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C H A P T E R

19
PCBs, Dioxins and Furans: Human
Exposure and Health Effects
Bommanna G. Loganathan and Shigeki Masunaga

INTRODUCTION were never used as chemical warfare agents, weap-


ons of mass destruction, or agents of threat or terror
Polychlorinated biphenyls (PCBs), polychlorinated by contamination of air, water, or food/feed. However,
dibenzo-p-dioxins (PCDDs), polychlorinated dibenzo inadvertent poisonings by these chemicals have caused
furans (PCDFs), polybrominated dibenzo-p-dioxins significant environmental and health problems (Yusho
(PBDDs), and polybrominated dibenzofurans (PBDFs) Support Center, 2007; Loganathan, 2012; Kodavanti
are members of the group of halogenated aromatic hydro- and Loganathan, 2012). In this chapter, historical back-
carbons. This group of chemicals has been identified by ground, chemical characteristics, analysis, pathways of
the national and international agencies as priority envi- human exposure to these compounds, and toxic effects
ronmental pollutants posing significant effects on aquatic associated with the exposures are presented.
and terrestrial animals, including humans (Loganathan
and Kannan, 1994; Jacobson, 1994; International
Programme on Chemical Safety, 1998; Van den Berg et HISTORICAL BACKGROUND
al., 1998; Kodavanti et al., 2008). PCBs do not occur in
nature except for forest fires and were synthesized by PCBs were first synthesized in the early 1880s
humans. PCBs were produced in large quantities (mil- (Schmidt and Schultz, 1881) and commercial production
lions of pounds) for a variety of industrial uses during began in 1929. Biphenyls were reacted with Cl2 in the
1940 to the late 1970s, especially by developed nations. presence of ferric chloride catalyst, where some of the
However, PCDDs and PBDDs (dioxins) and PCDFs and hydrogen atoms are replaced by chlorine atoms. PCBs
PBDFs (furans) were never produced commercially but were produced as complex mixtures potentially con-
are formed in small quantities as by-products of combus- taining 209 congeners formed by chlorinating biphenyl
tion of various industrial as well as natural processes. with from 1 to 10 chlorines (Figure 19.1). The amount
Because of their persistent, bioaccumulative, and toxic of chlorination of biphenyls corresponded to the dura-
properties, residues of these compounds are found in tion of chlorination process. For example, Aroclor 1221,
every component of the global ecosystem (Lipnick etal., 1242, 1248, 1254, 1260, and 1268 are commercial prepa-
2001; Kodavanti etal., 2008). Some PCBs (coplanar PCBs), rations that were formerly produced by the Monsanto
dioxins, and furans are three structurally and toxicologi- Chemical Company in the United States (St. Louis, MO)
cally related families of compounds that are classified as that contain 21%, 42%, 48%, 54%, 60%, and 68% chlo-
the most toxic synthetic chemical substances to a variety rine by weight, respectively, as indicated by the last two
of animal species, including humans (Tucker etal., 1983; digits in the numerical designation (Giesy and Kannan,
Loganathan et al., 1995; ATSDR, 1998). Production of 1998). The PCB mixture formulations were different
PCBs was banned during the 1970s; however, already depending on the country of origin and were produced
produced PCBs are still causing environmental and in Germany (Clofen), France (Phenoclor and Pyralene),
health problems (Loganathan etal., 2008; Sajwan etal., Japan (Kanechlor), Italy (Fenclor), Russia (Sovol), and
2008; Loganathan, 2012). Fortunately, these compounds Czechoslavakia (Delor). PCB mixtures were produced

Handbook of Toxicology of Chemical Warfare Agents.


