Incineration of wastes seems to be one of the major sources of PCDDs and PCDFs (dioxins). Their prevalence and extreme stability in the environment, bioavailability and bioaccumulation in the biota and human adipose tissues and breast milk are of much concern. 2,3,7,8-TCDD is one of the most toxic chemicals known and has been found to have teratogenic and carcinogenic activities in animals. Exposure to TCDD can result in chloracne, general weakness, drastic weight loss, hyperpigmentation of skin, hirsutism, porphyria cutanea tarda, liver damage, changes in activities of various liver enzymatic levels, abnormal lipid metabolism, abnormalities of the endocrine and immune systems, and possible teratogenic effects in humans. Moreover, chronic bioassay data indicate that TCDD is one of the most potent carcinogens known. It promotes liver and skin carcinogeneses, and is an initiator for various target organs in rodent test systems. There is only a limited number of human epi-studies on carcinogenic outcome as a result of exposure to TCDD in isolated population.
According to the classification system of the International Agency for Research on Cancer (IARC), the qualitative evidence for carcinogenicity of TCDD is considered to be "sufficient" in animals and "inadequate" in humans. Consequently, this chemical has been placed in IARC's 2B category. A modification of the multistage model is utilized for extrapolating high-dose, two-year animal cancer bioassay data to estimate human cancer risk for long-term, low-dose human exposure. The upper limit of incremental cancer risk is 3.3 x 10-5 for a continuous lifetime exposure to 1 pg m-3 of TCDD in ambient air. With the exception of 2,3,7,8-TCDD and a mixture of 1,2,3,6,7,8- and 1,2,3,7,8,9-HxCDDs, the chronic toxicity data on the rest of the 75 PCDD and 135 PCDF congeners are badly deficient. In the absence of chronic bioassay data on other PCDDs and PCDFs, several TCDD equivalent approaches have been proposed for risk assessment on other congeners or mixtures. This paper compares the various approaches.
Allen, J.R., Barsotti, D.A., Lambrecht, L.K. & van Miller, J.P. (1979), Reproductive effects of halogenated aromatic hydrocarbons on non-human primates, Annals of the New York Academy of Science, 320, 419-425.
2.
Bandiera, S., Sawyer, T., Romkes, M., Zmukda, B., Safe, L., Mason, G., Keys, B. & Safe, S. (1984a), Polychlorinated dibenzofurans (PCDFs): Effects of structure on binding to the 2,3,7,8-TCDD cytosolic receptor protein, AHH induction and toxicity, Toxicology, 32, 131-144.
3.
Bandiera, S., Farrell, K., Mason, G., Kelley, M., Romkes, M., Bannister, R. & Safe, S. (1984b), Comparitive toxicities of the polychlorinated dibenzofuran (PCDF) and biphenyl (PCB) mixtures which persist in Yusho victims , Chemosphere, 13, 507-512.
4.
Barnes, D. (1983), Dioxin Production from the Combustion of Biomass and Wastes. Presented at the Institute of Gas Technology , Chicago, IL, Symposium: Energy from Biomass and Wastes, Lake Buena Vista, FL, pp. 291-327.
5.
Barnes, D., Bellin, J. & Cleverly, D. (1986), Interim procedures for estimating risks associated with exposures to mixtures of chlorinated dibenzodioxins and dibenzofurans (CDDs and CDFs), Chemosphere, 15, 1895-1903.
6.
Bastomsky, C.H. (1977), Enhanced thyroxine metabolism and high uptake goiters in rats after a single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin , Endocrinology, 101, 292-296.
7.
Beatty, P.W., Vaugh, W.K. & Neal, R.A. (1978), Effect of alteration of rat hepatic mixed-function oxidase (MFO) activity of the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), Toxicology & Applied Pharmacology, 45, 513-519.
8.
Bellin, J.S. & Barnes, D.G. (1987), Interim procedures for estimating risks associated with exposures to mixtures of chlorinated dibenzo-p-dioxins and dibenzofurans , EPA/625/3-87/ 012.
9.
Bishop, C.M. & Jones, A.H. (1981), Non-Hodgkin's lymphoma of the scalp in workers exposed to dioxins, Lancet, 2 (8242), 369.
10.
Bradlaw, J.A. & Casterline Jr, J.L. (1979), Induction of enzyme activity in cell culture. A rapid screen for detection of planar polychlorinated organic compounds, Journal of the Association of Official Analytical Chemistry, 62, 904-906.
11.
Bradlaw, J.A., Garthoff, L.H., Hurley, N.E. & Firestone, D. (1980), Comparative induction of aryl hydrocarbon hydroxylase activity in vitro by analogues of dibenzo-p-dioxin, Food and Cosmetics Toxicology, 18, 627-635.
12.
