose smoking products are essentially a11 ftue-cured, has a much
ig~ier incidence of respiratory tract cancer than the U . S. A., whose smoking productsi
tT flue-cured
conin , buriey and p a percen ages
Turkish ius substantil o - types tem
tf GV
material . The claim is that the flue-cured is .diiuted in the American blend by
riclusion of tobaccos or tobacco materials which generate less active "tar" . Laborato
allegedly support this premise since the specific activity of flue-cured "tar" I
greater than those of burley, stem sheet, Maryland and slightly greater than
of the Turkish . The activity of flue-cured smoke is alleged to be due to the
wax and sugar content of the tobacco . Waxes in the tobacco are alleged to be
ursors of carcinogenic polycyclic hydrocarbons ; sugars, which constitute 12 to 20x'
fte tobacco, are precursors of phenols which are alleged to promote the activity of ;;
the*%!arcinogenic polycyclic hydrocarbons . Flue-cured usuall y g enerates an acidic
e which is more readily inhalable than the more basic smoke from burley or a
~d containing ntiai levels sf burley .
WHAT WILL HAP
~ '"The ME eal t claims against flue-cured tobacco will escalate dramatically .
estio s ema anced that the current flue-cured types should be altered
geneti%a to 0 0 0 pe flue-cured types with reduced waxes and sugar content .
FRERM WHAT WILL BE WNW PACT/ IF1PL I CAT I ON
If these cla bbcome too vociferous and the requests for altered flue-cured
ccos become too nding, chaos in the southeastern tobacco growing area could
olt . In addition, all blends in RJR products would require re-evaluation when
pft flue-cured types or reduced levels of flue-cured tobaccos are included . ,

ft wNEN WILL IT HAPPEN , '


Toward the end of the projection period : between 1983 and 1989 .

. . SOURCES S OF ENVIRONMENTAL ANALYSESIFORECASTS AND RATIONALF .


now
C Results of the biological study of the specific activities of the flue-cured
aiy, . Maryland, Turkish, and stem sheet material are summarized in Ftyndcr and
Noffmann', "Tobacco and Tobacco Smoke," Academic Press, 1967, pp . 516-518, 531-532 .
The role of smoke acidity from various tobacco types, ease of inhalation of these
smokes, relationship to respiratory tract cancer are sur,niarized in Larson and Silvett
"Tobacco : Experimental nnd Clinical Studies , " Suppl . I , Nilliams . and Wilkins, 1968 ;
pp. 612-615 . The claims that the use of flue-cured in smoking products is relaterto ;,
respira :ory tract cancer appear in articles by Passey and Elson, DifferPrct Smoking-
Rssks of Flue-cured and Air-cured Tobaccos, J . FATttGL . . 101, xviffi
assey et a ., mo ng, s s o D erent obaccos, BRIT . MED . J ., 1971 (4) 19R-zot .

, p,

RJ RZ4Z6 1
' • POSITION PAPER - FOR14/1L t)nCMF.NTATION

ING AND HEALTH : PRODUCT AND SMOKE COt1PONENT .S


i
r CT COt1PGaENTS : A. Filler . 2 . Processed Tobacco Products

1 . TREND, ISSUE OR EVENT IDEtJTIFIED/DESCRIBED


It has been alleged that inclusion of G7-type sheet in tobacco products decreases
specific carcinogenicity of smoke condensate . Uowever, increasing stem sheet content
to a very high level will eventually be criticized because stem sheet, on smoking,yields
excessive quantities of gas-phase components alleged to be detrimental to respiratory
tract defense mechanisms . Thus inclusion of additional stem materials in smoking
p?IS'du_qs may be 1 imi ted .
several expanded tobaccos jRJR (Freon 11), PN (ammonia/carbon (1ioxide), NCSU
freeze-drying)) , only the RJR product contains a non-tobacco component (Freon 11
rocessing . In the future, our use of Freon 11 and its residual level in tobacco
attacked on the basis of health . It is unlikely that such an attack will be
ful because of the demonstrated low toxicity of Freon 11 and the low residual
1~ of Freon 11 in expanded tobacco, but the attack itself may provide Omrelcome
p ~~ relations problems .

RJR's use of Freon 11 as an expansion bgent for tobacco becomes more widely
; governmental ~' Oedical agencies will question the safety of Freon 11-containing .
tobacco. Such ende :J ill not .substantially affect sales, but considerable public
re~#.o~ns work will . 1~ uired to discount and offset ensuing publicity .
Allft WIL-rjf ITL~~ I V
.CT/IMPLICATION
i
' If any ffftfut ~0vidence is presented that fluorocarbons in aerosol products pres,
bscure he .~lth~x~€:~em and the public is aware of this evidence plus the fact that
RJ .Wproducts contain F on 11, a decrease in sales mi ght occur . Ban on fluorocarbon
use~ii~ tobacco expan~ould have a serious economic impact .
4 . ti .ti ,~EN WILL IT HAPPEN
Zoward the middle of the projection period - 1982 to 1985 .
URCES OF ENVIROtudENTAL ANALYSES/FORECASTS AND RATIONALE
he beneficial effect of inclusion of moderate levels of stem sheets :n smoking pra~
cribed in Wynder and Hoffma m,"Tobacco and Tobacco Smoke," Academic Press, 1967,
2 ; in N I Re rt No . 1 . Tr*tard ess Ha ardous Ci aret s . The First Series o7
~imental i ar s (1976) . Increase in levels of gas-phase components in smo e fr
pr° s containing increased levels of stem materials is described in in-house reports ;;`
e.c ., e .kman (1974) . Impairment of respiratory tract defense mechanisms by gas-phase :
components is described in Larson and Silvette, "Tobacco : Experimental-and Clinical Stud:i
, Suppl . 111, Williams and Wilkins, 1975, 150-152,170- 173 .
The alleged effect of e!ccessive exposure to Freon 11 on the cardiovascular system f
described by Taylor and Harris, J . AM . MED . ASSOC ., 214, 81-85 (1970) but discounted by :'
Azar et a1 ., ibid, 215, 1501-1502 (1971) . t1ouse skin-painting experiments and chemistr,
of Freon 1'i=expande3 Lobacco smoke are described in NCI Re ort No . 2 . Toward Less Hazardcus
Ci ag rettes . The Second series of Ex erimental Cioarettes, n press , oagman, - x_pande
_acco an Freon V eb . .
, RJ R24262
LI

POSITIO9 PAPER - FORMAI . OQCUNCNTATION

NGAN p,~ HEALTH : PRODUCT AND SMOKE COt1PONENT S

PRODUCT C^MP014Et1TS : A . Fi l 1 er . 3 . Tobacco Substi tute s

1 . TREN-9, ISSUE, OR EVENTS IDENTIF1E0 DE S( CRIQED


Several tobacco substitutes are now available in the market . The two most importan t
for which considerable data are available are Cytrel (Celanese) and NSM (Ii,I) .
NSti sho:.s excellent smoke chemistry and in the NCI study and .biological studies
privat~ly contracted by ICI its smoke shows lower specific activity in mouse skin-paintin
thn to~acco smoke. Much of this lowered specific activity disappears at about an
80'k~ 5acco :IiSN nix .
ytrel smoke chemistry is satisfactory although our early studies indicated som e
ers" in its smoke . Biological data in skin-painting studies with Cytrel "tar "
ar~, eq'vivocal : contracted studies indicate lower specific activity than tobacco smol :e ;
ies indicate about the same activity as tobacco smoke . Studies to resolve thi s
are in rrogress .
2.b~.~ N'ILL HAPPE N
~ . .
~ RJR competitor in the U . S. A. will market a cigarette containing a tobacco
s ., ; ::~ ute admixed with t bacco . No health benefits will be claimed but will be
imi'ed .

MZ e use . to su6stitute by a competitor will prompt RJR to market a cigarettE


ing i .opri ary. substitute J10, a puffed grain . This will nave substantia l
c adO ge f :#f~ since' the J10 is much less expensive than tobacco, Cytre l
a9m~
1
is a puffed t and will replace three times its weight of tobacco, ha s
12" nt smoke composi n properties, smoking quality, and preliminary data indicate
nt biologicalq~~erties allegedly related to health .
4 . .~.~, N WILL IT HAPPEN
. fore 1982 .
,, . RCES OF ENVIRON1101TAL ANALYSES/ FORECASTS AND RATIONAL E
emical and biological data on the smoke from NSM and rytrzl tobacco substitute s
ei~ alone or admixed with tobacco appear in NCI Report No . 2 . Toward Less Hazardous
Ci ~ttes . The Second Set of Experimental CiQarettes n press), NC Report No . 3.
arettes . The Third Set of Experimental Cigarettes . ug . 976
n ormat on s ava a e n CONFIDENTIAL memoran a from Celanes e
and-ICI: Detailed J10 smoke studies are described in in-house reports by Lloyd et al .
(1974), Green et al . (1974 , 1976) . Our work showing "strangers" in Cytrel smokeis
described by ScTiu-ma-c-her et al . (1969) .

0
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0
POSITl01J PAPER - FORMAL WCUME1lTA'f ION
SMOKING AND HEALTH : PRODUCT AND SMOKE Ca•1PONENTS
C1 CO!1PONENTS : A . Filler . 4 . Nicotine
1 . TREND, ISSUE, OR EVENTS IDENTIFIED/DESCRIBED

The Mierican tobacco industry will find itself on the horns of a dilemna . It will
be pressured by two separate groups of proponents of the smoking-health theory . One
group claims that the nicotine content of the filler should be reduced so that the
nicotine transferred to smoke is at a reduced level . This group claims that nicotine
is~, .in olved not only in cardiovascular problems but is also a factor in respiratory
tract ancer . The other group claims that the nicotine content of the filler should
b eased so that the nicotine transferred to smoke is at an increased level for
t~e sams "tar" delivery . They will assert that, since people will continue to sroke
r" is the harsiful smoke ingredient, the smoker's physiological requirement
nicotine should be satisfied at the lowest "tar" delivery .
use of filter and/or air dilution systems with existing tobacco blends it is
le to fabricate low "tar"/la,r nicotine delivery cigarettes Hithout inte-tionally
Me content of the filler ; however, low "tar"/medium nicotine delivery cigarettes
wa "tar"/high nicotine delivery cigarettes will probably require addition of
e to the blend or use of specific high-nicotine tobaccos which yield low "tar" .

~, Solution of th .~.~tine problems as described above will result in further


pr~~~ation of th~br d mix in thp .market . Low and medium "tar" delivery cigarettes
wi ori an~dium}nico ine delivery, respectively, will continue to proliferate during :
rst p . .of t"' . jection period . Low and medium "tar" delivery cigarettes
inediu~ . hig tine delivery, raspectivEly, will appear and proliferate
the . le p the projection period if RJR or a competitor solves the
m of reducing 'tar" :nicotine ratio to 6 or 7 . .
. Q*4T WILL BE IT : PACTjMPIICATION
I&
urther proliferation of brands in the market place with low"tar"/lor+ nicotinc
cigai*ttes and low "tar"medium nicotine cigarettes commanding an ever-increasing share
ofXMA total market .
. EN WILL IT HAPPEN_

ressure by the smokinq-health proponents of the lower "tar"/loarer nicotine


t'po will continue frcxa the present through 1985 . The proponents of the other
th~~y (low "tar"/medium nicotine cigarettes) will become more vocal after 1980 .
RCES OF ENVIRO(it1ENTAL ANALYSES/FORECASTS AND RATIONALE
A typical proponent of the low "tar"/low nicotine concept is Hammond (paper
presented at meeting on "The Origins of Human Cancer," Cold Springs Harbor,
September 1976) ; typical proponents of the low "tar"/medium nicotine or medium "tar"/hi
nicotine concept are Russell , BRIT . MED . J . 1976 (1), 1430-1433 (see also references
therein ; and Goldfarb et al . , CLIO PHARt•IACOE.-MIER ., 19, 767-772 (1976) ; PSYCHOPHAk!laC4ii':`
17, 89-93 (1970) . 0
0

• a
M
D

R JR24264
I POSITION rAPER - FAtLW1L DOCUMEtITATI0t1

SMOKING AND HEALTH : PRODUCT AND SMOKE COMPONENTS

P•
. .. . T~„r_
CO<iPO~IENTS
. : A . Filler . 5. Casing Materials . a .__.SuQar
1 . TRENDL ISSUE, OR EVENTS IDFNTIFICD/DESCRIBED
For several years, sugar either occurring naturally in flue-cured tobacco or used to
case tobacco has been indicted as a contributor to the alleged hazardous nature of ci3are ;
smoke . It is claimed that increasing the levels of sugar in the tobacco rod increases
the levels of certain polycyclic hydrocarbons (alleged tumor initiators) and phenols
(~le ed tumor promoters) in smoke, decroasss the smoke pH thus increasing its inhalabili
a~fid ireases the levels in smoke of several gas-phase comQonents alle9ed to be detri-
to the respiratory tract defense mechrnisms .
Insofar as the specific carcinogenicity of smoke from sugar-treated tobacco
enstes is concerned, the recent tICI study on various types of cigarettes containing
t ividual or combinations of casing ma terials showed no significant effect from sugar
a :• lone. However, it is alleged that sugar plus glycerol added to,the tobacco did
i ~se the specific-activity of the "tar" from such cigarettes .
2OWMT WILL HAPPEN

oponents of the smoking-health theory will further press their claims that the
a~,~;'n of sugar t end either as it occurs naturally in the flue-cured component
or as casing mateM Aesults in a product r :hose smoke is hazardous to the smoker .
Injotry rembers wi <- •empt to reduce sugar casing levels in their products while
-i~ing smoking ~ua ty and consumer acceptability .
1, WT NIL < IT CT It•iPLICATION
he i1preY of ssue will eventually involve the reduction or complete removal
ed sugar •from ; ny product formulations . This will require some manipulation o
Com y blends to ma+ n uniformity of smoking quality before and after sugar removal
or• uction . Fort e .y, we do have in-house data which show that the sugar casing
leye may be reduced su•ttantially without serious impairment of smoking quality .
4. W~~SEU VILL IT HAPPEN ,
laims against sugar are already being made, but additional pressure on the
n dry will be exerted between 1980 and 1982 .
CMURCES OF ENVIRONMENTAL AttALYSES/FORECASTS AriD RATIONALE •

Wealth claims against sugar in ttibacco products are described by Elson et al .


L . CANCER INST ., 48, 1885-1890 (1972), INTL . J . CANCER, 9, 666-675 (1Q72)
ditional references therein) . Chemistry of snoke from. tobacco cased with sugar
at vari'ous levels is rcported by Wynder and Hoffmann, "Tobacco and Tobacco Smoke,"
Academic Press, 1967, 484-486 . In-house study of the effect of sugar on smoke
chemistry and quaTffy Is described by Best (1969) . Skin-paintiny studies with "tar"
from sugar-cased cigarettes are described in flCI Report No . 3 . Toa,rard Less Hazardous
Cic~arettes . The Third Set of Ex,perir.+ental CicLarettes ra , ugust .

a J R24265
'
3l1

POSITION PAPER - FORUAL pOCUt•1ENT11T10H

! NG AND itEALTH : PRODUCT AND SMOKE COt4POtlCNTS

PRODUCT COt1P0yENTS : A . Filler . 5 . Casing Materials . b . Licorice


1 . TREND, iSSUE OR EVENTS IDENTIFIED/DESCRIBED
During the projection period, health claims will be levelled at licorice used as a
casing material in snaking products . ,
To date, no serious allegations concerning the hazard of liccricb as a casing rrateri :
i ot acco products have appeared . However, several years ago the question was raised :
1N1ic~rice, because of the polycyclic structure of its•active co~,aonent, a contributor
egedly) haraiful carcinogenic polycyclfc hydrocarbons, prona ting compounds such as
p nol, and irritating gas-phase components in smoke?
one study it was alleged that pipe tobacco containing high levels of licorice
a sr,~bked in cigarette form yielded substantially higher levels of benzo(a)oyrene
i s»*ke than did licorice-free cigarette tobacco smoked under ideotical conditions .
t were obtained on the lavels in t!:e snoke froM the licorice-cased tobacco of
eno~s, aldehydes, or acids allegedly involved with health, but it was suggested that
f~"~"work should include such analyses .
_, T NILL HAPPEN
roponents of tKVI'Making-heal+h theory will allege that licorice used as a casing
Pat•e,rial in the smol~ roducts is the precursor of several toxic components in smoke
an~~V demand rema,ya ;f licorice from smoking products .
~~, ~ t
: AT IT~4WCTLItiPLICATION
~
;, . .Qemanlsmo - ealth proponents for removal of licorice from casing formulation
ecessitate C .compliance, discovery of an alternative to licorice, or
tion of data to count the allegations . Compliance with these demands to delete :
uce licorice, or use of an alternative will require detailed evaluation of
Company blend formulat s .
4.P#IEN WILL IT HAPPEN .

tween 't982 and 1985 .


5 . OURCES OF ENVIROrJNENTAL ANALYSES/FORECASTS AND RATIONALE
Comments on possible health-related problems from the use of licorice as a casing
a~~ial and suggestions for future research appear in Wynder and Hoffmann . Tobacco
bacco Smoke," Academic Press, 1967, 484-486 .

,
. RJR24266
0 POSITION PAPER - FORMAL V)CUt•tENTATION

ANG
~ AtID HEALTH: P:".ODUCT AND SttOY.E CONPQNENTS

PRODUCT CC'1POyENTS : A. Filler . 5 . Casing Materials . c. Cocoa

1 . TREND,_ ISSUE, OR EVENTS IDENTIFIEC/DESCRIBED

In a recently connleted NCI study on various types of cigarettes, several additives


and/or casing materials were investigated . Among these was cocoa, The results from
this mouse skin-painting study were alieged to indicate that the inclusion of 1% cocoa
in~the~tobacco blend increased the specific carcinogenicity of the "tar" from such
ci'are ~tes over that observed for the "tar" from the control, non-cocoa treated
i : tes . It is anticipated that proponents of the smoking-health theory will eventual
ETIY__ _& these and similar data to demand the rer,oval of cocoa from or substantial
n of cocoa in smoking products . ,
2 T wILL HAPPEN , •
;oponents of the smoking-health theory will al lege that cocoa used as a casing
in smoking products is the precursor of several . toxic components in smoke as
ed by biological and chemical data and will demand removal of cocoa from smoking

3.-, UHAT !lILL BE ITS ;.iMPACT/1t•SPLICATI4N •


nds by .srrok.ft g-h altl : proponents for removal of cocoa from the casing formulatio
ecessit-M Comompliance,•discovery of an alternative, or generation of data
:tttount thOalleg V ns . Compliance with demands to delete cocoa or the use of an
alternativot-Mreq*iXWM4etailed evaluation of Company blend formulations .
H 11111 IT NA

4atween 1980 an lro .


. . RCES OF ENVIRONJiENTAL ANALYSES/FORECASTS AND RATIONALE
e results from mouse skin-painting studies which allegedly show increased
'>aic carcinoc+enicity of "tar" from cigarettes containing 1% added coco3 are
sixo'nized in the NCI Re ort No . 3 . Toward Le_s Hazardous Ci arettes . The Third
SWK Exnerimenta parettes ra t, ugust .

RJ R24267
sl
.
4
POSITIOy PAPER - FORI4AL (1nCUUNTATION
'N i*ING AND HEALTH : PRODUCT At1D St4OKE CEN•1P4NENTS

UCTS Ca1P Ot1EtlTS : A . Filler. 5 . Casing Materials . d~


. Glycerol and Other Humectants
1 . TREND, ISSUE, OR EVENTS IDENTIFIED/DESCP.IBED

Past allegations against the use of glycerol as a humectant have involved the
possibility that it generated acrolein, an alleged ciliastat and irritant, during
the smokin; process . The recently completed NCI study on various,types of cigarettes
containing added glycerol or added glycerol plus sugar gave resultf alleged to indicate
~at addition of sugar plus glycerol to a tobacco blend increased the activity of the
tar "i nouse
. s ki n-pa i n ti ng exper i nen t s Additi on o f glycero l a l one h o<ever gave
.,Vs~ialythesamrultashecontrl .
Humectants other than glycerol but not generally used by RJRT have also been
troi~ed for their contribution to allegedly carcinogenic polycyclic hydrocarbons in
bacco smoke and generation of ciliastats on pyrolysis . Diethylene glycol has been
sed as a possible bladder carcinogen, but the data were obtained•from laboratory
s fed this compound and not from animals exposed in tobacco snoke•inhalation •

roponents of king-health theory will allege that glycerol and other polyols
used"as humectants king products are precursors of several toxic conponents in
srpoke or are hazar4mw'An smoke in themselves on inhalation and will demand the removal ;;
ooffi'bo humectants ~r A smoking products . -

T !' E I1~ACT 1NPLJCATI(1N Deman s, s health proponents for removal of glycerol and other humectants >`
moking produ"11 necessitate Company compliance, discovery of alternatives < ;:;
n ub3ect to criti , or generation of data to discount the allegations . Complianc~:,
w these demands ~~ d~lete glycerol or use of an alternative will require evaluation
o~ Qmpany blend formu tions . Glycerol is also used to facilitate tobacco cutting ;'
s~3~is aspect of the manufacturing process will have to be examined in light of no
g~yorol or use of an acceptable alternative .
EN WILL IT HAPPEN •.
IAW& Between 1982 and 1985 .
jj_SOURCES OF Ei1VIROtn•1EtITAL ANALYSES/FORECASTS AND RATIONALE
Discussion of humectants and their health-related problems appears in . tlynder and
F{,'inn, "Tobacco and Tobacco Smoke," Academic Press, 1967, 480-484 . 'The results of
mouse skin-painting studies involving "tar" from glycerTor'glycerol/sugar-,treated
tobaccos appear in NCI Re ort No . 3 . Toward Less Hazardous Cioarettes .'__Th_e Third
Set of Exverir,ental darettes ., ra t,, ugust

0
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R R`Z 2,6
, 4 16
ss
,

, POSITION PAPER - FORr1AL DOCIn•1ENIATION

~ Nr A ALTH : PRODUCT AND St•sOKE COMPONENTS

PRODUCT C0t1PANENTS : A. Filler . 6 . Flavorants


1 . TREND, ISSUE, OR EVENTS IDENTIFIED/DESCRIBED
Flavorants used on the tobacco filler not only may be transferred directly to the
mainstream smoke but also may yield decomposition products in the mainstream smoke
during the smoking orocess . Allegations concerning the hazard of'intact flavorants trans
f rreQ fre :~ the tobacco rod to the n~ainstream will also apply to filter-tip flavorants `:
t~ansf3erred intact to the smoke stream . Filter-tin flavorants . because of their senaratf
© ~€ he combustion zone, generally do not yield decomposition products . As early as
1967 it was suggested by proponents of the smoking-health theory that inclusion of
nts in smoking products is a deliberate introduction into tobacco of precursors
tants or toxic substances in t eFsmo e . It was also noted .that the sr.~oke from
ttes containing flavor additives very rarely have been assayed biologically .
.~restion was also raised whether such additives should be subject to regulation
g verroAenta l h ea l th auth or iti es . I1 ore recen tl y a lea d ing proponent (Hary.~on d ) o f
kin3-health issue stated that " . . .both (flavor) additives and the smoke
conde ate should be tested for carcinogenicity before putting such cigarettes on
rket." NCI in its continuing examination of "less hazardous cigarettes" has
sc*..ed an intensiV,.L&vestigation of flavorants used currently .
2 .~,_Wr1AT VILL HAPPELft
~ropon of khe s king-health theory will allege that sorle flavorants used on
bacco ~ ..ler ftwr filter are contributors of toxic components to the smoke and
dema~ ~her they not be added or that all flavorants used be evaluated for
effec co ; ion and ~+iological properties of smoke : They may also attempt
e the use of lavora :ts in tobacco products regulated by a governmental
he h agency .
3 T''ILL BE ITS IAVACT IMPLICATION
he Company's use of proprietary flavorants will be seriously disr-ipted is such
depWs .succeed . Appreciable effort will be required to demonstrate the safety of a
T number of specific compounds . Those not cleared will be removed from flavor
f lations, and this will necessitate substantial evaluation of our smoking products
w regard to quality . Economic advantages of the use of our proprietary Turkish-type
f ants on low-cost tobaccos may be lost or delayed because purchase of expensive
T~- i.sh tobacco will continue at the same or an increased level until at least one of o
TdMsh-type flavora~~ts (the tetraester) is cleared . _
N WILL IT HAPPEN
Soon after 1980 .

5 . SOURCES OF ENVIRONMENTAL ANALYSES/FORECASTS AND RATIOyALE


The concern by some proponents of the smoking-health theory about adCed tobacco
flavorants is suRrnarized in Wynder end Hoffmann, "Tobacco and Tobacco Siroke," Academic
Press, 1967, 486-488 . Comr,~ents by Hammond et al . appear in the text of a paper presented cn
~
the meeting on "The Origins of Human Cancer'7n Cold Springs Harbor, .Sept . 1976 . The ~
~
eposal to conduct research on the effect of flavorants added to tobacco on the biological m
properties of smoke was presented at a September 1975 meeting of the NCI Tobacco Working Ln
Group . H
00
m

, . .. ~;. .. .,
RJR24269 • •
,.. ;, . .. ~. . . . ..,, .,~ 7
o4
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0 P0SIT10N PAPER - FORttAL DOCUMENTATION

~ AND HEALTH : PRODUCT NZD S OKE COt•1PONEtrTS


~ING
PRODUCT COMPONENTS : B . Fi 1 ter . 1 . Fi', ter t9aterials

1 . TREND, ISSUE __OR EVENTS 1DENTIFIED/DESCRIBED

The anticipated emphasis on gas-phase components such as aldehydes alleged to he


harmful to health will result in a resurgence of the interest in carbon filters . The
interest in gas-phase components by proponents of the smoking-health issue declined
peve al years ago, particularly when it was demonstrated that such components were
Leffe~tively "scrubbed" out of the smoke stream by passage over the mucous films
ng the oral cavity and therefore did r+ot reach the lower respiratory tract where
gt Has alleged they interfered with the respiratory tract defense mechanisms .
. MT WILL HAPPEN '

Proponents of the smoking-health theory will claim that increaseduse of stem


ia1s, while lowering the alleged carcinogenicity of the "tar", is increasing the
of gas-phase components that allegedly impair respiratory tract defense
nisms . In response to this, industry members will market a carbon-filter
tte whose smoking quality does not suffer from carbon-filter off-taste .
. NHAT WILL BE
~ Y YTr'YNPACT/INPLICATIOlI .
jhe impact w rl the development of a superior carbon-filter cigarette . This
on fi~":r~ wil be esigned to minimize the carbon-filter off-taste so prevalent
eariip~rbon- •er cigarettes . Another alternative will involve modification
the s4-ijj;;j~eetjWW. ial to minimize generation of the allegedly harmful gas-phase
onents .
WHEN WILL IT H
~$*6efore 1985 .
., SOURCES OF ENVIROMENTAL AtiALYSES/FORECASTS AND RATIONALE
Charcoal filters and their effect on the gas-phase composition are discussed in
er and Hoffmann, "Tobacco and Tobacco Smoke," Academic Press, 1967,'S34-543 .
crubbing" action of oral cavity secretions on gas-phase components in humans
h*.been described by Dalhamn, EINVIROU . HLTH ., 16, 831- 835 (1968) . Increase in the
yp1s of various gas-phase smoke components with ' increasing stem content is
cribed by Heckman (1974) .