DOI: http://dx.doi.org/10.1016/B978-0-12-800159-2.00019-1 239 2015 Elsevier Inc. All rights reserved.
2012
240 19. PCBs, Dioxins and Furans: Human Exposure and Health Effects

Compound Molecular Wt Chemical structure

3 2 2 3
m o o m

PCBs 188498 4 p p
4
m o o m
5 6 6 5
Cl1 5 Cl1 5
9 10 1
O
8 2
PCDDs 218460
7 3
O
6 5 4
Cl1 4 Cl1 4
Dioxins
9 1
8 2
PCDFs 202444
7 3
O
6 5 4
Cl1 4 Cl1 4
Dibenzofurans

9 10 1
O
8 2
PBDDs 263816
7 3
O
6 5 4
Br1 4 Br1 4
Brominated dioxins
9 1
8 2
PBDFs 247800
7 3
O
6 5 4
Br1 4 Br1 4
Brominated dibenzofurans

FIGURE 19.1 Generalized structures of PCBs, dioxins, and furans.

for a variety of uses such as fluids in electrical trans- and chlorinated phenoxy-2-phenols (Hutzinger et al.,
formers, capacitors, heat transfer fluids, hydraulic fluids, 1985; Hryhorczuk et al., 1986; ATSDR, 2001; Masunaga
lubricating and cutting oils, and as additives in plastics, et al., 2001a). Similarly, PBDDs/DFs are found as by-
paints, copying paper, printing inks, adhesives, and seal- products in brominated organic chemicals, such as bromi-
ants (Loganathan etal., 1989; Safe, 1990). nated flame retardants (polybrominated diphenyl ethers
Dioxins and furans are not produced deliberately but (PBDEs), decabromobiphenyl, 1,2-bis(tribromophenoxy)
are produced unintentionally as by-products of combus- ethane, tetrabromobisphenol A (TBBPA)) (International
tions of organic matter in the presence of chlorine. Dioxins Programme on Chemical Safety, 1998). These compounds
and furans consist of 135 possible chlorinated (or bromi- are also formed during incineration of industrial and
nated) dibenzofuran and 75 chlorinated (or brominated) municipal waste, forest fires, fireplaces, and combustion
dibenzo-p-dioxins with from one to eight chlorine (bro- engines (Loganathan etal., 1997; Feil and Larsen, 2001).
mine) substituents (Figure 19.2). PCDDs/DFs are found Because of anthropogenic as well as natural processes,
as by-products during the manufacture of some indus- PCBs, dioxins, and furans are widely dispersed in the
trial chemicals such as PCBs, polychlorinated naphtha- global environment and their presence was reported in
lenes, chlorinated phenols, chlorinated phenoxyacids, air, water, soil, sediment, aquatic organisms, and ter-
polychlorinated diphenyl ethers, polyvinyl chlorides, restrial organisms, including human tissues (Safe, 1990;

II. AGENTS THAT CAN BE USED AS WEAPONS OF MASS DESTRUCTION


Human Exposure to PCBs, PCDDs, and PCDFs 241

PCBs Dioxins (PCDDs) Furans

Cl Cl

Cl O Cl Cl Cl

Cl Cl

Cl O Cl Cl O Cl

3,3,4,4-tetrachlorobiphenyl 2,3,7,8- tetrachlorodibenzo-p-dioxin 2,3,7,8-tetrachlorodibenzofuran

Cl Cl
Cl Cl

Cl O Cl Cl Cl

Cl Cl

Cl O Cl Cl O Cl

Cl

3,3,4,4,5-pentachlorobiphenyl 1,2,3,7,8-pentachlorodibenzo-p-dioxin 1,2,3,7,8-pentachlorodibenzofuran

Cl Cl
Cl Cl

Cl O Cl Cl Cl

Cl Cl

Cl O Cl Cl O Cl

Cl Cl
Cl Cl

3,3,4,4,5,5-hexachlorobiphenyl 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin 1,2,3,4,7,8-hexachlorodibenzofuran

FIGURE 19.2 Structures of highly toxic PCBs, dioxins, and furans.

