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19
PCBs, Dioxins and Furans: Human
Exposure and Health Effects
Bommanna G. Loganathan and Shigeki Masunaga
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
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;
Cl Cl
Cl O Cl Cl Cl
Cl Cl
Cl O Cl Cl O Cl
Cl Cl
Cl Cl
Cl O Cl Cl Cl
Cl Cl
Cl O Cl Cl O Cl
Cl
Cl Cl
Cl Cl
Cl O Cl Cl Cl
Cl Cl
Cl O Cl Cl O Cl
Cl Cl
Cl Cl
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;
LD50 Estimated
from Laboratory
Toxicity Level Compounds Animalsa (mg/kg)
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
NON-ORTHO-PCBs
MONO-ORTHO-PCBs
Clean-up spike
Lipid removal
Cleanup
Multilayered silica gel column chromatography or
H2SO4 treatment-silica gel column chromatography
Eluate for PCDD/DFs and PBDD/DF determination Eluate for dioxin-like PCB determination
Concentration Concentration
I-Standard spike
Determination by HRGC-HRMS
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.
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
and Raccanelli, 2004). By reducing the environmental Publishers, Amsterdam, pp. 239293.
contamination, we can diminish the food chain accumu- Guerzoni, S., Raccanelli, S. (Eds.), 2004. The Sick Lagoon. Dioxin and Other
lation and, ultimately, we can reduce the intake levels of Persistent Organic Pollutants (POPs) in the Lagoon of Venice Department of
the Environment, Venice City Council, Venice, Italy. p. 98.
PCBs and dioxins and their toxic effects. Hryhorczuk, D.O., Orris, P., Kominsky, J.R., etal., 1986. PCB, PCDF and PCDD
exposure following a transformer fireChicago. Chemosphere 15, 12971303.
Hutzinger, O., Choudhry, G.G., Chittim, B.G., etal., 1985. Formation of polychlo-
rinated dibenzofurans and dioxins during combustion, electrical equipment
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