R J R24270 !
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0
POSITION PAPER - F0M1AL DOCUMtCtITATION

'"WKIN6 AND kEALTH : PRODUCT AND SMOKE Ca,1PONENYS

PRODUCT C0MOPIENTS : C . Paper . 1 . Paper Additives :byes

1 . TREND, ISSUE, OR EVENTS 1DEHTIFIED/DESCRIBED

While very little has been written by proponents of the smoking-health theory on
the use of dyes in smoking products, it is anticipated that RJRT's success with the
WINCHESTER and MORE products will eventually direct the attention of the smoking-health :
;Pproppnents to the dyed tirn?pers . Allegations will be advanced that the dye systeris
'tneect chemical and biological evaluation, tlew dyed systems introduced in the future by
or other industry members will also fall into this category .
FJHAT WILL HAPPEN

g ? Proponents of the smoking-health theory will either allege that dye systems such
hose employed in WINCHESTER and t10RE are hazardous or will demand demonstration
eir safety . .
. d WHAT HILL BE ITS If4PACT/IMPLICATIOy
Other than a~ftio- ble flurry of adverse publicity which might temporarily hurt
sales of the F10RE •re in an excellent position to rebut any claims against the
#~c~>d~Hrapper of e •the b :ORE or WINCHESTER . Detailed smoke comparison studies
voWing over 150 colmoonents in the smoke from the MORE blend wrapped in regular
qr vs isK"10REel wrapped in dyed paper indicate no "strangers" in the sr.ake of
£ ciga~tires ma ~d in the U . S. A . or U . K. Similar evidence is available for
e WINCFIE-STA.R.
1JHEN WILL IT
Prior to 1980:
SOURCES OF ENVIRONIIENTAL ANALYSESIFORECASTS AND RATIONALE
Comrnents on the use of dyes in smoking products appear in liynder and Hoffmann,
acco and Tobacco Smoke," Academic Press, 1967, 486, in which a study by Kroller
Ptited . Experimental work conducted in-house on the absence of "strangers- trom rwr .i
4%"ke is described by Green (1973 1974), Best et al . (1976) and their .absence from
W-WCHESTER smoke by Green et al . 11971) .

. a
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POSITION PAPER - FOnUIL DOCUFIENTATION

~ING AND HEALTH : PRODUCT AND STIOKE C014PONENTS

SMOKE COMP0NENTS : B . EnyiPonmental Smoke


1 . TREND, ISSUE, OR EVENT IDENTIFIED/DESCRIBED
Proponents of the smoking-health theory will allege that exposure of the nonsmoker~" :.
involuntarily is subjecting him to an unwarranted health hazard . Yhey will claim that
jis~is particularly harmful when the nonsmoker is alreedy suffering soaheeilment such
s a• allergy, cardiovascular problem, respiratory problem . The arguments will be
ed that the environmental smoke contains the same allegedly noxious components to :
ch the smoker is exposed ; i .e ., carbon monoxide, nicotine, nitrogen oxides, hydrogen ;~
s, hydrogen cyanide, and the like .
These proponents will apply the same health-related arguments about the hazards
vironnental smoke components to the nonsmoker involuntarily exposed as they
V *been for the hazards of mainstream smoke inhaled by the smoker .
. W WILL
T HAPPEN •
- -
By constlsnt repetition of their claims on the alleged hazard of involuntary
sure to envirohina-tal smoi:e and its components, the proponents of the smoking-heaiti
theory will convi cesmore and more nonsmokers that they are being imposed upon and the "
~omokers in tur '•~h the help of various health agencies, t•itll push for additional
)itions to barrsmoking in more and more public places, business areas, work areas,
T LR1-tAME_IS"- PACTII_N,PLICATIOt~
Q&akma AM 1.40

If more ind r:rokers are restricted in their smoking regime by such regulatiori'
their daily ons .ption of cigarettes and other smoking products will decrease .
t he regulation ~ . n on smoking eventually extends to the workplace in any business :
~ern, the sncl:e , w01l have a great portion of his possible snoking time deleted froq' : .
e~ork day . This usually accounts for half a person ' s active day . This situation `
Meventually result in a decline in cigarette consumption, fewer new smokers, and
ation of smoking by many light smokers (less than 10 cigarettes/day) . .

F~"WHEN 19ILL IT HAPPEN


The condemnation of environmental smoke will continue but at an increased level
ftthe present until the proponents of this theory have obtained regulations
llannin9 smokin9 in almost all comrnunity_areas such as restaurants, work places, publi
rldings, etc . Eventually one nonsmoker in a given work area will be able to control
,0._*san,wking habi ts of the rest .
5 . SOURCES OF ENYIROh!tENTAL A .Nf:LYSES/FORECASTS AND RATIVIlALE
A host of references on this subJect have appeared over the past few years with
special emphasis on exposure of the nonsmoker to nicotine and the amount inhaled
involuntarily and appearing in the bloodstream ; e .g ., Russell et al . . LANCET 1975 (1) ;1;
179-181 ; Hinds et al .,, NEW ENG . J . t~~ED ., 292, 844-845 (1975) . ~nvo untary exposure to~ ~
ot~ier smoke com`porents has also beun the subfect of numerous articles ; e . g ., "Tobacco : 0
0
Experimental and Clinical Studies," Supp1 . III, Williams and Wilkins Co ., 1975, 288-291 . a
0
..
a
y
RJ RZq,272 N

LA
. POSITIO« PAPER - FOR1M
c..~OKING AND ttEALTH : PRODUCT AND SF10t ;E • C0.IPONENTS
~ICE CO'tP0l;EpTS : C : 1 . Particulate-Phase Comaonents :' a . FTC "Tar"

1 . TREND, ISSUE, OR EVENT IDEtlTIFIED/DESCRIBEO


Because of the allegations that the "tar" contains many co~~ponents harmful to the
smoker, many consumers have shifted their smoking habits from high_,,tar" to mediun-"tar
cigarettes or from nediun-"tar" to lori="tar" cigarettes ; i . e ., a•gradual downshift to
e next lower "tar" category . This trend has continued for over a decade ; the 30- to
S-mg~delivery cigarette is almost nonexistent ; 25-mg delivery cigarettes are at the
~~ the "tar" scale . .
'~Constant repetition of the allegations about the harmful properties of "tar" will
nce more and more smokers•to shift dotirn to lower "tar" levels ; the manufacturers
~11#-espond with products geared to match this trend and capture the market .
.
1T WILL HAPPEPI •
ventually the "tar" delivery will be lowered until the top "tar" delivery is 20 ng`= : :"'
~e 5 mg, then 10 mg, and so on . The pro onents of the smoking-health theory tiill still
nue their efforts to have the "tar" values lowered even more . It is obvious where
-trend will end 'ventual weaning of the smoker .
~WF4'1T WILL BE 14, $ACT/IHPLICATIOtI
Topr :, ea article with both flavor and nicotine satisfaction at lower
~ ower ~ta~" 1ev 11 require considerable expenditure of time, money, and effort'
an efi~o~~o di appropriate blends, filter and air dilution systems, flavor
ms, etc . 1hu cost of producing a satisfactory smoking article will rise
'inually as the ar yield decreases ; i . e ., the profit margin for such products
decrease . To ~ain the prosit margin, price increases will be necessary .
~ This fact, coup~drwith the gradual weaning of the smoker, will'result in a decline :,
( ~~ette consumption , fewer new smokers, and cessation of smoking by light smokers (less :
10 cigarettes/day) .
NNEN WILL IT HAPPEN
The scare tactics presently used by the smoking-health proponents to persuade the
r to smoke lower "tar"-delivery cigarettes will continue to be used well into the
07ection period . By 1985, cigarettes delivering 12 mg "tar" or less will represent
j3sabst half the mar :.et .
6J§QURCES OF ENVIRONMENTAL ANALYSES/FORECASTS AND RATIONALE
Recently Hammond et al . (paper presented at Cold Springs Harbon in September 1916) ..
extolled the benefits o' sm",ko ing 1ow-"tar" cigarettes . Additional reports of this type :;;
will continue to appear in the future . NCI . as a result of its work on .the fabricatio6:
of less hazardous cigarettes, has also commended the lon-"tar"'cigarettes to the publi .4
in various TV appearances by NCI personnel (Gori, Rauscher) .
.~
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POSITION PAPER • FORMAL DOCUf'IENTATION


0
SMOKING AND IIEALTH : PRODUCT AND SMOKE COMPONENTS
, . . .
SE CO~!PONEtITS : C . 1 . Particulate-Phase CU onents, b. Nicotine
1 . TRE!ID, ISSUE,_OR EVENT IDENTIFiEDIDESCRIBED
Cl.inical and biological studies on nicotine in smoke will result in one or other of
the fulloaring : nicotine will be glven a clean bill of health or nicotine will be
considered a hazard .
Some smoking-health proponents already allege that nicotine is involved in cardio-
v~s cu ar problems and is as hazardous as the "tar" ; other smoking-health proponents
a'Ileg that nicotine is essentially harmless and the hazard to the smoker resides in
t~t ar", not the nicotine . st
7he first group clairr.s both the " tar" and nicotine should be lowered ; the second
~ suggesting that people smoke for the nicotine satisfaction, claim that the "tar"
be lowered but the nicotine increased so that the smoker will smoke fewer ci5arett
e same daily nicotine intake, and thus be exposed to less "tar" .,
ecent evidence fron the NCI studies on various sets of experimental cigarettes is
Rd to de:onstrate that nicotine level of the "tar" correlates with*tumor yield in
rkoft~kin-painting experiments . .•
T WILL HAPPEN
i+o groups of ke EFC bents of the smoking-health theory will remain at cdds on the
alleqed harnful eff~- .,1 nicotine In smoke . Each group will attempt to persuade the
ew.
putr~ to its point~l
4 •
. AT t/iLVVE IMLi1PCT/ItdPLICATIa'1 - .
he y wi • e to decide whether to pursue products with lowered "tar",
d nt~cr` fie, o• ____ _ ducts with lowered "tar", increased nicotine, or both . . Nhicheve;
s selectc+d onP p of smoking-health proponents will be critical of the choice . :
owering both "t and nicotine delivery is possible with existing technology
, paper porosI a eir dilution and filtration, etc .) but lowering the "tar" while
r1c asing the nicotin"elivery will be a challenge . .

4 .umWEN !iILL IT HAPPEN


fSone time during the profection period, evidence allegedly demonstrating that
~ine is harr.~ful to the smoker wi11 be presented .
5 OURCES OF ENVIRONMENTAL At :ALYSES/FORECASTS {4"ID RATIONALE
~ Hammond et al„ proponents of the loN-"tar", low-nicotine theory, outlined their
tWaaty in a paper presented at a neeting on "The Origins of Human Cancer" .
nted at Cold Spring Harbor, September 1976 . Russell, a proponent of the
r", high-nicotine theory, outlined his ~`easoning in an article in the BRIT .
. J,M~D ., 1976 (1), 1430-1433 . Involvement of nicotine in "tar" carcinogenesis is
discussed-WNCI Reports 1 2and 3 . Tcxrard Less Hazardous Cinarettes, and also
by Bock (paper presente at ee ng, _,

RJ RZ4274
39
,

POSITION PAPER - FORMI)AL D`OCUMENTATION


w

~NIO ING AND HEALTH : PRODUCT AND SMOKE COIIPONENTS


J.CO'1P0NENTS : C . 2 . Gas-Phase Con2onents- a . Carbon Monoxide
TREND, ISSUE OR EVENT IDEflTIFIED/DESCRIQED

It is alleged that carbon Fanoxide in tobacco smoke is hazardous to the smoker as


are "tar" and nicotine . The sr,r,* critics of the smoking habit and its alleged hazard
to the smoker who succeeded in having the "tar" and nicotine levels in smoke reported
by a government agency (the FTC) are now pursuing similar efforts'for carbon monoxide .
Thk-FTq, in fact, is working on the analytical procedure for simultaneous determination
ta, nicotine, and carbon monoxide .
e country (Sweden) has already implemented legislation to report carbon monbxide
iver.ies ; several other European countries'are now in the process of implementing
'4gislation . •
T WILL HAPPEN
;'gislation to require the reporting of carbon monoxide delivery of each A+*rican
11 be vnacted . The FTC will probably handle the analysis for carbon monoxide
as_it Dbes the "tar" and nicotine analyses . •
is flow of events will eventually lead to a carbon monoxide "derby" similar
W""tar" derby .

3. ~.'!HAT M1LL RE ITS"