Loganathan and Kannan, 1994; Giesy and Kannan, 1998; 2002; Yusho Support Center Report, 2007). The epidemic
Masunaga etal., 2001b; Ogura etal., 2001). was identified later (1969) to be an unprecedented mass
food poisoning caused by the ingestion of commercial
brand rice oil that had been contaminated by PCB and
HUMAN EXPOSURE TO PCBS, PCDDS, their related compounds. The number of people who
AND PCDFS reported to have ingested the rice oil was approximately
14,000 and 1,867 persons were designated as Yusho vic-
Direct human exposure to PCBs/PCDF occurred tims. A similar outbreak of oil disease occurred in
because of inadvertent poisoning due to consumption of Taiwan in 1979. Toxicological studies revealed that
PCB contaminated food, resulting in Yusho and Yucheng PCDF congeners, including 2,3,4,7,8-pentachlorodiben-
poisoning (oil disease) in Japan and Taiwan during zofuran, played an important role in the manifestation of
1968 and 1979, respectively. The Yusho Support Center these diseases. Research conducted with Yusho victims
Report (2007) states that 39 years have passed since revealed harmful effects of the exposure continued two
the outbreak of YUSHO, the PCB/dioxin tragedythe generations (Yusho Support Center Report, 2007).
most unprecedented incident in the history of mankind Direct human exposure to dioxin occurred in south-
whereby people ingested toxic chemicals unknowingly, ern Vietnam and also in Seveso, Italy. It was estimated
directly through food. The outbreak of a strange disease that southern Vietnam has been contaminated by
Yusho (Kanemi Oil Poisoning) occurred in the western 160600kg of dioxin as a result of 80 million liters of
part of Japan in 1968. The major symptoms and signs of defoliant herbicides (Agent Orange, a 50:50 mixture of
the disease consisted of acne-like eruptions, pigmenta- 2,4,5-T and 2,4-D) being sprayed by the US military over
tion of the skin, nails, and conjunctivas, increased dis- a large area of forests and crops of southern Vietnam
charge from eyes, and numbness in the limbs (Yao etal., from 1962 to 1971 (Westing, 1984; Schecter et al., 2006;

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242 19. PCBs, Dioxins and Furans: Human Exposure and Health Effects

TABLE 19.1Toxicity Level of Various Chemical Compounds


(Prepared from Manahan, 1992)

LD50 Estimated
from Laboratory
Toxicity Level Compounds Animalsa (mg/kg)