Buser, H.R. (1979), Formation and identification of tetra- and pentachlorodibenzo-p-dioxins from photolysis of two isomeric hexachlorodibenzo-p-dioxins, Chemosphere, 8, 251-254.
13.
Buser, H.R. & Rappe, C. (1984), Isomer-specific separation of 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins by high resolution gas chromatography/mass spectrometry, Analytical Chemistry, 56, 442.
14.
Carlstedt-Duke, J.M. (1979), Tissue distribution of the receptor for 2,3,7,8-tetrahclorodibenzop-dioxin and its endocrine independence, Cancer Research, 39(11), 4653-4656.
15.
Carlstedt-Duke, J.M., Elfstrom, G., Hogberg, B. & Gustafsson, J.-A. (1979), Ontogency of the rat hepatic receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin and its endocrine independence , Cancer Research, 39(11), 4653-4656.
16.
Carlstedt-Duke, J.M., Harnemo, U.B., Hogberg, B. & Gustafsson, J.-A. (1981), Interaction of the hepatic receptor protein for 2,3,7,8-tetrachlorodibenzo-p-dioxin with DNA, Biochimica et Biophysica Acta, 672, 131-141.
17.
Choudhury, G.G. & Hutzinger, O. (1982), Photochemical formation and degradation of polychlorinated dibenzofurans and dibenzo-p-dioxins, Residue Reviews, 84, 113-161.
18.
Cook, M. (1983), TCDD Emissions for Municipal Waste Combustors , Memorandum, 16 December 1983.
19.
Crump, K.S. & Watson, W.W. (1979), Global 79: a Fortran program to extrapolate dichotomons animal carcinogenicity data to low dose. NIEHS Contract No. I-ES-2123.
20.
Eadon, G., Aldous, K., Hilker, D., O'Keefe, P. & Smith, R. (1983), Chemical data on air samples from the Binghampton State Office Building. Memo from Center for Laboratory and Research, NY State Dept. Health, Albany, NY 12201, July 1983.
21.
Eriksson, M., Hardell, L., Berg, N.O., Moller, T. & Axelson, O. (1979), Case-control Study on Malignant Mesenchymal Tumors of the Soft-Tissue and Exposure to Chemical Substances. Lakartidningen , 76, 3872-3875 (translation).
22.
Eriksson, M., Hardell, L., Berg, N.O., Moller, T. & Axelson, O. (1981), Soft-tissue sarcomas and exposure to chemical substances: a case-referent study, British Journal of Industrial Medicine, 38, 27-33.
23.
Gierthy, J.F., Grane, D. & Frenkel, G.D. (1984), Application of an in vitro keratinization assay to extracts of soot from a fire and a polychlorinated biphenyl-containing transformer, Fundamental and Applied Toxicology, 74, 91-98.
24.
Haile, C. & Stanley, J. (1983), Pilot Study of Information of Specific Compounds from Combustion Sources. EPA-560/5-83-004.
25.
Hardell, L. & Ericksson, M. (1981), Soft-tissue sarcomas, phenoxy herbicides, and chlorinated phenols, Lancet, 2, 8240.
26.
Hardell, L. & Sandstrom, A. (1979), Case-control study: soft-tissue sarcoma and exposure to phenoxyacetic acids or chlorophenols, British Journal of Cancer, 39, 711-717.
27.
Hardell, L., Ericksson, M., Lenner, P. & Lundgren, E. (1981) Malignant lymphoma and exposure to chemicals, especially organic solvents, chlorophenols and phenoxy acids: a case-control study, British Journal of Cancer, 43, 169-176.
28.
Henry, E.C. & Gasiewicz, T.A. (1986), Effects of thyroidectomy on the Ah-receptor and enzyme inducibility by 2,3,7,8-tetrachlorodibenzo-p-dioxin in the rat liver, Chemical and Biological Interactions, 59, 29-42.
29.
Hoar, S.K., Blair, A., Holmes, F.F. (1986), Agricultural herbicide use and risk of lymphoma and soft-tissue sarcoma, Journal of theAmerican Medical Association , 256, 1141-1147.
30.
Kimbrough, R.D. (1974), The toxicity of polychlorinated polycyclic compounds and related compounds, CRC Critical Reviews onToxicology , 2, 445-489.
31.
Kociba, R.J. & Cabey, O. (1985), Comparative toxicity and biological activity of chlorinated dibenzo-p-dioxins and furans relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), Chemosphere, 14, 649-660.
32.
Kociba, R.J., Keyes, D.G., Beyer, J.E., Carreon, R.M. & Gehring, P.J. (1979), Long-term toxicological studies of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in laboratory animals, Annals of the New York Academy of Science, 320, 397-404.
33.
Lynge, E. (1985), A follow-up study of cancer incidence among workers in manufacture of phenoxy herbicides in Denmark, British Journal of Cancer, 52, 259-270.