.~ ~*~A,T/IFIPLICATIOt1
r'a
.~ carbo ~.~noxi e"d~rby" will require research to discover more efficient ways to
the ~ . :gn mori~Tlx~e de1 ivery of a cigarette . At present the most effective
~~~is ~luti t air dilution also reduces "tar" . In view of the publicity
ted 5y recent .. les on carbon monoxide in smoke, the company that can discover
a~o reduce carb . oxide without reducing "tar" at the same time will have a
dec .ed advante9e .
verse public M~~~ta~ons concerning carbon monoxide in smoke will be a problem ;
rhon monoxide del"Tvery cigarettes will lose market'share .
4 . OMEN WILL IT HAPPEN
PRO
porting of carbon monoxide delivery of each brand will be required by 1980 .
URCES OF ENVIRU'C!ENTAL AlIALYSES/FORECASTS AND RATIONALE
Of the hundreds of articles In the scientific literature on carbon monoxide in
_ i i'`tte sr :oke and its alleged hazard, the one with the greatest impact on the
puVM is the recent READER'S DIGEST article (October 1976) .

R J R24275


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ft

POSITION PAPER - FORM/lL t)nCUt4EIiTATION


. I.
Sin, ING AND HEALTII : PRODUCT AND SMOKE C0t4PONENTS
PRODUCT COt1PONEtITS : C . 2. Gas-Phase Components . b . Nitrogen Oxides
1 . TREND . ISSUE, OR EVENTS IDEkTIFIED/DESCRIBED

It Is alleged that nitrogen oxides in tobacco smoke are hazardous to the smoker .
Cigarettes deliver beNeen 200 and 400 ug of nitrogen oxides per cigarette, and of these
n ro~,en oxid:s, over 98% is nitric oxide . Reporting of "tar" and nicotine deliveries
b the~FTC is an established fact ; requirements to report carbon monoxide delivery will
p~ y be next, followed by requirements tc report nitrogen oxides delivery .

,4gislation to require the reporting of nitrogen oxides delivery o.f each American
ill be enacted . The FTC will probably handle the analyses for nitrogen oxides
e.
3. ~t~' WILL BE ITS It1PACT/IMPLICATION
Nnitrogen oxid "c rby" will result . '
Articies in th •~ic press will inform the smoker of the nitrogen oxides
eeq~nt of tobacco ~4and its alleged hazard . At the present time most smokers
3r ~ too•knowlE .: .ab1 q' about nitro en oxides .
kklic•~tio s pro`bleras will arise . '
E!1 ! : .LL: ~ HAP
tNeen 1983 a V85 .

5 . ~#URCES OF ENVI .O ~~~'i,TAL ANALYSES/FORECASTS AND RATIONALE


'%wt.n the READER'S DIGEST article (October 1976) on carbon monoxide, it was noted
thW* foilow-up article will discuss nitrogen oxides in tobacco smoke much in the
sa~anrer as carbon r.wnoxide was discussed in the October article . Presumably the
d hazards of exn^sure to nitrogen oxides will be outl•ined in great•detail . The
ef ~ of nitric oxide on the cardiovascular system is discussed by Larson and Silvette
"T :, co : Experimental and Clinical Studies," Suppl . III, Williams and ::ilkins Co .,
1~100-101 .

04

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R S R2a''(6
POSITION PAPER - FORMAL DOCUh1ENT/1TI0N

SG AfiD I(EALTH : PR(1DUCT AND SMOKE C014PO1JENTS

PRO l1CT COMPONENTS : C.2 . Gas-Phase Components . c . Hydrooen Cyanide


1 . TREND, ISSUE . OR EVENTS IDEfiTIFIED,fDESCRIBED
Hydrogen cyanide in tobacco smoke is alleged to be hazardous to the sonoker . The
public is probably mre knovrledqeable about the toxicity of hydrogen cyanide than it
is about many other smoke components . Cigarettes deliver between 200 and 400 u9
p#T cfi9arette, but levels as high as 800 ug/cigarette have been reported . Methods to
the hydrogen cyanide content of cigarette snoke are available . The Threshold
Yalue for the comoound is 10 ppm or 11 nanograms/ml (about one one-hundredth of the
level in cigarette smoke)• .

:3egislation to require the reporting of hydrogen cyanide delivery of each Aaerican


6~;,~i11 be enacted . As in the case of "tar" and nicotine, the FTC will probably ,
conduct the analyses for hydrogen cyanide in smoke .
WILL BE ITS IMPACT/I!!PLICATION
~.F A hydrogen cya "derby" will result .
king product~ ; w 1 be manipulated to reduce hydrogen cyanide deliveries by
o us~ f~ppro te aTr d lution and/or filtration systems, filter-tip additives,
ate bl . ...d•s, e . .
ubiic ~ ~atiomor blems will arise .
4
EN WILL IT HA
Wetween 1983 a$5 .

5 .~ ~XIRCES OF ENVIRONMENTAI ANALYSES FORECASTS AFID RATIONALE

awd n the READER'S DIGEST article (October 1976) on carbon monoxide, it was noted
& n":L.1a folla~r-up article will discuss hydrogen cyanide in tobacco smoke In the same
as carbon monoxide was discussed in the .October article. The alTeged hazards
drogen cyanide in cigarette smoke are discussed by Wynder and Hoffmann in "Tobacco
bacco Smoke," Academic Press, 1967, 451-453 ; by Larson and Silvette in "Tobacco :
M imental and Clinical Studies, "~pl . III, Williams and Wilkins Co ., 1975,
~1 ~<. .'; 163, 279, 292, 298 ; Suppl . II, 1971, 112, 115, 205 ; Suppl . I, 1_968, 1N; 136,
0
275, 606, 613. •

R J R24277
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• . POSITION PAPER - FORMAL GOCUMENTATION

SHOKING AhD HEALTH : PRODUCT AND SMOKE C01•1PONENTS

PRODUCT CO;IPONENTS : C.2 . Gas-Phase Ca•mponents . d . Hydro_yen Sulfide


1 . TRENDs, ISSUE, OR EVENTS IOENTIFIEn/DESChIBED
To date very little has been written concerning the alleged toxicity of hydrogen
su id in cigarette smoke . Early reports on hydrogen sulfic'e indicate levels between
15 and 390 ug/cigarette, but more recent studies indicate levels of less than
10 '` igarette . Hydrogen sulfide in'the usual acute and chronic toxicity laboratory
teft s r1ith laboratory animals is found to be as toxic as hydrogen cyanide and has the
sa itted Threshold Limit Value of 10 ppm in the work place .
2. WWILL HAPPEN
is predicted that proponents of the smoking-health theory, if sJccessful .in
th -••empts to obtain le3islation for the reporting of carbon monoxide, nitrogen
ox s and hydrogen cyanide, will turn their attention to hydrogen sulfide .•
Ev ____._ ...__. ly, legislation will be enacted for the required reporting of this corrponent .
3 . Y.FL'1T ::ILL SE ITS ~I/iMPLICATION .
~».
drogen sulfi)ft " erby" will result .
~)king proOuct ili be manipulated to control hydrogen sulfide deliveries
NO f aoppip#late I dilution andJor filtration systems, filter additives, .
Fnate bVep ft;, etc•~ .
lic rela•.ion oblems Mi11 arise . '

ut 1985 . '
3, RCES OF ENVIRONMENTAL ANALYSESlFORECASTS AND RATIONALE
POW
drogen sulfide in cigarette smoke is discussed by Larson and Silvette in
"iofiwio : Experimental and Clinical Studies," Suppl . III, Williams and Wilkins Co .,
197

a d

cy° . ;<
V
.
M >`

N .~
~ . .

. RJR2427$ ' ~,
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. .. . .. . r . - • ~ 3„ > . . _. .. . , • _ .
0

~
SM~KIttG ANO f1EAt7N: PROOUC'. €~O
1977 - 1989

Probabtlt ot•Occtrrrence ~ -~'"~ Est/meteQ I ct I ltutions + or Earl test


~ Possible
Key Issues Q~+a nttta;S • L rear of
on Sales Prottts _

Qualitative Occurrence
lOt 30t SOt 70% 90% l0!/Yea Svrv4. .#i

I .A• PROOUCT ~
ConQeanation of nicotine X • •• • ~ t••6owere0 'tar' and nicotine on established brands ; If 1971
as health hazard by some (to 1983) lowerin9 of •tar` and nicotine progresses too far,
smoking-health proponents customers weaned froa~ smoking with subsequent sales
tncreased demand for low- ' - decliae .
nicotine tobaccos . (after 198 ) • flew brand opportunities .
(cf• pp . 7-8, 28) • Decline in smoking satisfaction 1n terms of both flaror
and physiological i .pact. .
~~ • Oeelfne of unit growth of Industry .
Some s.~oking-fr,~alth pro- • 8rana proliferation . ,
ponents allege sawke •. Low-nicotine tobaccos cotiw+Q prei .ius price .
nicotine Aarmful ;
simultaneous lowering ~ C~qlexity of low-'tar"/lox-ntcotine products 1n terms of
of "tar' and nicotine blend, air 011vtton/ftltration systems, manufacture,
~~d, denieotiniration, etc ., substantially reduces profit
aarqin .
(cf . pp . 15-17, 38) •
• I~nproved flavorant systems repvired as 'tar• delfrery
lowered.
• • Rccovery systems for nicotine and flavorants lost during
' tobacco processing (613, drying) . ,
~ • AOw~rse PR from smoking-health proponents who recoaa~end •
r increase0 nieotine .

N ' •
~ .

.,---^'.--
0

produ~eciw ' RJ] . 'I' C a

:0
ir
In
Probability of Occurrence Estimated Iapact Impiications (+ or -)• Earliest
Posssble
. . Kqy Issaes Year of
Occarrence -
~~ QualStattve
0% 30% SGZ 70% 90% ,

c% 1978
L8 . PROplfCT X ~
Many smokers continue to • New brand opportunities In low-•tar', increased nicotine
smoke despite health ute9ory.
clales ; recognizing tMs, a Smoke nicotine delivery should not exceed that in
some smolr.ng-Aealtn pro- tull-flevor cigarettes .
ponents reccmeend low-
;0 and aeedivo-•tar' cig- a Decline Sn smoker satisfaction Sn term of flavor but
T c_ arettes with 'tar'/ Saprovement in terms of pl8rsioto9ful Smpact .
N nicotine ratio less than • Ni9A-nieotine tobaccos reQuired .
8: tliqt,-nicotine •tobacco
~r 4 ~ and/or nicotine source . • Nicotine sonrce repuired : synthesis should selectively
N ` "epoired. provide correct Ssomer.
4 • laproved flavorant systems required as •tar" delivery
00 (cf . pp . 7-8 . 28)
lowered .
SypOCX . Recovery systems for nicotine and flavorants lost
dMrtn9 tobacco processin4 (G13, dryinq, etc .) '
Some smoking-health pro-
ponents allege smoke a Adve* PR froo smoking-health proponents who
nicotine harmless but reccmmend decreased nicotine.
-tar' harmful ; since ~
s1EClcers cCntinUe to
smoke despite health •
claims, lowered 'tar• •
delivery and tncreased
nicotine delivery
recanaended by these .
proponents•
(cf . pp . 1 ;-17, 38)

M
t

.:.~ .._~ . . r ...~~-w• . .- .~.,r,ra . .-• .... ._. . r•:..•.. .,w ... .~ .. - . . . . . . . .
r

.
NOTES ON KEY ISSUE I

(1) Because of the interrelationship between nicotine


in tobacco and nicotine in sr.•oke, the smoking-health
aspects of nicotine'`as both a product and smoke
component are discussed in this section . •
(2) It may appear anomalous to indicate both low-
and high-nicotine as key issues, but the consumer's
consideration of nicotine as either harmful or harmless
will be the force dictating his cigarette selection
in terms of nicotine delivery at a given "tar" level . ,

R J R2428 1 . .••c•• . .• .•. . . ..tl. :asi


,~v.J~. .~'.~- .r

Gr .~~....~
rit.v,7 .
: . ., . . . . . . . . . . . . . . . . . __ . . . . . ~r~ ~ .
pr o duced lNy ..

probabili •of Occurrence


-a-
V M EsLl meted tapatt Lnplications (+ or - :arliest
Posfible
Q' n ~ S '~ive : Effect year of
on Sa"tet~?rofits Qualitative Occurreccc
70% 190% t
Flarorants . added to tobacco ana/or • Mandatory labelling for all flarorants not occurringi 19E0 •
filter but not naturally occurring naturally in tobacco or saaks . ,
In tobacco or saoke, alieyed by •+Government interrention for complete evaluation i
sacktnq-health proponents to of a1l flavorants .'e . 9. FOA . fi
increase smoke toxicity because of
their transfer intact to smoke and/o# • Decline in smoking flaror satisfaction if certain t
their decoaposition to alie9edly proprietary flarorants dlleted from cavany products~
har+eful smoke components during the • oamonstration that certain proprietary flavorants
sm*in9 process . are Indeed tobacco or smoke canponents . '
.cf . pp . 10. 13,33) • Legislation to Place flarorant use under 9orernaenta
health agency (FDA) .
• Loss of profit pro1eeted from replacea:ent of 1owcos
~ tobacco treated with Turkish-type flavorant for j
high-cost Twrkish : prohibition of Turkish-type
flavorants necessitates continued purchase of
Turkish .
• Cemonstration of safety of specific flarorants
Oy Inexpensive short-term In vitro test (Ames Test) .

f
.

S' a: . ..:.: . .

::::: - . . . -'
.. . . ~ .. .. ..
.. . ... . ;:

:. . Z£9i _6t?OOZ ':. :


~37cr V car'M aRi?OR IN ftNrr s 'XI.IMO
v ta,
.• ,
~ _ _ ,. :. :.:: . . :::. . . . . . ::. . . . . : : :. . . . . . . . :: . . . . : ::. : :::: .:::::::. .. ..:..
... . . . . . -< . :::.. . . . .., . . . . :. . . . : :. . . . . . . . . . . . . . . . . :. :
. .. .. .. . r« _ . 66TS OILIS . ~. .:.rr . .• .. '
• p rodu ce 0

Probability of Occurrenci V 11 Estimated Iapact Implications (* or -)•


Qv~nti`i 1ve : Ettect
on Sales/Profits Qualitative .

~ III . 'Tar• condeined by siaoking-health • Lowered •tar• on established brands .


proponcnt, as prime risk factor • dnnd proliferation
in siaoking ; publicized at
continually increasing level by . • itaw brand op ortunities .
anta9onistic 9overnfnental and • Oecllne in smoker satisfaction (flavor) and unit
ffedical agencies despite further growth in tndustry .
reducttons In •tar" deliveries .
Realization by smoking-health • Cantfnual lowering of •tar• delivery weans light
proponents that 'tar• nuabers saakers (less than half pack/day) to quitting
Senerated by machine smoking point; loss of sales .
not aean :n9ful In terms of humen • fSandatory labelling for •tar• delivery at
smoking Labtts . Increased puff volume.
(cf . pp . 15, 37) • Uaproved flavor systems required as "tar' lowered .

.
Ot

I
i

/ i
Est mated •Impact Implications (+ or -)• Earliest
ProOability of Occurrence . Possible
tcey Issues Qq ' tative : Effect year of
I on Sales/Profits Qualitative Occurrenr
1 0% 30% 50% 1 70% 1 91 Year urv va ~

IY . Carbon mrnoxide indicted by smoking-


health proponents as harmful
a Carbon monoxide "derby' . 1 19?9 .

•mandatory labelling on cigarette package : extensive


i'nqredient of mainstream (and . involvement of R & 0 , Legal . in assuring correct-
environoental) smoke and publicized . . hess of analytical and reporting methods .
by antagonistic governmental and , .
medical agencies . . • Reduced carbon monoxide levels on estabtished b rands ,
~
(cf. pp . 20-21, 39) • Proliferation of brands with claims specifically
directed at :carbon monoxide level .
,.
• Decline in unit cigarette growth .
/ •?remenaons advantage to industry member discovering
effective and practical sidestrean carbon monoxide
~ control system .
x . . Increased re9ulations on smoking in public places : 1979
I. Envtroesnental smoke eonde`rr+ed by
smoking-health proponents as work places, etc .
hazardous to both the lutlft • Cecline in sales because of smoker's consumption
and ailing nonsmoker . limited to lunch, coffee breaks . during work Aours . !
.
(cf . pp . 14-1s . 36) • opportanities for new brands with reduced sides 'trea%
' smoke . 'tar", nicotine, carbon aonoxide . hydrogen '
.
cyanide, etc .
• Srand proliferation.
• tiandatory labelling for sidestreaai •tar", nicotine,
carbon eonoxide .

• + • opportllnity
- • threat

,
,
IOZS OILIS ~.~ . . . . .• .~• r ~__.. .._
. ..• .1T~^VYO.~•+f :v . .•T .! .wA'Y/. ..(.M~. .T' . ~ .. • .•V . .. .. uo~• .. . . . . .. . . . .
JEfl)dJ)Ce

-1

Probability of Occurrence Estimated Impact Implications (* or . Earliest


31
. Possible
Key Issues . mitative : Effect year of
on Sales/Profits Qvalitatire O:cnrrenc
10: 30% S0: 70S 90 ur~c va
YI . Tobacw substitutes endorsed by • Competitor markets cigarette contatniAg substitute : 1982
smoking-health proponents as tobacco blend.
effective means to reduce alleged
health hazards from smoke . • RJR responds by marketing cigarette containing
JlO :tobacco blend . (
(cf . pp. 6-7, 27)
• RJR profit margin substantially greater than that ~
of competitor because of cost of J10 relative to ,
other substitutes (Cytrel, NSti), expanded natu itre
ot J10.
Y11 . Nitraqdn oxides indieted by smoking- • 1H tro4en oxides •derby` . 1983
health procronents as harmful
ingredients of .rinstream (and • Mandatory labelling on cigarette packs9•st extensive .
enyiroanental) smoke and publicized involvement of R : 0, Legal In assuring correctness!
by antagonistic yoveraoental and of analytical ud repprting Methods .
oedtat agencies .

El
• Reduced nitrogen oxides on established brands . .
(cf. pp. 21, 40) • • Pro1lferation of brands with c1aim specifically
directed at nitrogen oxides level .
f
• Decline in unit cigarette growth .
• TreeenftA advantage to ind:atry member discovering
effective and practical nitrogen oxides control
system.
.

+ • opportunity .
• • threat

F
,

,
.

11 -A~~ ARDEtt IN 1'P 1SX~.'~i~N~


..: .
:. . ., . . . . . . . . . . . . . . . .. . . . :. . . . ..: <::.... . ... : . . . : . .. ., . . :: : ::.. ;;;;: ;- ;::>::::::::
..
::.
r
w :
ZAZ S OTLTS
. ;+

Probability of Occrirrence Estiee3ted Impact Implica :ions (' or Earliest


:ossible
Key Issues year of
~o•.~i Sa1es%PrWofiLifect Qualitattve . Occurrence
10% V3ox I sos

VIII . Hydrogen cyanide indicted by • Hydrogen cyanide 'derby" . 1983


smoking-health proponents as
. • Manaatory labelling on cigarette packages ; extensi
harmful Ingredient of mainstream involvement of R & 0, Legal in assuring correct-
(and environmental) smoke and ness of analytical and report :n9 methods .
publici=ed by antagonistic
9overnmental and medical agencies M • Reduced fUrdro9en cyanide on established brands .
(cf . pp. 21-22, 41) • Proliferation of brands with claims specifically
directed at-tqrdroqen cyanide levels .
• Oecline in unit cigarette growth .

IX . Use of stem sheet in exc4ss of • Need for alternate way to utilize steals . 1901
2SZ criticized by smoking-health
i proponents as contributor to • Modification of steps of stem sheet to reduce
allegedly harmful gas-phase generation of gas-phase conponents .
oomponents tn smoke . • Reduced profit margin if complete return of steo
(cf. pp . S-6, 26) - hampered by these clat,cs .
• Major revision of blends .

-T . I f t 1
o . .~. '

/'

© .
Q1Qi~~1~A : . ....
----. . . . . .._~. . . .. . . ..... . . . . . . . . . . . . . . . . .,. . . . . . .. . . . . . . . .. . .. . . . . . :>:.>.....
: . ... . . . .:...::.::..: . . . .. . .. .
EOZS 0ILI5
..

; rod~ceb `~.
~ Estimated Impact LplScattons (+ or Etrllest
Probabtltty•ot Occurrence PossSble
ICey Issues Qtl~Rn~t#1re : Effect year of
~ oir~St~al!ProtZts Qual (tatlYe Occurrencc
10% 30% SOY 70% 1 90% r va

X . Wcoa , used as casing a+atertal 1n


smokS "9 products, condemrKd h'
snokfng•healtA proponents .as
' t precursor
a11cged1y Aarmfu1 •
J 11 : •
R etonvu,atton of ex,sttn9 D1ends .
Search tor acuptable coooa altcrnate .
• Kandatory cocoa labelli n g on cigarette package .-
i~ 1480

,

o 1
4 coqonent in smoke . • Ilew brand opportunltles . ,
(cf . pp . 10, 31) • Provision of data to discount clatms . ~

X1 . Dye systans, used to color ' X (-~ • Mandatory labeilSng for qye system on cigarette ' 19E0
cigarette or cigar wrapper, package. ~
condemned by saoktag'realth • Yaltdatton ot futvre ay systems .
proponents as precvrsors ot i
allegedly harmful eompontnts •'Opportunttleslror new brandt with yred wrapper .
tn smoke.
(cf. pp. 13, 3S)

. ~

I 0

/ 8

~ .~~ , . .. . . .. ...,~..y.+ . . . .ra.w..~'t`.r .r•.. :•r .• . Dr'


.a
VOZS OZLIS
• pr o d uce d *o JJ1
. . .TC A/
r, _

Qualitative

XII . Residual Freon 11 le :als In prodwc • Alternate expansion process .


,containin4 expanded tobacco • Reduction in use level of Freon 11-expanded
coMennea as health hazard by tobacco with accompanin9 reduction in profit In
smoking-health proponents . both in-hwm and licensee payments .
(cf . pp . S-6, 26) • Reduction of resi0ual Freon 11- to level acceptable
V

to smokin9-tealth proponents .

XIII . Hrdrogen sulfide Indicted by • lRyQro3en sulfide •derby' . ~ 1965


saokinq-bealth proponents as harmfu • Mandatory labellin9 on cigarette packages ; extensive
Ingredient of mainstream (and involvement of R & 0, Legal in assuring correct-
environa~ental) smoke and publicized ness of an3lyticas and reportin9 methods . {
by antagonistic 4overnxntal and
medical agencies . . • Reduced Iprdro"n sulfiQe on established brands . 'f
(cf. pp . 22-23,42)

` + a opportunity
- - threat

h1--M Y;I' ORDFR!xN Pr.w i .

50ZS 0tiLti5 • . -- . . : . . . . . - . . . . . ,
RTC

Probabiltty of Occyrnnce Estimated Iapact Implications (r or Earliest


Possible
Key Issues Qlta •tfitttve : Effect ' year of
on Sales/Profiu ~ Qualitative . occvrrence
1~ ~ `
•'~ 2~ ~ r r va
XIV . Previously used or new filter . X ( • Canpetitor SntroducM s/perior carbon-filter with 1983
materials effective in reducing
qas-phase components appear in
response to allegations by
-
d _' H no urbon-filter, off-taste .
• New brand opportunities . !
saokin9-Aeaith proponents that • a Mandatory labelling for alieyed harmful components ~
such components are harioful . (e .Q ., aldehydes) readily removed by carbon. ,
(cf. pp . 12, 34) ~ • Proliferation of carbon filter brands . ~
Decline in sales of conventional filter brands .

4 as
XY . Svgar, a ded cusin9 material
saqktn9 products, condeaned as pre-
to X (-i • Reformulation existing
of blends . ~ 1981

cursor smoking-health
of all .yedly harmful coapo-
• Reduction of profit sr9in (tobacco aore costly than;
s~r . t
nents in smoke by
' proponents . • New brand opportunities. 1

cf . . 9 29 • Manda s ar labeili on cS rette acka t .


,
XVI. flue-cYred tobacco becavsc
by of high X - • Major
revision blends . 1983
sugar content condemned
healt .~ proponents
s~aokiny-
as cancer; push
contributor
• Restrvctartnq of tobacco
boprinq Prograe~s .
to respiratory tract • Alteration of tobacco-growing
practices In
for lower-svpr strains, removal
or reduction of fl•e-cured .
Southeast U . S . A.
• Search for lower-sugar flue-cureds : prdnia
t ~(d . pp . S . 25) ' price on such tosaccos .

UO
.. . /

..................

l~?iYY "A
..
:
~J)aCT'1~ eoNk~~i~'x~A~~
. ....:,.~RDE1't
. . . : IN PENNS '!f~A' :
.. . ._ ... ... . .. . :.:..::.. .::::...:.. . .. ...... _. : .. .:. . . ,, . .:,,;,
. ...
90ZS OZLZS
Y
pioduuda . :RJ C . T

probaOSlity o: Occurrence ' :stia~ated Impact Implications (+ or Earliest


poss ible
Xe; Issues 30% . t~Zative : Effect i yttr ot
on Sales/ProfSLs Qualitative +/Occrnnce
lOt SOS y0t 90S :
x • urvwa

XVII . ticoric^, used as casing a~aterSal X (•_ • Reformulation of existing blends . 1482 .
Sn smokinq prodacts, condenned • SearcA for acceptable licorice alternate .
by smoking-health proponents
as precursor of alle9edly harmful • lte+r brand .opportunities .
cwponents in saalce . . • Mandatory licorice labelling on cigarette pacta9l•n9l
(ct. pp . 9-10, 3D) • provision of data to discount claims .

XVIII . Glycerol and other hunectantt X (-) • Mandatory Mumectant labelling on cigarette ackage. 1982
currently used in smokin9 products • Reformulation of existing humectants and blends .
condeer.ed as precursors of
allegeQly lumful components in a Search for acceptable s•bstitute both for use in
~ sinoke by smokin9-tKa1tA proponents i product and aanutacturSrA operation .
C- (cf . pp . 10. 32) • Provision of data to discount claims . '
;U
J
~
/
J
~ , -

, .

' + • opporturtity N
Y
- • threa t

On'TASM:
.
. '~.. . .. . . • . . . .4; . ~ . .. .

LOZS OiLIS i~ .i~•.* ..r..J- X 'S"46


I-RoR'3
51710 5208
I. ~ : . . . V. .l t~S{l
~ RDR, 1954, Nos . 1-13 - DESTROYED

RESEARCH DEPARTMENT REPORTS RDR - 1954


if- 9- 4"7
.•
1%, to . Date Title Author

1 4/26/54 DEVELOPMENT OF A COMPRESSOMETER FOR MEASURING THE E .Barnhardt


FILLING CAPACITY OF CIGARETTE CUT TOBACCO

2 6/7/54 PREPARATION OF CYCLOPENTANECARBOXYLIC ACID 6 .E . Teague

3 7/2/54 THE PREPARATION OF 3-METEiYLVALERIC ACID C .E . Teague

4 7/6/54 DETERMINATION OF TOTAL REDUCING SUGARS IN TOBACCO Cundif f


AND TOBACCO PRODUCTS BY THE SOMOGYI PROCEDURE

5 7/14/54 DETERMINATION OF ALKALOIDS IN TOBACCO AND TOBACCO ® Cundiff


PRODUCTS

6 7/16/54 SYNTHESIS OF FATTY ACID CARRIERS Rowland, Giles,Aasic

7 8/20/54 TURKISH :TOBACCO . PROGRESS REPORT ON THE ISOLATION Latimer, Ashburn,Jonc


11ND IDENTIFICATION OF SOME OF ITS CONSTITUENTS

8 8/23/54 INVESTIGATION OF THE ANTHRONE COLORIMETRIC PROCEDURE Cundiff x


FOR SUGAR DETERMINATION

+ 9 8/23/54 ISOLATION OF CONSTITUENTS OF FLUE-CURED TOBACCO Rowland ;

_' 10 10/6/54 DETERMINATION OF CHLORIDE IN TOBACCO PRODUCTS Harrell k


11 11/4/54 CHEMICAL MODIFICATION OF BURLEY TOBACCO Tompson X
12 11/12/54 SMOKING QUALITY OF TOBACCO STEMS Tompson x
13 12/17/54 NICOTINE DERIVATIVES C .E . Teague x
14 12/20/54 SOME jr-BUTYROLACTONES C .E . Teague k

15 7/26/66 PENICK & FORD, LTD . RESEARCH REPORT, 4TH QUARTER - 1954 Penick & Ford
~ ( . 0

RDR, 1955, Nos . 1-14 - DESTROYED 4- 9%~


RESEARCH DEPARTMENT REPORTS (RDR) - 1955

leo . Date Title Author

1 1/6/55 alpha-SUBSTITUTED-gamma-BUTYROLACTONES AS FLAVORANTS Tompson, C . G ~(

2 3/28/55 SYNTHESIS OF FATTY ACID CARRIERS Hosick, T ~(

3 2/11/55 TREATMENT OF BURLEY TOBACCO WITH WATER AS A MEANS Tompson,C .G• x


OF DECREASING HARSHNESS

4 3/3/55 THE POTASSIUM, CALCIUM, AND SOLUBLE ASH CONTENT OF Elliott 3 . 8 . tl-
AGING TOBACCO

5 3/21/55 FLUORESCENT COMPOUNDS IN TOBACCO Bellin

6 3/29/55 QUATERNARY AMMONIUM HYDROXIDES AS TITRANTS FOR Cundif f


ACIDS IN NONAQUEOUS SOLUTIONS

7 4/8/55 FLAVORING ACIDS IN TURKISH TOBACCO Schumacher `+ .

8 8/4/55 DETERMINATION OF ACIDS IN SMOKE Cundiff

9 8/22/55 J TURKISH TOBACCO SECOND PROGRESS REPORT ON THE Henley &


ISOLATION AND IDENTIFICATION OF SOME OF ITS Mays
CONSTITUENTS

' r10 8/31/55 THE PREPARATION OF POLYVINYL ESTERS OF SOME FIVE- Teague, C .E . ~C
~ AND SIX-CARBON FATTY ACIDS

0 11 10/17/55 THE COMPOSITION OF THE VAPOR PHASE OF CIGARETTE SMOKE Laurene ~


12 11/9/55 ORGANIC ACIDS IN THE GROWING TOBACCO PLANT Smeby & Bellin *C

13 12/7/55 QUANTITATIVE STUDIES OF THE MICROBIOLOGICAL FLORA Flanders Y,


OF TOBACCO DURING AGING
=,5

14 12/27/55 J A7*SPECTROPHOTOMETRIC METHOD4OR THE DETERMINATION 0F Laurene &


VICOTINE IN CIGARETTE SMOKE, Harrell

15 7/26/66 PENICK & FORD, LTD . RESEARCH REPORT, 1ST QUARTER - 1965 Penick & Ford

16 7/26/66 DITTO 2ND QUARTER - 1955 ~ Ditto


Ln
17 7/26/66 DITTO • 3RD QUARTER - 1955 Ditto ~
~
~
18 7/26/66 DITTO 4th QUARTER - 1955 Ditto m

7..2 Z-7o
~' ~
RDR, 1956, Nos . 1-12 - •DESTROYED ~~ :~'~
.I

RESEARCH DEPARTMENT REPORTS (RDR) - 1956

*No . Date Title Author

1 2/3/5,6' SYNTHESIS OF AMIDES AND RELATED NITROGEN-CONTAINING Hosick X


, COMPOUNDS FOR USE AS TURKISH-TYPE ACID CARRIERS
,,y . . . . ... _.. .
2 2/ 15 / 56 rp):fiARMX,NATION ' OF ; . TOTAL' BAS ES ,. ~N CIGARETTE SMOKE Sullivan &
Harrell

3 3/22/56 PUNCH CARD CODE FOR AGING STUDY DATA Smeby X

4 4/4/56 PHENOLS AND PHENOLIC PIGMENTS IN TOBACCO Smeby

5 6-29-56 THE DETERMINATION OF MOISTURE IN TOBACCO BY Laurene & ~


KARL FISCHER REAGENT Sullivan /`

DETERMINATION OF MENTHOt IN MENTHOLATED TOBACCO Harrell >(


6 7/31/56
THE REACTION OF ISOBUTYL BROMIDE WITH M6 .LONIC ESTER Snyder, Harry , x
7 8 -8 -56
ISOLATION OF NEOPHYTADIENE FROM FLUE-CURED TOBACCO Rowland
8 9 -7 -56

9 9-28-56 THE ANALYSIS OF CIGARETTE SMOKE CONDENSATE . I . THE Rodgman _

ISOLATION AND/OR IDENTIFICATION OF POLYCYCLIC .


AROMATIC HYDROCARBONS IN CAMEL CIGARETTE SMOKE 11116 Jsl. 42~t %9~J
CONDENSATE

00 10-1-56 THE PREPARATION OF SOME PHENOLIC FLAVORANTS Rodgman

11 10-31-56 THE REACTION OF SEC-BUTYL BROMIDE WITH DIETHYL SEC- Snyder, Harry x .
BUTYIMALONATE
•1

12 11-1-56 THE ANALYSIS OF CIGARETTE SMOKE CONDENSATE . II . THE PRE-


TREATMENT OF CAMEL BLEND TOBACCO
r-AXID • f -1 ,-V .
S-Rf t-J-/ f

13 7/27/66 PENICK & FORD, LTD . RESEARCH REPORT, 1ST QUARTER - 1956 1 Penick & Ford

14 7/27/66 DITTO 2ND QUARTER - 1956 Ditto

15 7/27/66 DITTO 3RD QUARTER - 1956 X Ditto

16 7/27/66 DITTO 4TH QUARTER - 1956 Ditto

N
O
~
~
N
p
J
N
4
RDR, 1957, Nos . 1-21 - DESTROYED
1tESEARCti DEPARTMQiT REPORTS - (RDR) - 1957
4'~ r o2.-i9-JI
"• Date Title Author

0 1/10/57 A STUDY OF THE AGING OF TURKISH TOBACCOS Latimer x


:: : .
2 1/30/57 ~I TURKISti -4O8A"CC0 . THIRD PROGRESS REPORT ON THE•ISOLATION AND SchumaC
IDENTIFICATION OF SOME OF ITS CONSTITUENTS

3 2/1/57 PROCESS FOR PRODUCTION OF DISODIUM sec-BUTYL-MALONATE AND Mays & ?\agu
DISODIUM ISOPROPYIMALONATE ; LABORATORY DEVELOPMENT E.

4 3/14/57 THE ANALYSIS OF CIGARETTE SMOKE CONDENSATE . III . FLUE-CURED- Rodgma ~~ .;


ToBACCO F . T. a, S-it • .t'7 ) a,1Z . 7• ; 9- d;7

•5 3/15/57 DETERMINATION•OF NITRATES IN TOBACCO AND TOBACCO STEMS Harrell

6 5/21/57 VOLUMETRIC ANALYSIS OF DISODIUM sec-BUTYL MALONATE AND Cundiff X


DISODIUM ISOPROPyIMALONATE

5/30/57 METABOLIC PRODUCTS FORMED BY THE ACTION OF ARTHROBACTER OXYDANS ZimmermanX


ON NICOTINE

8 6/7/57 /THE ESTIMATION OF PENTANOIC AND HEXANOIC ACIDS IN TOBACCO AND Latimer 37-
TOBACCO SMOKE USING GAS CHROMATOGRAPHY

6/13/57,/ TURKISH'TOBACCO - FOURTH PROGRESS REPORT - ISOLATION AND Schumacti .~,dr


.
IDENTIFICATION OF SCLAREOLIDE

~ 6/13/57 FATE OF ALKYIMALONIC ACIDS DURING SMOKING Giles ® F

11 9/24/57 INVESTIGATION OF DILUTE SOLUTIONS OF TETRABUTYLAMMONIUM HYDROXIDE Sensabaugh -


AS BASIC TITRANTS IN NONAQUEOUS SOLUTIONS Cundiff X

12 10/2/57 DETERMINATION OF 2,4-DINITROPHENYPiYDRAZONES BY TITRATION WITH Sensabau* 6


TETRABUTYLAMHONIUM HYDROXIDE ~ Cundiff j `-

13 10/7/57 THE ANALYSIS OF CIGARETTE SMOKE CONDENSATE . IV . Rodgma


3,4,8,9-DIBENZPYRENE IN CAMEL CIGARETTE SMOKE CONDENSATE

14 10/10/57 `' THE. .FATE'OF"DISODIUM .ISOPROF~LMALONATE DURING SMOKING . •A`STABLE Latimer ¢t~~ 1
ISOTOPE STUDY .

10/10/57 PREPARATION OF SOME TERPENOID ETHERS Gilesx


15

10/11/57 THE PREPARATION OF SCLAREOLIDE BY THE OXIDATION OF SCLAREOL SchumacherX


16

17 10/23/57 ' Cb[~USTION-ZONE TEMPERATURES OF CIGARETTES Tompson


~
18 10/28/57 EVALUATION OF THE SARGENT_MAIMSTADT AUTOMATIC TITRATOR Cundiffxr
,

19 ~`a {{~ 0~ 0 E" D~ . ISOLATION OF STEROLS FROM FLUE-CURED TOBAC~, (VOID - SEE RDR, ;
~y!*" .1958, No . 1) .,~~. ':I
'ti3 :a .. r . . ..

'.7' 12/16/57 DETERMINATION OF TRIACETIN IN FILTER ,PLUGS


. .. . p

21 12/17/57 ANALYSIS OF 3,5-DINITROBENZOATES BY TITRATION WITH TETRA- Sensabaugh &


BUTYLAZ4fONIUM HYDROXIDE Cundiff A
51710 5213
. -/ + //-
RESEARCH DEPARTMENT REPORTS - 1957
RDR - /J`44#-~
Na L .. Date
1957
0 5/17/66 PENICK & FORD RESEARCH REPORT, FIRST QUARTER, 1957 P&F

23 5/17/66 PENICK & FORD RESEARCH REPORT, SECOND QUARTER, 1957 P&F
24 5/17/66 PENICK & FORD RESEARCH REPORT, THIRD QUARTER, 1957 P&F
25 5/17/66 PENICK & FORD RESEARCH REPORT, FOURTH QUARTER, 1957 P&F

6
b
i
i
i

{
• ~.
'RLSEAItCri DEPARTMENT REPORTS - (RDR) - 1958 RDR, 1958, Nos . 1-22 - DESTROYED

No . Date Author

1/24/58 ~/ ISOLATION OF STEROLS FROM FLUE-CURED TOBACCO Rowlan&


~
. 2/10/58 AN ISOTOPE DILUTION ANALYSIS FOR ISOPROPYLMALONIC ACID Latimerx

3 2/18/58 ~ ISOLATION OF a-TOCOPHEROL & SOLANACHROMENE FROM FLUE-CURED


TOBACCO Rowland

4 3/14/58 PRELIMINARY STUDIES OF CIGARETTE TASTE TESTING METHODS Bellin & Nyst~om

5 3/19/58 ANALYSIS OF SUBSTITUTED MALONIC ESTERS BY GAS CHROMATOGRAPHY Latimer (`e~C

6 3/19158 A STUDY OF THE AGING OF THE 1952 TURKISH TOBACCOS . THE


THIRD YEAR Latimer X
.
7 4/29/58 TURKISH TOBACCO ISOLATION AND CHARACTERIZATION OF DEHYDRO- Giles &
~
SCLAREOLIDE Schumacher

8 6/2/58 DETERMINATION OF PROPYLENE GLYCOL AND GLYCEROL IN TOBACCO

9 6/13/58 AN IMPROVED QUATERNARY AMMONIUM HYDROXIDE TITRANT FOR STRONG


ACIDS

10 6/13/58 REACTION OF SOLVENTS WITH STRONG ACIDS AS DETERMINED BY


TITRATION WITH TETRABUTYLAMMONIUM HYDROXIDE

'' 6/13/58 DETERMINATION OF STRONG ACID MIXTURES BY TITRATION WITH


TETRABUTYLAMhIONIUM HYDROXIDE
~
1% 6/19/58 VIISOLATION OF SOLANESYL ESTERS FROM FLUE-CURED TOBACCO Rowland b~+''~timez

13 7/9/58 REDUCTION'OF ALKALOIDS AND AMMONIA IN TOBACCO WITH THE AID


OF MAGNESIUM HYDROXIDE Ashburn ~`;i . ~
J
14 7/30/58 THE HEAT TREATMENT OF TOBACCO IN THE LEGG DUNMURRY ROTARY ~
