Beruflich Dokumente
Kultur Dokumente
Plaint`iffe,
) Alan Rodgman,
) Ph .D .
THE . .AMERICAN'TOBACCO''COMPANY, )
INC ., et al ;, ) Volume 4,
) Pages 522 - 739
Defendants . )
)
- ---~ ------~---------
----------- -- _ _)
-
forerioon .
(201) 992-4111
Vol . 4, Pg . 52 3
Plaintiffs ,
Defendants .
----- - --------0 .,-- --~ :. :--------- )
Plaintiffs ,
agains t
Defendants .
--~---------------------- )
(201) 992-4111
Vol . 4, Pg . 524
- 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 . )
- --- -- - ----- - -- =-------------------- -- )
-- - -------------- - -- --------------)
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
----- ------ - -- - -- _-- - --------- -)
-----•-- -----------------------------)
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 . )
----------- .. ....------- .-----------=------- )
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
A P P E A R A N C E S (Continued)
I N D E X
ALAN'RODGMAN, Ph :D . .
Maistros'' 532
j X H_ I B I T S
PESCRIPTION IDENTIFICATION
Vol . 4, Pg . 529
11
18 number 110953/96 .
25 number 110952/96 .
. :KNISEL'Y :
18 to start over?
19 MS . KNISELY : No .
(201) 992-4111
Vol . 4, Pg . 531
r
New Jersey .
pla3.ntiff .
11 MR . LEE :
12
(201) 992-4111
Vol . 4, Pg . 532
2 ALAN RODGMAN, Ph .D .,
EXAMINATION (Continued)
BY MR . MAISTROSs
8 you?`
10 R
11
12 Q
13 pleasurable experience .
22 A. Yes, sir .
25 probably .
(201) 992-4111
Vol . 4, Pg . 533
2 Mr . William Blancato .
Could :'you
8 R-Or-D-G-M-A-N :
10 Rodgman?
13 I m a Ph .D . in organic chemistry .
14 Q. Organic chemistry?
15
20 North Carolina .
22 of moving, relocating?
25
(201) 992-4111
Vol . 4, Pg . 534
4 No .
Yes .
Q . How many?
Three
12 BY"MR . MAISTROS
13
21 What- ' s,
22 Mark Rodgman .
23 manager,of personnel'trainingl
(201) 992-4111
Vol . 4, Pg . 535
Yes .
Q What years?
4
10 was born' in
11
12 Q When did y
14
15 °'Twenty-six-years :'
18
19
20
21 Did you .
221
231 I went i
24 R
25
chemistry .
4 Q
5 University of Toronto?
6 Eight yearsi .
11 respectively .
17
19 tobacco?
21 Q . What '`month?
25
2 Reynolds?
And for t .he summers, and then during the falls and
11 f .Medical Research?
15 carcinogenesis . ;
17 A. was a -- did_research .
18 What is "carcinogenesis?
20 carcinoma is formed_ .,
21 0. What is a
22 Carcinoma is a tumor .
25 N
cancer .
10 certain compounds?
11 3t e s . That'a=what I was-there-for .
14 Yes .
17 . It wasn't too'succeseful .
19 left?
20 Yes .
21 Q•
22 No .
4 know?
15 4 What is a polycyclic?
17~
18 Poly
20 Q
21
22"
A . Mice .
7 mouse .
animals ?
19 the question .
15 gueds, '51/'52 .
16 Q . "They" ;; w o is they?
21 By who? .
22
23
i &
24 hydrocarbons?
(201) 992-4111
Vol . 4, Pg . 543
And
Q . Are they`all,carcinogenic?
10 Q . Are there
11 MS . KNIS.ELY :
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
(201) 992-4111
Vol . 4, Pg . 544
that correct?
. Carcinoma-p'ro'ducing .
carc,inogenic or carcinbma-producing?
the question .
BY MR .'=MAISTROS :
14 1954, or '55?
15 BY MR . MAISTROS t
16 Q Let
25 Compound .
(201) 992-4111
Vol . 4, Pg . 546
1 BY MR . :MAISTROSs
"tumor-producing' or "carcinogenic" or
9 'w .ith?
13 determining'that effect .
19 happen in a mouee :
21
3 different reactions .
9 inhalation .
12 .Right .
13 Q . -- the compound .
14 What_ Y
15 assume, .• . .1
16
18 word .
19 That's
(201) 992-4111
Vol . 4, Pg . 548
Q . ' I , apologize`.
14 Wynder wrote .
17 the .inventor .
18 Q. I wi11 t
23
24 I
25
(201) 992-4111
Vol . 4, Pg . 549
10 Okay .
15 3-methylcholanthrene ;
17 brackets, .
'21, you .get some .that aren'.-t active at all, some are
6 o that ; even?
10 by Kennaway in England .
11 Q . In what beast?
12 Mouse .
18 Q
17 potent?
background to fall'back o
25 cause anything .
(201) 992-4111
Vol . 4, Pg . 553
developed-tumore, or 90'percent0
could -- D
18
19 That would' b
20 aseume1 ` y
.not, promote --
a threshold,limit value .
19 benzoCa]anthracene,'which is a borderline
(201) 992-4111
Vol . 4, g 555
r
25i
(201) 992-4111
Vol . 4, Pg . 556
11 war .
19
14 no .
19 any .
20
(201) 992-4111
Vol . 4, Pg . 558
Q~
mustards?
(201 992-4111
Vol . 4, Pg . 560
7 it .
16 mixture .
25 Yes .
confidentiality agreement?,_
f;riendship things .
11 the workers .
18 hydrocarbons
today?
8 Yes .
Q-
10 work?
11 cigarette smoke .
13 you were doing from '47, .to '53 was -- the end goal
16 . A . Tumor-initiated .
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
(201) 992-4111
Vol . 4, Pg . 56 4
Well, I thin k
Q . Did :you do
10 53 ?
17 coupl e
18 history, .sir .
19
(201) 992-4111
Vol . 4, Pg . 565
studies?
12 hydrocarbon .
16 hydrocarbons in the'environment .
18 eubcutaneously-injected animals,
23 virus-caused tumor .
24 0 Was there a
guessing?
And he
20 I talked about,
21 tumorigenic?
a weird name .
8 0
9 A .
to .dibenzanthracene .
publications .
14 smoke?
21 connection .
6 Q
12 cigarette smoke .
15 H-U-R-T-E-R .
19 future work?
5 Q . What is a nitrosamine?
it .
9 with nitrosamines?
14 Magee?
15 .Magee, M-A --
17 No .
19 . Barnes' work?
feeding .
8 Q . Mostly on what?
9 On feeding .
13 bacon .
17 .tumorigenic?
19 mean
1 Q . W-Y?
2 N-D-E-R .
Q . D-E-R .,
5 that -
A. Wynder .
10 Q . 41 .
14 1950 .
16 get it'right .
20 No .
23 tobacco smoke?
(201) 992-4111
Vol . 4, Pg . 577
9 Yes .
10 Q . How many_times?
16 you given?
23 during .,'-that .
24 Q
25
(201) 992-4111
Vol . 4, Pg . 578
No . American paid up .
A. Yes .
5 Q . What process?
letter, G1'3?
G13 .
13
14
15
16
17
18
19 court action?
20 I have no idea .
(201) 992-4111
Vol . 4, Pg . 579
Charlotte .
4 case7 ~ ~ ~
was guess .
10 N
17 otherwise, notarized?
21 health cases .
24 correct .
25 BY MR .' MAISTROS :
21 record at 10 :44 a .m . m
~
22 (Recess taken from 10 :44 a .m . to 11 :00 w
~
N
23 a .m .)
25 record at 11 :00 a .m .
MR . BLANCATO : I think --
now, but if~we can, .at the break, just check and
.7 a
9 MR . BLANCATOs- Sure .
10 BY-MR: MAISTROS
18 informal setting?
22 talk to him .
23 4. Did he do an article-eventually or
(201) 992-4111
Vol . 4, Pg . 582
4 1970 .
. :
Q . And 'this was,what newspaper?
series, in that'article?
17
18
24 meetings .
(201) 992-4111
Vol . 4, Pg . 583
About my work?
6 Q . Yes .
12 been --
20 A. No .
23
A . No .
A . No .
13 Q . Sure .
1.1 labeling?
16 levels?
(201) 992-4111
Vol . 4, Pg . 586
r
11 Q
12
14 Pritchard?'
15 . . : a . ... .
19 governmental agencies?
25
looking for?
Q . Indirectly, ]
10 governmental-related, but
The ``FDA, ii
16
20 No . Not that I
24 testimony?
25
(201) 992-4111
Vol . Pg . 588
Reynolds in 1994?
17 BY MR . MAISTROS
20 the`:tobacco litigation?
21 Just myself .
24 many' times
'©
. : . Let's l.t' a
six . I don't
Q And i f :: you
11 The documents?
15 so forth .
19
(201) 992-4111
Vol . 4, Pg . 590
Mr . Brancato`-
MR .
7 BY MR .`MAISTROS :
10
14 Womble Carlyle .
16 are they?
17
19
21 MR . .-,ShANCATO : Objection .
2 BY MR. . MAISTROS :
Q Do you have
11 No .
14 Yes .
18 -Reynolds .
21 Q . How, indirectly?
counsel?
Yeah .'
©'
what .
14
15
16 Which'onee?
17
19 court .test-imony?
20
21
22
the'transcript?
Yes .
I :.asked for it .
13 Q
14
15 did .
16 Who else?
18
19 1961 . .
20 Who i Ochsner?
2 testimony?
>
3 Well, he was a :great proponent of the fact
15 So he was .ul
16
24
(201) 992-4111
Vol . 4, Pg . 59 6
What :were`yo u
10 hooking at som e
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 .
I didn't .
MR . BLANCATOs-
10 BY`'MR : MAISTROS3
14
16 o, I didn't .
21
22
23
24
(201) 992-4111
Vol . 4, Pg . 598
there?
10 BY MR .•`MAISTROS
24 production thereof . .
of t.hem .
13 bibliography .
14 MR . BLANCATO : Correct .
16 BY MR .-MAISTROSs
18 counsel?
22
24
25
(201) 992-4111
Vol . 4, Pg . 600
or Bowman Gray?
13 BY MR . MAISTROS s
21
1 N
2 Q .
or~
stuff is now .
11
12
16
19 other testimony?
20 A. No .
25
to him about it .
10 No .
13 A. No .
15 Wallace Hayes?
17 1987 .
20
(201) 992-4111
Vol . 4, Pg . 603
10
11
13 most of my
14
16
17
18
19
20 .
1 Twice .
0 Okay . -you-are a
9 Womble'Carlyle,'t .hough? .
10 . Right .
11 And`'d
13
14
1 before .
4 Yes . Yes .
7 A .
©'
those documents?"
10
11 Q
23 addiction or habituation?
25 areas, sir .
Q. No .
10
15 No . . Up till
16 after ; that .
17 .Q .
19
20 Q
(201) 992-4111
Vol . , Pg . 607
2 $12 0 an hour .
Yes .
,$140 an hour .
4 8
14 A .
15
16 Arch?
17
18
19
m
20 s Ochsner,still .alive?- ~~
~
%D
21 think so,
in New Orleans?
And : -
11 And, 'o
25 health situation .
6 litigation .
15 activities . And
16
18 .{ MR . MCD$RMQTT
19
21 MR . MCDBRMOTT .
Ln
22 approximately, to 1966''or I-A
%4
251BY MR . MAISTROS :
1 Q . Is .that_'correct,
. Yes .
7 Well I had
13 al1 that stuff .in New Orleans . .- You .come with it,
19
21 VIDEOQRAPHER : : M
22
23
24
25
14
17 division .
20
22
24
(201) 992-4111
Vol . 4, Pg . 612
what?
8 0 Okay .
12 record at 11 :41 :a .m .
14 a .m .)
18 BY MR . MAISTROS :
20 opening at .Reynolds? :;
(201) 992-4111
Vol . 4, Pg . 613
Q •; Had you
companies?
advertised?
Research chemist .
10
11 particular division?
13
14
20
21 old
you joined?
of ; ;years .
10 know?
11
12 It sti11 exists .
19 Everything : .
23 bad?
doing?
10 aoodyear .?
11
13
18 Oh, yeah .
19
21 articles to tobacco?
23 D
18 No . I , don
19 Colby 'was
20
Ln
21
22 manager, as opposed
24 Univereity in Switzerland .
©'
A .
5 20 .
18 .-so on .
department?
14 chemical division .
17
13 called
16 biological work .
19 Yes', in
22
23
24
251
or was it
10
11 Nothing specific .
12 4 Chemical research .
13
19 . No .
20
23
24
10
19
23 finished .
24
25
(201) 992-4111
Vol . , Pg . 625
Can we get
the'record to show
3 MR . LEEs
fr-om"Philadelphia .!
16 I've forgotten
17j
18 it like a .Confidentiality
19 agreement,
' . .80s
first?
10 Thatl s
12 St6el or whoever .
15 Reynolds?
16 No .
23 provided?
(201) 992-4111
Vol . 4, Pg . 627
2 BY MR . .MAISTROS
11 is 'or
14
15a
16
17 ;_anything .
22 period?
(201) 992-4111
Vol . 4, Pg . 628
have no I
12 that case?