Slightly toxic Ethyl alcohol 10,000


Sodium chloride 5,000
Moderately Malathion 1,000
toxic (organophosphorus pesticide)
Chlordane (termite 500
exterminator)
Very toxic Heptachlor (pesticide) 100
Extremely toxic Parathion (pesticide) 10
Dioxin (2,3,7,8-TCDD) 5 (hamster)
Tetraethyl pyrophosphate 1
FIGURE 19.3 Dioxin poisoning. Ukrainian former Prime Minister (pesticide, raticide)
and presidential candidate Viktor Yushchenko, with his face disfigured
by illness due to dioxin poisoning. Source: Photo: www.mindfully.org; Super toxic Tetrodotoxin 0.1
November 19, 2004 (accessed on July 13, 2008). (toxin of blowfish)
Dioxin (2,3,7,8-TCDD) 0.0006 (guinea
pig)
Le Hong Thorn etal., 2007). The defoliant was contami- Botulin (toxin of botulinum) 0.00001
nated with a very toxic form of dioxin (TCDD) known
a
to have caused adverse effects on human health. Dioxin LD50 are rough values estimated from oral-dose experiment on laboratory animals
(usually rats). Unit: mg/kg body weight.
may cause harmful effects on the whole body and can
affect separately the functioning of the systems such as
the nervous system, immune responses, carcinogenic- Muir, 2001; Loganathan et al., 2008). In PCBs, dioxins,
ity, hepatotoxicity, and metabolic and enzyme toxicity and furans, the properties vary widely and depend
(Le Hong Thorn etal., 2007). Another example of direct on the number and position of chlorine (or bromine)
human poisoning of dioxin was food poisoning of Viktor atoms attached to the molecule. In general, vapor pres-
Yushchenko (Figure 19.3), Ukrainian Presidential candi- sure, water solubility, and biodegradability decrease
date, in 2004. The dioxin poisoning caused a mysterious with increasing number of chlorine atoms. Lipophilicity
illness that resulted in his face becoming pockmarked adsorption capacity shows a reverse trend (Loganathan
and ashen (www.mindfully.org). Manahan (1992) classi- and Kannan, 1994). Because of these unique proper-
fied dioxin (2,3,7,8-TCDD) as super toxic in comparison ties, PCBs, dioxins, and furans have been detected in
with other known toxic substances (Table 19.1). air and water (rivers, lake ecosystems) (Pearson et al.,
1997; Loganathan etal., 1998a,b, 2001). Apart from this,
these compounds were recorded in fish, birds, and
PHYSICO-CHEMICAL PROPERTIES AND marine mammals of several other ecosystems such as
GLOBAL DISTRIBUTION the Atlantic, Baltic, and Pacific Oceans and Swedish
environments (Kawano et al., 1988; Loganathan et al.,
The unusual industrial versatility of PCBs was directly 1999). They have been identified in processed fish and
related to physical and chemical properties that include other food products (Kannan etal., 1997; Patandin etal.,
resistance to acids and bases, compatibility with organic 1999). Further, the residues of these contaminants were
materials, resistance to oxidation and reduction, excel- found in human adipose tissue, blood, and milk, and
lent insulating properties, nonflammability, and thermal also in numerous other matrices (Loganathan etal., 1993,
stability (Hutzinger etal., 1985). Physical and chemical 1998a,b, 1999; Petreas etal., 2001; Czaja etal., 2001). The
stability of PCBs are vital to the industrial applications comparison of PCDD/DFs and PBDD/DFs in terms of
and the same properties have been responsible for global toxic equivalents (TEQs) calculated based on WHO-TEF
environment contamination. In addition, multi-media (World Health Organizations toxic equivalent factors)
releases and volatility lead to long-range environmen- in pooled human milk samples of 17 countries showed
tal transport, both via water and atmosphere, resulting that PBDD/DF levels are significantly lower than the
in widespread environmental contamination of humans PCDD/DF (mean PBDD/DF:PCDD/DF-TEQ ratio was
and wildlife at sites distant from their use (Lipnick and 0.13 and its range was 0.060.25), indicating that exposure

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Mechanism of Action and Toxicity 243
of PCDDs/DFs is much greater than PBDD/DFs and calculated by isotope dilution method. Stable isotope-
more important to human health (Kotz et al., 2005). labeled target compounds are used as internal stan-
Because of the large production and indiscriminate use dards and spiked into samples. Calibration with internal
of PCBs in industries, these contaminants extended their standards and determination by isotope dilution are
boundaries of distribution over the global environment, necessary to obtain reliable data under very low con-
and this was evidenced by their detection even in pris- centrations and after repeated pretreatment and clean-
tine environmental media and biota such as the Arctic up procedures.
and Antarctic atmosphere, hydrosphere, and biosphere Solid samples such as soil and sediment are air-dried
(Muir et al., 1988; Corsolini et al., 2002; Kumar et al., and extracted using the Soxhlet/Dean-Stark apparatus.
2002). The discovery of the widespread environmental Aqueous samples are separated into solids and filtrates
occurrences, the increased general environmental con- by filters. Solids are Soxhlet extracted similar to bio-
cern, and the apparent link to carcinogenesis and other logical samples and filtrates are liquidliquid extracted.
health disorders prompted public outcry that resulted in Then, these extracts are cleaned and injected into HRGC-
prohibition of PCBs as well as chlorinated pesticides in HRMS, similar to biological samples.
several developed nations during the early 1970s. The In cases when congener-specific information is not nec-
following section deals with the chemical analysis of essary, other simpler methods can be used. EPA Methods
PCBs, dioxins, and furans in environmental and biologi- 608 and 8082a use GC/ECD to determine concentrations
cal samples. of PCBs in terms of Aroclor (Federal Register, 1984; US
EPA, 2007). EPA Method 680 (US EPA, 1985) uses GC/
MS (low-resolution mass spectrometry) to determine the
ANALYTICAL METHODS homolog concentration of PCBs (Figure 19.4).