m
PANNER~ kSawyer

15 7/30/58 NONAQUEOUS TITRATION OF INORGANIC SALTS WITH TETRABUTYLAMMONIUM


HYDROXIDE x Cundiff

16 10/6/58 AN ISOTOPE DILUTION ANALYSIS FOR SECONDARY-BUTYI2•lALONIC ACID Latimer &'WiZes

17

18
11/7/58

12/1/58
ANALYSIS OF 3,5-DINITROBENZOATES

THE ANALYSIS OF CIGARETTE SMOKE CONDENSATE . V . THE


x Robinson*

POLYCYCLIC HYDROCARBON PRECURSORS IN TOBACCO Rodgman & Coo

19 12/8/58 ANALYSIS OF 2,4,7-TRINITROFLUORENONE-POLYNUCLEAR HYDROCARBON


COMPLEXES BY TITRATION WITH TETRABUTYLAMMONIUM HYDROXIDE Cundif f N
0
~
Newel lx ot
u 12/12/58 ANALYSIS OF SCLAREOL BY ISOTOPE DILUTION N
O
.
12/10/58 STUDY OF TOBACCOPRETREATMENTS Ashburn ~'r'? o I
~

22 12/31/58 THE ANALYSIS OF CIGARETTE SMOKE CONDENSATE VII . SOLANESYL AND Rod n& Cook
SOLANESYL ACETATE
RESEARCH DEPARTMENT REPORTS - RDR - 1958

'"") . Date Ti t le Author(s)

PENICK & FORD, LTD ., RESEARCH REPORT, 1ST QUARTER, 1958 Penick & Ford
23 5/16/66

PENICK & FORD, LTD ., RESEARCH REPORT, 4TH QUARTER - 1958 Penick & Ford
24 5/16/66

25 7/27/66 PENICK & FORD, LTD ., RESEARCH REPORT, 2ND QUARTER - 1958 Penick & Ford
x
26 7/27/66 DITTO 3RD QUARTER - 1958 Ditto
RDR, 1959, Nos . 1-23 - DESTROYED
1/301j61
RESEARCH DEPARTMENT REPORTS - RDR - 1959 Page 1

• Date

1 . 1/29/59 THE ANALYSIS OF CIGARETTE SMOKE CONDENSATE . VI . THE INFLUENCE


OF SOLVENT PRETREATMENT OF TOBACCO AND OTHER FACTORS ON THE
POLYCYCLIC HYDROCARBON CONTENT OF SMOKE CONDENSATE .

2 2/10/59 THE ANALYSIS OF CIGARETTE SMOKE CONDENSATE . VIII . SOLANESYL Rodgma


ESTERS AND PHYTOSTERYL ESTERS

3 3/16/59 THE USE OF IBM METHODS FOR HANDLING AND INTERPRETING DATA WITH Bellin x
SPECIAL REFERENCE TO THE AGING OF TOBACCO

4 3/23/59 / FURTHER STUDIES ON THE CONSTITUTION OF THE LIPID FRACTIONS OF Rowland


FLUE-CURED TOBACCO

5 4/17/59 AN .APPARATUS FOR THE COLLECTION OF MAINSTREAM AND SIDESTREAM Haefele


SMOKES : THE ANALYSIS OF THE SMOKE FRCht CIGARETTES MADE WITH
A SPECIAL POROUS PAPER
Fredrickson
6 4/27/59 THE PREPARATION OF REFERENCE 2,4-DINITROPHENYLHYDRAZONES FOR Chappell4s,
NINETY-ONE CARBONYL CONIPOUNDS Rodgman

7 4/28/59 THE DETERMINATION OF MOISTURE IN LICORICE BY KARL FISCHER Sullivan x


REAGENT

~ 5/12/59 PILOT PLANT STUDY OF THE PRODU,CTION OF DISODIUM ISOPROPYL- Teague + x


MALONATE AND DISODIUM sec-BUTYIMALONATE Mays

9 5/15/59 PROCESS FOR PRODUCING SCLAREOLIDE FRCM SCLAREOL : LABORATORY Henley, W~sc
. DEVELOPMENT & Teague .
t~s
10 5/18/59 V TURKISH TOBACCO - THE ISOLATION AND IDENTIFICATION OF SCLARAL Schumaches~. ; t
®
11 5/18/59 THE ANALYSIS OF CIGARETTE SMOKE CONDENSATE . IX . PHYTADIENES
I
12 5/21/59 TURKISH TOBACCO . ISOLATION AND CHARACTERIZATION OF AMBREINOLIDE Schumact~d.' .. &
Bernase~'~' ~

13 5/21/59 A RAPID OPTICAL METHOD FOR THE DETERMINATION OF SCLAREOL Laurene & X
i Greene

14 6/22/59 MODIFICATION OF THE EXTRACTION PROCEDURE FOR DETERMINATION OF Cundif f A


ALICALOIDS IN TOBACCO ~.~
15 6/24/59 / SCME VOLATILE CONSTITUENTS OF CELLULOSE SMOKE Fredrickson

a
0
r
~
N
F
51710 5217 J
W
N
RESEARCH DEPARTMENT REPORTS - RDR - 1959 Page 2

„" Date Author

16 7/13/59 TURKISH TOBACCO . CHARACTERIZATION OF COMPOUNDS II AND III Gi1es„

17 7/21/59 ATTEMPTED SYNTHESIS OF SCLAREOL Giles X


18 7/22/59 TITRATION STUDIES OF ALKyL AND PHENYL 3,5-DINITROBENZOATES AND Robinson,~,Ir .
PHENOLIC ESTERS WITH TMABUTYLAt4i0NIUM HYDROXIDE

19 8/31/59 A COMPARISON OF THE CHEMICAL COMPOSITION OF FLUE-CURED TOBACCO Bellin x


OF THE 1954 THROUGH 1958 CROPS

20 9/4/59 THE QUANTITATIVE ANALYSIS OF CIGARETTE SMOKE, PART I . urene, Young


& Greene

21 9/11/59 DETERMINATION OF CR GANIC HALIDES BY TITRATION WITH TETRA- Cundiff x


BUTYLArMONIUM HYDROXIDE

22 9/28/59 DETERMINATION OF ACTIVE HYDROGEN BY TRITIUM EXCHANGE Giles X

23 9/29/59 THE ANALYSIS OF CIGARETTE SMOKE CONDENSATE XI . a-TOCOPHEROL odgman & Cook

24 3/2/66 PENICK & FORD, LTD . RESEARCH REPORT, 1ST QUARTER - 1959 Penick & Ford
25 3/3/66 DITTO 2ND QUARTER - 1959 Ditto
0 3/3/66 DITTO 3RD QUARTER - 1959 Ditto

27 3/3/66 DITTO 4TH QUARTER - 1959 . Ditto


RESEARCH'DEPARTMENT REPORTS - RDR - 196 0 Page 1 1 //' (0,5 •

0 Dat e Autho r

1 1/7/6 0 DETERMINATION OF THE DILUTION OF MAINSTREAM S OKE BY AIR PASSING P~_' Haefel e
i ~
THROUGH A POROUS CIGARETTE PAPER `y ~ ',
L
2 2/4/6 0 SYNTHESIS OF AMBREINOLID E Bernasek

3 2/10/6 0 THE ANALYSIS OF CIGARETTE SMOKE CONDENSATE . XII . SQUALENES AND odgman
SOLANESENES . ook & Mims

4 2/18/6 0 SUPPLEMENT - THE USE OF IBM METHODS FOR HANDLING AND INTERPRETIN G
DATA WITH SPECIAL REFERENCE TO THE AGING OF TOBACCO
(See RDR, 1959, No . 3 - dated 3/16/59)
x
5 2/29/6 0 DETERMINATION OF SCLAREOLIDE CONTENT OF TOBACCOS BY ISOTOPE , ;Newe11
DILUTION

6 3/21/6 0 CORRELATION OF CHEMICAL CONSTITUENTS AND~AGING CHANGES OF Bellin


BURLEY TOBACCO

7 3/30/6 0 A PROCESS FOR RECOVERY OF SCLAREOL FROM CLARY SAGE CONCRETE Teague,
Jame s

8 4/1/6 0 THE ANALYSIS OF CIGARETTE SMOKE CONDENSATE . XIII . SCLAREOLIDE $ . odgman &
FROM TURKISH TOBACCO SMOKE . Cook

Ir~ 4/11/6 0 THE RAPID DETERMINATION OF SCLAREOLIDE BY INSTRUMENT ANALYSIS Laurene, Youn .
Moser

10 4/20/6 0 THE PYROLYSIS OF AMBREINOLIDE AND THE RELATED SYNTHESIS OF AN Mims x


UNSATURATED LACTON E

11 4/21/6 0 THE OXIDATIVE NATURE OF POLYMER FORMATION IN FLUE-CURED TOBACCO Elliott ~C

12 4/22/6 0 THE DETERMINATION OF SUGARS IN TOBACCO Elliott

13 4/26/6 0 THE ABSORPTION OF OXYGEN AND THE LIBERATION OF CARBON DIOXIDE Elliot t
BY AGING TOBACCO - l~

14 4/27/60 THE DETERMINATION OF ORGANIC AND INORGANIC SULFUR IN PROCESSED Elliott


9
TOBACCO AND HYDROGEN SULFIDE IN THE SMOKE - ANALYTICAL METHODS
AND RESULTS

15 4/29/60 FLAME PHOTOMETRIC DETERMINATION OF POTASSIUM IN CURED TOBACCO Dobbinsx

~
O i
N ~
N

v
51710 5219
. • .

42

*ESEARCH DEPARTMENT REPORTS - RDR - 1960 Page 2

No . Date Author

16 5/12/60 V/ TURKISH TOBACCO . ISOLATION, CHARACTERIZATION & SYNTHESIS OF Schumac. 40


6-ACETYL-2,3,4-tris-d-B-METHYLVALERYL-B-D-GLUCOSE

17 5/9/60 +ol FLUE-CURED TOBACCO . SUMMARY REPORT 1954-1959 8owlandW

18 5/11/60 J THE PYROLYSIS OF a-ACETOXYAMBREINOLIDE Mims ~

19 5/16/60 ELEMENTAL ANALYSIS VIA THE SCHONIGER OXIDATION . I . Cundiff ~(


DETERMINATION OF ELEMENTAL SULFUR .

20 5/26/60 THE ANALYSIS OF CIGARETTE SMOKE CONDENSATE . XIV . POLYCYCLIC ~;~,odgman & Cook
AROMATIC HYDROCARBONS

21 6/30/60 THE ANALYSIS OF CIGARETTE SMOKE CONDENSATE . XV . COMPARISON f~~~Rodgman, Cook &
OF DIFFERENT TOBACCO TYPES `~ Chappell

-A
22 7/1/60 THE ANALYSIS OF CIGARETTE .SMOKE CONDENSATE . XVI . NORMAL ~A~Cook, Rodgman &
LONG-CHAINED PRIMARY ALCOHOLS Young

23 7/8/60 NONAQUEOUS TITRATION OF ORGANIC HYDROXYL GROUPS Robinson x


Z{7z*
7/27/60 / THE DETERMINATION OF FIVE-CARBON AND SIX-CARBON ACIDS BY Latimer & :ikl 'ser
& GAS CHROMATOGRAPHY

25 7/27/60 ATTEMPTED SYNTHESIS OF DEHYDROAMBREINOLIDE Bernasek ~" .


,.
/--//- ` ~l
ESEARCH DEPARTMENT REPORTS - RDR - 1960 Page 3

st o . Date Author

A PRELIMINARY SURVEY OF THE HIGHER FATTY ACIDS IN


FLUE-CURED, BURLEY,
~.. : ; AND TURKISH TOBACCOS
.; .
CHANGES IN FATTY ACID COMPOSITION DURING GERMINATION,
GROWTH, AND,,CURING OF HICKS VARIETY TOBACCO PLANTS

ORGANIC ACIDS IN AGING FLUE-CURED AND BURLEY TOBACCOS WITH


SPECIAL REFERENCE TO CITRIC, MALIC AND OXALIC ACIDS

PROCESS FOR PRODUCING SCLAREOLIDE FROM SCLARF.OL . PART II . Bernasek X


CHRCMIC ACID OXIDATION OF MIXTURES OF METHYL KETONE,
CYCLIC OXIDE AND SCLAREOLIC ACID

30 9/1/60 A RAPID DETERMINATION OF MANOYL OXIDE AND 13-EPIMANOYL OXIDE Laurene &,fi~Younl
r -;~
IN ISOMER MIXTURES

31 9/6/60 DETERMINATION OF ALKOXYL GROUPS

32 9/19/60 41 DEHYDRATION OF SCLAREOL . I . THE EPIMERIC MANOYL OXIDES

33 10/20/60 A METHOD FOR SYNTHESIS OF SCLARAL : LABORATORY EQUIPMENT

4 10/20/60 /BURLEY TOBACCO COMPONENTS . I'. ISOLATION PROCEDURES,


0 PREVIOUSLY KNOWN COMPOUNDS AND DITERPENIC GLYCOLS

35 11/8/60 SYNTHESIS OF DIHYDROSCLAREOLIC OXIDE Bernasek & Henl

36 • 12/2/60 THE ANALYSIS OF CIGARETTE SMOKE CONDENSATE . XVII . THE EFFECT


OF ALUMINA-SUPPORTED .CATALYSTS ON TOTAL POLYCYCLIC HYDRO- Rodgman~ ook
CARBONS, TOTAL SOLIDS AND NICOTINE

37 12/6/60 ISOTOPIC FATE STUDIES WITH TO~CCO CONSTITUENTS . I . THE Haefele & Gilee
FATE OF n -H ENTRIACONTANE - 16 - C DURING SMOKIN ~G

38 12/7/60 THE ANALYSIS OF CIGARETTE SMOKE CONDENSATE . XVIII . CHLORANIL :411odgman & Cook
, AND 2,4,7-TRINITROFLUORENONE AS FILTER TIP ADDITIVES

39 12/7/60 TURKISH TOBACCO . ISOLATION AND CHARACTERIZATION OF Giles &3*umac


12a-HYDROXY-13-EPIMANOYL OXIDE

40 12/16/60 /TURKISH SAND . PROGRESS REPORT ON THE ISOLATION OF SOME 0 , Schumache


ITS CONSTITUENTS IE ~ iG

41 12/19/60 ~
SMOKING QUALITY OF BURLEY STRIPS DENICOTINIZED BY F ON Squires~Y

42 3/3/66 PENICK & FORD, LTD . RESEARCH REPORT, 1ST QUARTER - 1960 Penick & Ford

43 3/3/66 DITTO 2ND QUARTER - 1960 Ditto

3/3/66 DITTO 3RD QUARTER - 1960 Ditto

DITTO 4TH QUARTER - 1960 Ditto


~ 3/3/66

51710 5221
, 7.112W • pdo-*~. ete'u°
RESEARCH DEPAR2MENT REPORTS - RDR - 1961 //, /H 4- {O,3
. ..

No :' y Date •Title

1/6/61 THE ANALYSIS OF CIGARETTE SMOKE CONDENSATE . XIX . THE DETERMINA-


0 TION OF POLYCYCLIC AROMATIC HYDROCARBONS

2 1/9/61 V THE DISTRIBUTION OF PHENOL BETWEEN DIETHYL ETHER AND AQUEOUS Laurene 6
SOLUTION . Lewallen

3 1/12/61v( IMPROVED PROCEDURE FOR THE DETERMINATION OF ACIDS IN TOBACCO Sensabaug


SMOKE .
Alh
4 1/13/61 V/ DETERMINATION OF COUMARIN IN TOBACCO AND TURKISH DUST BY ISOTOPE ' ~~[ewell
DILUTION .

1/26/61 THE ANALYSIS OF CIGARETTE SMOKE CONDENSATE . XX . A NOTE ON THE Rodgman d


NORMAL LONG-CHAINED PRIMARY ALCOHOLS : AN ADDENDUM TO m Cook
RDR, 1960, No . 22

6 1/27/61 /PHOSPHORIMETRIC DETERMINATION OF POLYNUCLEAR AROMATIC HYDRO- df Walker


CARBONS

7 2/3/61 EFFECT OF OZONE ON BURLEY TOBACCO Giles


'~ps ,'(k4j(o -
8 2/6/61 ,HIGHER FATTY ACIDS IN THE SMOKE CONDENSATE OF BURLEY & FLUE-CURED
I/ TOBACCOS . A FACTORIAL DESIGN EXPERIMENT SHOWING THE EFFECT OF Bellin,!
VARIATION•OF CIGARETTE MOISTURE, WEIGHT & TOBACCO TYPE


10
2/14/61

2/23/61
GROSS SEPARATION AND DETERMINATION OF THE PHENOLIC FRACTION FROM
TOBACCO SMOKE CONDENSATES

THE ANALYSIS OF CIGARETTE SMOKE CONDENSATE . XXI . PHENOLS


Cundiff

,~Rodgman +
• ~' Cook

11 2/23/61 /THE PYROLYTIC FORMATION OF POLYNUCLEAR AROMATIC HYDROCARBONS . I . ~° ~ Mims


EXPLORATORY STUDY

12 3/3/61 V/TURKISH TOBACCO . ISOLATION AND CHARACTERIZATION OF DEHY9R0-


AMBREINOLIDE AND THE ISOLATION OF COMPOUNDS XVI AND XVII ~~~ Schumachei

13 3/22/61 OXIDATION OF MANOYL OXIDE . I . SYNTHESIS OF SCLAREOLIDE ~CGi1es

14 3/27/61 SAMPLING PROGRAM FOR THE AGING PROJECT ~ Shiffert

15 3/27/61 THE ANALYSIS OF CIGARETTE SMOKE CONDENSATE . XXII . THE COMPOSITION Rodgman,
OF AN.'ALIPHATIC ESTER FRACTION FROM TOBACCO AND TOBACCO SMOKE . ® Cook, Belli
Mims, Young

51710 5222 J
J ,.
,0), .,_. ,cl.f...4,s 0..
RESEARCH DEPARTMENT REPORTS - RDR - 1961 ~
0 114- -2
io . Date Author(s)

16 3/30/61 QJALITATIVE STUDY OF THE MICROBIOLOGY OF STORED CIGARETTE Long, Margaret~


TOBACC 0 / `

17 4/4/61 PROCESS FOR PRODUCING SCLAREOLIDE FROM SCLAREOL : LABORATORY Mays, Hen1x &
DEVELOPMENT : SUPPLEMENTARY REPORT Wilson

18 4/11/61 ION EXCHANGE CHROMATOGRAPHY OF AMINO ACIDS IN TOBACCO ~James, W . B .

19 4/24/61 ELEMENTAL ANALYSIS VIA THE SCHONIGER OXIDATION . III . if Robinson X


DETERMINATION OF ELEMENTAL CARBON

20 4/25/61 POLYPHENOLS OF TOBACCO . II . DETERMINATION OF CHRLOROGENIC ftystrom


ACID, RUTIN, AND SCOPOLETIN IN CIGARETTE BLEND TOBACCO
FRACTIONS

21 4/28/61 THE ANALYSIS OF CIGARETTE SMOKE CONDENSATE . XXII . AND 4L ~~~k & Rodgman
LEVANTENOLIDE FROM TURKISH TOBACCO SMOKE
~a
22 -'' ~~/9/G1 THE-D4ygRMIN&,iON-0$_P1iENOL" XSIGAREtTE SMO QN~~~NSAT
l ,tl~%, G ~
23 5/11/61 TOBACCO FERMENTATIONS : DENICOTINIZATION OF BURL~LEAT' . *uires & Hayes

~ 5/15/61 THE INVESTIGATION OF NONAQUEOUS TITRIMEfiRIC SYSTEMS USING Sensabaugh


TETRABUTYLAMMONIUM HYDROXIDE X
• 25 5/16/61 TURKISH TOBACCO . THE CHARACTERIZATION OF THE "COCONUT-OIL" 02thumacher
FRACTION IDENTIFICATION AND SYNTHESIS OF MARIOLIDE ~
(COMPOUND XIII)

26 5/16/61 FREE AMINO ACIDS IN AGING TOBACCO ~ James

27 5/17/61 POLYPHENOLS OF TOBACCO . I . THE QUANTITATIVE DETERMINATION j W ystrom


OF CHLOROGENIC ACID, RUTIN, AND SCOPOLETIN IN TOBACCO AND
TOBACCO PRODUCTS

28 5/23/61 BIOCONTROL OF LASIODERMA SERRICORNE BY BACILLUS PULVIFACIENS Long, Margar X


29 5/31/61 GAS CHROMATOGRAPHIC ANALYSIS OF THE VOLATILE ESSENTIAL
OILS OF TOBACCO . I . PRELIMINARY INVESTIGATION OF BURLEY La timer®
TOBACCO

30 5/31/61 FLUE-CURED TOBACCO : SUMMARY REPORT 1959-1961 Rowlandal

51710 5223
RESEARCH DEPARTMENT REPORTS - RDR - 1961

No . Date ' Author(s)

31 6/12/61 NICOTINE RECOVERY FROM DILUTE AQUEOUS SOLUTIONS BY


DISTILLATION OF NICOTINE AZEOTROPES AT PRESSURES ABOVE
ONE ATMOSPHERE • ,
Neal
x
32 6/28/61 ATTEMPTED NOMAQUEOUS TITRATION OF DDVP (0,0-Dimethyl-2,2- Robinson ~
dichlorovinyl Phosphate) IN PYRIDINE AND ETHYLENEDLAMINE
WITH TETRABUTYLAt4tONIUM HYDROXIDE

33 6/28/61 THE DDMERIC PEROXIDE OF SCLAREOL OXIDE AND ITS DECOMPOSI-


TION PRODUCTS

34 7/6/61 BURLEY TOBACCO COMPONENTS . IL . CHARACTERIZATION OF TWO oberts


DITERPENOIDS, - AND -1,3-DUVENDIOL, AS CYCLOTETRADECYL
GLYCOLS

35 7/14/61 DETERMINATION OF FATTY ACIDS IN TOBACCO - QUANTITATIVE Bellin ~'


R
STUDIES OF'THE PROCEDURES USED FOR SEPARATING THE FATTY
ACIDS AFTER SAPONIFYING HEXANE EXTRACTS OF TOBACCO

7/17/61 THE QUANTITATIVE EVALUATION OF CARBOHYDRATES IN AGING Shiffert'~


9 TOBACCO / `

37 7/25/61 V/ THE DETERMINATION OF PHENOL IN CIGARETTE SMOKE CONDENSATE Latimer ~

38 7/25/61 J THE DEVELOPMENT OF A MASS SPECTROMETIC ANALYSIS OF PHENOLSrurene & Young


IN TOBACCO SMOKE
r

39 8/1/61 POLYPHENOLS OF TOBACCO . III . FACTORS INFLUENCING THE __ 6hifz"


CHLOROGENIC ACID, RUTIN, AND SCOPOLETIN CONTENT OF FLUE-
CURED TOBACCO

40 8/3/61 NICOTINE,FERMENTATIONS, PROCESS FOR THE CONVERSION OF Squires & Hes


TO 3-SUCCINOYLPYRIDONE-6 BY DEEP-CULTURE BACTERIAL FERMENTA-
TION

41 8/3/61 STABILIZATION OF THE HEOPFNER REACTION WITH ALUMINUM IONS ; Nystrom


REACTION OF ALUMINUM NITRITE WITH ORTHO-DIHYDROBENZENES

42 8/18/61 THE ANALYSIS OF CIGARETTE SMOKE CONDENSATE . XXIV . 6-ACETYL-


2,304-TRIS-d-B-METHYLVALERYL-B-D-GLUCOPYRANOSIDE FROM TURKISH 'ftbdgman & Cook
TOBACCO SMOKE Ln
~
~3 8/21/61 TURKISH TOBACCO CHARACTERIZATION OF i~-LEVANTANOLIDE Giles to •.a
i ~
4 9/22/61 THE ANALYSIS OF CIGARETTE SMOKE CONDENSATE, 70CV . 12q- ok & Rodgman
HYDROXY-13-EPIMANOYL OXIDE•FRCM TURKISH TOBACCO SMOKE .

3010/20/61 EVALUATION OF MALEIC HYDRAZIDE (MH-3Q) TREATED BURLEY Shiffert


TOBACCO Harrell-Latim
•• Pz,~. Sc6 _ .r'8'
REJEARClH DEPARTMENT REPORTS - RDR - 1961 ~C s

No . ~ Date Author(s)

11/7/61 'FURTHER IMPROVEMENTS IN PREPARATION AND UTILIZATION OF Cundiffx


QUARTERNARY AMMONIUM HYDROXIDE. TITRANTS l'

i1/7/61 INVESTIGATION OF MEANS FOR DETERMINATION OF THE ACETYL GROUP Cundiff (`

11/9/61 TOBACCO FLORA : •QUANTITATIVE STUDIES • Squire~,&


.. Haye 1(s

11/14/61 EXPERIMENTAL GROWTH OF CLARY SAGE IN FORSYTH COUNTY, N . .C ., Henley, Te e


FOR THE PRODUCTION OF SCLAREOL Allen, Liv

50 11/15/61 THE PYROLYSIS OF MIXTURES OF HEXANE AND ETHANOL-1-C14 aefele-Mims


~ Latimer

51 11/15/61 RDR, 1961, NO . 31 . TITLED "NICOTINE RECOVERY FROM DILUTE Neel ~


AQUEOUS SOLUTIONS BY DISTILLATION OF NICOTINE AZEOTROPES A l`T
PRESSURES ABOVE ONE ATMOSPHERE"- SUPPLEMENT TO

52 11/16/61 OXIDATION OF MANOYL OXIDE . II . A STUDY OF OXIDANTS OTHER THAN •Giles x


PERMANGANATE IN THE SYNTHESIS OF SCLAREOLIDS

53 11/17/61 . REVISION OF THE OPTICAL METHOD FOR THE DETERMI&TION OF SCLAREOL Laurene-v
Moser 6f N
Drummong

11/27/61 THE ANALYSIS OF CONTAMINANTS ON CAPACITOR FOIL Laurene-LyerNv &


Lamb

12/4/61 ISOLATION OF SOLANESOL FROM FLUE-CURED TOBACCO Rowland-Le.fAmer•


G es

12/6/61 VAPOR-PHASE REMOVAL OF NICOTINE FROM TOBACCO Ashburn &~"'

57 12/11/61 BURLEY TOBACCO CONSTITUENTS . I . SURVEY OF SEPARATION AND Rohd


ISOLATION PROCEDURES OF THE METHANOL EXTRACTABLES

58 12/27/61 VAPOR PHASE REMOVAL OF NICOTINE FROM BURLEY TOBACCO IN Weel


PILOT PLANT AND PLANT-SCALE COMMERCIAL EQUUPMENT .

59 3/3/66 PENICK & FORD, LTD . RESEARCH REPORT, 1ST QUARTER - 1961 Penick & Ford

60 3/3/66 DITTO 2ND QUARTER - 1961 Ditto

61 3/3/66 DITTO 3RD QUARTER - 1961 Ditto

62 3/4/66 DITTO 4TH QUARTER - 1961 Ditto


1

.
.• RESEARCtI DEPARTMENT REPORT - RDR - 1962

S Date

1/10/62
Author(s)

NONAQUEOUS TITRATION OF INORGANIC PERCHLORATES WITH TETRA- ~ Sensabaugh


BUTYLAM4IONIUM HYDROXIDE

2 1/10/62 EVALUATION OF THE MODEL 29 COLEMAN NITROGEN ANALYZER ~ Robinson

3 1/12/62 TURKISH TOBACCO . THE MOLECULAR DISTILLATION OF TURKISH AfA Schumacher


TOBACCO EXTRACT . THE ISOLATION OF TWO TOBACCO FLAVORANT
PRECURSORS (SCLAREOL OXIDE AND COMPOUND XXIII)

4 1/15/62 CORRELATIONS OF MASS SPECTRA OF BIOYCLIC AND TRICYCLIC ' Laurene b~(
DITERPENES WITH THEIR MOLECULAR STRUCTURE ~~S •° Young

5 1/29/62 IDENTIFICATION OF C15 AND C17 SATURATED FATTY ACIDS, AND C15, Bellin ~
C16, C17, UNSATURATED FATTY ACIDS IN TOBACCO AND IN SMOKE

2/15/62 DEHYDRATION OF SCLAREOL . III . THE SCLARENES AND RELATED ENOL F~~ Mims
LACTONES .

7 2/19/62 ANALYSIS OF SCLAREOL BY ISOTOPE DILUTION . II . USE OF SCLAREOL "~,ZNewe11


C-14

3/5/62 AN ATTEMPTED SYNTHESIS OF SCLAREOLIDE FROM CATIVO GUM ~~Giles


.~

• 3/12/62
VOID

THE DETERMINATION OF CARBAMATES BY HYDROLYSIS WITH PERCHLORIC


s
: k,, Sullivan
ACID

11 4/19/62 COLORIMETRIC DETERMINATION OF SCLAREOLIDE AND RESOLUTION OF r Cundiff


. ,.
SCLAREOLIDE-ACETOXY ACID MIXTURES

12 5/1/62 CHARACTERIZATION OF M-II-b, AN UNSATURATED GLYCOL ISOLATED ,Rowland


FROM FLUE-CURED TOBACCOS, AS 12-ISOPROPYL-1,5,9-TRIMETHYL-
3,8,13-CYCLOTETRADECATRIENE-1,5-DIOL

13 5/8/62 EFFECT OF AGII~G ON THE SCLAREOLIDE CONTENT OF TURKISH TOBACCOS Newe11A

THE ANALYSIS OF CIGARETTE SMOKE CONDENSATE . XXVI . HETEROCYCLIC ~< i dgman &
14 6/21/62 04
Krq ook
NITROGEN COMPOUNDS FROM TURKISH TOBACCO SMOKE . .

15 6/21/62 THE ANALYSIS OF CIGARETTE SMOKE CONDENSATE . XXVII . PHENOLS FROM4~odgman &
TURKISH TOBACCO SMOKE : EUGENOL AND ISOEUGENOL ook

~ KNN

: .~ . RESEARCH DEPARTMENT REPORT - RDR - 1962

Date TITLE Author(s)

6/21/62 FLUE-CURED TOBACCO . VOLATILE COMPONENTS, 1962 '~°~" Rowland &


Giles

17 6/25/62 CARBOHYDRATES IN COMPETITIVE BRANDS OF CIGARETTES Shiffert

18 6/25/62 TURKISH TOBACCO . THE ISOLATION AND IDENTIFICATION OF THE Alk Schumacher &
ESSENTIAL OIL OF TURKISH TOBACCO DUST Vestal

19 6/27/62 PREPARATION AND NONAQUEOUS TITRATION OF THE p-NITROPHENYL- Robinson &


HYDRAZONES OF ALDEHYDES, KETONES, AND CARBOHYDRATES r Sensabaugh

20 6/28/62 FATTY ACIDS OF TOBACCO LEAVES . FRACTIONATION AND SAPONIFICATION &',,Bellin ~


OF THE HEXANE EXTRACT OF TOBACCO

21 6/29/62 THE DEGRADATION AND DISTRIBUTION OF PALMITIC ACID-C1400H , .--\Be11in


P
DURING AIR CURING DETACHED BURLEY LEAVES

22 7/5/62 OCCURRENCE OF SCLAREOL IN BURLEY TOBACCO-C14 "• •;f Newell-Haefel


~~+ Latimer

23 7/6/62 FLUE CURED TOBACCO . THE K-I AND K-II COMPOUNDS Rowland &
Cabiness
24 7/10/62 EXTRACTION OF SCLAREOL-C14 FROM CLARY SAGE-C14 AND ITS Newell A,
CONVERSION TO SCLAREOLIDE-C14

~ 7/12/62 CONDENSATION OF ALDEHYDES WITH ISOPHORONE q-4-Rowland &


t' `'~Cabiness

26 7/19/62 ELUTION COLUMN PREPARATION OF TOBACCO FOR FLAME PHOTOMETRIC .~4~y"Dobbins


CALCIUM DETERMINATION

27 7/19/62 THE QUALITATIVE EVALUATION OF TOTAL ALKALOIDS, NICOTINE, TOTAL ,~F~,,,Shiffert


NITROGEN, POTASSIUM, CHLORIDE AND pH (SLURRY) IN AGING TOBACCO ~

28 7/31/62 TURKISH TOBACCO . THE CHARACTERIZATION OF BOVOLIDE Schumacher


(COMPOUND XXXI) r

29 8/1/62 CHARACTERIZATION OF M-II-f AS A-3,8,13-DUVATRIENE-1,5-DIOL `4Roberts &


Rowland

30 8/7/62 G-7 TYPE PLUG WRAPPER FOR CHEWING TOBACCO ~~yMoser


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• C"
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.RESEARCN DEPARTMENT REPORTS - RDR - 1962
. .
No . Date
~ 1962
8/13 NONAQUEOUS TITRATION OF HYDRAZIDES WITH TETRABUTYLAMMONIUM Sens abau'il
HYDROXIDE Robinson`

32 8/16 COLORIMETRIC DETERMINATION OF SCLAREOL Cundiff ~~

33 8/21 SUBSTITUTED MALIC ACIDS AS TOBACCO FLAVORANTS Fredrickson

34 9/10 TOBACCO PRODUCT FROM THE SMOKABLE COMPONENTS OF BURLEY STEMS Ashburn 40

35 9/27 SYNTHESIS OF (-)-6-ALKOXYNICOTINES AND THEIR TARTRATE SALTS Bernasek `i.,

36 10/10 MA`CROCYCLTC .`:DITERRENES, a- AND 5-4,8,13-DUVATRIENE-1,3-DIOLS Roberts 0


• FROM TOBACCO
37 11/2 THE~~.FATE`l OF,jTH,E_:;,FLAVORANTS OF TOBACCO DURING SMOKING . I .
SCLAREOLIDE
38 11/2 THE PREPARATION OF MARIOLIDE FROM S-IONONE

39 11/6 SHREDDING STEMS WITH A DISC REFINER FOR USE AS CIGARETTE CUT
FILLER:
40• . 11/15 SCLAREOL FROM CLARY SAGE - AVOCA FARM, .1962
41 12/11 I'SOLATION OF LONG-CHAINED ALIPHATIC ESTERS OF S-AMYRIN FROM
TURKISH AND BURLEY TOBACCOS
42 '12/17 EXTRACTION OF NICOTINE FROM BURLEY TOBACCO Ashburn %

43 12/28 .T4i,, : STUDY. .pF BURLEY SMOKE CONDENSATE . I . PRELIMINARY SURVEY Fredrickson ~
OF THE ODOROUS CONSTITUENTS OF BURLEY SMOKE CONDENSATE
I a
/ - 'f " e 7"

44 ~ :3/4/66 PENICK & FORD, LTD . - RESEARCH REPORT, 1ST QUARTER - 1962 Penick .& .Ford
. ; . m
45 ; ;3/7/66 DITTO 2ND QUARTER - 1962 . }

go r
46 : 3/4/66 DITTO 3RD QUARTER - 1962 , :.
m
47 3 `3/4/66 DITTO 4TH QUARTER - 1962
~
48 ! :5/17/66 PENICK & FORD DEVELOPMENT-REPORT, 3RD QUARTER - 1962 Penick :& iFord

49 :5/17/66 DITTO 4TH QUARTER - 1962


Penick & :Ford
50 ~ 5/16/66 PENICK,& FORD DEVELOPMENT REPORTS - JULY 1961-MAY 1962
;

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,
RDR, 1963, Nos . 1-61 DESTROYED, exaept as noted .
RESEARCli DEPARTMENT REPORT - RDR - 1963

Date TITLE

a 1/8/63 THE ANALYSIS OF CIGARETTE SMOKE CONDENSATE . XXVIII . POSSIBLE


a PRECURSORS IN TOBACCO OF PHENOLS IN TOBACCO SMOKE

2 1/14/63 THE STUDY OF BURLEY SMOKE CONDENSATE . II . THE ISOLATION OF Fredrickson


DISUBSTITUTED MALEIC ANHYDRIDES FROM STRONG ACID FRACTION

3 1/21/63 DEHYDRATION OF SCLAREOL . IV . MISCELLANEOUS COMPOUNDS DERIVED Mims


©
FROM SCLAREOL

4 1/24/63 NONAQUEOUS TITRATION OF INORGANIC SALTS FOLLOWING REACTION,WITH Robinson


8-HYDROXYQUINOLINE

5 1/30/63 FRACTIONATION OF EXTRACTS OF TURKISH BLEND TOBACCO Fredrickson

6 1/31/63 THE FATE OF FLAVORANTS DURING SMOKING . II . CO UMARIN Newell' . ..

7 2/1/63 DETERMINATION OF CONSTITUENTS OF TOBACCO BY ISOTOPE DILUTION . Newell,


III . PHENYLACETIC ACID

8 2/6/63 GAS CHROMATOGRAPHIC ANALYSIS OF THE VOLATILE ESSENTIAL OILS OF (l~'. Latimer-Moser
TOBACCO . V . INVESTIGATION OF 1960 BURLEY TOBACCOS .BEFOREiAGING
AND AT THE END OF ONE YEAR OF AGING

9 2/6/63 THE ANALYSIS OF CIGARETTE SMOKE CONDENSATE . XXIX . PHYTOL ,~I Rod ma~ n-Cook
(3,7,11,15-TETRAMETHYL-2-HEXADECEN-1-OL)
• 2/7/63 DETERMINATION OF TOBACCO HUMECTANTS BY VAPOR CHROMATOGRAPHY
`
~$R
(t j~
.. .
_
ne-Laurene- \ ,
Cliag-an) '
~ ~ .~ .

12 2/8/63 THE ANALYSIS OF CIGARETTE SMOKE CONDENSATE . XXX . VOLATILE Fredrickson-


ALDEHYDIC AND KETONIC CONSTITUENTS "7Chappell-Rodgmai

11 2/8~/63 EFFECT OF TOBACCO TREATMENTS ON POLYNUCLEAR HYDROCARBONS IN ~Ashburn


CIGARETTE SMOKE

13 2/15/63 SCHARDINGER CYCLODEXTRINS Sinfert cn


~
~
14 2/15/63 ANALYTICAL EVALUATION OF LICORICE . I . COLORIMETRIC DETERMINATION Cundif f x r
m
OF GLYCYRRHIZIC ACID . II . DETERMINATION OF REDUCING, NON-REDUCING
AND TOTAL SUGAR CONTENT

CHARACTERIZATION OF M-II-e AND COMPOUND X . MACROCYCLIC DITER- cm owland


PENES ISOLATED FROM TOBACCO

THE LOSS OF SCLAREOL DURING HEAT DRYING OF CLARY SAGE FLOWERING ' Hhefele
,
PARTS

THE RECOVERY OF SCLAREOL FROM CLARY SAGE FLOWERING PqTS BY A Haefele,~o


DIRECT EVAPORATION CONDENSATION PROCESS
9- z8-t ~F
THE INSECTICIDAL ACTIVITY OF NICOTINE DERIVATIVES AND RELATED

• ,COMPOUNDS AGAINST THE GREEN PEACH APHID

3/13/63 SYNTHESIS OF (-)1-ALKYL- AND (-)-[p-(,h1~k1)phenoxyethoxyethyl]-


5-(N-methyl-2-pyrrolidinyl)-2-pyridones

20 3/1YI63 CULTIVATION OF BACILLUS MACERANS FOR PRODUCTION OF AMYLASE Long, Marga`


RESEARCH DEPARTMENT REPORT - RDR - 1963

Date TITLE Author


0
3/15/63 AN INVESTIGATION OF SOME POSSIBLE METHODS OF ISOLATING TOBACCO
s CONSTITUENTS

22 3/19/63 INVESTIGATION INTO THE POSSIBILITY OF DETERMINING ACTIVE HYDROGENXobinson


UTILIZING GRIGNARD REAGENTS AND NONAQUEOUS TITRIMETIC TECHNIQUES

23 3/25/63 BURLEY TOBACCO COMPONENTS . III . STUDIES ON CONDENSATE FROM ~


DENICOTINIZATION PROCESS

24 3/25/63 THE ANALYSIS OF CIGARETTE SMOKE CONDENSATE . XXXI . -1,5-Dimethyl ; r odgroan-Cook


12-Isopropyl-9-Methylene-5,8-Oxido-3,13-Cyclotetradecadien-1-0L
and -12-Isopropyl-5,8-Oxide-1,5,9-Trimethyl-3,9,13-Cyclotetra-
decatrien-l-ol from Turkish Tobacco

25 3/25/63 COLUMN ELUTION OF HUMECTANTS FROM TOBACCO AND DETERMINATION BY MCundiff-Greene


VAPOR CHROMATOGRAPHY

26 4/4/63 ISOLATION AND CHARACTERIZATION OF COMPOUND XI . A MACROCYCLIC ~ Roberts-


DITERPENE ISOLATED FROM TOBACCO Schumacher

27 4/5/63 NONAQUEOUS TITRATION OF MISCELLANEOUS ORGANIC COMPOUNDS WITH ASensabaugh


TETRABUTYLAMMONIUM HYDROXIDE

"' 4/9/63 SYNTHESIS OF FATTY ACID CARRIERS X Mays

"' 4/10/63 FLUE-CURED TOBACCO VOLATILE


1963COMPONENTS,
•Rowland-Cabine
~

30 V 0 I D V 0 I D

31 4/16/63 THE EXTRACTION OF BURLEY TOBACCO redrickson Ln


J
N
m
32 4/17/63 THE FATE OF FLAVORANTS OF TOBACCO DURING SMOKING . III . ~ Newe11
RRNg PHENYLACETIC ACID Ln
N
W
33 4/29/63 INTERFERENCES IN FLAME PHOTOMETRIC ANALYSIS OF TOBACCO SAMPLE X Dobbins m
ELUATES FOR POTASSIUM AND CALCIUM

34 4/29/63 ANTIMICROBIAL ACTIVITY OF DERIVATIVES OF (-)6-HYDROXYNICOTINE . IIIxong, Margaret

35 5/8/63 ANALYTIS OF CIGARETTE SMOKE CONDENSATE . XXXII . ISOPRENOID ALCOHOLSW


.'dgman-Cook

36 5/13/63 ISOLATION, CHARACTERIZATION & SYNTHESIS OF COMPOUND XXVI . WSRoberts_JNS

37 5/14/63 PILOT PLANT STUDY OF PROCESS FOR CONVERTING SCLAREOL TO SCLAREOLIDE Henley et a1V10

38 5/15/63 BY-PRODUCTS FROM OXIDATION OF SCLAREOL . I . NEUTRAL BY-PRODUCTS

39 5/15/63 GROWING TOBACCO IN A GREENHOUSE . I . GROWTH CHARACTERISTICS, CURING


& CHEMICAL COMPOSITION OF BURLEY & FLUE-CURED VARIETIES
-p
~ 5/23/63 IMPROVING THE SMOKING QUALITY OF BURLEY STEMS Jackson,~~ ~
` ~tr i
41 5/24/63 BURLEY STEM TREATMENTS Ashburn ,y

42 5/28/63 FIVE- AND SIX-CARBON ACID CONTENT OF TURKISH TOBACCOS atimer-Moser


' Page 3
RDR - RESEARCH DEPARTMENT REPORT - 1963

• Date

6/5/63
TITLE ~'~"Author"I

GAS CHROMATOGRAPHIC ANALYSIS OF VOLATILE ESSENTIAL OILS OF TOBACCO . Latimer


VII . EVALUATION OF GREEN LEAF SAMPLES OF 1961 & 1962 BURLEY CROPS

44 6/6/63 BURLEY TOBACCO COMPONENTS . IV . ISOLATION, CHARACTERIZATION, AND qgRoberts


SYNTHESIS OF COMPOUND BV-20

45 6/7/63 EFFECT OF PLANT GROWTH REGULATOR (2 CHLOROETHYL) TRIMETHYL- Bellin ~


AMMONIUM CHLORIDE ON HEXANE EXTRACTABLES OF CURLEY BURLEY LEAVES

46 6/7/63 BY-PRODUCTS FROM OXIDATION OF SCLAREOL . II . OXIDATION OF BY-PRODUCTSY\ Giles

47 6/21/63 DEVELOPMENT OF METHODS FOR DETERMINATION OF TOBACCO HUMECTANTS IN eene6undiff


CIGARETTE SMOKE Waureneo

48 7/8/63 TURKISH TOBACCO . THE QISOLATION OF ACID CARRIERS FROM TURKISH ~Schumacher
TOBACCOS

49 7/18/63 BURLEY TOBACCO COMPONENTS . V . ISOLATION, CHARACTERIZATION, AND ~ Roberts


SYNTHESIS OF COMPOUND BV-21

50 8/22/63 'EVALUATION OF LABORATORY FUNCTIONS AT AVOCA FARM DURING PLANT CAdiff-Robinson-


START-UP, 1963 VanHoy

;,L 9/3/63 SYNTHESIS OF DEHYDROIONONE ~ Rowland

9/6/63 THE F1TE OF FLAVORANTS OF TOBACCO DURING SMOKING . IV . (A) MENTHOLvewell-Latime

53 9/27/63 RAPID METHOD FOR DETERMINATION OF FIVE- AND SIX-CARBON ACID CONTENT~~iystrom-
OF SUGAR ESTERS AND SUGAR ESTER FRACTIONS ISOLATED FROM TOBACCO . Sizemore
UTILIZATION OF ALCOHOLYSIS REACTION FOR PREPARATION OF ETHYL ESTERS
FOR GAS CHROMATOGRAPHIC ANALYSIS

54 9/30/63 SYNTHESES OF DIMETHYLMALEIC ANHYDRIDE BY CATALYTIC, VAPOR PHASE,~'~,,~ Mims cnN


AIR OXIDATIONS ~
~
~
55 10/3/63 DIRECT RELATIONSHIP BETWEEN FLUE-CURED TOBACCO QUALITY AND TOTAL ~ Nystrom
Ln
0-DIHYDROXYBENZENE (POLYPHENOL) VALUE DETERMINED BY STABILIZED '' N
w
HAEPFNER REACTION ~

56 10/8/63 ISOLATION OF A TOXIC FRACTION FROM BACILLUS PULVIFACIENS Jackson


x
57 11/12/63 GROWTH & PREPARATION OF BACILLUS PULVIFACIENS CELLS TOXIC TO © Long, Margare
LASIODERMA SERRICORNE LARVAE

58 11/13/63 FACTORS WHICH AFFECT PHENOL CONTENT OF CIGARETTE SMOKE urene-Young-Lyerlv


r • • • . ...-. - -- M

59 11/20/63 BURLEY TOBACCO COMPONENTS . VI . ISOLATION, CHARACTERIZATION ~ Roberts ~


AND SYNTHESIS OF 2-ACETYL-5-METHYLPYRROLE ~
N

~ 12/9/63 BURLEY TOBACCO COMPONENTS . VII . ISOLATION, IDENTZFICATION?11D ~ Roberts J


SYNTHESIS OF 2_•ACETYLPYRAZINE 0

61 12/11/63 NICOTINE FERMENTATIONS : CHARACTERIZATION OF CULTURE .B43-3 AS ~( Squires-Hayes


PSEUDOMONAS NICOTINOLYTICUS, N .S .P .
RESEARCH DEPARTMENT REPORTS - RDR - 1963 f Page 4

No . Date Title Author(s)


1963
66 3/7/66 PENICK & FORD, LTD . - DEVELOPMENT REPORT, 1ST QUARTER - 1 63 Penick & Ford

67 3/7/66 DITTO 2ND QUARTER - 963 Ditto

68 3/7/66 DITTO 3RD QUARTER - 963 Ditto

69 3/7/66 DITTO 4TH QUARTER - /1963 Ditto


RESEARCH DEPARTMENT REPORT - RDR - 1964

.. Date TITLE

1/6/64 BURLEY TOBACCO CONSTITUENTS . VIII . ISOLATION, CHARACTERIZATION AN


SYNTHESIS OF TWO PYRROLE CARBOXALDEHYDES

2 1/8/64 BY-PRODUCTS FROM THE OXIDATION OF SCLAREOL . III . NEUTRAL BY-PRODUCTS ',_ Giles

3 1/8/64 ~~Mays-Henley
RECOVERY OF SCLAREOL FROM CLARY SAGE CONCRETE THROUGH THE USE OF `~~`
SURFACE-ACTIVE AGENTS

4 1/9/64 THE FATE OF FLAVORANTS OF TOBACCO DURING SMOKING . IV . (B) MENTHO• ewell'=LatimE
CONTENT OF MAINSTREAM VERSUS NUMBER OF PUFFS Moser

5 1/9/64 THE STUDY OF BURLEY SMOKE CONDENSATE . III . CONSTITUENTS 0 THE •Fredrickson}
STRONG ACID FRACTION .. .~

6 1/10/64 GROWING TOBACCO IN A GREENHOUSE . PART II . A COMPARISON OF GENERAL Bellin


ELECTRIC POWERGROOVE LAMPS AND SYLVANIA GRO-LUX LAMPS FOR
ILLUMINATING CONTROLLED ENVIRONMENT GROWTH CHAMBERS a .'~-e-o /11 . S•

7 1/17/64 PILOT PLANT PROCESSING OF CLARY SAGE CONCRETE FOR SCLAREOL Henley X

8 2/3/64 4S,YNTHESIS OF FATTY ACID CARRIERS` Bernasek ~'

9 2/11/64 BURLEY TOBACCO COMPONENTS . IX . FURTHER ISOLATION AND SYNTHESIS Woberts


OF 2-ACETYLPYRAZINE AND RELATED COMPOUNDS .

~ 2/12/64 THE ANALYSIS OF CIGARETTE SMOKE CONDENSATE . XXXV . A SUMMARY OF }ri V~~ Rodgman
AN EIGHT-YEAR STUDY

11 4/12/64 DEVELOPMENT OF AN INSTRUMENTAL METHOD FOR THE DETERMINATION OF ~ Laurene-Greer


A TRIACETIN IN FILTER PLUGS

12 2/14/64 THE USE OF DRI-DIE 67 SILICA FOR PROTECTING STORED TOBACCO FROM Bellin ~s
DAMAGE BY THE CIGARETTE BEETLE

13 3/13/64 PREPARATION AND NONAQUEOUS TITRATION OF THE DIPHENYL-ACETYL- Sensabaugl~


1,3-INDANDIONE-I-AZINES OF ALDEHYD$S AND KETONES

14 3/17/64 AN EVALUATUON OF BIOLOGICAL ACTIVITY . I . HERBICIDAL ACTION OF Bellin ~ .


NICOTINE~'DERIVATIVES AND RELATED COMPOUNDS AS DETERMINED BY
TESTS WITH LEMNA MINOR (DUCKWEED)

15 3/17/64 AN EVALUATION OF BIOLOGICAL ACTIVITY . II . THE TOXICITY OF Bellin


NICOTINE'"AND~•ITS DERIVATIVES+TO MINNOWS ..
~
16 3/20/64 ISOLATION OF C14-LABELED NICOTINE FROM C14-LABELED BURLEY TOBACCO Nys tro~~' N
BY A PROCEDURE RELATIVELY NON-DESTRUCTIVE TO OTHER CONSTITUENTS Sizempre~v
r
17 3/27/64 POLONIUM-210 IN TOBACCO . I . EVIDENCE THAT A MAJOR PORTION NYSTROM-~
ORIGINATES FROM ATMOSPHERIC CONTAMINATION OF TOBACCO PLANTS Bellin
~~~
4/1/ 6 4 THE QUANTITATIVE ANALYSIS OF CIGARETTE SMOKE . PART II . Laurene-Greene-Drunmo
i 4/8/64 DEHYDRATION OF SCLAREOL . V . THE DEHYDRATION OF SCLAREOLIC ACID Mims