15 was .
17 trial?
18
19
20
2i
22 Did you
23
I've forgotten . .
Another
8 New Orleane .
9 a . I
11 in .:New -0rleans :
14 bel,ieve .
15
24
Louis?
the
10 4
11
16 quit•
19 him . .
23 .
24 .m , . to . 1 :26 : p .m . )
25
Vol . 4, Pg . 632
f
12 Q.
13 being tumorigenic promoters, are there different
14 kinds of phenols?
15 V3.tamin E °
18 divert cancer :=
19 Q . Vitamin E?'
20 MR . SHELLER : I knew it .
21 THE WITNESS3
24 various phen,ols .
25 BY MR . MAISTROSi
18 promoters .
doesn't promote? E
Q .: Forever?
8 Q
It .was then . It i
15
24 than promoters .
(201) 992-4111
Vol . 4, Pg . 635
such work?
5 Q
or verify or dispute whether`phenols were
promoters?` :
19 as,'promoters? . .
20 No . Once the -
25
wro~'lg .
Q . What's an'indicator?
14 wrong,conceptg
18 smoke?
19
25
smoke?
17 were potentially`,promoters?
21
Ln
N
22 with a level'of polycyclice that normally wouldn't
(201) 992-4111
Vol . , Pg . 638
,Right .
, test
20
(201) 992-4111
Vol . 4, Pg . 640
-the'polycyclics :
11
12 When?
13 t i '84 . I've
14
21 statistical standings :`
Ln
22 And ; as
. ..
I. say, Wynder and Hoffmann, '~
. . . ~. .. ~ ~ - . ~ . '~. F..
cancer?
hydrocarbons or benzo[alpyrene .
10 forms of cancer?
11 Oh, no . Nc
14 and cancer?
15 A . A statistical association .
23
24 it surprised me .
(201) 992-4111
Vol . 4, Pg . 642
24 Q Were-you --
(201) 992-4111
Vol . 4, Pg . 643
done .
17 polycyclic
23 nonsense?
24 A. Ln
the form .
2 BY MR . MAISTROS :
15 fa.nd it .
16 And in our•
24 0c)
25 0
(201) 992-4111
Vol . 4, Pg . 645
6 controversy as to whether
13 tested?
M
23 they are there? m
~
24 I knew that in '56 . . 1 said -- I think you're ~
cn
-1
1 I think I-did .
10 problem .
21 Naphthalene .
,
22 Q . Was your'research to reduce the
14 .cigarette`ligh"ter .
15 Well, ` it
16 well, it come from something in the tobacco . And
NELLI
Vol . 4, Pg . 648
And in ..1960
19 problem?
20 The .other
(201) 992-4111
Vol . 4, Pg . 649
r
14 ended that .
18 period?
-second, on filtration --
A . . Pardon?
22 t for
r
23 did'it . Dr . Samuel Jones invented it .
it fast .
6 Tobacco Company .
19 start over .
20 The .'
23 to 'smoking?
25
(201) 992-4111
Vol . 4, Pg . 653
exptored?
y. ;
A ." `"Not "that- I .recall . It may have been
15 1957 .
(201) 992-4111
Vol . 4, g . 654
No . As
reconstituted-tobacco .
15 his wishes .
('201) 992-4111
Vol . 4, Pg . 655
expanding it .
13
18
19
22 in ;sequence ,
2 3
cigarette?
11 cigarette program?
24
25 Q
(201) 992-4111
Vol . 4, Pg . 658
cigarette"?
cigarette?
21 association?
association .
BY MR . MAISTROSt
11 unsafe?
(201) 992-4111
Vol . 4, Pg . 660
4 cigarette smoke .
6 seven years, you did :mice and rat and some chicken
7 studies?
8 A . Well, as I
12 animal work .
17
18 MR .'MCDERMOTT :
19
20 I mean,
251 initiation .
c,ertain compounds? .
14 tumors in .
251 you look at what Reynolds did from 1952, when they
(201) 992-4111
Vol . 4, Pg . 663
4 work?
21 in Chi,cago,
MR . MCDERMOTT :
really, in May_;
6 BY MR . MAISTROS :
biological research?
project?
getting a move on .
21 parties?
23 the question .
25 BY MR . MAISTROS :
19 terminated in 1970 .
21 Pardon?
2 taken in by people .
already .
14 Q . Who's that?
24 week .
25 Who is=that?
(201) 992-4111
Vol . 4, Pg . 670
13 minutes .
14 BY MR . MAISTROS :
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 .
record at 2 :23 p .m .
p .m,)
record at 2 :40 p .m .
7 BY MR . MAISTROS :
11 Yes .
24 employees?
11 "Mouse Houee
12 A . `` I have no idea
15 A .` Dr . `Eldon,Nielson . ;
18 House?
19 I have no idea .
21 No .
23 party conversation?
5 N
9 cancer?
10 No .
they were .
(201) 992-4111
Vol . 4, Pg . 676
3 Tempo .
24 Q. Why not?
(201) 992-4111
Vol . , Pg . 677
there it was .
10 .that matters?
12
14 between cigarettes .
15 Q . Pardon me?
20 MR . MCDSRMQTTs . "Related"?
21 MR . MAISTROS : Related .
23
24
25
it .
the question .
around so much
10
11 4. Let me
12
20
23 association .
caused by smoking?
7 by smoking?
9 the question .
15 BY MR . MAISTROS
20 experience?
anything .
10 existence .
14 and cause .
(201) 992-4111
Vol . 4, Pg . 681
12 4•
(201) 992-4111
Vol . 4, Pg . 682
4 inhale .
(201) 992-4111
Vol . 4, Pg . 683
MR . MCDERMOTT : Objection . No
foundation .
or not .
BY MR . MAISTROS :
13 MR . MCDERMOTT : Objection . No
14 foundation .
17 mistake .
18 BY MR . MAISTROS :
22 MR . MCDERMOTT : Objection . No
23 foundation .
25 1 opinion?
1 MR . :MAISTROS : Yes .
THE WITNESS : No .
3 BY MR . MAISTROS :
inappropriate .
BY MR ;MAISTROS s
14 MR . MCDERMOTT : . Objection :
15 foundation .
all this
10 No, I do not .
5 related to smoking?
14 itself .
16 misstating --
18 spoken to that .-
19 BY MR . MAISTROSs
21 A . Yes .
23 No .
g I randchildren smoked?
12 Not particularly .
17 control of it .
25 A . Did I?
Yes .
2 A .. No .
was`published?
10 might take it on .
13 department?
14 Edited?
15 Yes .
16 0
can do it again .
(Record read)
5 BY MR . MAISTROS :
7 Agreement?
8 A . . .~Yee .
13 of it, I think .
15 Agreement?
16 MR . MCDERMOTTs Objection .
171 foundation .
19 BY MR . MAISTROS :
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
companies?
15 Q . Talk to who?
16 Management .
17 What year?
18
19 Did` -- I
20
research in-house?
10
16
(201) 992-4111
Vol . 4, Pg . 692
and -
10
12 eubstitute .
22 of Industrial"Bio-Test?
23 A, Did I ever<see'any?
24 Yes . Ln
0
14
on our work?
Yes .
were tumorigenic?
2 BY MR . MAISTROSs'
18 something else .
10 so on and so forth .
15 A. No .
5 retirement or whatever :
19~ there that Penick & Ford would have the rights to
BY MR . MAISTROS ;`
11 fashion . Maybe ao .
14 with-those documents?
15 I think so .
181 litigation?
19 A. .' Yes .
22 business at Reynolds? .
25 Q Okay .
(201) 992-4111
Vol . 4, Pg . 698
11 University of Toronto .
12 BY MR . MAISTROSs
17 Reynolds?
18 Yes .
22
25 A . Yes .
12 documents?
13
16 relevancy?
10 MR . MAISTROS : Historically
14 4 :30 .
15 BY MR . MAISTR,OSt
16 Q. Now -
18 BY MR . MAISTROS :
23 A.
Ln
24 4 Was one of those in 1994?
(201) 992-4111
Vol . 4, Pg . 702
21 Someplace, yeah .
25 A . Yeah .
today?
19
20 4 -Sutton?
tobacco .
13 product?
19 developing
Commercially?
Commercially .
11 when --
18 months .
(201) 992-4111
Vol . 4, Pg . 708
20 _ so
23 safer cigarette?
you?
f course,
10 t
19 method or -
20 Right .
25 Right .
c,igarettes?
BY MR . MAISTROSs
12
13 They don't
14 And, now,
the question .
8 BY MR . MAISTROSs
13 A . Well --
21 at 20 below zero
22 BY MR .`MAISTROS :
17 published?
22 testing method?
4 cigarette?
10 ciga,rette,, An your''opinion?
21 safer cigarette?
cn
22 ; I don't know . You know, you'd have to say :
J
F-A
(201) 992-4111
Vol . 4, Pg . 714
reports .
16 polycyclics per se .
(201) 992-4111
Vol . 4, Pg . 715
Barclay cigarette .
Q What' prob],em?
tar yield . But when ;the smoker smoked it, and was
12 machine'. And
14
19 substitutes .
4 No, I didn' t .
smok'ing?,
19
20 .
21
22
23
24
(201) 992-4111
Vol . 4, Pg . 71 8
health consequences .
literature ?
14 people .
16 duplicate ?
the question .
8 0 avoid-artifactual formation of
24 w
what was happening, you were preventing the 1~
17 back up a littI le . .
251 supervi.sors .
What year?
24 75,
Reynolds?
6 Tobacco .
13 research?
18 were six•
19 Q . New products?
24 A. Fundamental .
25 Q Unt il when?
Until I retired .
3 Right .
6 another group?
11 doing .
25 biologically-oriented part .
thel .queetion .
BY MR . MAYSTROSs
16 RJR~
17
25 Q Sure .
(201) 992-4111
Vol . 4 g . 725
respond?
17 process?
24 specific
. ones tomorrow, but there's -- there's
6 concept at all?
12
15 demotion?
16 No . I was fired .
17 Q . ; By Reynolds?
18 By Mr . Hoover .
7 You
13 I didn't .
16 Why don't you phone Mr . Ramm and ask him the last
18 when it was .
21
23 incident?
Q. On .what`research project?
6 tired?
name .
13 A . Yes .
24 around 1958 .
something .
12 correct?
3 nicotine .
11 there .
22 bought to put in it . Ln
Q . How° is that?
16 is expensive .
5 country .
10 of a .solution .to it .
11 What's that?
15 that .
16 Q •-
17 manufacturing process?
18
19
20
23
24 You weren't?
25
process?
11 ammonia,
14 where it may .
20
21 Why?
23 nicotine?
(201) 992-4111
Vol . 4 g . 737
11 this day .
14 MR .-MCDERMOTT : Yeah .
16 record 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
changes :
10
11
12
13
14
15
16
17
18
19
20
23 d a y o f -------~------------
25
REPORTER'S CERTIFICATE
14 by the witness .
22
25
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
(Caption continues . . .)
CONFIDENTIAL
TRANSCRIPT of testimony as taken by and
------------------------------------)
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 . )
------------------------------------)
------------------------------------)
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 . )
------------------------------------)
-------------------------------------)
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
--------------------------------------)
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
•
WAGA & SPINELLI (201) 992-4111
Vol . 5, Pg . 745
A P P E A R A N C E S ( Cont inued )
•
WAGA & SPINELLI (201) 992-4111
Vol . 5, Pg . 746
I N D E X
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 .
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
901
903
7B . . . . . . . . . . . . . . . . . . 903
910
928
937
. . . . . . . . . . . . . . . . . 940
. . . . . . . . . . . . . . 954
972
. . . . . . . . . . . . . . . . . 996
996
•
WAGA & SPINELLI (201) 992-4111
Vol . 5, Pg . 747
r
1 ALAN RODGMAN, Ph .D .,
7 9 :50 a .m .
8 EXAMINATION (Continued)
9 BY MR . MAISTROS :
11 you?
• 13
14
correct one thing from yesterday .
Q . Okay .
6 fall apart .
17 A . Pardon?
24 Q . Not me .
3 A . Yes .
19 on and so forth .
21 over to?
22 A . When?
24 BY MR . MAISTROS :
1 attorney?
2 A . Mr . Blancato .
4 this yesterday .
15 MR . MAISTROS : Well . . .
16 BY MR . MAISTROS :
8 invoking privilege .
17 That's nonsense .
18 BY MR . MAISTROS :
9 counsel, correct ?
10 A . That's right .
12 them?
15 BY MR . MAISTROS :
17 the documents ?
2 1 You know -
• m
CO
25 they got from the garage to this room, do that .
• 2
3
MR . MAISTROS : I don't know how that's
privileged .
5 talking about?
6 BY MR . MAISTROS :
8 store them?
9 A . There --
11 answered .
13 BY MR . MAISTROS :
1 additional documents .
10 MR . BLANCATO : No .
24 knowledge of that .
• 25 MR . McDERMOTT : And I --
• 2 perfectly appropriate .
• 13
14
declined that, just so the record is clear .
24 boxes .
2 BY MR . MAISTROS :
4 records of Reynolds?
6 BY MR . MAISTROS :
22 correct .
3 about .
• 13
14
are doing now .
• 25 Mr . Blancato .
12 BY MR . MAISTROS :
Q . Which gentleman?