PCBs and PCDDs/DFs consist of a total of 419 indi-


vidual congeners and PBDDs/DFs have 210 congeners. MECHANISM OF ACTION AND
In addition, dioxins and furans with mixed chlorine TOXICITY
and bromine substitution can occur. These congeners
have quite a variety of toxicity and some of these con- The toxicity of PCBs, PCDDs/DFs, and PBDDs/
geners, especially planar dioxins, furans, and dioxin-like DFs is complicated by the presence of a large number
PCBs (non-ortho chlorine substituted coplanar PCBs), are of congeners, each with its own toxicity. Commercial
extremely toxic even at very low concentrations (Table PCB mixtures elicit a broad spectrum of toxic responses
19.1). Therefore, determination of some toxic conge- that are dependent on several factors, including chlo-
ners to a very low concentration (parts per trillion) has rine content, purity, dose, species, age, sex, and dura-
become important. tion of exposure. Immunotoxicity, carcinogenicity, and
Congener-specific determination was required for developmental toxicity as well as biochemical effects of
those congeners that have toxic equivalency factors commercial PCB mixtures have been studied extensively
(TEFs), namely 2,3,7,8-chlorine substituted dioxins and in various laboratory animals, fish, and wildlife (Giesy
dioxin-like PCBs (Table 19.2). Thus, they are analyzed and Kannan, 1998). Several studies have confirmed the
using high-resolution gas chromatographyhigh-reso- common receptor-mediated mechanism of action of
lution mass spectrometry (HRGC-HRMS). A schematic toxic halogenated aromatics and have resulted in the
flow chart of a representative analysis procedure for development of a structureactivity relationship for this
environmental and biological samples is shown in class of chemicals (Safe, 1990). The most toxic haloge-
Figure 19.3 based on standard analytical methods such nated aromatics is 2,3,7,8-tetrachlorodibenzo-p-dioxin
as US EPA Methods 1613, 1668, 1668a, and JIS K0312 (US (TCDD), which is assigned the maximum toxicity fac-
EPA, 1994, 1997, 1999; JISC, 2008). tor of 1; the relative toxicities of individual halogenated
Biological samples are either freeze-dried or dewa- aromatics have been determined relative to TCDD (i.e.,
tered (homogenized) with anhydrous sodium sulfate toxic equivalents). The 17 congeners of PCDD/DFs and
salt and spiked with internal standards (clean-up spike) the 12 congeners of dioxin-like PCBs are assigned TEFs
and then extracted using Soxhlet apparatus. Obtained lower than TCDD (Table 19.2). In June 1997, the World
extracts are concentrated and their solvents are changed Health Organization established the levels of toxicity
to an appropriate solvent such as hexane, followed by a factors (WHO-TEFs) to be applied to evaluating the risks
series of clean-up procedures to remove lipids and other for humans and animals (Van den Berg etal., 2006). The
interfering chemicals. Then, the eluates are concentrated WHO consultation set the tolerable daily intake (TDI)
again and spiked with internal standards. The prepared between 1 and 4pg TEQ/kg body weight, emphasizing
samples were injected into HRGC-HRMS and monitored that the aim was to lower the TDI to a level less than 1pg
by multiple ion monitoring mode. Concentrations are TEQ/kg body weight (Guerzoni and Raccanelli, 2004).

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244 19. PCBs, Dioxins and Furans: Human Exposure and Health Effects

TABLE 19.2Toxic Equivalency Factors (TEFs) for Dioxins, Furans and Dioxin-like PCBs.