20 4/16/64 START-UP AND OPERATION OF AVOCA PROCESSING PLANT Teag e Z et al


'
~7; 'l
.
51710 5233
.
~ge 2
RESEARCH DEPARTMENT REPORTS - RDR - 1964
~
Date Author(s)

4/16/64 SUPPLEMENTARY REPORT : THE QUANTITATIVE ANALYSIS OF CIGARETTE AM'Laurene-Lyer7


SMOKE . PART II . Greene-Harbir

22 4/22/64 DETERMINATION OF HYDROGEN CYANIDE IN CIGARETTE SMOKE ®rbin-Lyerly-Yot

23 4/30/64 THE FATE F DISODIUM ISOPROPYLMALONATE-3-C14 DURING SMOKING ® Haefele

24 5/5/64 AGRONOMIC RESEARCH ON CLARY SAGE AT AVOCA FARM, BERTIE COUNTY, f~ Collins-
N . C ., IN 1963 a-?.-Q /s'! • S . ~ • S'ta}lings-Ma11oi
" .•
25 5/6/64 PREPARATION OF 4-(2-BUTENYLIDENE)-3,5,5-TRIMETHYL-2-CYCLOHEXEN_ ~ Bluhm
1-ONE (THE K-1 AND K-Z COMPOUNDS) p•," M• S .