A . Mr . McDermott .
you that?
11 the one that was -- the opinion list that was sent
20 of cigarettes?
3 BY MR . MAISTROS :
• 13
14
case management order where the final list of
16 BY MR . MAISTROS :
19 at Reynolds?
• 25 its control .
2 manufacturing process?
13 certain ways .
5 and mixed, and it's cut . And there you have the
12 machine .
cigarettes?
10 the question .
• 14 BY MR . MAISTROS :
18 the question .
20 question .
21 BY MR . MAISTROS :
22 Q . What compounds?
24 casing material .
6 process?
7 A . Yes .
8 Q . What compounds?
11 Q . Anything else?
15 Q . What's that?
16 A . It's Freon 11 .
24 chlorofluorocarbon .
process --
10 Q . What was --
16 1987?
• 13
14
problems .
18 in refrigeration .
10 of Freon 11?
11 it .
8 c i garettes .
9 Q. Which agent?
12 you misunderstood it .
• 13
14 process,
Did RJR use any other expansion
16 f rame ?
19 is .
22 BY MR . MAISTROS : Ln
~
J
N
23 Q. Was that the only expansion process m
~
Ln
24 RJR use d? CO
m
13 mixture .
23 Freon 11 .
11 respiratory system?
• 2
3
would -- say, 25 milligrams is 25 million
8 name escapes me .
18 possible .
5 phosgene generation .
18 cigarette .
2 question .
8 balance study .
• 13
14
nanograms, parts per million - that we examine
23 the cigarette .
2 Freon 11?
• 13
14
the -- the tobacco part of the butt, so much in
19 of it .
1 choose .
• 2 BY MR . MAISTROS :
• 13
14
General -- not the Surgeon General, I'm sorry, the
1 was it?
4 Dr . Fredrickson's proposal --
• 13
14
particulate matter in the smoke . And if you
19 answered .
20 BY MR . MAISTROS :
1 A . No, it wasn't .
3 particulate matter?
9 above money .
10 MR . MCDERMOTT : Objection .
12 BY MR . MAISTROS :
17 smoke?
5 tobacco?
13 procedure .
16 A . Pardon?
21 ammonium bicarbonate .
23 process?
• 25 for it .
15 for sure .
18 expansion?
24 process?
9 licensed it from us .
12 overseas?
• 13
14
A . No .
16 Freon 11?
18 prior testimony .
24 would be .
• 25 BY MR . MAISTROS :
1
dioxide expansion?
12 believe --
• 13
14
Q . Do you know if Reynolds ever used
16 back up .
19 process?
• 25 sheet .
• 13
14
ammonium salt .
15 that?
11 they had .
• 13
14
popularity of Marlboros?
18 BY MR . MAISTROS :
• 25 '69 .
15 the lamina .
19 reconstituted tobacco?
21 again, sir .
22 BY MR . MAISTROS :
14 record at 10 :51 a .m .
16 a .m . )
20 BY MR . MAISTROS :
5 the tobacco?
6 A . I didn't .
19 A . No, I don't .
20 nicotine .
22 chemical world?
23 A. Yes .
24 Q. Who?
1 number?
4 number?
12 Marlboro?
17 tobacco process?
1 or to do things .
13 A. 1954 .
17 the question .
19 BY MR . MAISTROS :
20 Q . What research?
3 process .
19 them .
4 pyrolysis of nicotine .
18 '92? Just as a --
19 A . Who?
20 Q . You .
24 tobacco?
25 A . Tobacco smoke .
4 about?
9 determine --
10 A . Van Duuren .
• 13
14
A . No . When we couldn't find it in the nicotine
18 A. No .
Q . A bug killer?
10 A . Bug killer .
13 company?
18 stems to process .
21 been? vn
N
v
22 A . If it wasn't done in R & D, I don't know m
bN
15 A . Largest particulate?
16 Q . Yes .
18 Q . Greatest quantity .
19 A. Water .
21 A . Nicotine .
1 MR . McDERMOTT : Objection ; no
2 foundation .
6 BY MR . MAISTROS :
11 body?
12 MR . McDERMOTT : Objection ; no
13 foundation .
15 BY MR . MAISTROS :
19 A . No .
1 recall .
7 BY MR . MAISTROS :
12 BY MR . MAISTROS :
25 concerned?
3 expertise, sir .
7 A. John H . Robinson .
9 development?
12 there .
23 reported to me .
9 Commission .
11 nicotine?
• 13
14
nicotine work while I was director of research .
1 again, sir .
2 BY MR . MAISTROS :
13 record, please?
17 a .m . )
19 record at 11 :44 a .m .
20 EXAMINATION
21 BY MR . SHELLER :
7 with that?
8 A . Yes, I am .
11 particulate matter?
16 through .
21 A . Well --
23 the jury .
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 -- ~
12 Q . Tar per --
17 A . Uh-huh .
11 to go very --
14 A . No .
18 A . Okay .
20 matter .
21 A . Right . Okay .
8 phase .
16 A . Right .
18 A . Okay .
21 Q . Approximately 20 .
1 A . Right .
2 Q . Approximately .
3 A. Ri g ht .
5 A. Roughly .
6 Q . Roughly four --
8 whatever, krypton .
15 A . Two --
16 Q . Which is carbon -
17 A . Dioxide .
18 Q. -- dioxide .
20 about 20 .
Q . Okay . Now --
13 A . Right . Right .
17 the question .
19 question .
21 the question . ~
~
-3
22 THE WITNESS : I don't quite ~
m
6 the question .
7 BY MR . SHELLER :
11 burn differently .
12 Q. Okay .
4 then - -
7 A. What?
11 generate it .
13 A . Right .
16 A . Uh --
18 the question .
19 Generate what?
20 BY MR . SHELLER :
1 A . Right .
3 about .
6 I object -
8 question .
12 vapor?
17 you --
18 BY MR . SHELLER :
5 filter pad .
9 Q . All right .
8 going to impinge .
21 TPM?
22 A . Uh-huh .
24 A . No .
1 enough -
5 Q . Right .
9 temperature?
10 A . What --
11 Q . 350 degrees ?
15 350 degrees ?
18 centigrade .
25 the particle .
6 is vaporized?
9 isn't in tobacco .
13 A . No .
14 Q . Okay .
20 MS . EASON : Objection .
22 particulate matter .
23 BY MR . SHELLER :
4 A . Nicotine, water .
6 the most --
7 A . Water . Water .
9 A . Nicotine .
11 ones?
15 Q . I see .
20 glycol .
2 word was?
3 A . Humectants?
6 Q . Yes .
18 Two percent .
19 Q . All right .
24 the question .
25 BY MR . SHELLER :
Q . As TPM .
7 A . As far as I know, no .
BY MR . SHELLER :
24 the question .
3 BY MR . SHELLER :
8 Q. Well --
11 Q . I understand .
12 A . Personally .
15 smoke?
16 A . Yes .
23 Many scientists .
5 Q. Uh-huh . Right .
8 Q. Right .
10 be f ree .
12 it will be in the --
13 A . Vapor phase .
17 A . Right .
22 able to measure it .
4 measure it?
5 A . Yes .
6 Q . When?
10 in it .
11 Q . Who was?
12 A . Somebody in analytical .
15 who .
20 it?
23 and tried it .
5 the question .
7 stems .
8 BY MR . SHELLER :
16 A . Sodium hydroxide .
25 it --
Q . But --
whatever .
9 BY MR . SHELLER :
13 nicotine .
• 14 Q . I see .
18 seen it?
19 A . What?
23 A . Water .
24 Q . Water . Is it wet?
Okay .
water?
8 BY MR . SHELLER :
10 water .
11 A . Nicotine vaporizes .
12 Q . Hmmm?
14 Q . It will vapor --
16 an equivalent of steam .
22 BY MR . SHELLER :
24 filter?
1 answered .
2 BY MR . SHELLER :
14 BY MR . SHELLERt
15 Q . -- if it's boiled?
18 question .
21 MR . BLANCATO : Objection --
Ln
22 BY MR . SHELLER : ~
~
~
m
23 Q . -- similar to, for example, the way
~
m
~
24 nicotine is freed? m
question .
3 BY MR . SHELLER :
12 tobacco .
17 A . Pardon?
18 MS . EASON : Objection .
19 BY MR . SHELLER :
~
~
20 Q . It will free it in the tobacco that J
N
m
1 BY MR . SHELLER :
MR . MCDERMOTT : Ditto .
7 BY MR . SHELLER :
9 Yeah .
12 Q . Bug killer .
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
now .
that nicotine?
12 of the question .
13 BY MR . SHELLER :
23 A . Well --
5 BY MR . SHELLER :
19 A . Right .
23 A . Right .
5 the question .
6 BY MR . SHELLER :
7 Q . To your knowledge .
11 A . Nornicotine .
14 the question .
20 BY MR . SHELLER :
2 nornicotine?
4 of the question .
5 MR . BLANCATO : Objection .
7 BY MR . SHELLER :
14 A . Aliphatic hydrocarbons?
16 them?
25 A . Yeah .
Q. What?
the filter?
12 size .
19 A . Uh-huh .
21 A . I don't understand --
23 the question .
1 BY MR . SHELLER :
the question .
12 BY MR . SHELLER :
14 for you .
23 MS . EASON : Objection .
1 BY MR . SHELLER :
5 nicotine .
6 Right .
15 counted it .
20 BY MR . SHELLER :
24 matter?
the question .
3 BY MR . SHELLER :
the question .
anything .
9 BY MR . SHELLER :
16 now --
17 MR . BLANCATO : Objection .
18 BY MR . SHELLER :
1 the question .
2 MR . BLANCATO : Objection .
13 break?
14 MR . BLANCATO : Sure .
16 record at 12 :19 p .m .
18 Mr . Sheller .
20 the record?
22 respond .
3 with .
5 record?
• 13
14
video record at 12 :19 p .m .
interfering .
19 Mr . Blancato is not .
general .
10 further .
14 BY MR . SHELLER :
20 know .
3 BY MR . SHELLER :
I'm sorry .
A . Ingredthsen .
10 to --
16 here or not .
24 does Reynolds --
25 A . I have no idea .
5 or am I mistaken?
11 BY MR . SHELLER :
18 BY MR . SHELLER :
19 Q. I see .
6 BY MR . SHELLER :
10 procedure had come up, about what did the FTC tar
• 25 listen to .
2 A . For myself .
disseminated anywhere?
11 A . That's Dr . Townsend .
20 Gaithersburg or someplace .
25 wasn't there .
Q. I see .
10 A . For this?
12 paper?
` 13 A . No .
say : (Reading)
U .S . was intended to
12 cataloging of sequential
19 conditions . Subsequently a
22 (FTC, 1981) .
24 was : (Reading)
whose MS 11 tar --
Q . I see . (Reading)
MS tar --
11 Q. I see . (Reading)
16 health .
22 cigarette smokers .
23 "Smokers"?
24 A . "Smokers," right .
1 right?
2 A . Well --
3 Q And --
13 BY MR . SHELLER :
A . I think it --
MR . McDERMOTT : Objection . No
foundation .
some packs .
10 BY MR . SHELLER :
17 A . What?
18 MR . McDERMOTT : What?
19 BY MR . SHELLER :
21 method .
23 Q . I see . I see .
The Cigarette
Advertising Guides
promulgated by the
Commission --
13 MR . McDERMOTT : Yeah .
16 itself .
18 BY MR . SHELLER :
19 Q. Okay . (Reading)
20 The Cigarette
21 Advertising Guides
such a difference or
16 (expressed in milligrams) of
23 -- in -- (1) [according to
2 nicotine contents of
10 in an article entitled
11 "Determination of Particulate
13 nicotine) in Cigarette
18 No . 2, 1964 . It is the
22 truthful information
method?
Q . I see .
17 BY MR . SHELLER :
20 it, please .
22 BY MR . SHELLER :
1 method?
2 A . That's right .
6 of the question .
8 BY MR . SHELLER :
10 that .
23 A . Yes .
that time?
say .
document?
MS . KNISELY : Page 37 .
11 BY MR . SHELLER :
16 MR . McDERMOTT : What's 3?
251 on it .
2 believe .
7 BY MR . SHELLER :
13 the question .
14 BY MR . SHELLER :
20 BY MR . SHELLER :
251 frame?
4 BY MR . SHELLER :
7 Commission?
11 to the FTC .
22 gave you?
2 no idea .
9 BY MR . SHELLER :
16 be .
17 BY MR . SHELLER :
21 date on it?
23 the question .
24 BY MR . SHELLER :
1 no difference .
8 11 -- 8 pages of it .
12 it?
16 document .
18 You got me .
20 (Reading)
21 The conclusion is
2 as to the amount or
12 that correct?
13 A . That's right .
15 these years?
20 Q . Now, Doctor
10 system, correct?
12 Q. Right .
18 using it .
19 Q . They did .
20 A . Yeah .
7 see here .
20 and --
22 1973?
13 BY MR . SHELLER :
14 Q . I see .
22 titration .
20 before .
25 the question .
1 BY MR . SHELLER :
3 A . What letter?
5 BY MR . SHELLER :
14 BY MR . SHELLER :
it -
12 words .
22 BY MR . SHELLER :
that?