34.
Mason, G., Sawyer, T., Keys, B., Bandiera, S., Romkes, M., Piskorska-Pliszczynska, J., Zmudzka, B. & Safe, S. (1985), Polychlorinated dibenzofurans (PcDFs): correlation between in vivo and in vitro structure-activity relationships, Toxicology, 37, 1-2.
35.
Mason, M.E. & Okey, A.B. (1982), Cystolic and nuclear binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin to the Ah-receptor in entra-hepatic tissues of rats and mice, European Journal of Biochemistry, 123, 209-215.
36.
McConnell, E.E. & Moore, J.A. (1979), Toxicopathology characteristics of the halogenated aromatics, Annals of the New York Academy of Sciences, 320, 138-150.
37.
McConnell, E.E., Moore, J.A., Haseman, J.K. & Harris, M.W. (1978), The comparative toxicity of chlorinated dibenzo-o-dioxins in mice and guinea-pigs, Toxicology and Applied Pharmacology , 44, 335-356.
38.
McKinney, J.D. & McConnell, E. (1981), Structural specificity and dioxin receptor. In Chlorinated Dioxins and Related Compounds. Impact on the Environment (O. Hutzinger, R. W. Frei, E. Merian & F. Pocchiari, Eds), p. 367. Oxford: Pergamon Press.
39.
Moore, J.A., McConnell, E.E., Dalgard, D.W. & Harris, M.W. (1979), Comparative toxicity of three halogenated dibenzofurans in guinea-pigs, mice and rhesus monkeys, Annals of the New York Academy of Science, 320, 151-163.
40.
Moses, M. & Selikoff, I.J. (1981), Soft-tissue sarcomas, phenoxy herbicides and chlorinated phenols, Lancet, 1 (8234), 1370.
41.
Mukerjee, D., Stara, J.F. & Schaum, J.L. (1986), Rationale for assessment of risk from exposure to 2,3,7,8-TCDD, Chemosphere, 15, 1805-1813.
42.
NTP (National Toxicilogy Program) (1980a), Bioassay of 2,3,7,8-Tetrachlorodibenzo-p-dioxin for Possible Carcinogenicity (Gavage Study), DHHS Publ. No. (NIH) 82-1765, Carcinogenesis Testing Program, NCI, NIH, Bethesda, MD, and NTP, RTP, Box 12233, NC.
43.
NTP (National Toxicology Program) (1980b), Bioassay of 1,2,3,6,7,8- and 1,2,3,7,8,9-Hexachlorodibenzo-p-dioxins (Gavage) for Possible Carcinogenicity, DHHS Publ. No. (NIH) 80-1754, Carcinogenesis Testing Program, NCI, NIH, Bethesda, MD, and NTP, RTP, Box 12233, NC.
44.
Nebert, D.W. (1980), The Ah locus. A gene with possible importance in cancer predictability, Archives of Toxicology (Supplement 3), 195-207.
45.
Nebert, D.W. & Jensen, N.M. (1979), The Ah locus: genetic regulation of the metabolism of carcinogens, drugs, and other environmental chemicals by cytochrome P-450 mediated monoxygenases, CRC Critical Reviews of Biochemistry , 6, 401-437.
46.
Okey, A.B. (1983), The Ah receptor: a specific site for action of chlorinated dioxins. In Human and Environmental Risks of Chlorinated Dioxins and Related Compounds (R. E. Tucker , A. L. Young & A. P. Gray, Eds), pp. 423-440. Plenum Press , New York.
47.
Olie, K., Lustenhouwer, J.W.A. & Hutzinger, O. (1983), Formation and fate of PCDD and PCDF from combustion processes, Chemosphere, 12, 627-636.
48.
Ontario Government (1982), Chlorinated Dioxins and Chlorinated Dibenzofurans. Ambient Air Guidelines. Health Studies Services, Ministry of Labor, 16 December.
49.
Parkinson, A. & Safe, S.H. (1981), Aryl hydrocarbon hydroxylase induction and its relationship to the toxicity of halogenated aryl hydrocarbons, Toxicology and Environmental Chemistry Research, 4, 1-46.
50.
Pazdernik, T.L. & Rozman, K.K. (1985), Effect of thyroidectomy and thyroxine on 2,3,7,8-tetrachlorodibenzo-p-dioxin induced immunotoxicity, Life Science, 36, 695-703.
51.
Pitot, H.C., Goldsworthy, T. & Poland, A. (1980), Promotion by 2,3,7,8-tetrachlorodibenzo-p-dioxin of hepatocarcinogenesis from diethylnitrosamine, Cancer Research , 40, 3616-3620.
52.