26 5/6/64 BY-PRODUCTS FROM THE OXIDATION OF SCLAREOL IV . OXIDATION ON ~~~"''~~~ ~ Giles


ACIDIC BY-PRODUCTS
14
27 5/6/64 ~ SYNTHESIS OF 2,3-DIMETRYLMALEIC ANHYDRIDE r4,~~ Shackelforc

28 se.c,, Du2
~
.~[ •

29 5/11/64 THE SPECTROPHOTOMETRIC DETERMINATION OF HYDROGEN CYANIDE IN : ;~ : : Cundiff


CIGARETTE SMOKE d-~ m' S•

5/11/64 BY-PRODUCTS FROM THE OXIDATION OF SCLAREOL V . OXIDATION OF J Giles


COMPOUND B4G1
6
5/14/64 SYNTHESIS OF DEHYDROIONONE . II . r ;Rowland o

EXPERIMENTAL GROWTH OF CLARY SGAE IN FORSYTH COUNTRY, N . C . FOR ~~ N


32
THE PRODUCTION OF SCLAREOL . SUPPLEMENTARY REPORT . r
J
~
33 6/3/64 GROWING TOBACCO IN A GREENHOUSE . III . A COMPARISON OF FLUE-CURED Be l l in'~:: `o
F 4
AND BURLEY VARIETIES OF TOBACCO GROWN BY NUTRICULTURE METHODS IN
A GREENHOUSE AND OUTSIDE

34 6/5/64 NONAQUEOUS CONDUCTIMETRIC TITRATIONS USING TETRABUTYLAMMONIUM Sensabaugh


HYDROXIDE

35 6/17/64 LABORATORY SYNTHESIS FOR BOVOLIDE AND DIHYDROBOVOLIDE . ~, Davis, T .C .


(ALSO TWO-PAGE ADDENDUM TO THIS REPORT) `

36 7/13/64 DESCRIPTION AND OPERATION OF DENICOTINIZING PLANT AT SHED 131, ~ Neel, R .M .


WHITAKER PARK - OCTOBER, 1962 - FEBRUARY 1964 . ~'

37 8/12/64 SYNTHESIS OF SAFRANAL AND SM36C X Rowland-Roberts

38 9/2/64 THE DEVELOPMENT OF A DIRECT VAPOR CHROMATOGRAPHIC DETERMINATION Laurene-


OF ACETYLALDEHYDE,ACROLEIN, AND ACETONE IN CIGARETTE SMOKE . yerly-Young

VOID VOID

6 9/3/64 THE SYNTHESIS OF SUGAR ESTERS J Davis T .C .

41 9/8/64 MEASUREMENT OF ARREST OF RADIANT HEAT BY REFLECTIVE MATERIALS `'p,~ Laurene


~,,

51710 5234
RESEARCH DEPARTMENT REPORTS - RDR - 1964

M Date

9/9/64 TURKISH TOBACCO . THE INVESTIGATION OF THE STEAM CONDENSATE 4D;chumacher


Author(s)

43 . 9/16/64 SYNTHESIS OF N,N DIALKYL-N'-BENZYL-N'-[5-(1-METHYL-2-PYRROLIDINYL)- BernasekX


2-PYRIDYLJ-ETHYLENEDIAMINES

44 9/24/64 BY-PRODUCTS FROM THE OXIDATION OF SCLAREOL . VI . NEUTRAL BY-PRODUCTS Giles X

45 9/29/64 BURLEY TOBACCO CONSTITUENTS . II . SURVEY OF SEPARATION AND ISOLATIONI~de


OF THE CHLOROFORM EXTRACTABLES

46 10/2/64 ACIDIC CONSTITUENTS OF BURLEY VOLATILES I . ISOLATION, CHARACTERI- ohde


ZATION AND SYNTHESIS OF COMPOUND S015C

47 10'/.2/64 BURLEY TOBACCO COMPONENTS . XI . ISOLATION AND SYNTHESIS OF TOBACCO MWoberts


CONSTITUENTS

48 10/6/64 ACID CONSTITUENTS OF BURLEY VOLATILES . II . ISOLATION AND SYNTHESIS (1:1eRohde


OF S017C

10/7/64 THE FATE OF RADIOACTIVE LINOLENIC AND PAIMITIC ACIDS DURING THE Bellin
AIR-CURING OF BURLEY TOBACCO

10/28/64 POLONIUM-210 IN TOBACCO . III . FURTHER EVIDENCE THAT A MAJOR PORTION Bellin- ~
ORIGINATES FROM ATMOSPHERIC CONTAMINATION OF TOBACCO PLANTS Nystrom-Sizemc

51 11/4/64
11/4/64 EFFECT OF NICOTINE DERIVATIVES AND RELATED COMPOUNDS ON PLANT James",!-
GROWTH ~ ~

11/6/64 BY-PRODUCTS FROM THE OXIDATION OF SCLAREOL . VII . ACID BY-PRODUCTS Giles%,4

12/4/64 SYNTHESIS OF DEHYDROIONONE . III . Rowland)~

12/28/64 AN EVALUATION OF BIOLOGICAL ACTIVITY . III . HERBICIDAL ACTION OF Bellin ~.+~


NICOTINE DERIVATIVES AS DETERMINED BY ROOT IMMERSION TESTS WITH
SOYBEAN AND CORN SEEDLINGS

55 12/28/64 LABORATORY OPERATION AT AVOCA FARM - 1964 Robinson-Cundi~`~~


Vanl~'oy ,

56 12/28/64 INTERIM REPORT NO . 1 TO R . J . REYNOLDS TOBACCO COMPANY - STUDY ~ 1 ; Industrial


OF THE CILIARY-DEPRESSANT ACTIVITY OF CIGARETTE SMOKE `' Bio-Test, I

57 12/28/64 INTERIM REPORT NO . 2 TO R . J . REYNOLDS TOBACCO COMPANY - STUDY a Industrial


OF THE CILIARY-DEPRESSANT ACTIVITY OF CIGARETTE SMOKE w Bio-Test Labs

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51710 5235 0
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RESEARCH DEPARTMENT REPORTS - RDR - 1964


S
No . Date Title Author(s)
1964
62 3/7 PENICK & FORD, LTD . - DEVELOPMENT REPORT, 1ST QUARTER, 19 4 Penick & Ford

63 3/7 PENICK & FORD, LTD . - DEVELOPMENT REPORT, 2ND QUARTER, 19 4 Penick & Ford

64 3/7 PENICK & FORD, LTD . - DEVELOPMENT REPORT, 3RD QUARTER, 1P64 Penick & Ford

65 3/7 PENICK & FORD, LTD . - DEVELOPMENT REPORT, 4TH QUARTER, 1P64 Panick & Ford
p
.~. ~
~
/.Z-e. _4
RESEARCH DEPARTMENT REPORTS - RDR - 1965

Date Title 'Author(s)

1/4/65 DESCRIPTION AND OPERATION OF DENICOTINIZING PLANT AT BLDG . 60~XNeel, R . M .


WHITAKER PARK, FEBRUARY .1964 - SEPTEMBER 1964

2 1/13/65 DE AiT-OE .ANAS CHROMATOGRAPHIC METHOD TO DETERMINE /, rly-Young-


ARBON MONOXIBE I CIGARETTE SMOKE ~( urene

3 1/18/65 PROCESS FOR INCREASING THE VOLUME OF TOBACCO ' aredrickson

4 1/18/65 EFFECT OF CULTURAL PRACTICES ON QUALITY, YIELD AND SOME Ne as


CHEMICAL CONSTITUENTS OF THE 1963 BURLEY CROP

5 1/21/65 BURLEY TOBACCO COMPONENTS . XII . SYNTHESIS ANb CHARACTERIZATIONORoberts


RELATED TO SM2C

6 1/28/65 DETERMINATION OF OXIDES OF NITROGEN IN TOBACCO SMOKE asens ab augh

7 VOID

8 2/4/65 INTERIM REPORT NO . 3 TO R .J .R . - STUDY OF THE CILIARY_ ~ INDUSTRIAL BIO-


DEPRESSANT ACTIVITY OF CIGARETTE SMOKE TEST LABS ., INC :

9 2/9/65 . BURLEY TOBACCO COMPONENTS . XIII . ATTEMPTED SYNTHESIS OF SM400wj" . Roberts

10 2/22/65 REPORT NO . IITRI-C8036-4 - DEVELOPMENT OF HOUSEHOLD PRODUCTS v"' .0~,IITRI Res . Inst .

2126/65 VARIATION OF ARTHROBACTER OXYDANS, a2 Squires-Hayes


0
LL 2/26/65 BURLEY TOBACCO COMPONENTS . XIV . ATTEMPTED SYNTHESES OF ISO- g2 ;Roberts, tJ1
PHORENE-RELATED COMPOUNDS ~
~
~
13 3/15/65 DETERMBNATION OF FORMALDEHYDE IN THE GAS PHASE OF CIG . SMOKE WCundiff-VanHoy m
Ln
N
14 3/24/65 THE HYDRATION OF NITRILES TO AMIDES USING MANGANESE DIOXIDE . I . .,.~aefele w
PRELIMINARY REPORT . SCOPE AND LIMITATIONS ~

15 3/24/65 INTERIM REPORT NO . 4 TO R .J .R . - STUDY OF THE EFFECT OF a Industrial Bio-


CIGARETTE SMOKE ON CILIARY ACTIVITY Test Lab ., Inc .

16 3/24/65 INTERIM REPORT NO . 5 TO R.J .R . - EXPERIMENTAL WORK ON THE ~ Industrial Bio-


eZ EFFECTS OF CIGARETTE SMOKE ON CILIARY ACTIVITY Test Labs ., Inc .

17 3/25/65 INVESTIGATION OF AN IMITATION PEACH BRANDY FLAVOR Schumacher

18 4/1/65 GAS CHROMATOGRAPHIC DETERMINATION OF THE WATER IN CIGARETTE Thome


MAINSTREAM SMOKE AND TOTAL PARTICULATE MATTER (TPM)

19 4/14/65 BY-PRODUCTS FROM THE 01 OATION OF SCLAREOL . . .VIII . IMPURITIES V,.Gi1es


IN THE AVOCA PRODUCT ~

20 2/9/65 THE SYNTHESIS OF LACTONES ISOLATED FROM TURKISH TOBACCO STEAM Vestal

• 5/4/65
CONDENSATE y~44

BURLEY TOBACCO COMPONENTS . XV . AUTOXIDATION OF a-IONONE AND t~~ Roberts


DERIVATIVES

22 5/5/65 MASS SPECTROMETRIC ANALYSIS OF CIGARETTE SMOKE . PART I : Young-Drummond


DETERMINATIONOF METHYL CHLORIDE AND CARBONYL SULFIDE '
i'
A
RESEARCH DEPARTMENT REPORTS - RDR - 1965 ~Page 2

No . Date Title Author(s)

0 5/5/65 DIRECT VAPOR CHROMATOGRAPHIC DETERMINATION OF MENTHOL, PROPYLENE ~~?=


GLYCOL, NICOTINE, AND TRIACETIN IN CIGARETTE SMOKE M!p

24 5/6/65 INTERIM REPORT NO . 6 TO R .J .R . _ 90-DAY SUBACUTE VAPOR INHALATION Industrial Bio


TOXICITY OF SR6C (~ Test Labs ., Inc

25 5/6/65 INTERIM REPORT NO . 7 TO R .J .R . - 90-DAY SUBACUTE INHALATION Industrial Bio-


TOXICITY OF THE PYROLYTIC PRODUCTS OF:,`SR6C Rk Test Lab .,Inc

26 5/19 FLAVORED CARBON AS AN ADDITIVE FOR TOBACCO PRODUCTS Vflarwood & Teague

27 5/20/65 SOLVENTS IN THE OONVERSION PLANT AT AVOCA FARM Ashburn ~,~

28 6/1/65 DETMN . OF EXPERIMENTAL NEMATOCIDE UC 21149 IN FLUE-CURED Johnson


TOBACCO AND CIGARETTE SMOKE

29 6/14/65 INTERIM REPORT NO . 8 TO R .J .R . - STUDY OF THE CILIARY- REM Industrial Bio-


DEPRESSANT ACTIVITY OF CIGARETTE SMOKE m Test Labs ., Inc .

30 6/21/65 THE ANALYSIS OF CIGARETTE SMOKE CONDENSATE XXXVI . PHYTONE


(HEXAHYDROFARNESYL ACETONE) AND SOLANONE (2 METHYL-5-ISOPROPYL-
1,3-NONADIEN-8-ONE)FROM TURKISH TOBACCO SMOKE

-kt 7/9/65 TURKISH TOBACCO . THE INVESTIGATION OF THE STEAM CONDENSATE,


PART II .
0

7/12/65 DEVELOPMENT OF METHODS OF PIPE SMOKE ANALYSIS : PROGRESS REPORT

33 7/14/65 INVESTIGATION OF IMITATION "SHERRY"

34 7/26/65 AN EVALUATION OF BIOLOGICAL ACTIVITY . VI . GREENHOUSE TESTS OF


CHEMICALS FOR THEIR HERBICIDAL PROPERTIES

35 8/6/65 GROWING TOBACCO IN A GREENHOUSE . PART IV . EXPERIMENTS WITH


LIQUID CULTURE

36 8/18/65 SUBACUTE TOXICITY STUDIES OF SCLAREOLIDE IN RATS AND MONKEYS

37 8/18/65 THE ANALYSIS OF CIGARETTE SMOKE CONDENSATE . XXXVII . A PHYTYL odgman-gak cook
ESTER FRACTION FROM TURKISH TOBACCO SMOKE

38 8/23/65 REACTION PRODUCTS OF PHENYLACETONITRILE WITH ACTIVATED


MANGANESE DIOXIDE
Bluhm X
®
39 9/7/65 AN INVESTIGATION OF NITROGEN OXIDES AND METHYL NITRITE IN ~r~q~~
.~, .-
TOBACCO SMOKE
r,o Laurene-Drum .
4 9/13/65 THE DEVELOPMENT OF A METHOD TO DETERMINE THE ACTIVITY OF
CARBON IN GRANULAR OR BONDED ROD FORM a%w Whalen
;~
9/17/65 THE SYNTHESIS OF VARIOUS COMPOUNDS ISOLATED FROM THE STEAM Vestal-
CONDENSATE OF TURKISH TOBACCO

42 fJ i
RESEARCH DEPARTMENT REPORTS - RDR - 1965

~ Date Title

42 9/21/65 ;.MASS~SPECTROMETRIC ANALYSIS OF CIGARETTE SMOKE, PART II .


DETERMINATION OF ACETYLENE, ETHYLENE AND ETHANE

43

44 10/8/65 CILIAS.TATIC ASSAY Fluck-Kelly

45 10/11/65 FLU0R0ME .TRIC DETERMINATION OF POLYNUCLEAR HYDROCARBONS Stamey-Dobbins

46 11/1/65 PENICK & FORD, LTD . RESEARCH REPORT, 1ST QUARTER - 1963

47 11/1/65 DITTO, 2ND QUARTER - 1963

48 11/1/65 DITTO, 3RD QUARTER - 1963

49 11/1/65 DITTO, 4TH QUARTER - 1963 ,to

50 11/1/65 DITTO, 1ST QUARTER - 1964

51 11/1/65 DITTO, 2ND QUARTER - 1964


.~ 11/1/65 DITTO, 3RD QUARTER - 1964

~ 11/1/65 DITTO, 4TH QUARTER - 1964 to

54 11/1/65 DITTO, 1ST QUARTER - 1965 to

55 11/1/65 DITTO, 2ND QUARTER - 1965

56 11/4/65 INVESTIGATION OF NATURAL CARDAMOM OIL

57

58 11/9/65 PERCHLORIC ACID HYDROLYSIS OF CARBAMATES, AMIDES, NITRILES


AND IMIDES

59 12/3/65 ABSCISIN II . SYNTHESIS OF 1-HYDROXY-4-KETO-a-IONONE

60 12/8/65 PREPARATION OF SCLAREOL DERIVATIVES FOR BIOLOGICAL TESTING Gil,~-

61 12/15/65 INTERIM REPORT NO . 9 TO R .J .R . - THE SMOKING MACHINE, THE Iti ust`r al Bio-
IN VIVO STUDIES OF CILIASTATIC EFFECTS OF TOBACCO SMOKE W~est LaN's ., Inc .
~tl

62 12/20/65 FATTY ACID CARRIER ~~Fluck ~'`~

63

~ Jan-March PENICK & FORD, LTD . DEVELOPMENT REPORT, 1ST QUARTER - 1965
1965
c. .a",' .. &4..e.4..e- ~ uI'.~*~ , ,.C-~ . -~,,. .. 4 /
RESEARCH DEPARTMENT REPORTS - RDR - 1966 ~
No . Date Title 'Muthor(s)
~ 1966
1/5 INTERIM REPORT #10 TO R .J .R TOB . CO . - STUDIES ON THE CILIASTATIC _Industrial Bio-
EFFECTS OF CAMEL CIG . SMOKE ON CAT TRACHEA IN VIVO ~1Test Labs .,Inc .

2 1/13 AN EVAL . OF BIOLOGICAL ACTIVITY . VIII . TESTS OF CHEMICALS FOR Bellin ~ .


THEIR HERBICIDAL PROPERTIES USING EIGHT SPECIES OF PLANTS

3 2/7 THE ANALYSIS OF CIG . SMOKE CONDENSATE . XXXIV . 4-(2-BUTENYLIDENE)- odgman-Cook


ISOPHORONES FROM TURKISH TOBACCO SMOKE ~

4 2/22 INTERIM REPORT #11 TO RTR TOB . CO . - STUDIES ON CILIASTATIC ,l9h Industrial Bio-
EFFECTS OF WINSTON CIG . SMOKE ON CAT TRACHEA IN VIV '~'0 Test L ab s ., Inc .

5 2/28 INVESTIGATION OF MEANS FOR AUTOMATING THE PROCEDURES FOR Cundiff-


DETERMINING THE SUGAR CONTENT OF TOBACCO X Robinson

6 3/9 PIPE SMOKE ANALYSIS : ACROLEIN, ACETALDEHYDE, ACETONE, HYDROGEN~YHarbin-Laurene


CYANIDE, OXIDES OF NITROGEN, NICOTINE AND TOTAL SOLIDS

7 3/10 BIOLOGICAL ASSAY OF RJR COMPOUNDS FOR INSECTICIDAL ACTIVITY a~~Walton


~
8 3/18 INVESTIGATION OF NUTMEG OIL ~Schumacher
I
9 3/29 PRODUCTION AND CHARACTERIZATION OF TETRONIC ACIDS FROM ~ . ~ W . B . James -
PENICILLIUM CHARLESII r~ .Y Hayes
e
~ 4/6 THE FILTRATION OF CIGARETTE SMOKE ~Mims ~
a
~
~1 4/5 EXAMINATION OF THE VAPOR PHASE OF CIG . SMOKE USING HIGH I Thome
RESOLUTION GAS CHROMATOGRAPHY WITH ELECTRON CAPTURE AND HYDROGEN ~
N
FLAME DETECTION ~
m
12 4/13 SOME FACTORS INFLUENCING THE FILTRATION OF THE VAPOR-PHASE OF 'i`; Rodgman-Cook,
CIGARETTE SMOKE

13 4/13 DETERMINATION OF ANTIOXIDANTS IN VEGETABLE .OIL & PEANUT CHIPS ~.~: D . P . Johnson

14 4/19 SYNTHETIC STUDIES RELATED TO THE SYNTHESIS OF ABSCISIN II, A , ;`~,".Heclmtan, Robert
PLANT HORMONE - -

15 4/25 pH MEASUREMENTS OF TOBACCO SMOKE

16 4/28 INTERIM REPORT #12 TO RJR TOB . CO . - STUDIES ON THE CILIASTATIC ndustrial Bio-
EFFECTS OF TEMPO CIG . SMOKE ON CAT TRACHEA N VIVO est Labs .,Inc .

17 5/4 USE OF DRI-DIE SILICA DUST TO CONTROL THE CIGARETTE BEETLE IN Bellin ~
WAREHOUSES :
~. . .. ;:~,.
18 5/9 PRELIMINARY INVESTIGATION OF THE PYROLYSIS-GAS CHROMATOGRAPHY 4 ..atiiner
OF POLYMERS, TOBACCOS AND STARCH DERIVATIVES
A
5/10 THE SYNTHESIS OF SEVERAL TOBACCO CONSTITUENTS FROM S-IONONE Vestal ~~ ~QK~
0
20 5/16 THE EFFECT OF A FREEZING PERIOD BEFORE NATURAL AGING ON THE Shif fertN
QUALITY OF FLUE-CURED TOBACCO a-
. RESEARCH DEPARTMENT REPORTS - RDR - 1966
No . Date Title Author(s)
+ 1966
5/17 SYNTHETIC ROUTES TO ABSCISIN II Roberts e,
Heckman . "'R .

22 5/23 THE OXIDATIVE COUPLING OF ACTIVATED METHYLENE COMPOUNDS BY Leffingwell~


METAL OXIDES '`

23 6/21 INTERIM REPORT #13 TO RJR TOB . CO . - STUDIES ON CILIASTATIC 'dustrial Bio-
EFFECTS OF SALEM CIG . SMOKE ON CAT TRACHEA IN VIVO st Labs ., Inc .

24 6/27 STUDIES OF CIG . SMOKE IRRITATION I : DEVELOPMENT OF A BIOLOGICAL••• Loe


TEST AND SOME PRELIMINARY RESULTS .. ::.
• 25 6/30 TRIACETIN CONTENT OF CIG . SMOKE AS A FUNCTION OF THE AGE OF THE leland-
FILTER rly

26 7/11 DETERMINATION OF THE BENZYL CONTENT OF BENZYLATED STARCH D . P . Johnibn


.
(rec'd 2 copies - 1 filed in starch file ; 1 destroyed) .. ,:

27 7/25 AN INVESTIGATION OF RANCIDITY AND OTHER FACTORS AFFECTING THE D . P . Johnm


.pQUALITYOFCKNGLS

28 7/25 POLYMERIC HYDRAZIDES AS SELECTIVE ABSORBENTS FOR CARBONYL CPDS .

29 7/26 INTERIM REPORT #14 TO RJR TOB .•C0 . - THE IN VIVO STUDIES OF ndustrial Bio-
~ CILIASTATIC EFFECTS OF CIG . SMOKE ON CAT TR~CHEA est Labs .,Inc .

. 7/26 INTERIM REPORT #15 TO RJR TOB . CO . - SALIVA-SOLUBLE CILIASTATIC Industrial Bio-
COMPONENTS OF TOBACCO SMOKE 4WTest Labs .,Inc .

31 8/4 STUDIES OF CIGARETTE SMOKE IRRITATION . II : ADAPTATION OF THE Moew


GRANULOMA POUCH TEST FOR VAPOR-PHASE IRRITANTS

32 8/18 THE CHEMISTRY OF CATALYTIC MANGANESE DIOXIDE Piehi X

33 9/1 SYNTHESIS OF SOME GLUCOSE MONO-ETHERS J . G . JonesA

34 9/2 INTERIM REPORT #16 TO R,JR TOB . CO . - THE EFFECTS OF SALIVA- 4 Industrial Bio-
SOLUBLE CILIASTATIC COMPONENTS OF TOBACCO SMOKE ON THE CAT Test Lab`s ., Inc .
TRACEA IN VIVO
, . . . . , . ., : ,
35 10/19 T~F~,•.SYNTHESISF . . OF FATTY ACID CARRIERS . II ; Bernasek '`

36 10/21 INTERIM REPORT #17 TO RJR TOB . C0 . - STUDIES ON CILIASTATIC ~ndustrial Bio-
EFFECTS OF LUCKY STRIKE CIG . SMOKE ON CAT TRACHEA IN VIVO - est Labs ., Inc .
IBT NO . E4662 (A
0
37 10/25 SYNTHESIS OF Y-PHENYL-Y-[5-(1-METHYL-2-PYRROLIDINYL)-2-PYRIDYL]- Bernasek ~r
Id,N-DIMETHYLPROPYLAMINE N
P
38 10/26 STARCH SULFITE Giles ~
0
~ 11/14 INTERIM REPORT #18 TO RJR TOB . CO . - STUDIES ON CILIASTATIC 4 ndustrial Bio-
EFFECTS OF CHESTERFIELD NONFILTER CIG . SMOKE ON CAT TRACHEA est Labs ., Inc .
IN VIVO IBT N0 . E4662

51710 5241
RESEARCH DEPARTMENT REPORTS - RDR - 1966

o. Date Title Author(s)


1966
40 12/7 COLORIMETRIC DETERMINATION OF OXIMES AND UNSUBSTITUTED Delwin Johnson
HYDROXYLAMINE

41 12/21 MICROBIAL BIOSYNTHESIS OF PRECURSORS FOR SPECIFIC TOBACCO AVORZLong-Hayes


COMPOUNDS +Shiffert

. ~ .C~' ~2 l96 ~, n~o S, 3 S a.r.•e s C

° 'I
: t...L .. . .a.,

RESEARCH DEPARTMENT REPORTS - RDR - 1967


1747 v
" ., Date Title Author(s) C
I-
, v
101/9 PRELIMINARY REPORT ON EFFECTIVENESS OF VARIOUS METHODS FOR CONTROL- hP'Walton R
LING CIGARETTE BEETLE (LASIODERMA SERRICORNE) IN TOB . WHSES . :• . r
~
v.
CONVERSION OF D-GLUCOSE TO A MIXTURE OF D-GLUCOSE AND D-FRUCTOSE *Shi ~~ffer t a
USING GLUCOSE ISOMERASE

3 1/20 STARCH DERIVATIVES : DETERMINATION OF SUBSTITUTED PYRIDINIUM 1% Johnson, D . I


ALKYL HALIDE GROUPS IN MODIFIED STARCH

4 2/1 ANORECTIC AND SUBACUTE EFFECTS OF MARIOLIDE ' ..`,:'. _,~r Tompkins & Fluck

PRELIMINARY INVESTIGATIONS OF ORGANIC COATING ON FOIL ~~ Latimer


rt
DETERMINATION OF Q-39 SURFACTANT IN STARCH ,,1Johnson & Latimer
~~ ; .
PARTICLE SIZE DISTRIBUTION OF SMOKE Weinstein & Sue Stevensc

SYN THESIS OF (-)-6-ALKYLTHIONICOTINES

9 3/17 DERIVATIVES OF 2,5-FURANDICARBOXALDEHYDE

.10 3/30 INTERIM REPORT #19 - STUDIES OF CILIASTATIC EFFECTS OF TEMPO


CIGARETTE SMOKE ON CAT TRACHEA IN VIVO - IBT NO . E-4662

CHEM . RESEARCH ON FLAVORANTS ~ PART I . CONSTITUENTS OF MAPLE SYRUP ;!~tohde


~,, .. .
INVESTIGATION OF STYRAX OIL ~~'~Ves
:~;, . tal

TOTAL SYNTHESIS OF (-)-MENTHOL Shackelfof Leffingwell

14 4/6 IDENTIFICATION OF HOMOLOGOUS SERIES OF a,$-DIKETONES AND a-KETOALDEHYDES PThome


IN CIG . SMOKE BY GAS CHROMATOGRAPHY WITH ELECTRON CAPTURE DETECTION

15 5/3 MASS SPECTROMETRIC ANALYSIS OF CIG . SMOKE, PART III . DETERMINATION OF ",oung, G . W .
ACETALDEHYDE, PROPANE, PROPYLENE AND ACETONITRILE

16 5/24 COMPARISON OF ANALEPTICS I MOUSE EXPERIMENTS Crosby Tompkins

17 6/6 NEW SYNTHETIC METHOD FOR PREPARATION OF AROMATIC ALDEHYDES, tt-Aeffingwell & Bluha
KETONES-- AND- SCHIFF-- BASES-- -- - - - --- ----- --- -- -- --- -

18 6/6 CHARACTERIZATION OF A COMMERCIAL SYNTHETIC FLAVORANT Schumacher


6. A
19 6/13 STARCH LEVULINATES ~, Calley Eaton

20 6/28 ABSCISIN II RELATED COMPOUNDS Rob~~~ ts & B . Hege

21 7/25 APPLICATIONS OF THERMAL ANALYSIS TO CARBOHYDRATES, TOBACCO AND Pi'~"Pieh1, D . H .