11 BY MR . SHELLER :
• 13
14
the tar and nicotine levels on the cigarettes?
A . No, it doesn't .
15 Q . It doesn't .
16 A . No .
19 the question .
20 BY MR . SHELLER :
7 it that way?
9 don't --
15 his answer .
17 advertising business .
18 BY MR . SHELLER :
25 of the question .
2 the question .
3 BY MR . SHELLER :
5 remember that?
6 A. Yes .
15 MR . McDERMOTT : Objection ; no
16 foundation .
17 BY MR . SHELLER :
24 A . I don't know .
10 loud .
13 again .
14 A . Why in --
16 A . (Reading)
17 No collateral
20 nicotine contents of
25 please .
1 A . (Reading)
2 No collateral
5 nicotine contents of
8 implication, as to reduction
9 or elimination of health
10 hazards .
13 A . (Reading)
14 No collateral
17 nicotine contents of
20 expressly or by implication,
21 as to reduction or
22 elimination of health
23 hazards .
2 BY MR . SHELLER :
5 Dr . Townsend --
7 BY MR . SHELLER :
Q . -- "expressly or by implication, as to
13 testimony .
16 BY MR . SHELLER :
19 Q . You goofed .
20 A . Umm .
your article .
A . Uh-huh .
16 health .
20 drawn permitted .
23 the question .
24 BY MR . SHELLER :
2 for .
7 the question .
9 MR . McDERMOTT : No foundation .
11 question .
12 BY MR . SHELLER :
20 question .
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
7 BY MR . SHELLER :
Q . I see .
9 A . And that was the reason the FTC got into the
18 was going on --
20 the question .
21 BY MR . SHELLER :
22 Q . -- in the '60s?
24 MR . BLANCATO : Object .
• 25 BY MR . SHELLER :
1
5 A . Well, it's -
18 safer?
21 MR . BLANCATO : Objection .
23 the question .
24 BY MR . SHELLER :
contended?
the question .
7 question .
9 MR . McDERMOTT : No foundation .
11 BY MR . SHELLER :
17 the question .
18 BY MR . SHELLER :
20 MR . McDERMOTT : No foundation .
22 BY MR . SHELLER :
3 MR . McDERMOTT : Dr . Rodgman --
4 BY MR . SHELLER :
6 in 1970?
13 getting outrageous .
21 BY MR . SHELLER :
1 A . What page?
5 A . Uh-huh .
9 am I up to?
11 MR . SHELLER : Six .
12 BY MR . SHELLER :
14 as : (Reading)
15 85-millimeter Winston
20 smoking parameters .
24 Reynolds, I believe .
1 According to Reynolds . .
3 the question .
7 BY MR . SHELLER :
10 A . It may be .
12 report?
13 A . Right .
17 there .
4 format .
6 not sure who did the table, now . But the table
10 Morris ?
11 A . That's right .
13 A . Right .
25 16 .2 ; is that correct ?
1 A . Right .
5 A . Right .
9 A. Yes .
15 the question .
18 different -- under --
19 BY MR . SHELLER :
24 answer .
3 BY MR . SHELLER :
5 mean? The 35 .
6 A . Close to that .
8 A . Right .
10 the opposite .
11 MR . SHELLER : No . I think he --
13 BY MR . SHELLER :
• 14 Q . As I understand it, in 1955 the
16 weren't they?
18 35-milliliter puff .
19 Q . They were?
21 Q . I see .
7 35-milliliter puff?
16 Q . So, then --
17 A . And --
24 today?
6 A . Pardon?
8 how it was --
10 the question .
11 BY MR . SHELLER :
18 graph .
23 calculated numbers?
25 witness, please .
11 Let's -
14 BY MR . SHELLER :
21 today --
3 1955 .
5 talking about the values they got here for tar and
6 nicotine --
7 MR . SHELLER : Uh-huh .
12 smoking in 1955 .
17 BY MR . SHELLER :
20 1955?
22 quotation marks . N
N
23 Q. Right . But why would -- wouldn't m
2 smoking level?
5 question .
7 the question .
8 BY MR . SHELLER :
10 you?
15 you -- in 1955?
21 Q . For now .
24 BY MR . SHELLER :
MR . SHELLER : Fine .
4 BY MR . SHELLER :
7 Dr . Rix reported .
11 him?
14 MR . BLANCATO : Objection .
16 mean, "agree" .
17 BY MR . SHELLER :
24 BY MR . SHELLER :
5 idea .
7 A . No .
9 A . At one time .
12 A . Research .
14 under you?
15 A . Right .
18 A. No .
19 Q . I see .
15 BY MR . SHELLER :
1 A . No, I don't .
the question .
7 don't ."
13 that one?
16 exhibit?
17 MR . SHELLER : Yes .
19
20 MR . SHELLER : Yes .
22
25 1
4 record at 2 :22 p .m .
6 p .m .)
10 BY MR . SHELLER :
16 A . I don't know .
19 A . I don't know .
1 the question .
2 BY MR . SHELLER :
5 the question .
6 BY MR . SHELLER :
11 the question .
13 question .
15 MR . McDERMOTT : No foundation .
17 BY MR . SHELLER :
3 BY MR . SHELLER :
10 time period .
16 improper .
25 argument .
2 BY MR . SHELLER :
10 number on this?
14 BY MR . SHELLER :
19 preparing this?
together?
Q. At Reynolds?
A . Yes .
that correct?
10 it .
16 BY MR . SHELLER :
19 A . That's right .
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 .
1 an expert on nicotine .
6 or 11/2/95?
9 11/25/95 .
10 A . Uh-huh .
13 together .
19 and 7B .
21 comments .
25 BY MR . SHELLER :
6 nicotine level in
7 high-nicotine tobaccos)
16 Q . I see .
19 incorrect?
25 efforts .
5 tobacco?
6 A . Right .
7 Q . It says : (Reading)
8 On an equal weight of
14 Is that correct?
16 tobaccos .
18 that, though?
23 A . Mainstream smoke .
25 mainstream smoke? j
3 testimony .
4 BY MR . SHELLER :
5 Q . Only by particulate?
9 Q . I see .
13 right?
18 saying?
19 A . Right .
21 ammonia, right?
22 A . Right .
A . A little bit .
1 Q . A little bit .
2 smoke .
4 mistaken?
7 Q . Uh-huh .
9 Q . I see .
18 itself . No salt .
24 A . I guess that's --
methods .
3 the question .
6 BY MR . SHELLER :
8 measures things .
12 right .
15 you .
16 I understand . I understand .
21 BY MR . SHELLER :
4 BY MR . SHELLER :
6 A . Oh, yes .
7 Q . So you recall it .
10 Doctor?
13 A . Right .
15 BY MR . SHELLER :
17 says : (Reading)
20 aromatic hydrocarbons in
24 to various species of
• 2 influence of cigarette
8 a carcinogenic factor in
13 data" --
17 f rom?
20 MR . SHELLER : Oh . (Reading)
4 condensate . This
11 MR . SHELLER : (Reading)
12 -- pyrolysis of the
14 process .
17 then?
18 BY MR . SHELLER :
2 is a carcinogenic factor in
4 condensate .
8 change?
12 (Reading)
16 condensate -- condensate, or
20 individual carcinogenic
21 hydrocarbons, anthracene,
22 pyrene, chrysene?
23 A . Chrysene .
24 Q . (Reading)
• 25 1, 2-benz --
1 A . "Benzanthracene" .
4 A . m 3,4-benzpyrene" .
5 Q . (Reading)
6 -- present . Three --
9 plausible at present .
11 (Reading)
12 The carcinogenic
13 activity of the
14 hexane-soluble, neutral
18 powerfully carcinogenic
19 polycyclic aromatic
20 hydrocarbon .
21 A synergistic effect is
• 2 polycyclic aromatic
3 hydrocarbons .
7 behaving as a cocarcinogen
10 compound present as a
11 pollutant in air .
14 disagree with?
16 is wrong .
17 Q . Number 1 is wrong?
13 never found it .
22 Q. Well --
25 subsequently .
2 A . The --
3 Q• Synergistic effect .
15 about --
17 polycyclic hydrocarbons .
25 mixtures --
1 A . No, we didn't .
3 A . No, we didn't .
5 did?
6 A . Oh, yes .
7 Q . Who?
8 A. Dr . Wynder .
10 A . Well --
6 A . -- but -- yeah .
9 Q . I see . I see .
13 smoke?
• 14 A . Well, the tumor promoters were -- the first
17 in smoke?
19 smoke .
20 Q. I see .
5 Q . I see .
14 A . Huh-uh .
24 to be tumor -- ~J
W
J
25 Q . How about nitrosamines? Is that a
5 A . Right .
16 elsewhere .
17 Q . I see .
20 Q . They feed it .
3 MR . McDERMOTT : Objection ; no
4 foundation .
6 BY MR . SHELLER :
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?
18 humans .
2 the lung?
5 his answer .
13 MR . SHELLER : Good .
14 BY MR . SHELLER :
polycyclic aromatic
hydrocarbons --
Q. Page 37 . (Reading)
In considering the
11 of a number of these
16 smoke is required .
23 getting .
11 A . I did?
14 church?
15 A . Yes .
16 Q . Which church?
18 Episcopalian .
21 BY MR . SHELLER :
7 And the fact that that has been done has gotten,
9 Q . I see .
11 him?
16 exhibit?
20 MR . SHELLER : Sure .
22 record at 3 :15 p .m . . Ln
FA
J
24 p .m . )
1 record at 3 :24 p .m .
2 BY MR . SHELLER :
6 Exhibit 9 .
11 I'll just -
12 BY MR . SHELLER :
21 A . Right .
24 correct ?
25 A . Yes .
6 No . 14 .
16 heterocyclic nitrogen
17 compounds identified in
19 again, my pronunciation is
21 methyl-something . Indole
- 25 reported carcinogenic
2 compounds .
3 A . Right .
6 this presentation?
• 13
5 biological issues .
8 Publication?"
12 planning to do that?
16 A. No .
18 smoke .
J
24 Q . Well, how about -- were there any of
8 A . Omit discussion .
10 MR . McDERMOTT : Excuse me .
14 BY MR . SHELLER :
20 conference .
3 promoting, and --
15 carcinogenic .
20 thereafter .
answer .
9 BY MR . SHELLER :
10 Q . I see .
14 MR . BLANCATO : Objection .
15 BY MR . SHELLER :
24 BY MR . SHELLER :
6 MR . McDERMOTT : Objection, no
7 foundation .
10 times .
11 MR . BLANCATO : Objection .
15 BY MR . SHELLER :
16 Q . In a publication?
22 somewhere in there .
5 10 .
7 description, please --
10 BY MR . SHELLER :
• 13
14
of RDM, 1963, No . 4 ." The copy where it's marked
"voided by KHH" .
21 different number .
13 BY MR . SHELLER :
15 this report?
16 A . Oh, yes .
18 "voided by KHH°?
19 A . Mr . Hoover voided it .
20 Q . Meaning what?
2 Mr . Lee .
3 BY MR . SHELLER :
10 Number 4 .
17 this one .
20 "four"?
5 MR . SHELLER : Yes .
8 BY MR . SHELLER :
12 evidence accumulated to
14 health hazard is
20 necessitates acceptance of
2 statement .
5 to it .
8 variation .
9 BY MR . SHELLER :
14 resubmit it to Mr . -- to Dr . Hoover?
15 A . No . No .
17 MR . SHELLER : Page 7 .
11 other one .
12 BY MR . SHELLER :
15 A . Uh-huh .
17 paragraph : (Reading)
18 This report is an
19 extension of a companion
25 mentioned before, if
1 requested, a thorough,
2 fully-documented exposition
4 prepared .
13 say : (Reading)
15 evidence accumulated to
17 health hazard is
18 overwhelming .
22 from epidemiological,
1 cancer is caused by or
3 smoke, is paralleled by
6 cancer is caused by or
8 pollutants . In some
10 to be stronger in support of
11 cigarette smoke as a
12 causative or associated
16 pollutants as a causative or
17 associated factor .
21 proposition, statistical
23 cause-and-effect
1 (criticism of biological
2 evidence) .
4 Metaplasia and
8 no experimental evidence to
10 constituent is carcinogenic
16 cancer-air pollutant
17 proposition .
24 '63 .
5 Q. Right .
19 Recommendations : After
asterisk there] it is
6 Americans classified as
• 13
14
supposed relationship of
15 cholesterol-caused
24 obligations by pointing an
2 smoke-health problem!
3 A . Right .
5 A . Yeah .
8 (Reading)
9 It is recommended that
12 be acquired to study
15 additives .
25 General's Committee on
4 dexterity in biological
5 techniques .
10 right?
12 Q . I see .
14 It is recommended that
16 physiologically active
18 example, polycyclic
19 hydrocarbons, phenols be
20 published . It is recommended
23 published . These
12 unfavorable atmosphere of a
13 lawsuit?
16 he?
17 A . Right .
24 Dr . Hoover .
6 difference .
10 number A and B .
12 we up to? 12 A and B .
14 which is .the B?
17 Hoover -
21 copy by Dr . Bruce .
25 BY MR . SHELLER :
2 supervisor, right?
3 A . At one time .
4 Q . At one time .
10 to be heard, despite my
18 legal department .
21 A . Right .
251 version .