TEF

I-TEF Van den Berg etal. (1998) Van den Berg etal. (2006)

Human and
Congener Human Mammals Fish Bird Human and Mammals

PCDDs

2,3,7,8-TCDD 1 1 1 1 1
1,2,3,7,8-PeCDD 0.5 1 1 1 1
1,2,3,4,7,8-HxCDD 0.1 0.1 0.5 0.05 0.1
1,2,3,6,7,8-HxCDD 0.1 0.1 0.01 0.01 0.1
1,2,3,7,8,9-HxCDD 0.1 0.1 0.01 0.1 0.1
1,2,3,4,6,7,8-HpCDD 0.1 0.01 0.001 <0.001 0.01
OctaCDD 0.001 0.0001 0.0003

PCDFs

2,3,7,8-TCDF 0.1 0.1 0.05 1 0.1


1,2,3,7,8-PeCDF 0.05 0.05 0.05 0.1 0.03
2,3,4,7,8-PeCDF 0.5 0.5 0.5 1 0.3
1,2,3,4,7,8-HxCDF 0.1 0.1 0.1 0.1 0.1
1,2,3,6,7,8-HxCDF 0.1 0.1 0.1 0.1 0.1
1,2,3,7,8,9-HxCDF 0.1 0.1 0.1 0.1 0.1
2,3,4,6,7,8-HxCDF 0.1 0.1 0.1 0.1 0.1
1,2,3,4,6,7,8-HpCDF 0.01 0.01 0.01 0.01 0.01
1,2,3,4,7,8,9-HpCDF 0.01 0.01 0.01 0.01 0.01
OctaCDF 0.001 0.0001 0.0001 0.0001 0.0003

NON-ORTHO-PCBs

3,4,4,5-TeCB (#81) 0.0001 0.0005 0.1 0.0003


3,3,4,4-TeCB (#77) 0.0001 0.0001 0.05 0.0001
3,3,4,4,5-PeCB (#126) 0.1 0.005 0.1 0.1
3,3,4,4,5,5-HxCB (#169) 0.01 0.00005 0.001 0.03

MONO-ORTHO-PCBs

2,3,3,4,4-PeCB (#105) 0.0001 <0.000005 0.0001 0.00003


2,3,4,4,5-PeCB (#114) 0.0005 <0.000005 0.0001 0.00003
2,3,4,4,5-PeCB (#118) 0.0001 <0.000005 0.00001 0.00003
2,3,4,4,5-PeCB (#123) 0.0001 <0.000005 0.00001 0.00003
2,3,3,4,4,5-HxCB (#156) 0.0005 <0.000005 0.0001 0.00003
2,3,3,4,4,5-HxCB (#157) 0.0005 <0.000005 0.0001 0.00003
2,3,4,4,5,5-HxCB (#167) 0.00001 <0.000005 0.00001 0.00003
2,3,3,4,4,5,5-HpCB (#189) 0.0001 <0.000005 0.00001 0.00003

II. AGENTS THAT CAN BE USED AS WEAPONS OF MASS DESTRUCTION


Mechanism of Action and Toxicity 245

Biological sample Solid sample Air sample Aqueous sample

Freeze-dry or Freeze-dry or High-volume Filtration through


Homogenized with Air-dry air sampling glass-fiber filter
Na2SO4

Urethane Solids Solids Filtrate


foam on filter on filter

Clean-up spike

Soxhlet extraction Soxhlet/Dean-stark extraction Separatory


funnel extraction

Lipid removal

Concentration and solvent change


(Rotary evaporator or Kuderna-Danish apparatus or nitrogen gas)

Cleanup
Multilayered silica gel column chromatography or
H2SO4 treatment-silica gel column chromatography

Alumina activated carbon column chromatography

Activated carbon column chromatography

Gel permeation chromatography

Eluate for PCDD/DFs and PBDD/DF determination Eluate for dioxin-like PCB determination

Concentration Concentration

I-Standard spike

Determination by HRGC-HRMS

FIGURE 19.4 Analytical procedure of dioxins, furans, and dioxin-like PCBs.