CHEMICAL COMPOUNDS ,

, . . . . .• , . . . .. ,: . : ..r f: .
8/8 GAS- CHROMATOGRAPHIC METHOD TO DETERMINE COUMARIN IN CIG . SMOKE Wyerly & Gi1lBlan

8/9 INORGANIC DERIVATIVES OF STARCH I . FORMATION, NATURE & APPLICATIONS °~ Pieh1, D . H ;

24 8/17 FAS'CHROMATOGRAPHIC DETERMINATION OF PHENOL IN CIGARETTE SMOKE Lyerly & Gillelan

51710 5243
I
Page 2

1967
RESEARCH DEPARTMENT REPORTS - RDR - 1967 OIL
0 Date Title Author(s)

L5 8/18 STARCH DERIVATIVES . DETERMINATION OF ALLYL AND METHALLYL x Johnson, D . l


GROUPS IN MODIFIED STARCH

26 8/23 AN IMPROVED SYNTHESIS OF MARIOLIDE AND RELATED PRODUCTS x Schumacher, J .N .

27 8/31 POTENTIAL PLANT GROWTH REGULATORS RELATED TO ABSCISIN II K He ckman , R . .

28 8/31 SURFACE AREAS OF•VARIOUS FILTER rows K Harbin, B . A

29 9/5 THE CHEMISTRY OF TETRAMETHYLSUCCINALDEHYDE • 1 Rice, Wm . Y .

30 9/19 SYNTHESIS OF HERBICIDAL PYRIDINE AND PIPERIDINE COMPOUNDS ~ Moates, R . F .

31 10/2 A STUDY OF THE CALOROGENICITY OF PAF-2006 ~ Fluck

32 10/2 ANALYSIS OF CIG . SMOKE CONDENSATE . XLV . BRANCH-CHAINED ACIDS ~;took & Rodgman
FROM TURKISH TOBACCO SMOKE .
v
c
33 10/13 THE CHEMISTRY OF 2-METHYL-2-(2-METHYLPROPENOXY)-PROPIONALDEHYDE x Rice, W . Y . ~
N
34 10/23 PRODUCTION OF A THERMOSTABLE BACTERIAL a-AMYLASE x Lartigue r
J
~ 10/20 CHARACTERIZATION OF CORIANDER OIL AND FURYLONE Schumacher So

36 10/23/ FJLTRATION EFFICIENCY OF VARIOUS FILTERS : PART I , MONODISPERSE AEROSOL tS


.fWeinstein
,
37 10/19 GROSS EFFECTS OF SYNTHETIC PLANT HORMONE, ABSCISIN II, ON PLANTS AND ABehlin
EFFECTIVENSSS OF RELATED COMPOUNDS FOR FLOWER ABSCISSION & ROOTING

38 10/24 BIOSYNTHESIS OF AMYLOGLUCOSIDASE BY A STRAIN OF THE MOLD ASPERGILLUS <Hayes &


• AWAMORI Lartigue

39 10/30 ANALYSIS OF CIG . SMOKE CONDENSATE . XLVI . GERANYL ACETONE AND ,.4k~ Cook & Rodgma
FARNESYL ACETONE FROM TURKISH TOBACCO SMOKE W- ;

40 11/22 STARCH DERIVATIVES . DETMN . OF RATIO OF TERTIARY AND QUATERNARY x Johnson, D . P


PYRIDINIUM GROUPS IN MODIFIED STARCH

41 11/29 STARCH DERIVATIVES . DETMN . OF HYDRO GROUP CONTENT OF MODIFIED STARCHxjohnson, D . P

42 12/6NICOTINE FERMENTATIONS, PROCESS FOR THE BIOSYNTHESIS OF (1)-6- A Squires &


HYDROXYNICOTINE BY FERMENTATION WITH ARTHROBACTER OXYDANS, a2, Hayes
VARIANT NO . 8
43 12/12 DETERMINATION OF NITRATE IN TOBACCO

44 12/14 INVESTIGATION OF AN IMITATION CHOCOLATE FLAVOR

• 12/26 SORPTION ISOTHERMS AND PORE SIZE DISTRIBUTIONS OF SOME FLAVOR


RELEASE .CARBONS ,

46 12/27 STARCH DERIVATIVES . A STUDY OF THE DISTRIBUTION OF SUBSTITUENTS


IN MODIFIED STARCH

51710 5244
~~..~ . . „
m,N t.. . ~ n/d . .C.0 O~ e<~- ~L.~t~,~i~i
Page 1
/~ '9" • 7~ l~ .
a.~ ..~ .~
RESEARCH DEPARTMENT REPORTS - RDR - 1968 02 `

„"' Date Title Author(s)


1968
1 1/2 TETRAMETHYLSUCCINALDEHYDE AS A STARCH INSOLUBILIZING AGENT Kirby, K . W .K

2 1/3 SOLVENT-STEAM TREATMENT OF STARCH Kirby, K . W . l(

3 1/5 HYDROPHOBIC STARCH DERIVATIVES Kirby, K . W . l`

4 1/9 NEW METHODS FOR PREPARATION OF CARBALKOXYMETHYLENETRIPHENYL- Roberts, D . L, )<


PHOSPHORANES

5 1/23 OXIDATIVE COUPLING REACTIONS IN ORGANIC CHEMISTRY . II . OXIDATION


OF KETONES, ALDEHYDES AND SCHIFF BASES WITH LEAD DIOXIDE
Leffingwell X
6 1/25 BLENDS OF BENZYL STARCH WITH PLASTICIZERS AND EXTENDERS Kirby, K . W . X

7 1/30 HYDROPHILIC STARCH DERIVATIVES Kirby, K . W .YN


0
..
8 2/1 RAPID ANALYSIS OF INDIVIDUAL COMPONENT(S) OF CIGARETTE SMOKE ;raves, Harry N

9 2/5 HALOGENATION AND HALOHYDRINATION OF STARCH DERIVATIVES CONTAINING Kirby, K . W .x Q


UNSATURATED GROUPS ~ ~o

10 2/14 SYNTHESES OF SOME POTENTIAL CENTRAL NERVOUS SYSTEM STIMULANTS Heckman, R. A .x

10 2/14 INVESTIGATION OF DAVANA OIL Schumacher Bw

12 2/27 CYCLIC SULFITES AND THIONYL CHLORIDE DERIVATIVES Roberts-Hege (a'bni

13 3/4 THE CATALYTIC FORMATION OF OLEFINS FROM CARBONYL COMPOUNDS Piehl x


USING A PULSED MICROCATALYTIC REACTOR

14 3/18 COMPARISON OF ANALEPTICS II GUINEA PIG EXPERIMENT Tompkins, Cex sby

15 3/19 THE EFFECT OF REACTION PARAMETERS ON THE PYROLYSIS OF Piehl y


1-HYDROXYNEOCAR9-^%.iENTHYL ACETATE

16 4/2 EXPLORATORY STUDIES OF OXIDATION REACTIONS Rowland ~<

17 5/3 CATIONIC STARCHES BASED ON VINYLPYRIDINE . I . QUATERNARY Giles, Neuman411-


CATIONIC DERIVATIVES Jones (J . Glenwoo

18 5/9 THE 1,4-DIPOLAR BICYCLOADDITIONS OF N,N'-DIALKYL-2,2,3,3- Young, Harve?Y\


TETRAMETHYLSUCCINALDIMINES TO ISOCYANATES & ISOTHIOCYANATES

19 5/13 PREPARATION OF COMPOUNDS FOR BIOLOGICAL EVALUATION McKenzie, J . .A

20

~ 5/20 DEVELOPMENT OF A METABOLIC SCREEN

A .- 5/27 THE EFFICIENCY OF VARIOUS FILTERS TO MONODISPERSE AEROSOLS `

23 5/29 RESULTS OF EXPERIMENTAL CIGARETTE BEETLE CONTROL PROGRAMS FOR 1967

51710 5245
I /A
It
~
, RESEARCH DEPARTMENT REPORTS - RDR - 1968

Date Title Author s


'0 1968
24 6/6 THE CHEMICAL AND MECHANICAL MODIFICATION OF STARCH X Piehl-Whisnant

25 6/21 PHYSICAL PROPERTIES OF X-CELOSE ; TOTAL SUGAR (PAF-2011) ~( Piehl-'r/hisnant•et al

26 6/25 NICOTINE FERMENTATIONS, PROCESS FOR THE BIOSYNTHESIS OF X Squires-Hayes


3-SUCCINOYLPYRIDINE BY FERMENTATION WITH CULTURE B43-3

27 6/26 A STUDY OF THE CALOROGENICITY OF SEVERAL HYDROXYPROPYLATED ~ Fluck, E . R .


STARCH DERIVATIVES .
i " ;, . . .
' ,
28 7/11 A STUDY OF THE TOXICITY OF ACETYLPYRAZINE "~+ ." . %VF1uck & Doyle Johnso

29 7/23 FATE OF SMOKE CONSTITUENTS IN ANIMALS . I . COMPARISON OF METHOD VColucci-Sizemore


OF ADMINISTRATION ON THE DISTRIBUTION OF C-14 FROM PHENOL-C-14
PALMITIC ACID-C-14 , AND NICOTINIC ACID-C-14 IN THE RAT

30 7/23 THE OXIDATIVE COUPLING OF IMINES Bluhm ,.

31 7/25 PREPARATION OF SUBSTITUTED PYRROLIDINES Bluhm

32 8/1 STARCH DERIVATIVES : THE DETMN . OF HYDROXYETHYL GROUP x Johnson-D .P . &


CONCENTRATIONS IN MODIFIED STARCH '\Musselwhite

S 9/13 ENZYMATIC CONVERSION OF D-GLUCOSE TO D-FRUCTOSE : ISOLATION &


IDENTIFICATION OF AN ACTIVE NEW BACTERIAL SPECIES
f' Long, Margaret

34 9/25 CONVERSION OF D-GLUCOSE TO D-FRUCTOSE BY ARTHROBACTER RJR 2453-2 X Pheil, C . G .

35 9/23 3-PYRAZOLIDINONES AND RELATED HYDRAZINO ACID HYDRAZIDES X Roberts & Hege (Bonit

36 10/18 TERTIARY PYRIDYLMETHYL STARCHES . X Neumann-Bernasek

37 10/23 XYLOSE PRODUCTION FROM CORN HULLS AND SUGAR CANE BAGASSE ^ Rix-Eaton-J . G . Jone

38 11/6 CATALYTIC HYDRATION OF 3-P-MENTHENE TO (-)-MENTHOL x Piehl

39 10/30 -A TOTAL SYNTHESIS OF (-)-MENTHOL . II XI Shackelford-Leffingwell

40 11/21 RECOVERY OF NICOTINE FROM GREEN TOBACCO p,~Shackelford-Hudson, R .B


~
41 11/26 THE USE OF NICKEL CYANIDE-AMMONIA COMPLEXES IN THE Piehl
SELECTIVE FIL"TRATION OF TOBACCO SMOKE OL

42 12/10 A SELECTIVE SINGLET OXYGEN REACTION, II < Roberts

43 12/11 SUTRO POLYOLS AS PLASTICIZERS K Pratt, George W .

44 12/19 COLORIMETRIC DETERMINATION OF PERCENT CARBOXYL IN Rush-Sensabaugh-


CARBOXYMETHYL CELLULOSE usse1white

~ ,.0
ts.
~
N
r
J
51710 5246 «.
.. . I
RESEARCH DEPARTMENT REPORTS - RDR - 1969

Date Title Author(s)


a
1969
1 1/3 STUDY OF SMOKE GENERATION, TRANSPORT AND FILTRATION IN i James Harris
TOBACCO ROD

2 1/23 BIOSYNTHESIS OF GLUCOSE ISOMERASE BY A STRAIN OF ARTHROBACTER ~ L . E . Hayes

3 1/27 A GAS CHROMATOGRAPHIC DETERMINATION OF FREE FORMIC AND ACETIC ~ Lyerly & Goodale
ACIDS IN CIGARETTE SMOKE

4 2/19 PHYSICAL PROPERTIES OF SPRAY CRYSTALLIZED SUCROSE, COMMERCIAL X Piehl


SUCROSE AND AMEROSE
e;, ) d-
5 2/24 EXPOSURE OF RABBITS TO WHOLE SMOKE Johnson & Fluck

6 2/26 A SURVEY OF THE LITERATURE REGARDING CARBON MONOXIDE, WITH ~ J ~ Reynolds ~~


SPECIAL REFERENCE TO ITS OCCURRENCE IN CIGARETTE SMOKE AND
REMOVAL FROM SMOKES AND GASES

7 2/28 GAS-CHROMATOGRAPHIC DETERMINATION OF THE OXYGEN PERMEABILITY A Latimer & Clapp


OF FILMS AND FILM COMBINATIONS

8 3/6 THE IDENTIFICATION OF ACIDS FORMED DURING GLUCOSE-TO-FRUCTOSE X Clapp


INVERSION
,Pik
INITIAL ATTEMPTS AT EXPOSING RABBITS TO WHOLE CIGARETTE SMOKE Doyle Johnson

• 10 4/10 SORPTION OF PHOSPHINE BY TOBACCO, RESIDUES, AND FATE OF RESIDUESABellin & C . Walton
ON SMOKING AS DETERMINED BY MASS SPECTROMETRY AND RADIOACTIVE
ISOTOPE STUDIES

11 4/14 DEVELOPMENT OF MUTANT OF ARTHROBACTER PRODUCING GLUCOSE ISOMERASFY\ Chin Lee


WHICH IS CONSTITUTIVE AND INSENSITIVE TO CATABOLITE REPRESSION

12 4/15 OXIDATIONS OF a-IONONE 2('R . Heckman

13 4/18 CONTROL OF MICROFLORA OF FACTORY AIR CONDITIONING WATER - K Squires & Hay.es
14 4/29 QUATERNARY 1-ALKYLPYRIDYLMETHYL STARCHES ~ Neumann, Giles &
Bernasek

15 5/2 NICOTINE FERMENTATIONS . BIOSYNTHESIS OF COMPOUND 350 BY ` l Squires & Hayes


FERMENTATION OF NICOTINE WITH ARTHROBACTER OXYDANS, a2, VARIANT #5

16 5/13 SYNTHESIS OF SUBSTITUTED PHENYLPYRROLIDINES K .. Wendelboe

17
`\
~;*e N
• 6/11 THE HYDRATION OF NITRILES TO AMIDES USING MANGANESE DIOXIDE

-~r v1f1'40`'4~j W
. II . Hay

%`'?
h i`~i~~„r' w
r
~ 0.
%j
20 51710 5247 ni
(/ 7o
RESEARCH DEPARTMENT REPORTS - RDR - 1969

~ Date Item Author(s)


1969
._ 6/23 INTERIM REPORT NO . 20 TO R .J .R . TOBACCO CO . - RESULTS OF Industrial Bio-Test
PRELIMINARY SCREENING OF SR13C AND SR1A, IBT NO . E-5052

22 6/23 INTERIM REPORT NO . 21 TO RJR TOBACCO CO . - RESULTS OF LC50 Industrial Bio-Test


DETERMINATION OF SR13C, IBT
. ; NO . T6667
23

24

25 7/11 SYNTHETIC TROPANE ALKALOID ANALOGS K Moates

26 7/22 THIRTY-DAY ACUTE TOXICITY STUDY OF GLUCOSE - RJR 2453-F Fluck, Ridlon, et a

27 8/6 TOTAL SACCHARIFICATION PROJECT : EFFECT OF SACCHARIFICATION x Lartigue & Ayers


CONDITIONS ON ACTIVITY OF GLUCOAMYLASE PREPARATIONS

28 8/20 PRODUCTION AND USE OF MALTOSE-FORMING AMYLASE FROM BACILLUS ~ Lartigue & Hayes
POLYMYXA

29 8/26 ENZYMATIC ISOMERIZATION OF D-GLUCOSE BY ARTHROBACTER CELLS ~ Lartigue

~ 8/19 THE ALUMINA CATALYZED AIR OXIDATION OF 4-KETO-a-IONONE ~ Rice

31 9/16 SYNTHESIS AND REACTIONS OF 1,2,3-OXATHIAZOLIDINE-2-OXIDES `~ Heckman


AND 1, 2, 3-TETRAHYDROOXATHIAZINE-2-OXIDES -- . __~,~-_ ...---~

32 9/19 THE INVESTIGATION OF THE CIGARETTE SMOKE FROM'CELANESE ~ Green, Vestal &
SMOKING MATERIAL Schumacher . .

3333 9/29 AMIDOXIME STARCH Il T . Edwards & C . Rix

34 10/23 KINETICS OF OXIDATION OF ALUMINUM FOIL DURING HOMOGENIZATION )( Piehl

35 11/3 AZOMETHINE IMIDES AND RELATED PYRAZOLIDINONES AND PYRAZOLINONESK B . Hege

36 11/10 USE OF HOT GAS JETS FOR SIMULTANEOUSLY PUNCHING 16 HOLES IN [\ Harris, Stowe &
PLASTIC FILM

37 11/20 INSOLUBILIZATION OF BENZYL STARCH ASH ~ Rix & Pratt

38 11/20 BENZYL STARCH PRODUCTION USING CONTROLLED pH t~ Pratt & Rix

39

40 12/9 NINETY-DAY FEEDING EXPERIMENT WITH PENSWEET K Fluck, Ridlon et al

~ 12/16 SOLID-LIQUID CHELATION OF METALS BY AMIDOXIME CORN STARCH ~ Piehl a

42 12/19 METABOLIC SCREEN ~[ Pluck ~


lll~~\ ro .
~ F
v
o
51710 5248 4/ !
R ESEARCH DEPART MENT REPORTS - RDR - 1970

'"'
s Date Title Author(s)
1970
r 1 1/9 SMOKING EXPOSURE STUDIES d0 V / N Pluck, E. R.
AOL
2 1/14 THIRTY-DAY TOXICITY STUDY OF SRR4A ~9) /z •Fluck, Ridlon et a

3 1/22 PREVENTION OF SED MENT AND SUSPENSION FORMATION IN PURE x Dickerson, James
MAPLE SYRUP ' (14J /,3 ' `

r 4 1/26 AN ATTEMPT TO ESTABLISH A SIMPLE PROCEDURE FOR DETERMINATION Tompkins &


OF A DRUG' S ADDICTING PROPERTIES ~O'r ~,Thornloe

6 1/30 SUGAR CONTENT OF FLUE-CURED TOBACCO AND ITS RELATIONSHIP TO


TOBACCO AND SMOKE COMPOSITION

7 2/2 DETERMINATION OF TOBACCO FLAVORANTS PIPERONAL, ETHYL VANILLIN Martin, John &
& VANILLIN BY GAS-LIQUID CHROMATOGRAPHY AND FLUORIMETRIC Thacker, Aubrey
)4
THIN-LAYER CHROMATOGRAPHY (,t,6 /

8 2/3 RECOVERY OF NICOTINE FROM TOBACCO ~ZZ, /2 x Hudson & Shackelfo~


/`~
2/9 LABORATORY PREPARATION OF BENZYL STARCH (/ L ~/6~ x Rix, Bruce & Edwar(
`! /
2/10 SELECTIVE FILTRATION OF HCN IN TOBACCO SMOKE BY METAL -A)IID~O~X~MF~Piehl, Don
STARCH COMPLEXES (iLL
.ikn.

11 2/19 PILOT PLANT STUDIES OF THE PREPARATION OF BENZYL STARCH ~8v) 2 0~ruce, Sellers~,•et

12 2/24 PURIFICATION OF DEXTROSE SYRUP BY PREFERENTIAL ADSORPTION ON Nelson, Nancyrx U


A GRANULAR CARBON COLUMN (/z ) ~ S- 0
.•
13 3/5 THE STRUCTURE OF NORMAL, DEHYDRATED AND REHYDRATED TOTAL SUGAR iehl & Woodsx\ nr
USING SCANNING ELECTRON MICROSCOPIC AND X-RAY DIFFRACTION ~ . r
` TECHNIQUES J

14 3/16 REMOVAL OF BENZYL ALCOHOL FROM BENZYL STARCH EFFLUENTS ~3r ) 2 0 Carey, et al

/ 15 3/19 DEVELOPMENT OF A NEW SCREENING PROCEDURE WHICH DETECTS AND Tompkins, E . C .~(
DIFFERENTIATES MAJOR AND MINOR TRANQUILIZING AND SEDATIVE- f
HYPNOTIC ACTIVITY I~f ®7" !IJ )91 L0_