2 BY MR . SHELLER :
3 A. No .
4 Q . All right .
10 copies of that?
• 13
14
copied, do we?
16 BY MR . SHELLER :
21 BY MR . SHELLER :
23 entitled "Discussion" .
6 cigarette smoking, to
15 consistent picture to be
1 statistical, pathological,
BY MR . SHELLER :
9 Q . (Reading)
19 disease, et cetera .
21 (Reading)
1 fluorescent components of
2 cigarette smoke --
3 MS . KNISELY : Biological .
4 MR . SHELLER : (Reading)
5 -- are absorbed b y
11 ciliastatic -- ciliastasis is
15 tobacco smoke is no t
18 cigarette smoke is
19 carcinogenic, cocarcinogenic,
20 and ciliastatic .
24 or arsenious oxide i n
cigarette smoke i s
6 experiment to determine
carcinogenic polycyclic
10 of the carcinogenic
11 heterocyclic nitrogen
1 additively, or inhibitively .
6 components is ridiculous . As
7 an absolute criterion of
11 highly suggestive, is
12 physiologically meaningless .
15 None of the --
20 in studies conducted
21 elsewhere is inconsistent
1 Recommendations . Future
2 Work, 1 .
7 host .
10 Q . Your recommendations .
13 biological host?
15 Q . All of them?
16 A . As far as I know .
18 going to do that .
• 2 A . And --
6 MS . EASON : Objection .
7 BY MR . SHELLER :
9 A. What?
13 Q . No?
14 A. No .
17 BY MR . SHELLER :
1 BY MR . SHELLER :
3 take, Doctor?
' 13 animals they need and what the cost would be?
20 snowballs .
1 your knowledge -
3 to anybody .
5 tobacco industry --
7 Q. Right .
9 Ames testing?
10 A . Dr . Chin Lee .
12 tobacco?
20 tobacco, do you?
25 75, 100 of them, and he had run them all and found
2 Q . Seventy-five or a hundred .
4 Q . Additives .
6 tobacco?
7 A . Additives in tobacco?
10 Q . In cigarettes .
product .
cigarette brand?
15 BY MR . SHELLER :
20 BY MR . SHELLER :
! 25 very simple .
9 no casing, no flavorings .
25 mutagenicity .
6 brands?
10 mutagenicity, right?
12 Q . I see . I see .
18 substitutes .
20 A . Well . . .
5 painting .
10 Q . On the substitute .
13 show you the one that I have, 'cause it's the only
21 A . Giles is a Mister .
23 Dr . DiMarco?
3 Project Area 3 . In
6 carcinogenesis literature
10 cocarcingoens, promoters,
14 Therefore, we propose
15 standardized animal
16 carcinogenesis tests
20 chemical carcinogens,
21 et cetera, to,determine
22 interrelationships more
24 situations .
2 Doctor?
5 Q . I see . Is he a doctor?
6 A . Mister .
10 Q . At 1982?
15 the time?
18 recommended?
19 A . No .
15 BY MR . SHELLER :
22 you prepared?
Ln
H
J
23 A . I assume so . Let me look at it . ~
6
25 this?
2 that .
4 copies?
8 copies?
12 on that?
14 BY MR . SHELLER :
23 It says (Reading)
24 I .A ., Product .
25 Condemnation of nicotine as a
2 smoking-health proponents
4 low-nicotine tobaccos,
5 probability of occurrence
6 70 percent .
10 nicotine on established
15 decline .
17 A . Yes, sir .
21 decline?
1 sell .
7 smoking .
13 A . Oh, certainly .
16 don't you?
18 BY MR . SHELLER :
3 A . No .
5 A . The library .
14 was Mr . Hoover .
22 patent lawyer .
15 to check things .
9 Q . I understand .
12 A . Uh-huh .
16 checkmark is that?
17 A . I don't know .
20 page .
25 looking at .
3 hand .
5 these help .
7 MR . SHELLER : 501524764 .
9 BY MR . SHELLER :
11 checkmark there?
12 A . No .
20 there's a checkmark .
24 page . (Reading)
6 "Not in file" .
18 studies .
23 the authors?
2 know?
3 A . I don't know .
5 number 15 .
9 properties?
18 Q . Where is he now?
1 are?
3 Reynolds' library .
6 A . I would assume so .
8 A . They should be .
10 produced, please?
18 this material .
MR . SHELLER : Okay .
witness deposition .
see if we have to --
11 disadvantage here .
13 leave at 4 :30 .
21 forth .
23 Dr . Rodgman .
2 back - -
4 to be questioning again .
13 following --
5 way .
4 management --
8 extremely distracting .
• 13
14
(Reading)
18 the deponent .
• 13
14
was improper under the orders governing this case .
23 Th an k you . , ~
-J
r
24 MS . EASON : May I also make a m
Ob
10 Perry .
• 13
14
As far as I'm concerned, the Arch
19 record at 4 :30 p .m .
2 1 p .m . )
0
25
WAGA & SPINELLI (201) 992-4111
Vol . 5, Pg . 990
I
1 EXAMINATION (Continued)
2 BY MR . MAISTROS :
4 A . I'm tired .
11 A . Yes, sir .
14 A . Yes .
4 work in-house .
9 tobacco smoke .
11 A . Pardon?
14 develop a cigarette .
15 A . R-A-N .
4 about .
• 13
14
those initials . I mean, I don't know exactly what
19 what it does .
24 A. No .
4 work .
7 Exhibit 16 .
16 more?
18 couple of copies .
23 BY MR . MAISTROS :
5 16, is it not?
6 A. Yes .
8 A . Right .
9 Q . It's to you?
10 A . Yes .
12 A . Dr . Donald Piehl .
15 division .
17 1978?
18 A . Director of research .
2 right .
5 Reynolds?
8 did .
13 was .
23 underneath "Objective"?
24 A . (Reading)
6 "tar" cigarettes .
9 (Reading)
11 characteristics of nicotine
perception .
17 the question .
19 sir .
20 BY MR . MAISTROS :
23 A . Right .
research at RJR?
2 A . (Reading)
10 don't .
22 A . First paragraph?
24 court reporter .
0 25 A . (Reading)
3 A . As far as I know .
16 them .
19 A . (Reading)
23 smoker satisfaction .
2 satisfaction .
12 for satisfaction?
15 report on it .
21 you?
25 paragraph .
1 BY MR . MAISTROS :
8 regarded as unconfirmed at
10 of interest to speculate,
22 someplace else .
1 acceptable to consumers?
9 done .
14 trying to think .
• 2 test substitutes .
• 13
14
Q . Could you look at page 4, at the
24 saliva .
7 smoke .
22 tobacco, and the other you had 20, well, if you Ln~
~
23 increased the transfer rate, you could keep m
~
OD
3 A . It does .
8 they not?
10 BY MR . MAISTROS :
13 the question .
16 BY MR . MAISTROS :
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
8 system, correct?
14 nicotine, correct?
15 A . Right .
20 tobacco?
juggling it and so on .
16 documents .
24 review -
4 resolved .
8 BY MR . MAISTROS :
11 A . Uh-huh .
16 A . Yeah .
21 A . Yes .
25 Hayes, and --
1 A. Right .
2 Q . -- copied to you?
3 A . Right .
7 I probably did .
11 A . Right .
14 A . No .
17 A . (Reading)
18 Chemically-bonded
25 products .
reconstituted tobacco?
11 so well .
• 13
14
from -- I'm reading from the document
15 (Reading)
18 pectin in tobacco .
20 January of '78?
2 that : (Reading)
3 It is believed that
12 respectively?
15 Q . What's a CIM?
2 BY MR . MAISTROS :
• 13
14
if -- there's a possibility the ammonia will help
16 the nicotine .
22 A . Yes .
15 bought it .
16 BY MR . MAISTROS :
13 BY MR . MAISTROS :
16 A . Right .
22 transfer rate .
2 this one?
13 four days .
25 it will take?
2 day .
16 time .
18 hours .
21 what?
25 that Mr . Lee -- i
6 be .
8 record at 5 :24 p .m .
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
1 JURAT
6 changes :
10
11
12
14
15
16
17
18
19
20
21 DATE :
23 day of -----------------•
3 REPORTER'S CERTIFICATE
14 by the witness .
22 ~~.~y. e1e6 T
WIti.13C 5;?:I
25
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
•
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 .
"" 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-
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 .
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
}
.;.
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 .
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
DATA
30 August , 1994 Ln
~
~
~
m
~
HEALTH ASPECTS OF POORLY DEFINED "TARS"
OBTAINED FROM TOBACCO BY A VARIETY
OF METHODS 35
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
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
• 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
• 7PM behavior
' 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 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'
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 .
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) :
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 .
• 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)] .
• 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) .
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 .
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) .
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 .
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
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!
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 :
9
/
dissemination of truthful information concerning cigarettes which may be materia) and desired by
the consuming public .
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 :
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
`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
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
' 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
"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
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
' 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).
~ . 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
~ . 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
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
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
• 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
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
' 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 .
N'-nitrosoanatabine +
N'-nitrosoanabasine llg/g 6 .37 47 .69 77 .06 113 .33
4-(N-methylnitrosamino)-1-
(3-pyridinyl)-1-butanone Ng/g 21 .14 11 .54 8 .26 19 .22
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 .
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)
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 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%
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 .
LecM Tobacco Co . Method (Keith and UK Methods (Bentley and Burgan, 1961)
Newaome, 1956, 1957, 1958; Newsome
and Keith, 1916, 1957)
• Smoking machines
• Smoking parameters
- the origins of puff volume, puff duration, puff interval, butt length'=
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
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
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
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
ia.eRion depth, mm 11 11
TPM trappinp tyatem CFI+i CFFi CF14 CFFi CFpi CFpi
SSPti BSFt ESpk
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
ineertion depth, mm 11 11 1l
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
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:
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 :
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 :
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°
VI . HISTORICAL TRENDS
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 .
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 .
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
47 .5 2 .0 60 32 .4 1 .81 8 .2
13 26 .3 2 .0 43 24 .0 1 .48 12 .5
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 .
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)
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 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
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 .
• "tar" have been paralleled by declines in the sales-weighted nicotine [yield] per cigarette .
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.
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 .
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 .
• 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 . . .
[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 .
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 .
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 .
The following five methods for measuring total solids and nicotine are described in Table
APP B-1 :
• 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
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 .
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%
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] .
• 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 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 :
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 .
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 .
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 .
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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46
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Wenusch A(1936a), The Nicotine Content of the Mainstream Smoke of Thick and Thin Cigarettes . Z . UNTERSUCH . LEBENbM. 72: 213-
218 .
Wenusch A(1937a), The Determination of Nicotine In Tobacco Smoke . Z . UNTERSUCH. LEBENSM . 74: 46-51 .
Wenusch A(1937b), The Influence of Cut Width on the Passage of Nicotine into Mainstream Smoke . Z . UNTERSUCH. LEBENSM. 73: 182-
184.
Whisnant CC and Stevenson SL (1969a), Smoke Inhalation Studies . 1. Compariwn of Human Puff Profiles to the Puff Profile Generated by the
Filamadc Smoking Machine . RDR, 1969, No. 19 (June 16) .
Whisnant CC and Stevenson SL (1969b), Smoke Inhalation Studies . II. The Effect of Flow Rate on the Efficiency of Estron and Multjjet Filters .
RDR, 1969, No. 20 (June 16) .
Whisnant CC and Stevenson SL (1969e), Smoke Inhalation Studies . lII . A Preliminary Study of the Deposition of Particulate Matter in Human
Smokers Using WINSTON-Filtered Cigarettes . RDR,1969, No. 23 (June 24) .
Whisnant CC and Stevenson SL (1969d), Smoke Inhalation Studies. iV. The Deposition of Particulate Matter in Human Smokers - A
Comparison of the WINSTON and Muldjet Filters . RDR, 1969, No. 24 (June 24).
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TOB . CHEM. RES. CONF., Knox .iBe TN: Paper No. 49.
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131 .
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143 .
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Cold Spring Harbor Laboratory, Cold Spring Harbor NY : 3-12 .
61
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32:119-132.
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62
Yamazaki M, Tom9muro R, and Miteuhuhi K(1963), Relation between Stalk Position of Tobacco Leaf and Nicotine and Tar Contents in Its
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63
DRAFT • January 22, 1965
Introduction
memorandum .
w
N
r
~
Suand-Conclusion
could be arb_itrarily
. selected as the standard . But the
of the same brand, assuming that all possible steps are taken
• -3-
_ . .... .. .~. .. ...._....-...~.,.,...~_ ......... .. .... ....r.~.. .. .. . . .. ;~ ...__.__ . ..._ .__.__._ .. . .. .. .r. .~_ , _ . .
Methods for Measuring Total Solids and Nicotine
be as follows :
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
-, .
-S-
smoked .
-6-
smoker receives .
hold the smoke in the lungs for different times, some exhaling
who do not inhale admit the smoke to their mouths ; the duration
! ; 51710 4927
the burning temperature of cigarettes varies from smoker
smoker to smoker .
consume a cigarette .
Variations in Cigarette s
.. . _ . . _ . . _..._.~ ..,.. ._..-. __ ~ . --- . ••- .~.-. _~, _,.. .. . . . .. . .. _ ... ~.. .
\
~J .