Poland, A.P. (1984), Reflection on the mechanism of action of halogenated aromatic hydrocarbons. In Biological Mechanisms of Dioxin Action, Banbury Report 18 (A. Poland & R. D. Kimbrough, Eds), pp. 109-117. Cold Spring Harbor Laboratory.
53.
Poland, A. & Knutson, J.C. (1982), 2,3,7,8-Tetrachlorodibenzo-p-dioxin and related halogenated aromatic hydrocarbons: examination of the mechanism of toxicity , Annual Review of Pharmacology and Toxicology, 22, 517-554.
54.
Poland, A., Glover, E., Kende, A.S. (1976), Stereospecific, high affinity binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin by hepatic cytosol. Evidence that the binding species is receptor for induction of aryl hydrocarbon hydroxylase, Journal of Biological Chemistry , 251, 4936-4946.
55.
Poland, A., Greenlee, W.F. & Kende, A.S. (1979), Studies on the mechanisms of action of the chlorinated dibenzo-p-dioxins and related compounds, Annals of the New York Academy of Sciences, 320, 214-230.
56.
Poland, A., Palen, D. & Glover, E. (1982), Tumor promotion by TCDD in skin of HRS/J mice , Nature, 300, 271-273.
57.
Puntoni, R., Merlo, F., Fini, A., Meazza, L. & Santi, L. (1986), Soft tissue sarcoma in seveso, Lancet, 2, 525.
58.
Rappe, C., Berggvist, P.-A., Hansson, M., Kjeller, L.-O., Lindstrom, G., Marklund, S. & Nygren, M. (1984), Chemistry and analysis of polychlorinated dioxins and dibenzofurans in biological samples. In Biological Mechanisms of Dioxin Action, Banbury Report 18 (A. Poland & R. D. Kimbrough, Eds), pp. 17-25. Cold Spring Harbor Laboratory.
59.
Rizzardini, M., Ramano, M., Tursi, F., Salmona, M., Vecchi, A., Sironi, M., Gizzi, F., Benfenati, E., Garattini, S. & Fanelli, R. (1983), Toxicological evaluation of urban waste emissions , Chemosphere, 12, 559-564.
60.
Rozman, K., Rozman, T. & Greim, H. (1984), Effect of thyroidectomy and thyroxine on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced toxicity, Toxicology and Applied Pharmacology , 72, 311-376.
61.
Safe, S.H. (1986), Comparative toxicology and mechanism of action of polychlorinated dibenzo-p-dioxins and dibenzofurans, Annual Review of Pharmacology and Toxicology, 26, 371-399.
62.
Sarma, P.R. & Jacobs, J. (1981), Thoracic soft-tissue sarcoma in Vietnam veterans exposed to agent orange, Lancet, 306 (18), 1109.
63.
Sawyer, T. & Safe, S., In vitro AHH induction by polychlorinated biphenyl and dibenzofuran mixtures: additive effects, Chemosphere, 14, 79-84.
Swiss Federal Office for Environmental Protection (Bundesamt Für Umweltschutz, Bern) (1982), Environmental Pollution Due to Dioxins and Furans from Chemical Rubbish Incineration Plant . Schriften veighe Umweltschutz, No. 5.
66.
Taylor, J.S. (1979), Environmental chloroacne: update and overview , Annals of the New York Academy of Science, 320, 295-307.
67.
Toth, K., Samfai-Pelle, S., Sugar, J. & Bence, J. (1979), Carcinogenicity testing of herbicide 2,4,5-trichlorophenoxyethanol containing dioxin and of pure dioxin in Swiss mice, Nature , 278, 548-549.
68.
Tukey, R.H., Hannah, R.R., Negishi, M., Nebert, D.W. & Eisen, H.J. (1982), The Ah locus: correlation of intranuclear appearance of inducer-receptor complex with induction of cytochrome P1-450 mRNA, Cell, 31, 275-284.
69.
U.S. Environmental Protection Agency, OSW, OPTS ( 1981), Interim Evaluation of Health Risks Associated with Emissions of Tetrachlorinated Dioxins from Municipal Waste Resource Recovery Facilities . November, Washington, DC.
70.
U.S. Environmental Protection Agency (1985 ), Health Assessment Document for Polychlorinated Dibenzo-p-dioxins . EPA/600/8-84/014F. Final Report. NTIS PB86-122546.
71.
van Miller, J.P., Lalich, J.J. & Allen, J.R. (1977), Increased incidence of neoplasms in rats exposed to low levels of 2,3,7,8-tetrachlorodibenzo-o-dioxin, Chemosphere , 6, 625-632.
72.
Yoshihara, S., Nagata, K., Yoshimura, H., Kuroki, H. & Masuda, Y. (1981), Inductive effect on hepatic enzymes and acute toxicity of individual polychlorinated dibenzofuran congeners in rats, Toxicology and Applied Pharmacology, 59, 580-588.