The most toxic PCB congeners are those that have chlo- enzymes primarily in the liver. 2,3,7,8-TCDD evokes
rine substitution in most of the non-ortho positions, such dose-related induction of cytochrome-P-450associated
as 3, 4, and 5 in each ring. These coplanar PCB con- aryl hydrocarbon hydroxylase (AHH) activity. The most
geners (Figure 19.2) are structurally similar to highly widely studied of these responses are induction of AHH
toxic 2,3,7,8-TCDD and exhibit similar toxic responses and EROD (markers of CYP1A activity) in mammalian
(Ah receptormediated toxicity) (Figure 19.5). There are cell cultures and in laboratory rodents (Goldstein and
no TEFs for 2,3,7,8-substituted PBDDs/DFs that have Safe, 1989).
international agreement; however, use of the same TEF Ah receptormediated toxicity resulted in a wide
values for the corresponding PBDD/DF congeners as range of biological responses, including alterations in
described for the chlorinated analogues appears to be metabolic pathways, body weight loss, thymic atrophy,
justified (International Programme on Chemical Safety, impaired immune responses, hepatotoxicity, chloracne
1998). 2,3,7,8-TCDD and structurally related halogenated and related skin lesions, developmental and reproduc-
aromatic compounds induce a variety of microsomal tive effects, and neoplasia.

II. AGENTS THAT CAN BE USED AS WEAPONS OF MASS DESTRUCTION


246 19. PCBs, Dioxins and Furans: Human Exposure and Health Effects

FIGURE 19.5 Possible mechanism of toxic action of 2,3,7,8-TCDD.

CONCLUDING REMARKS AND Corsolini, S., Kannan, K., Imagawa, T., etal., 2002. Polychlorinated naphthalenes
and other dioxin-like compounds in Arctic and Antarctic food webs. Environ.
FUTURE DIRECTIONS Sci. Technol. 36, 34903496.
Czaja, C., Ludwicki, J.K., Robson, M.G., etal., 2001. Concentrations of persistent
organochlorine compounds in the placenta and milk of the same women. In:
PCBs, dioxins, and furans are persistent organic pol- Lipnick, R.L., Hermens, J.L.M., Jones, K.C., Muir, D.C.G. (Eds.), Persistent,
lutants that have negative effects on the environment Bioaccumulative, and Toxic Chemicals I: Fate and Exposure American
and health of humans, including skin toxicity, immuno- Chemical Society, Washington, DC, pp. 284291. ACS Symposium Series
Monograph 772.
toxicity, neurotoxicity, negative effects on reproduction, Federal Register, 1984. US EPA: Method 608. PCBs and Organochlorine Pesticides,
teratogenicity, endocrine disruption, and a predisposi- vol. 49, pp. 89104. <http://www.epa.gov/region9/qa/pdfs/40cfr136_03.pdf>.
tion to cancer. A major pathway of exposure to these Feil, V.J., Larsen, G.L., 2001. Dioxins in food from animal sources. In: Lipnick, R.L.,
Hermens, J.L.M., Jones, K.C., Muir, D.C.G. (Eds.), Persistent, Bioaccumulative
chemicals is through consumption of food contaminated and Toxic Chemicals I: Fate and Exposure, vol. 772, pp. 245251.
by PCBs and dioxins. The Committee of Experts on Food Giesy, J.P., Kannan, K., 1998. Dioxin-like and non-dioxin-like toxic effects of
of the European Commission proposed a dose called polychlorinated biphenyls (PCBs): implications for risk assessment. Crit.
Rev. Toxicol. 28, 511569.
tolerable weekly intake given by the total of dioxins Goldstein, J.A., Safe, S., 1989. Mechanism of action and structure activity rela-
and PCBs of 14pg TEQ/kg of body weight, which is an tionship for the chlorinated dibenzo-p-dioxins and related compounds. In:
average of 2pg TEQ/day/kg of body weight (Guerzoni Kimbrough, R.D., Jensen, A.A. (Eds.), Halogenated Biphenyls, Naphthalenes,
Dibenzodioxins and Related Compounds, second ed. Elsevier Science
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the Environment, Venice City Council, Venice, Italy. p. 98.
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II. AGENTS THAT CAN BE USED AS WEAPONS OF MASS DESTRUCTION