-9-
. . . .._ . . . .- .~--• . .- ..._.. . . .._ . . . . . . .. . . .~ _ . . . .. . . .,. . . . . . . . . .. .~_ .. ..~ . . . . . . . . . ._ . .. . . . .... . .~ ... ..... . ~ .. .
-9A-
1.
~. :
-10-
Changes in ~
the Composition of Smoke and Total Solids
with some of the factors named, they (and others) may also
.,
t.
y
Int~.i.°o .
smoke consists of the particulate phase and the gas phue . The
the total solids end the nicotine in the ss+oke of cigar .ttes ssioked
selected a1 the standard . but the total solids and nicotine received
another sample of the same brand, assuming that all possible steps "
those fouad_ia the total solids fro* the othsr cigarette . iiace it
s+ethod (3) ; the loster D . Snell method (4) ; and the Liggett i l~rers
to be as follows :
Solids, mg ./cig . 18 .8 $4 .2 19 .1
Nicotine, mg ./cig . 2 .2 2 .9 3 .5
different results, because they do not start with the same smoking
conditions .
seconds, and the most comson frequency of puff is otu per sinute .
The Wolsun method and the Caabridse Tilter tiatbod* s .oked a fisad
has adopted arbitrary smoking babita for the smoking tachine, which
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
smoked also varies among smokers (7-9, 11, 13) . lbese variations
Moreover, smokers who inhale hold the smoke in the lungs for
different times, some exhaling more Quickly than others (15) .
and exhaling . Smokers who do not inhale adait the smoke to their
and the total number of puffs per cigarette and the time necessary
are other variable factors, .fiich have not been reported in the
scientific literature, and which saay affect the asount or
nb'rthern states .
is smoked .
or abnormally dry .
d . Smoking from a pack which has been open for more than
of smoke .
Variations in Ciaarettes
~.
The following variables affect the yield of total solids per
and the higher the pressure drop, the lwrer the total
packed .
d .. Number of euffs ~~
.~~.~.~•
taken
.
to .~i~g~leattb
oonaus a w~
... r ~~~.
of
.~..r~L
tobaccos .
a. Moisture content qfciasrettes (27, 29, 38) . tbe ap of
t. Additives on tobacco (16, 18, 20, 21, 259 30, 36) . The
uniformly .
It has been pointed out that the a .amt of total solids aad
the filter, and the porbsity of the citarette paper . As has been
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
be different .
-il-
.APp
._ .EMIX
IiE1'HODS FOR DETEMNATION QZ KICOTINE A& IMDS_
Smoking conditions :
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
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 :
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
Smoking conditions :
. . L . and
.Wynder,E Hoffmsn, D ., So` Practical Aspects of the .; ~
Smoking-Cancer Problem . NEW ENG . J . MED ., 2 2, 540-545 (1960) . `'
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) .
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 .
51710 4950
L .J
~ The Federal Trade Comission today announced that it,has sent identical letters
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.
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)
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
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.
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
-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
polycyclic aromatic hydrocarbon
precursor) and/or removal of r.itrate
from the tobacco or use of low-
nitrate tobaccos
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
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
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:
Revised 11-25-95
In its 1995 report, the FDA discussed the chemical manipulation, particularly the use of
ammonia and ammonium compounds, to enhance nicotine delivery' .
in the tobacco
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 .
didutmenk
TPM, anS Jcijt 32.76 22.33 -32 18 .66 19 .56
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:
These changes in tobacco composition produce changes in the smoke composition and
its biological properties :
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:
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
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
MS ev~idJnesd
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 . . .
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 .
Ammonia inaaasea the pH of the smoke and thereby enhances the absorption of
nicotine In the body." (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 :
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.
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 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 .
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. '
0 .34
even with the slight increase in
0 . - -&
sales-weighted average nicotine 0 .31 0 0 , _.
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
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'=).
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 ~
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
. . .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 :
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 :
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 .
• 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 .
• 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
•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
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
0
Table 3 (Continued) :
Effect
Cigarette Design on MS
TechnoloQV Original Goal Subsequent Findings Nico jpg
AbbnWmiona:
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
, . .
To6acc+o Proc+esslnp
Ciparette Paran~eters
air dilution:
via paper porosity' sig = 50% sig insig sig
via filter-tip ventilation! sig n 30% sig insig 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 :
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:
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
particulafe phase
64tarp , , an 31 .0 23 .2
benzo[a]Pyrevo+ a8 20 .8 12 .4
Ys122CP~
formaldehyde, µ8 55 45
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
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
.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
"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
• 10
TABLE A . STATUS OF ASSERTIONS MADE ABODT CIGARETTE SMOKE, ITS
FORMATION, ITS COMPOSITION, AND ITS PROPERTIES
Asswlon Statr~s
§ PAHs in MS result from transfer of air pollution-derived PAHs on leaf surface false
11
TABLE A. (Continued) :
Assertlon &g{9
12
TABLE A . (Continued) :
Assertion Status
Abbrevfatfona:
13
.
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
T"T?IS 0F CCfi'f'FnT:Ss
11-^7 L° . . . . . . . . .. • . . . • • • • . • • • . • • • • •
LI~:' CP r'S~'n'~A~TS . . . . . . . . . . . . . . . . . . . • . . . . •
+ ~ .~ .- .. . ...,.
Ii . . . . • 4, • • • . • • • • • • •
rwA~~.i?iJ'.:.:fLAL .• • . . . • , • • • 9 • • • . • • • • • • • • . .
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
Na ph i.Da iG ne
b. Antt...acom . . . . . . • . . . . . . . . • ~7
^? 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
~-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
~ .. 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
III Preliminary
~ ~ ~ ~ Chrosat0 , ~,~~rup~ of the tIezaaoluble,
~. ~}
. .
•~Y4i"ii.~Y4i"ii"
~~Ai li'i0tion \F~7' . s • . . . . • . . . . . .
CF
Fiv~ure "~tQ,
_F].cnrsho,,~ e ~
~ . . . ....- .. ..~•~nr
..r.~.~.~...:1.~.. .5
:.: +::. 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
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.
17
•
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
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 .
`: :.: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
.~ ~:•
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
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 .
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
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 .
9
„
u
3,4-bana,,-yreaa .r.~ 63
:.lvc ;~: <r .~n .~nw }3wK
.I1.. :~ bY
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
• ;; L~ 1 (coat'd )
3,l,-bon: yyroae 08
1,12,-beasoperylea .
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
"> '"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
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
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.
Ln
m
m
CO
15
. •... .
. .
. . T
, ,- ~- 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
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
~••
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
0T0S OTLTS
17
:r-o arcld .DZ " .^.: :old ( ::~aa 1) was arrar.ged as shc~a in i'i2 .
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
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
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
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
;°r'LS'pI^!?
~rr. : ..
C» 'f '
k'FL LF C^':'J''!'+r 7F
6 .94o c.
Ln
m
~
cn
Tf FiI iy III
CfiRfTA'i'')f:nfFi:Y rF
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
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
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
910S OZLTS
23
~ ..' •.r
. :.~ .y I L `' = ~ C T T ^ ~ ~
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?.
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 ~•
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
~ .•C .~ a :
..~ 4 ..•
VC .~ ~ ii
w i•
..6
g._C! 7.-.,-,etZ=a2hZ
DJ'sc:~~y1tS
.
U :Rt P 4'lY.GRA M Y C E :^ ..:.:...,.~...
5.330 C.
Chroratog=Fh on alumim
;
~rLi 7 7 1, .i
C
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
.~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.
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
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 . +
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
b• ~nt~ ~. ~Ms
1. CcT.C .A Z"'~•GIVFIR
2. CF o .tS
CC, IV F'um
~ ~ r . .
1
T
0.3:3 E•
-x
; ., . ..;.. C n c.l•=! :-.a ( 25 -~ .
- ~ .~,T .) r~•• ;~
. .,
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 .- -
~.~..~.
~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 .)•
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 .
G EP-C ;^s
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
~ . .. . ~~=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
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 ) .
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
~~~H+~~lf0
;- . .~L-z _ .
.T', 'liT
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..
3 . Ap!'CF:PT2Gtl "r7PrEC':F.A
.^~ . ..i{li",n
..*- i.a;'i~`~a' .•i1e
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
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
- :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 .
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) .
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•
51710 5032
:7
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 .
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
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+~
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,- .
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 .
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 .
`~~ ~ ., .
' ( .^ ~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 .
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
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
~.~.~..
' 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
• '
(195L ) .
, ^ot ::cco . R. J .
•~n . ~ . . . ., _ .. . , . . r•-• - . ..
. ~ ` .
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•
c1
~ 607
•
:...Jr,iiw~
. ~.. . Aa A
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) .
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 .
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.
51710 5039
( Ccnt' d)
: .«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 .
,~ ., ~o v
f, .
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.^'~~ ~^r^• ^
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~. 7 tn4c' s-b iy!T= ' `
f..~:~!/!t~r . ^r ;'^'='"
. . ~~
1 ►Cii~ r,
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-50 (1955) .
f ~ I`+• . . ..~^ ..!.aO p
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of.J ~,i~ if..9 :a1~If'4'•
/7• :
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• :.~'..; ~ • lF : ~ 1+~.%.~.. .
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0
36. ^oll R . ar.d F. . A . L . T+cc•a~ !n "el~•ticn t o
~. ~'-~T~nn
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'
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t~ w ;~~r
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~
~9 (1955) . •
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► n ~P~•~nn~ .~
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., 5 «,.,
(2 . •)
+ .
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~ w .~r+ 4 i :.LJ," 2.wd ai:,+
/~ + .A+wA .. .. w
A
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Ca1ia: : QC Y -~VGi , 1~i 5 1 •
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55. Z. L. p :,jo 7, .^. .r^-~.tion
.. cf C:;
:r rur `z ..w,.c h• ...r
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. ~'C : .~ , ., ~33-,,~~0 (1'>~G) . -
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d V LL.wr
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: :^7 ..e1 2' .~.{M~'.1• 's I
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02:5:-<60 (1953) .
~~ ~~ ., I~ ~',1 "~,
V. . . ~r..i. J r~J ..^C!AqN!1
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:7 .i :',= .^.=~ * .•,. : ~C .
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r rna+.e
63 . . .~i1 ~«•~ . • D ~• r-
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21, 1954 . • -
.;1i / . T'/.•.tC. . .'.-r•r ~;~iL~'~ .'l>.
~~ r .`~^ Mwr1 T~!. ." ^n aJe.rt D~• /N'tr
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r ::a;rt.~l cr.~s3 t a , a3 n. • «r r •w ~ {
uZ~'•a! " Fn~
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:(1942)•
5 .44 ~
.
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n
I7)
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t- Il..• ~ Cra t. ;'c~ . C
+T .~
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C'
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.,~. . . .
.. .. . . ....^ .~w,., ..
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k :9 :4 .
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63355 (19b3) .
95. ~ '~ 1
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1; 37-1252 t1953)•
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'.
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• ~ r... .r..wrr~rr~:rY. - ~
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• • .'.L~
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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 ~.'~
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. ' ..'^ . . . .. _ _ :.
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: .• # a .'. CC» v
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._. . ~.. . . .f . ^ ~ y
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• . ... . ., i~~ .•. •
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./~ .v~ rVI
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4
.5 .1: ::A ::' 46 • B.`l :•
li s L+1 , 10,28 .
51710 5044
49
(Cor.ted)
.r .to
F„r .l Fr . ~ ;y, i'ri :s 1 .1 : 246-247 (1939) .
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'
C4 !1f:C:2' ..^nd Lw
o .P C~U ~ 9~*. .^ .^,fl'.3 i n
Fc2.strd Fc+od, tIA :'':E, " 9 64 (1939) .
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)
1
July 25, 1962
Mr . Kenneth H . Hoover :
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 ;: : . . :
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~..
• , ,
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
-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-
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 .
Ln
m
Ln
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 ~
,,, _ . .
-10-
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 :
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
_ 76, 78, 84-86, $$-, 92, 101, 114.) or with patentable material
effect exists?
It is not my intent to suggest that this Company accept the
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-
than they would be if their main informat ion sources were the
. ~. . •
nIBLIOGRAPHY
{ 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) .
16 . Boqland, E., The Biolo ical Examination of Carcino enic Substances . BFtIT . 2~D ;
BULL ., 11 (2 ) , 93-9 (1958) .
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 .
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
• 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 .
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) .
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) .
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 .
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
53A . Little$ C . C ., Smokinu and Lung Cancer . CANCER RESEARCH, ]6, 183-184 (1956) .
68A . Rodgman, A ., The Pre ration of Some Phenolic Flavorants . RDR, 12~6,
No . 10 (OCT . 1 .
73 . Ro%,grmn, A .,
aDa, 1 7 Q, No . 11 ( : I:lY 1~ ) .
N1
'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 . ! .
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 .
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 .
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 .,
109 . Spain, D . t•i., The Distinction Between Re eneration and Atyaical Alterations
. ip he Bronchia lMucosa . ANf. REV. TDffaC . , 7, 5''1- ?09 .
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 .
.
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-.