16 3/20 ELECTROSTATIC SEPARATION OF PROTEIN FROM STARCH IN CORN FLOUR(0 Mazeika, W . A . eX

17 3/23 THE EFFECT OF VARYING JET DEFLECTION ANGLE ON THE EFFICIENCY Harllee, Floria x
OF MULTIJET TYPE FILTERS &,t) l7

18 4/3 INVESTIGATION OF GLUE FAILURE IN THE C-1 FILTER, II : THE I~ Reynolds, J . H . 1w


~ ROLE OF FILTER TEMPERATURE (f S r

~ . 4/17 FLUOROMETRIC DETERMINATION 0 SELENIUM ]1N CIGARETTE PAPER AND (Vacker & Stamey
TOBACC O

51710 5249
RESEARCH DEPARTMENT REPORTS - RDR - 1970

Date Title Author s


1970 ~/Z
20 4/22 THE REACTION OF SUCCINALDIMINES WITH AMIDES AND SULFONAMIDES Young, Harvey ~(

21 4/22 CHROMATOGRAPHIC SEPARATION OF FRUCTOSE AND GLUCOSE ON CATION Lloyd, Robert/ -~C
EXCHANGE RESIN (¢7) /j

22 4/28 AUTOMATED METHOD FOR DETERMINATION OF NICOTINE ALKALOIDS IN Diffee, John~


TOBACCO, USING CYANOGEN BROMIDE (7,S 1 /3

23

24 5/22 DETERMINATION OF HUMECTANTS IN TOBACCO P4) /7 %les & Gilleland

,/25 5/25 NINETY-DAY TOXICITY STUDY ON GLUCOSE-FRUCTOSE SYRUPS


. .. Ridlon'& Heise~

26 6/4 SOME 1,3-DIPOLAR CYCLOADDITIONS OF STABLE AZOMETHINE IMIDES Rice, William ~


(-I' /'d
27

28

~~~•
6/18 THE ALKALI TRANSFORMATION OF GLUCOSE TO FRUCTOSE (/7 Bruce, Robert ; r,`,,
0 .
30 6/18 DETERMINATION OF CARBOXYL CONTENT OF CARBOXYCELLULOSE (lf) /A/ Sensabaugh, Ricey&
Musselwhite N

31 6/24 PREPARATION OF DISUBSTITUTED CYCLOOCTANONES ellt l /2 Ezzell, Bobby (11

32 6/29 THE ISOLATION OF FRUCTOSE FROM INVERT SYRUP BY THE HARA PROCESS Lloyd, R . & Br~e,l

33 6/30 REACTIONS OF SCHIFF BASES )/2 Roberts, D . x

W` _

35

36

37 5/22 REPORT TO RJR TOBACCO CO . : NINETY-DAY SUBACUTE ORAL TOXICITY OF~~dustrial Bio-
GLUCOSE-FRUCTOSE MIXTURE IN BEAGLE DOGS - IBT NO . C7809 (S1) (; Test Labs, Inc .

38 7/31 A SURVEY OF LITERATURE REGARDING HYDROGEN CYANIDE, ITS OCCURRENCE Andrews, Mary 011
IN & REMOVAL FROM CIGARETTE SMOKE & REMOVAL FROM INDUSTRIAL WASTE (14> /qL

39 8/17 NONAQUEOUS TITRIMETRIC DETERMINATION OF CARBONYL CONTENT USING Sensabaugh & ®


p-TOLUENESULFONYLHYDRAZINE C/q1 13 Musselwhite o,
0
r
0. 9/2 ISOLATION OF ESSENTIAL OILS -FROM/ FLUE-CURED TOBACCO dwards, et al (n
N
r
4D v
a
~
51710 5250
RESEARCH DEPARTMENT REPORTS - RDR - 197 0

Date TLtle Author(s )


0
197 0 (1 10
42 9/ 9 SYNTHESIS OF A 2,8-DIAZA-BICYCLO-[3 .2 .1]-OCTAN-3-ONE RING StEM X Harvey Youn g

43 9/1 6 1-(3-PYRIDYL)METHYLENE-3-OXOPYRAZOLIDINIUM INNER SALTS . A~ EW_ x Rice, Wm . Y .


CLASS OF DIURETICS (9 ) /~3 r o~! 11 a
44 10/1 3 THE USE OF Cu(II)-AMIDOXIME STARCH FOR THE REMOVAL OF HP FROM Andrews, Mary4 p
CIGARETTE SMOKE f /7J
L /:
45 10/2 3 DETERMINATION OF AMMONIA IN TOBACCO SMOKE (3jr) /7 Rush, K. et a l

46 10/2 9 PRODUCTION OF PENSWEET ON DEAE-CELLULOSE BOUND ENZYME 'COLUMNS : xMays, Charles


11,
PILOT STUDY // (, ) /

47 11/1 3 SYNTHESIS OF 4-( 2J-OXOETHYLIDENYL)-3,5,5-TRIMETHYL-2-CYCLOHEXEN=~-,,,Rice, W . Y . x


1-ONE (SM29C) ( 71 l 3

48 12/ 4 THE SUTTON RESEARCH CORP : SMOKING MATERIAL S r "`'~ 3 ~odgman + 1 1 am


Y s•. . .i •t ; R• t~ ,•'d.~t..y+, ...e: ~ .. .~ 1 : i / f e . .~ •

49

50 12/3 A RAPID GAS CHROMATOGRAPHIC ANALYSIS FOR FLUORANTHENE AND / Stowe, Mary & Pr;
PYRENE FOUND IN CIGARETTE SMOKE (4 1 / S 4 Harris, James
No . Date Title '~ ` Author(s)
,
RESEARCH DEPARTMENT REPORTS - RDR - 1971 (24)WPage 1 of 1

1/6 CATION-EXCHANGE COLUMN CHROMATOGRAPHY OF DEXTROSE FROM THE Dickerson, JameA


ENZYMATIC HYDROLYSIS OF STARCH
1/11 AROMATIC CANE JUICE PROCESS Heckman x
1/22 AUTOMATED METHOD FOR DETERMINATION OF NICOTINE ALKALOIDS IN Diffee X
CIGARETTE SMOKE USING CYANOGEN BROMIDE
1/28 AUTOMATED METHOD FOR DETERMINATION OF REDUCING AND TOTAL SUGARS Diffee ~C
IN TOBACCO
vmlD
SMOKE BALANCE CONTROLi II . COMPARISON OF pH OF SMOKE FROM WINSTON AND t"
6 2/15 MARLBORO CIGARETTES AND ANALYSIS OF THEIR FILTER MATERIAL •

7 2/26 SMOKE COMPOSITION : PUFFED VS . UNPUFFED TOBACCO BLEND %.~ Green & Schumacher
8 3/19 DICARBOXYCELLULOSE AS A TOBACCO SUBSTITUTE 0 Schumacher, et al
9 3/23 COLORIMETRIC DETMN . OF DIALDEHYDE IN DIALDEHYDE CELLULOSE as,, Musselwhite, et al

10 voto

11 v 0 l40

12 5/18 FLUbROMETRIC METHOD FOR DETMN . OF POLYNUCLEAR HYDROCARBONS IN Stamey, et a1


CIGARETTE SMOKE
5/27 STUDY OF SMOKE GENERATION AND FILTRATION ® Harris, James
~ 6/24 INSTRUMENT & METHOD FOR ANALYZING PARTICLE SIZE OF CIG . SMOKE Q Harrington & Myse1t
15 VOI to

16 7/29 REMOVAL OF CARBON MONOXIDE FROM CIG . SMOKE . II . DEVELOPMENT &'XOnolds & And rews
APPLN . OF RAPID METHOD FOR SCREENING PROSPECTIVE CO REMOVAL AGENTS I

17 8/5 ' TOBACCO ADDITIVES FOR REDUCTION OF CARBON MONOXIDE, HYDROGEN~ Andrews & Reynold
1CYANIDE & OXIDES OF NITROGEN IN CIGARETTE-SMOKE ` Wp`

18 9/17 EVALUATION OF MACHINE-MADE "C" FILTERS .,t_ ,Mwe, et al


19 9/20 ACTIVATED BAUXITES AS CIGARETTE FILTER ADDITIVES 1M''b' rjoeynolds & Andrews
20 9/16 RAPID THIN-LAYER METHOD FOR FLUOROMETRIC DETERMINATION OF (Ptamey, et al
. BENZO[aJPYRENE IN CIGARETTE SMOKE
OjL I .4
21 9/27 SELECTIVE FILTRATION OF GAS PHASE OF SMOKE o- Andrews & Reynolds

22 9/29 PROCESS FOR CONVERSION OF ACRYLONITRILE TO ACRYLAMIDE USING A Haefele & Young~
MANGANESE DIOXIDE CATALYST
23 10/18 ADDITIVES TO ENHANCE FORMATION OF AMADORI COMPOUNDS DURING AGING Dickerson, JamesK
24 10/28 EFFECT OF AGRICULTURAL CONDITIONS & PRACTICES ON THE EXPANSION ~~ ;redrickson, et al
OF TOBACCO BY G13-TYPE PROCESSES . V . TOBACCO TYPE, MARKET,
COMPANY GRADE, PARTICLE SIZE, AND FERTILIZATION
.~.~.-.~-
~Q~ .e i s 4- 7sl
RESEARCH DEPARTMENT REPORTS - RDR - 1972


ivo . Date Author(s)
1972
(\
1 1/4 DERIVATIVES OF 3,3,4,4-TETRAMETHYL-2-IMINOPYRROLIDINE H . Young/Dickerson

2 2/25 PHYSICAL PROBLEMS OF G-13 CIGARETTES Harris/Wheeler ^

3 2/29 FLOUVE ABSOLUTE : ISOLATION OF FLAVORFUL COMPONENTS Edwards/Rix/L1dy2i

4 3/20 ANALYSIS OF COCOA ON TOBACCO BY INDIRECT DETERMINATION OF Thacker/Martin/K


THEOBROMINE McHargue

5 3/27 SMOKE COMPOSITION : HOMOGENIZED VS . UNHOMOGENIZED TOBAC 0 BLEND


~ t,(,Orj ; Best - ~~
Schumacher/Gre `r

6 4/12 PREPARATION OF ARTHROBACTER WHOLE CELL AGGREGATES FOR THE


CONTINUOUS ENZYMATIC CONVERSION OF GLUCOSE TO FRUCTOSE

7 4/13 GAS CHROMATOGRAPHIC DETERMINATION OF CHLORINATED PESTICIDE


RESIDUES ON TOBACCO

8 4/27 USE OF ADDITIVES TO ENHANCE FORMATION OF AMADORI COMPOUNDS


DURING AGING . II .

r 5/2 AMADORI COMPOUNDS AS FLUE-CURED TOBACCO FLAVORANTS Dickerson, James ~

1_v 5/17 COMPOSITION OF THE CONDENSATE FROM STEAM FLOTATION EXHAUST Moates ~

11 5/31 AUTOMATED METHOD FOR DTMN . OF TOTAL &REDUCING SUGARS IN LIQUID SUGAR Diffee/Sheppard x

12 6/1 AUTOMATED METHOD FOR DTMN . OF TOTAL & REDUCING SUGARS IN LICORICE Diffee/Sheppard x

13 7/21 A STUDY OF THE DTMN . OF NICOTINE ALKALOIDS IN TOBACCO Diffee/Sheppard X

14 9/6 NICOTINE SALICYLATE AS A PRIMARY STANDARD FOR NICOTINE Diffee/Sheppard x

16 10/4 SYNTHESIS OF HERBICIDAL PYRIDINE & PIPERIDINE COMPOUNDS II Moates/Dickersonx

17 11/16 SYNTHESIS OF TOBACCO COMPONENTS AND FLAVORANTS Moates ~

18

19 12/7 FOREIGN SOLIDS ON TOBACCO Harris/Wheeler K


:
c. I. . . / . ~,~;urow, wr4el M e-1~~- v f 717~ x

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I n t er-off i ce Memo~ran d um
~ Subject : Nicotjpe and Smoker Satisfaction Date : January 4, 1978

P..y s3

To: Dr . Alan Rodgman


SECRET From : D . H . Piehl

OBJECTIVES :
The ultimite goal of this research is to provide the means to maximize
smoker satisfaction for all RJR cigarette brands, with particular emphasis on
low''tar" cigarettes .

Specific 1977-78 objectives are :


1 . Determine the taste_ characteristics of nicotine and factors that
affect its perception .
Determine the means to alter and control "tar"/nicotine ratio and
inc A Y icotine transfer efficienc . r

r3 .' Define the optimum nicotine level in cigarette sroke required to


maxi:mize moker satis action . etermine the existence of a minimum or
r"'"'thre*i value of nicotine required for satisfaction .

Identify any other factors that are important to smoker satisfaction .

, 1 . Nicotine Taste and Perception


~
~M4 Good progress has been made on defining the taste and perception of nicotine
and this objective is nearly met . However, future work will be aimed at an
attempt to establish nicotine limits with respect to irritation and more direct
correlation with smoke .
•Nicotine is irritatin - All of the evidence on the taste of nicotine, '
eitherin solution or in aerosol form, supports the conclusion that it is harsh,
particularly in the back of the throat, and contributes to tongue bite and nasal
sting . The intensity of irritation is related to concentration . Panel tests with
a new monadic ballot also show that smokers highly associate perceived irritation
and nicotine strength with actual smoke nicotine level . Nicotine irritation can
be masked by the addition of certain acids and sugars, but high levels are required .

•Some nicotine irritation is necessar - Nost panel smokers describe their


ideal c garette as av ng some rr tat on and moderate nicotine strength . However,
most test cigarettes and competitive brands are rated as too irritating . This
suggests that there is a desired nicotine level for optimum taste, tw t it may or o
may not be related to the level required for optimum satisfaction . ~
. N

RJR2106
RJRI FORM 2422-Rvv . 7/70
2

•There is a threshold value for detection of nicotine - Tests with


nicotine-water so utions s ow t at very low concentrat~ons of nicotine are
still detectable (ti .005% w/w compared to ti6x for smoke) and buffering capacity
of saliva is sufficiently great to offset any differences in pH of the solution .
However, when nicotine is in aerosol form, similar to smoke, a higher concentra-
tion is required to be detected . It is clear that nicotine taste is concentra-
tion dependent, but it is not clear how this relates to smoke, and the threshold
value for nicotine irritation has not been established .

•"Tar" masks nicotine taste - The "tar" level and "tar"/nicotine ratio
are important to t e-perce ve taste of nicotine . In triangle tests wtih small
panels and the Reynolds #1 cigarette, smokers can distinguish a cigarette with
11 .1 mg "tar" and 1 .4 mg nicotine (T/N = 7 .9) from a control cigarette with the
same blend without nicotine, but surprisingly cannot distinguish a cigarette
with higher "tar" (26 .5 mg) and nicotine (1 .76 mg) (T/N - 15 .1) from a control
cigarette without nicotine, due to an apparent masking effect .

•Puff volume affects taste - Harshness was found to increase linearly with
the concentration o per puff in controlled puffs delivered to smokers .
Nasal sting and tongue bite also increase, but not as sharply at large puff
volu Flavor and preference increase linearly up to the TPM level delivered
by t rage puff then preference decreases and flavor shows marked curvature
at 1 t-puff volumes .

{iLit le nicotine transfers to saliva - Experiments to neasure how much


icot s trans erre from t e smo e to the mouth have shown that an average
0-40 difference) of the nicotine taken into the mouth remains there, but
nly l-~ •of available nicotine transfers to the saliva . This residual nicotine
in t 1 cavity may be further implicated with taste or aftertaste .

2 . "Tar_*Nicotine Ratio and Nicotine Transfer Efficiency


Iwo
Good information on the contribution of individual blend components and
tobacco type to "tar" and nicotine delivery has been obtained . It has been
demonstrated that blending alone can greatly alter T/N ratio, while to date
other techniques, such as adding nicotine or other additives,have been less
expedient . No breakthroughs in substantially increasing nicotine transfer ~
efficiency were achieved . Work in 1978 is aimed at determining how nicotine is _j
bound in tobacco and transferred to smoke so that specific means for increasing m
transfer efficiency might be developed . Ln
N
The question of what T/N ratios are optimum at various"tar''deliveries is N
still unresolved . Most of the evidence suggests that full flavor cigarettes
(>15 mg "tar") have sufficient nicotine . In fact, Marlboro continues to show
increased T/N ratio . At low "tar" delivery (<10 mg "tar") the most acceptable
experimental'blends, have T/N ratios no lower than 9 or 10 . Our best 1977 Research
low "tar" cigarette designs have T/N ratios of 10 and 11 at a "tar" delivery of
7 mg• ow
~
~

RJR2107
3

%Flue-cured tobacco most im ortant nicotine contributor - Data collected


on major components show t at ue-cure tobacco has t e i ghest tobacco to
smoke nicotine transfer efficiency (14%) . Flue-cured tobacco also has the
lowest smoke T/N ratio (10) and is usually the largest blend component . There-
fore, despite the fact that burley tobacco usually has a higher nicotine level,
flue-cured tobacco contributes more nicotine in most blended cigarettes than -
any other blend component . However, uncased burley tobacco has a nicotine
transfer efficiency comparable to that for flue-cured tobacco . G7 has the
lowest nicotine transfer efficiency (8 .4%) and a high smoke T/N ratio (23)
and therefore contributes the least nicotine to the smoke . Experimental blends
with T/N ratios Aown to 5 were prepared demonstrating that very low T/N ratios
can be achieved at low "tar" delivery, but all of these cigarettes were disliked
by smokers .

•Added nicotine transfers less efficientl - Experiments with nicotine


added as t e free base an as ma ate sa t to various blend components show that
it transfers less efficiently (6-8") than inherent nicotine and with little
difference between tobacco types . These results do not agree with some litera-
ture reports . However, much higher transfer efficiencies were achieved when
nicotine malate was added to the denicotinized tobacco used in the Reynolds #1
ciga

ticed casing lower "tar"/nicotine ratio - A comprehensive P.SM-designed


casi" s u y sho .ved s~gni icant pre erence or a 4IINSTOy-tyce cigarette with
~i-edu~e sing . The cigarette design with a minimum "tar"/nicotine ratio and
~al so gas-phase delivery had approximately a 30% reduction in total sugar,
4~lico nd cocoa .

rw.%rlboro i ncreases T/N rati o whi 1 e WINSTON remai ns constant - A hi storical


stud 'IN T N and ~•;ar boro tar' a-n-a n cotine va ues s owzd that with the
exc~~
e ,, of annual crop variations and a gradual decrease in "tar", WINSTON
T/N rat o has remained relatively constant since 1972 . However, there have been
several apparently intentional major changes in Marlboro since 1969 that have
caused its 7/N ratio to increase significantly . This was achieved by reduction
in "tar", but even greater reduction in smoke nicotine . It would appear that
the Marlboro T/N ratio is trending in the opposite direction compared to WINSTON .
Compensation for an increased T/N ratio by increasing smoke pH and therefore
higher free nicotine is not'the total explanation, because WINSTON pH has increased
to the point that the free nicotine values for both WINSTON and Marlboro are now ,
much closer, the Marlboro still having a higher value .

Somehow annual crop variations are leveled out very effectively, in Marlboro
and although the changes that are probably intentional are seemingly in the
wrong direction, the consumer appears to have proven them right . We must admit
that they likely know something that we do not .

3 . 0 tp imum and Threshold Nicotine Values

Little progress has been made on defining the optimum nicotine value to
maximize satisfaction and no progress has been made on defining the existence
of a threshold or minimum value . However, a consumer study planned for 1978 is
intended to help shed some light here and progress has been made on designing
test cigarettes for this study .

RJR2108
51710 5283
4

a.Ex erimental blends reoared - Ideally, a series of test cigarettes


with t e same tar de iveryan taste characteristics, but varying nicotine
level is required to determine optimum and minimum nicotine requirenents . The
same test series should then be repeated at different "tar" deliveries so that
both high and low "tar" cigarettes are evaluated . If possible, pH should also
be controlled as an independent variable . Except for Reynolds #1 cigarettes
with various levels of added nicotine, test cigarettes of this type, meeting
all requirements, have never been successfully prepared . In 1977 some success
was achieved in preparing test cigarettes at "tar" levels of 5, 10 and 15 mg/cigt
with various nicotine values and T/N ratios from M to 22 .5 . Taste characteristics
were held reasonably constant so that trends could be observed with the Research
booth panel and a new monadic ballot . As reported under the section on nicotine
taste a high correlation was observed for reported irritation and nicotine strength
with actual smoke nicotine level . No success was achieved in the variation of pH
independent of nicotine level .

•Preliminar o timum nicotine value identified - The preliminary data above


apparent y revea an opt mum n co ine eve o , mg/puff . These results
•should be regarded as unconfirmed at this point . However, it is of interest to
speculate since the value for tiINSTON has usually been over 0 .15 mg/puff and the
valutA wMarlboro 0 .13 mg/puff or less .

l . ioloQical response to nicotine difficult to quanti .fy - Measurement


of t p sioT-ogical response to nicotine by some rapt and non-invasive technique
r0oul be convenient indication of nicotine satisfaction . Nicotine is known to
~ause ' mber of small changes, such as increased pulse and heart rate, decreased
empee e of the fingertips, and altered EEG . Pilot studies on the measurement
f f .• ip temperature and pulse rate for a small group of Research subjects
showe i ferences before, during and after smoking, but they were almost impossible
M,
.to qu ate . Individual differences and day-to-day variations are great . There
is li expectation that a successful technique will be discovered, but we will
continue~o search .

•Consumer stud bein lanned - Together with Marketing Research a special


consumer stu yIs being eslgne t at will involve the use of the experimental
cigarettes described above . Smoking habits, cigarette consumption and preferences
will be followed for a large representative consumer panel with the aim of
establishing optimum and minimum nicotine levels as well as obtaining a better
understanding of smoker satisfaction . Final plans will be completed in January
with results scheduled for 4th quarter 1978 . We will work closely with MRD through-
out this study and with•their consumer psychologist, if they hire one .

4 . Other Factors Important to Smoker Satisfaction


•Im ortance of smoke pH is unclear - The role of smoke pH in smoker satisfac-
tion is no c ear . t s o v ous y important to taste, but how this relates to
nicotine level and T/N ratio is not well established . It has also usually been
assumed .that smoke pH determined "free nicotine" content of the smoke, and it
is calculated on that basis . However, recent evidence suggests that "free nicotine"
in the mouth is determined by the pH of the smoker's saliva . It is hoped .that ~,
experimental cigarettes can be designed with smoke pH as an independent variable . W
but the probability for success is low . ~+

' • R J R2109 - 51710 5284


5

9Smokin behavior is bein activel studied - An increasing amount of


research n the wor d is being devoted to smo ing behavior . Unfortunately
most of it is aimed at smoking cessation . The importance of smoking behavior
and basic motivations for smoking could be critical to understanding smoker
satisfaction . Unlocking the key to smoking pleasure or the positive motiva-
tions for smoking whether they be physiological or psychological, could mean
the difference between success or failure of future tobacco products . RJR is
funding some basic research on the relationship between personality and smoking
behavior and we will stay abreast of that research as well as staying up-to-date
through the use of outside consultants . Together with these consultants we will
decide on the desirability of hiring our own in-house behavioral scientist .

•~Nicotine pha~rmaco~loa - There are no plans to do any in-house research


relate to o icotine pharmacology, but 'recent research on brain chemistry suggests
that certain chemicals, some of which are nicotine-like alkaloids, act on the
"pleasure centers" of the brain . In fact, some researchers are actively working
on nicotine and its role in brain chemistry in an attempt to identify how it works .
This research could provide breakthroughs in understanding nicotine satisfaction
and we will at least try to keep up-to-date with the literature .

COPag.U$IONS :

?°"lde have yet to adequately understand smoking satisfaction . Obviously,


" nic in• is important but just how important has not been defined . The relation-
""ship een nicotine taste and nicotine satisfaction is not clear . Smokers
a ,app be able to identify nicotine on the basis of its taste, which they
ass with irritation, but surprisingly cannot detect, on the basis of taste
alo e, v ey high levels of nicotine when accompanied by high "tar" delivery and
'ther high T/N ratios . Whether upon extended smoking they would be able to
dist sh different nicotine levels on the basis of nicotine response alone
is not kriown . Nicotine taste and satisfaction may be totally independent responses .

Although it appears that T/N ratios below 10 are not required, these results
are based primarily on taste and limited smoking . An extended-use consumer study
hopefully will be more definitive in identifying optimum and minimum nicotine
levels . Increased nicotine may not be required in the near future, particularly
with record high nicotine values for flue-cured tobacco in 1976 and 1977, but
we must be prepared for those low nicotine crops that will surely come . .

We have made substantial progress in obtaining general knowledge, but as


in all new research areas, we have probably raised more new questions than we
have answered .
6

ACKNOWLEDGMENTS :

The work to date represents the combined effort of several different


groups in two sections . The following individuals have contributed :

Dr . W . M . Henley Dr . M . E . Stowe
Dr . J . P . Dickerson Dr . C . E . Rix
Dr . C . L . Neumann Dr . D. Lynm
Mr . M . D . Shannon Dr . T. A . Perfetti
Mrs . M-J . Wallace

:ki

*2h1'1'l
SECRET
~~ ~
Authors : Thomas A . PerlfilEQi ~`°'~ Y anuary 30, 1978
• Lawrence E . Nayes
Division : Chemical Research Notebook Pages : 306351-306353

CIM, 1978, No . 2 Dated . . : January 26,. . 1978


No . of Pages : 2 Previous Reports : None

Disclosure No :

.IMPROVED AMMONIATED RECONSTITUTED SHEET

SUMMARY :

Chemically bonding ammonia ;as the pectate amide and nicotine as the
pectate salt into ammoniated reconstituted sheet should improve the nicotine
transfer a vor of RJR•tobacco products .

\ MEMORANDUM :}

~~ m0cotit nsfer may be increased by the incorporation of ammonia


~~ i n ~:4forin 't.he pectate amida in reconstituted tobacco sheet . This may
be~"M.1,eved ~ hddiifhhh
e aton o ammonium pospate eitern the form ih of te
mono- or di ium phosphate in the pulping process . It is known that
ammonia is to breaak down the pectin in tobacco . It is believed that
pectin chemi ~~y binds the ammonia and available nicotine as the amide and
nicotinic sa I-respectively . T.hese compounds, therefore, will be chemically
bound into the s•heet . The transfer•of nicotine may be enhanced by this
process since the nicotine pectate is relatively thermally stable . The
temperature needed for the release of free nicotine from this salt occurs at
a temperature higher than that needed for pyrolysis of nicotine . What this
may mean is that in our present reconstituted sheet where most of the nicotine : :
is sprayed onto the surface, pyrolysis of nicotine may be taking place before a :
sufficient quantity is transferred . The proposed ammoniated sheet should
resist nicotine pyrolysis and merely cleave the salt releasing more intact,
freein cot
i nein to t h e ma i
nstream 0
. ur present
i ammont a ed uses ammon
.s ee th ia
~ gas . It has been shown in our laboratories that this ammonia is predominately
adsorbed in some manner onto the sheet . This ammonia is released on standing
and can be removed entirely by heating at 80-90° C for a short period of time
(1 hr .) . The Philip Morris sheet also releases some aminonia but seems'to
transfer more nicotine than our sheet . It is our belief that a portion of the
ammonia and most of the available nicotine are chemically bound in the sheet .
The taste of WINSTON A using the ammoniated sheet resembles Phi1i Morris'
Marlboro but on heat treatment the WINSTON A reverts back to WINSTON while the
Marlboro retains its same taste .
,r

Distribution :
Dr . A . H . Laurene, Dr . M . Senkus(file)
Dr . A, Rodgman, Dr . H . J . Bluhm,
Library (file)
Mr . R. H . Cundiff
Dr . D . H. Pieh1, Dr . M . E . Stowe (file)
Mr . J. A. Giles, Mr . J . P. Clingman,
Dr. W. L . Clapp, Dr . C . T. Mansfield,
Dr. J . T . Dobbins, Dr. W . M. Henley,
Dr . J . N . Schumacher, Library (file)
Dr. T . A. Perfetti
Mr . L . E . Hayes

~..
~

RJR23g10
2

Considering the facts that :

1 . The blends of Marlboro and WINSTON are very similar


except for the type of reconstituted sheet,

2. WINSTON A and Marlboro both use ammoniated sheets and


resemble each other in taste, and .
3 . On heat treatment WINSTON A reverts to WINSTON but
Marlboro retains its identity,
the composition of the twb different reconstituted~sheels represent the
major difference .
It is our belief that if ammonia is incorporated into our sheet, in its
preparation, that both amidation and salt formation will occur and will afford :';
a better, more stable reconstituted sheet exhibiting the properties of the
Philip Morris sheet and hopefully increasing the nicotine transfer .

Distribut_io_n_a

Read and understood by me :

f. ~
&A .. I 3a
Ai ness
•' l. ~ .J

~~~
' • FEDERAL TRADE COMMISSION
TVaslilng ton, D.C. 20S80
OFFICE OF lNFORMATlON M-6800 Ext. 197 .
For ItCLEASE:It.4EDIAT%, Friday, tlarch 25, 1956 . ~-

, The Federal Trade Cosmission today announced that it has sent identical letters

~ to each of the nation's major cigarette manufactui•ers and to Mr . Robert D . Meyner,

: Administrator ot The'Cigarette Advertising Code, Inc ., in regard to factual state-


sunts of tar annicotino
d' content on labels and in advertising of cigarettes . ,
,
~ The text of the letter is as follows : .
.i
i
i i . , Gentlemens
. The Cigarette Advertising Guides promulgated by the Commission in
, September 1953 provided that no representation should be made that "any .
brand or cigarette or the smoke therefrom is low in nicotine or tars * w* '
when it has not been established by competent scientific proof applicable
at the ti wa o f di ssem i nation that the claim is true , and if true , that ;
such difference or differences are significant ." On the basis of the ~
---•--••--••- •• facts now available to it, the Cosmission has determined that a factual .• .
statement of the(ar and nicotine content (expressed in milligrams) of ~
the mainstream ar.oT ce lrom a cigarette vould not be ! a vi ola tion of such
Guides, or of any of the provisions of law administered by the Co=sission,
so long as (1) no collateral representations (other than factual state-
meats of tar end nicotine contents of cigarettes offered for sale to the ,
public) are made, expressly or by implication, as•to reduction or elimina-
; , , tion of health haaards, and (2) the statement of tar and nicotine content
is supported by adequate records of tests conducted in accordance with
the Cambridge Filter Method, as described in an article entitled " Deterrai -
nation of Particulate Matter and Alkaloids (as Nicotine) in Cigarette
Smoke," by C .,L . Ogg, which appeared in the Journal .of the Association ~ :
. of Of,ficial Agricultural Chemists, Vol . 47, No . 2, 1964 . It is the
Comission's position that it is in the public interest to promote the
• dissemination of truthful information concerning ,eigarettes which msy be
materi~al and desired by the consuming public . ~•-
~' . Hy direction of the Cosoaission .
Joseph W . Shea,
Seereteay.

,
O
r

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