,
' Author : Alan Rodgman
are 4iade .
v
u
several recommendations
=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
cigarette smoke . The benefits antbio* from such '.cr.owledg3 are obvious, particularly
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
L- NP1d44o1oZiaa1 Rata_ •
~ The results of 34 different statistical studies show that cigarette
The results of these studies can, however, account for only a small
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 ;
k. _Patho_lggi_cLl. Dg,tL
qIt has been observed that cigarette smokers' lungs show profound cellular
smoke and some of its constituents cause ciliary paralysis, and that
• m
Contradictory evidence indicates that the above-described cellular
areas of extreme air pollution, and that ciliary paral,ysis can be caused by
re k ot_th a_c_tor__to be
_c. P.i412g&CL1.Pg.tL
the fact that the dosage level used exceeds that of the human exposure . Other
investigators, using nominal dsage levels, did not obtain positive results .
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 .
been produced although the previously mentioned cellular changes and bronchitic
conditions have .
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
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
.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
human lung tissue . It is unlikely that such experiments will ever be carried out .
Attempts to shift the blame to Ither faotors, e .g., air pollutants, necessitates
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
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
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~
This Company is studying in detail the composition of cigarette smoke, but much
data remain unptblished because they are concerned with carcinogenic or cocarcinogenic
cn
P.
~
~
m
Ln
m
~
m
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
some other disease, can the company justifiably take the position that publication
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
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 :
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
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
~..~._~n^~ ~ . ..
, . •t .. ~ .~
~-- ~„ .A .W o jL&. ..v.:w .. ~rs M tA ., ,% r +1 L ~,;~
.YJ LLal.L k, . -:
e;Cdtl1
!s
~...._ /?~. .~ t.Liu
~• a .4
1 r•
.Ta .A
. . f""Z-L r
/T._ . .+~.t~
k,- tt t •.:. e. 't
~ tNtJiA .jZ_•~_. r%L •= V 1 ard
.••
.I~IL~ Sr~7++r . .~_
L.iA'~tl~ r74 ...IOG~f/... . . V . <<wr~a pM• }i'~{A+t GO ~~pJy~ .
• , ' ( l
e+~...~.
r,
L : :o_ : r.lan Rodg:::an February 12, 196 4
No . of Pages : 70
OBJECT :
SUMMARY :
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 .
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
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.
7 . Solanesyl esters
9 . Lactones
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
11 . Phenols
14 . Miscellaneous compounds
^ ~ :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
2 . Phytadienes . . . . . . . . . . . . . . . , , 10
4. Solanesenes . . . . . . . . . . . . . . . . . 13
II . Esters . . . . . . . . . . . . . . . . . . . . . . . . 37
b. Solanesyl Esters . . . . . . . . . . . . . . . . . 40
1 . Solanesyl Acetate . . . . . . . . . . . . . . 40
III . Lactones . . . . . . . . . . . . . . . . . . . . . . . 42
a. Sclareolide . . . . . . . . . . . . . . . . . . . 42
a- and A-Levantenolide : . . . . . . . . . . . . . 43
IV . Alcohols . . . . . . . . . . . . . . . . . . . . . . . 43
a . Solanesol . . . . . . . . . . . . . . . . . . . . 43
c . Phytosterols . . . . - . . . . . . . . . . . . . . . 44
f . Macrocyclic Hydroxyethers . . . . . . . . . . . . 45
V. Pheno l s . . . . . . . . . . . . . . . . . . . . . . . . 46
1. cx-Tocopherol . . . . . . . . . . . . . . . . 46
3 . Other Phenols . . . . . . . . . . . . . . . . 47
, IX . Miscellaneous Compounds . . . . . . . . . . . . . . . . 51
XI . Summary . . . . . . . . . . . .~. . . . . . . . . . . . 54
B . E};PERIMEhTAL . . . . . . . . . . . . . . . . . . . . . . . . 55
7 „
C. DISCUSSIO,\` . . . . . . . . . . . . . . . . . . . . . . . . 5 6
D . CO\CLUSIONS . . . . . . . . . . . . . ,. . . . . . . . . . 61
E. RECOP^WN'AATIO\S . . . . . . . . . . . . . . . . . . . . 6 2
I. Future Work . . . . . . . . . . . . . . . . . 6
II . Patentability . . . . . . . . . . . . . . . . . . . . 63
BIBLIOGRAPHY . . . . . . . . . . . . . . . . . . . . . . . . . . 64
0
;._S^ 0 :' :r, :LES
0
10
:~ . T' ;i:07L'C^IOiy
I . Hydrocarbons
u,
CH3(CH2)nCH3 ~3(~2)n~(~3)2 ~
N
m
II cn
m
2 . PHYTADIENES
III
V
fIH2
H[CH2CH(CH3)CH2CH2]mCH2CH(CH3)CH2CH=CHCCH2CH2[CH2CH(
VI
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
XXI
}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
4 . SOLANESENES
~2
H[CH2C(CH3)=CHCH2]8CH2CCHgCH2
XXV
H[CH2C(CH3)-CHCH2jgCH-C(CH3)C=CH2
XXVI
H[ CH2C(CH3)=CHCH2] 90H
XxVII
14
0
~H[CH2C(CH3)=CHCH2J90C H3
}:XVIII
C / \ \
\ ~ / /
XXXVIII XL XLI
~
m
..• . .~ . ' • .fl
9thylanthracene (} :LV), 9-rwzhylpne :.anthrene (}:LVI),
CH3
XLV XLVI
% ~% / / (
H ~' . . ~
\
/ \ \
ri
\' / / C:'.
L LI LII
LIII LIV LV
:7
/I
/ \\
\ II
/ /
m
L]X LXI
// \
I
/ / ( \ /
\ \ /
I
.
I
LXV LXVI LXVII
~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-
3. FluoranL•hene (XXXVIII) 260 152 190 247 205 266 330 1i,0 205 208
6. Benzja]anthracene (XXXIX) 17 2 .5
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
18 . 9-Methylphenanthrene (XLVI) 43
19 . Dibenz[a,h]anthracene (XLII) 15
20 . 1-Methyl-3,4-dihydronaphthalene 250
(XLIII) ,.,
V
22 . 9-Methylanthracene(XLV) 60
23 . 4-Methylpyrene (XLIX) 62
24 . 2-Methylpyrene (XLVIII) 51
25 . 5-Methylbenz[a]anthracene (L) 3
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
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
Estron 8/70 17 50 .5 13
Estron 8/70 17 _ 46 .2 2 1
Dico 240 17 -- -- 32 .3 45
Ecusta TOD 705 10 1 .19 40 16 .4 37 39 .4 32 63 29
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
Alumi-
nized Estron 8/70 1.50 5 19 .4 -4 49 .5
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:
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 -- 12 43 .0
Chloranil 6 .0 12 33.0 23
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)
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~
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
~ 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 : •
OtZS OZLIS
30
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)
ZZZS OILTS
TA13LE VI (Cont'd)
WINSTON Blend Tobacco (70-asn . tobacco rod, 15-mm . Estron 8/70 filter tip, type AAA3 p :+.p('i) :
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
£TTS OrLIS
TABLE VI (Cont'd)
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 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:
XLII
Sclareolide
.! J
T ALB.T+:'+ M
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
TT T`sta i s
CH3(C_'2)n+200CR
L?:VIII
V V NY W
RCOOMe CH3(C"2)n+1C00H RCOOMe CH3(CH2)nC00H
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
TABL:: VIII
Alcohols Acids
"LY:iL.l'
H[ CH2C(CH3)-CHCH2190H
TABLE IX
Alcohol Acids
3 . Palmitic
4 . Oleic (9-Octadecenoic)
5 . Linoleic (9,12-Octadecadienoic)
? 1
C.
TABLE X
Alcohols Acids
CH(CH3)CH=CHCH(C2H5)CH(CH3)2
HO
LM I
43
LXXXIII
0
MV s CH3CH2CH(CH3)CH2-C-
III . Lactones
a._ Sclareolide
IXCXIV
'0~
~ ~._1 . . .
=V =VI
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) .
CH3(CH2)nOH
c.
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
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 .
?.C I XCII
V. Phenols
1 . a-TOCOPHEROL
HO
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
OH OE OH
I I
XCVI XCVII
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
WINSTON,
no filter
tip 159 241 38 57 70 107 267 405
SALEM 33 48 8 12 26 39 67 99 ~~
~
6 . Does spinach as rep :._ :.ad p :Lv :.ousiy : n smoke studies yield
less phenols on pyro=ysis does tobacco?
- . .-Jw . .--
nn•. .,
~ ..~'. : ..Il .. .i
= . . .. .nT n . . .r.- .-..
.~ . '.~ ./ v .~ ..- .. ~-
Pheno 1,
. :croa=ams/c . vx*rolyzed
- - - i° C . ?''.L^oi u-Cresol
,-
0
C'r.3C: C : `C :~C H3 OC::CHO
~ Ci:O
C: CII CIII
XCIX C
C :V CV CVI
i~
0
(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 .
IX . Miscellaneous Comnounds
:i~Cr
.~C: iC
CXII X
C III
•
5:
: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)
dlncludes neophytadiene .
~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
rC.sJ_ _ .. . .. . . .r . . . . . rv .
*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
\': ~r .Z irritants favors t .. c;-- r . .. . . .. .. o. C . . ..1. .: IZL .r.. . . Ll-: S pir .r..bVry
-
tr . :.V t . .
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 .
cr
.. Vr 4r c o . .J~
:c
t~ :. ..ra:b ..ra :1
?,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 .
,,, . .
:/• .V. . .r .!
~. 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) .
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) .
:
E . Rr.COr~~k'DATIOAS Lnr
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 :
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) .
II . Patentabilitv
~.
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
Approved :
,
,
04
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) . .
_: . 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
.. ^ ~ 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 .. .•!
.
at ~7t : T ;;-acc ; ~ :._ . . ._ ~s' .~~sc~rch
_. -23 J
`_iVJ)
/. !.
-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 .
1
> :. . . . ~ .:i. :, t`. . , CoOn,
:~o r .- :1
•
n
Q ::i o DeL 13 -a~i ~ ..i 6 G )
uEUBpog ualy
i~
s
~
Yo . J-:
.+J, . .J . i .~ . .
•
Alan Rodgman
R !4 D LONG-RANGE PLANNING
. .;.r .. .~..__. ..
:.3' - . .C: . . .. .. . . .•V.~- . . . .1 . .. . . . . . .
. :~.:: :.:,•~• . . : s. :' . r : .~ ., .,~.. . .. . . . . •r . . : . . = .a . . ; ;
INTRODUCTORY NOTES
%o
V, , R2,236
/
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 .
~.
i
,
s
TABLE I
. ' PRCDUCT AND ShiOKE COMPONENTS
Materials .
Additives
!lasticizers
« lavorants
F5
C . Paper
~ 1 . Paper'AddStives : Dyes
b . Nicotine
c. Pesticides
d. Polycyclic Hydrocarbons
imw
.
2 . Gas-Phase Components
a. Carbon Monoxide
b. Nitrogen Oxides
c. Hydrogen Cyanide
d. Hydrogen Sulfide
e. Other
Tobacco yyoe
~
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 -
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
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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4
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
4A
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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 .
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
.
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R S R24251
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c. Pesticides
RJR2425 4
19
e . Metallic Compounds
1 . Polonium-210
R ~ R2,4255
20
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2 ._ Gas-Phase CoMponents
a . Carbon Monoxide
M
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R J R24256
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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
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 .
.
R~Rz~2~9
. ., ,, : . .
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0
Five years ago such studies were run sporadicallx in our laboratory,
but since then, the number of analyses has substantially increased :
.~ R
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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 . ,
, p,
RJ RZ4Z6 1
' • POSITION PAPER - FOR14/1L t)nCMF.NTATION
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
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~ RJ R24263 ~o
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28
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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" .
• a
M
D
R JR24264
I POSITION rAPER - FAtLW1L DOCUMEtITATI0t1
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 •
a J R24265
'
3l1
,
. RJR24266
0 POSITION PAPER - FORMAL V)CUt•tENTATION
ANG
~ AtID HEALTH: P:".ODUCT AND SttOY.E CONPQNENTS
RJ R24267
sl
.
4
POSITIOy PAPER - FORI4AL (1nCUUNTATION
'N i*ING AND HEALTH : PRODUCT At1D St4OKE CEN•1P4NENTS
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
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RJR24269 • •
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0 P0SIT10N PAPER - FORttAL DOCUMENTATION
R J R24270 !
JJ
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POSITION PAPER - F0M1AL DOCUMtCtITATION
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
0
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~~
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, . O%
N
..
sa
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) . .
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"
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R~R2~2~3 W
, • 30
RJ RZ4274
39
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R J R24275
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40
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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 .
04
0
CD
n
R S R2a''(6
POSITION PAPER - FORMAL DOCUh1ENT/1TI0N
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
r
A
N
J
.
* Z; :,o.~:~ :z
i ..t .
. 42
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$ ' ~,
~Aj,V
.••i
. .. . .. . r . - • ~ 3„ > . . _. .. . , • _ .
0
~
SM~KIttG ANO f1EAt7N: PROOUC'. €~O
1977 - 1989
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
: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
Gr .~~....~
rit.v,7 .
: . ., . . . . . . . . . . . . . . . . . __ . . . . . ~r~ ~ .
pr o duced lNy ..
f
.
•
S' a: . ..:.: . .
::::: - . . . -'
.. . . ~ .. .. ..
.. . ... . ;:
.
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 ~
• + • opportllnity
- • threat
,
,
IOZS OILIS ~.~ . . . . .• .~• r ~__.. .._
. ..• .1T~^VYO.~•+f :v . .•T .! .wA'Y/. ..(.M~. .T' . ~ .. • .•V . .. .. uo~• .. . . . . .. . . . .
JEfl)dJ)Ce
-1
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
,
,
.
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
,
•
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
Qualitative
to smokin9-tealth proponents .
` + a opportunity
- - threat
50ZS 0tiLti5 • . -- . . : . . . . . - . . . . . ,
RTC
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
UO
.. . /
..................
l~?iYY "A
..
:
~J)aCT'1~ eoNk~~i~'x~A~~
. ....:,.~RDE1't
. . . : IN PENNS '!f~A' :
.. . ._ ... ... . .. . :.:..::.. .::::...:.. . .. ...... _. : .. .:. . . ,, . .:,,;,
. ...
90ZS OZLZS
Y
pioduuda . :RJ C . T
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; . ~ . .. .
15 7/26/66 PENICK & FORD, LTD . RESEARCH REPORT, 4TH QUARTER - 1954 Penick & Ford
~ ( . 0
4 3/3/55 THE POTASSIUM, CALCIUM, AND SOLUBLE ASH CONTENT OF Elliott 3 . 8 . tl-
AGING TOBACCO
' r10 8/31/55 THE PREPARATION OF POLYVINYL ESTERS OF SOME FIVE- Teague, C .E . ~C
~ AND SIX-CARBON FATTY ACIDS
15 7/26/66 PENICK & FORD, LTD . RESEARCH REPORT, 1ST QUARTER - 1965 Penick & Ford
7..2 Z-7o
~' ~
RDR, 1956, Nos . 1-12 - •DESTROYED ~~ :~'~
.I
11 10-31-56 THE REACTION OF SEC-BUTYL BROMIDE WITH DIETHYL SEC- Snyder, Harry x .
BUTYIMALONATE
•1
13 7/27/66 PENICK & FORD, LTD . RESEARCH REPORT, 1ST QUARTER - 1956 1 Penick & Ford
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
3 2/1/57 PROCESS FOR PRODUCTION OF DISODIUM sec-BUTYL-MALONATE AND Mays & ?\agu
DISODIUM ISOPROPYIMALONATE ; LABORATORY DEVELOPMENT E.
8 6/7/57 /THE ESTIMATION OF PENTANOIC AND HEXANOIC ACIDS IN TOBACCO AND Latimer 37-
TOBACCO SMOKE USING GAS CHROMATOGRAPHY
14 10/10/57 `' THE. .FATE'OF"DISODIUM .ISOPROF~LMALONATE DURING SMOKING . •A`STABLE Latimer ¢t~~ 1
ISOTOPE STUDY .
19 ~`a {{~ 0~ 0 E" D~ . ISOLATION OF STEROLS FROM FLUE-CURED TOBAC~, (VOID - SEE RDR, ;
~y!*" .1958, No . 1) .,~~. ':I
'ti3 :a .. r . . ..
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
4 3/14/58 PRELIMINARY STUDIES OF CIGARETTE TASTE TESTING METHODS Bellin & Nyst~om
17
18
11/7/58
12/1/58
ANALYSIS OF 3,5-DINITROBENZOATES
22 12/31/58 THE ANALYSIS OF CIGARETTE SMOKE CONDENSATE VII . SOLANESYL AND Rod n& Cook
SOLANESYL ACETATE
RESEARCH DEPARTMENT REPORTS - RDR - 1958
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
3 3/16/59 THE USE OF IBM METHODS FOR HANDLING AND INTERPRETING DATA WITH Bellin x
SPECIAL REFERENCE TO THE AGING OF TOBACCO
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
a
0
r
~
N
F
51710 5217 J
W
N
RESEARCH DEPARTMENT REPORTS - RDR - 1959 Page 2
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
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
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
13 4/26/6 0 THE ABSORPTION OF OXYGEN AND THE LIBERATION OF CARBON DIOXIDE Elliot t
BY AGING TOBACCO - l~
~
O i
N ~
N
v
51710 5219
. • .
42
No . Date Author
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
st o . Date Author
30 9/1/60 A RAPID DETERMINATION OF MANOYL OXIDE AND 13-EPIMANOYL OXIDE Laurene &,fi~Younl
r -;~
IN ISOMER MIXTURES
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
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
51710 5221
, 7.112W • pdo-*~. ete'u°
RESEARCH DEPAR2MENT REPORTS - RDR - 1961 //, /H 4- {O,3
. ..
2 1/9/61 V THE DISTRIBUTION OF PHENOL BETWEEN DIETHYL ETHER AND AQUEOUS Laurene 6
SOLUTION . Lewallen
•
10
2/14/61
2/23/61
GROSS SEPARATION AND DETERMINATION OF THE PHENOLIC FRACTION FROM
TOBACCO SMOKE CONDENSATES
,~Rodgman +
• ~' Cook
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)
17 4/4/61 PROCESS FOR PRODUCING SCLAREOLIDE FROM SCLAREOL : LABORATORY Mays, Hen1x &
DEVELOPMENT : SUPPLEMENTARY REPORT Wilson
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
51710 5223
RESEARCH DEPARTMENT REPORTS - RDR - 1961
No . ~ Date Author(s)
53 11/17/61 . REVISION OF THE OPTICAL METHOD FOR THE DETERMI&TION OF SCLAREOL Laurene-v
Moser 6f N
Drummong
59 3/3/66 PENICK & FORD, LTD . RESEARCH REPORT, 1ST QUARTER - 1961 Penick & Ford
.
.• RESEARCtI DEPARTMENT REPORT - RDR - 1962
S Date
1/10/62
Author(s)
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 .
• 3/12/62
VOID
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
18 6/25/62 TURKISH TOBACCO . THE ISOLATION AND IDENTIFICATION OF THE Alk Schumacher &
ESSENTIAL OIL OF TURKISH TOBACCO DUST Vestal
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
• C"
C
r
~
N
p
v
r
N
.RESEARCN DEPARTMENT REPORTS - RDR - 1962
. .
No . Date
~ 1962
8/13 NONAQUEOUS TITRATION OF HYDRAZIDES WITH TETRABUTYLAMMONIUM Sens abau'il
HYDROXIDE Robinson`
34 9/10 TOBACCO PRODUCT FROM THE SMOKABLE COMPONENTS OF BURLEY STEMS Ashburn 40
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
Ln
F"
_j
~
m
Ln
N
N
co
,
RDR, 1963, Nos . 1-61 DESTROYED, exaept as noted .
RESEARCli DEPARTMENT REPORT - RDR - 1963
Date TITLE
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) '
~ ~ .~ .
THE LOSS OF SCLAREOL DURING HEAT DRYING OF CLARY SAGE FLOWERING ' Hhefele
,
PARTS
30 V 0 I D V 0 I D
37 5/14/63 PILOT PLANT STUDY OF PROCESS FOR CONVERTING SCLAREOL TO SCLAREOLIDE Henley et a1V10
• Date
6/5/63
TITLE ~'~"Author"I
48 7/8/63 TURKISH TOBACCO . THE QISOLATION OF ACID CARRIERS FROM TURKISH ~Schumacher
TOBACCOS
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
.. Date TITLE
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 .. .~
7 1/17/64 PILOT PLANT PROCESSING OF CLARY SAGE CONCRETE FOR SCLAREOL Henley X
~ 2/12/64 THE ANALYSIS OF CIGARETTE SMOKE CONDENSATE . XXXV . A SUMMARY OF }ri V~~ Rodgman
AN EIGHT-YEAR STUDY
12 2/14/64 THE USE OF DRI-DIE 67 SILICA FOR PROTECTING STORED TOBACCO FROM Bellin ~s
DAMAGE BY THE CIGARETTE BEETLE
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 .
28 se.c,, Du2
~
.~[ •
VOID VOID
51710 5234
RESEARCH DEPARTMENT REPORTS - RDR - 1964
M Date
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
t"0
r
~
N
~
.4
N
51710 5235 0
.
. i
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
7 VOID
10 2/22/65 REPORT NO . IITRI-C8036-4 - DEVELOPMENT OF HOUSEHOLD PRODUCTS v"' .0~,IITRI Res . Inst .
20 2/9/65 THE SYNTHESIS OF LACTONES ISOLATED FROM TURKISH TOBACCO STEAM Vestal
• 5/4/65
CONDENSATE y~44
26 5/19 FLAVORED CARBON AS AN ADDITIVE FOR TOBACCO PRODUCTS Vflarwood & Teague
37 8/18/65 THE ANALYSIS OF CIGARETTE SMOKE CONDENSATE . XXXVII . A PHYTYL odgman-gak cook
ESTER FRACTION FROM TURKISH TOBACCO SMOKE
42 fJ i
RESEARCH DEPARTMENT REPORTS - RDR - 1965
~ Date Title
43
46 11/1/65 PENICK & FORD, LTD . RESEARCH REPORT, 1ST QUARTER - 1963
57
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
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 .
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 .
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 - -
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 .
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 .
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 .
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
° 'I
: t...L .. . .a.,
4 2/1 ANORECTIC AND SUBACUTE EFFECTS OF MARIOLIDE ' ..`,:'. _,~r Tompkins & Fluck
15 5/3 MASS SPECTROMETRIC ANALYSIS OF CIG . SMOKE, PART III . DETERMINATION OF ",oung, G . W .
ACETALDEHYDE, PROPANE, PROPYLENE AND ACETONITRILE
17 6/6 NEW SYNTHETIC METHOD FOR PREPARATION OF AROMATIC ALDEHYDES, tt-Aeffingwell & Bluha
KETONES-- AND- SCHIFF-- BASES-- -- - - - --- ----- --- -- -- --- -
, . . . . .• , . . . .. ,: . : ..r f: .
8/8 GAS- CHROMATOGRAPHIC METHOD TO DETERMINE COUMARIN IN CIG . SMOKE Wyerly & Gi1lBlan
51710 5243
I
Page 2
1967
RESEARCH DEPARTMENT REPORTS - RDR - 1967 OIL
0 Date Title Author(s)
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
39 10/30 ANALYSIS OF CIG . SMOKE CONDENSATE . XLVI . GERANYL ACETONE AND ,.4k~ Cook & Rodgma
FARNESYL ACETONE FROM TURKISH TOBACCO SMOKE W- ;
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 `
20
51710 5245
I /A
It
~
, RESEARCH DEPARTMENT REPORTS - RDR - 1968
35 9/23 3-PYRAZOLIDINONES AND RELATED HYDRAZINO ACID HYDRAZIDES X Roberts & Hege (Bonit
37 10/23 XYLOSE PRODUCTION FROM CORN HULLS AND SUGAR CANE BAGASSE ^ Rix-Eaton-J . G . Jone
~ ,.0
ts.
~
N
r
J
51710 5246 «.
.. . I
RESEARCH DEPARTMENT REPORTS - RDR - 1969
3 1/27 A GAS CHROMATOGRAPHIC DETERMINATION OF FREE FORMIC AND ACETIC ~ Lyerly & Goodale
ACIDS IN CIGARETTE SMOKE
• 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
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
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
24
26 7/22 THIRTY-DAY ACUTE TOXICITY STUDY OF GLUCOSE - RJR 2453-F Fluck, Ridlon, et a
28 8/20 PRODUCTION AND USE OF MALTOSE-FORMING AMYLASE FROM BACILLUS ~ Lartigue & Hayes
POLYMYXA
32 9/19 THE INVESTIGATION OF THE CIGARETTE SMOKE FROM'CELANESE ~ Green, Vestal &
SMOKING MATERIAL Schumacher . .
36 11/10 USE OF HOT GAS JETS FOR SIMULTANEOUSLY PUNCHING 16 HOLES IN [\ Harris, Stowe &
PLASTIC FILM
39
'"'
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 ' `
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 /
11 2/19 PILOT PLANT STUDIES OF THE PREPARATION OF BENZYL STARCH ~8v) 2 0~ruce, Sellers~,•et
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_
17 3/23 THE EFFECT OF VARYING JET DEFLECTION ANGLE ON THE EFFICIENCY Harllee, Floria x
OF MULTIJET TYPE FILTERS &,t) l7
~ . 4/17 FLUOROMETRIC DETERMINATION 0 SELENIUM ]1N CIGARETTE PAPER AND (Vacker & Stamey
TOBACC O
51710 5249
RESEARCH DEPARTMENT REPORTS - RDR - 1970
21 4/22 CHROMATOGRAPHIC SEPARATION OF FRUCTOSE AND GLUCOSE ON CATION Lloyd, Robert/ -~C
EXCHANGE RESIN (¢7) /j
23
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
32 6/29 THE ISOLATION OF FRUCTOSE FROM INVERT SYRUP BY THE HARA PROCESS Lloyd, R . & Br~e,l
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
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
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
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`
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
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
18
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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
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 .
RJR2106
RJRI FORM 2422-Rvv . 7/70
2
•"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 .
RJR2107
3
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 .
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
COPag.U$IONS :
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 . .
ACKNOWLEDGMENTS :
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
Disclosure No :
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 :}
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
Distribut_io_n_a
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
,
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