For definition of Groups, see Preamble Evaluation.
Supplement 7: (1987) (p. 219)
A. Evidence for carcinogenicity to humans (inadequate)
No report of a direct association between hexachlorobenzene and human cancer is available. Hepatocellular carcinoma has been associated with porphyria [ref: 1-5]. However, although abnormal porphyrin metabolism persisted at least 20 years after an epidemic of porphyria cutanea tarda in Turkey, caused by consumption of grain treated with hexachlorobenzene [ref: 6], no excess cancer occurrence has been reported in this population 25 years after the accident [ref: 7].
B. Evidence for carcinogenicity to animals (sufficient)
Hexachlorobenzene was tested by oral administration in one experiment in mice and in one in hamsters. In mice, it produced liver-cell tumours in animals of each sex; in hamsters of each sex, it produced hepatomas, liver haemangioendotheliomas and thyroid adenomas. An experiment involving intraperitoneal administration in mice was considered to be inadequate [ref: 6]. In a study in rats fed hexachlorobenzene in the diet, hepatomas, hepatocellular carcinomas, bile-duct adenomas and renal-cell adenomas were observed [ref: 8]. In a two-generation feeding study in rats with lower dose levels, increased incidences of parathyroid adenomas and adrenal phaeochromocytomas were observed in animals of each sex and liver neoplastic nodules in females of the F1 generation [ref: 9]. After 90 weeks' feeding of hexachlorobenzene to rats, 100% of surviving females and only 16% of males had developed liver tumours [ref: 10].
C. Other relevant data
No data were available on the genetic and related effects of hexachlorobenzene in humans. It did not induce dominant lethal mutations in rats treated in vivo. It did not induce chromosomal aberrations in cultured Chinese hamster cells or mutation in bacteria [ref: 11].
Hexachlorobenzene is possibly carcinogenic to humans (Group 2B).
For definition of the italicized terms, see Preamble Evaluation.
Subsequent evaluation: Vol. 79 (2001)
Also see previous evaluation: Vol. 20 (1979)
1. Kordac, V. (1972) Frequency of occurrence of hepatocellular carcinoma in patients with porphyria cutanea tarda in long-term follow-up. Neoplasma, 19, 135-139
2. Solis, J.A., Betancor, P., Campos, R., Enriquez de Salamanca, R., Rojo, P., Marin, I. & Schüller, A. (1982) Association of porphyria cutanea tarda and primary liver cancer: report of ten cases. J. Dermatol., 9, 131-137
3. Lithner, F. & Wetterberg, L. (1984) Hepatocellular carcinoma in patients with acute intermittent porphyria. Acta med. scand., 215, 271-274
4. Hardell, L., Bengtsson, N.O., Jonsson, U., Eriksson, S. & Larsson, L.G. (1984) Aetiological aspects on primary liver cancer with special regard to alcohol, organic solvents, and acute intermittent porphyria - an epidemiological investigation. Br. J. Cancer, 50, 389-397
5. Axelson, O. (1986) A review of porphyria and cancer and the missing link with human exposure to hexachlorobenzene. In: Morris, C.R. & Cabral, J.R.P., eds, Hexachlorobenzene: Proceedings of An International Symposium (IARC Scientific Publications No. 77), Lyon, International Agency for Research on Cancer, pp. 585-589
6. IARC Monographs, 20, 155-178, 1979
7. Peters, H.A., Gocmen, A., Cripps, D.J., Bryan, G.T. & Dogramaci, I. (1982) Epidemiology of hexachlorobenzene-induced porphyria in Turkey. Clinical and laboratory follow-up after 25 years. Arch. Neurol., 39, 744-749
8. Ertürk, E., Lambrecht, R.W., Peters, H.A., Cripps, D.J., Gocmen, A., Morris, C.R. & Bryan, G.T. (1986) Oncogenicity of hexachlorobenzene. In: Morris, C.R. & Cabral, J.R.P., eds, Hexachlorobenzene: Proceedings of an International Symposium (IARC Scientific Publications No. 77), Lyon, International Agency for Research on Cancer, pp. 417-423
9. Arnold, D.L., Moodie, C.A., Charbonneau, S.M., Grice, H.C., McGuire, P.F., Bryce, F.R., Collins, C.T., Zawidzka, Z.Z., Krewski, D.R., Nera, E.A. & Munro, I.C. (1985) Long-term toxicity of hexachlorobenzene in the rat and the effect of dietary vitamin A. Food chem. Toxicol., 23, 779-793
10. Smith, A.G., Francis, J.E., Dinsdale, D., Manson, M.M. & Cabral, J.R.P. (1985) Hepatocarcinogenicity of hexachlorobenzene in rats and the sex difference in hepatic iron status and development of porphyria. Carcinogenesis, 6, 631-636
11. IARC Monographs, Suppl. 6, 331-332, 1987
See Also: Toxicological Abbreviations Hexachlorobenzene (EHC 195, 1997) Hexachlorobenzene (HSG 107, 1998) Hexachlorobenzene (ICSC) Hexachlorobenzene (PIM 256) Hexachlorobenzene (FAO/PL:1969/M/17/1) Hexachlorobenzene (WHO Pesticide Residues Series 4) Hexachlorobenzene (IARC Summary & Evaluation, Volume 20, 1979) Hexachlorobenzene (IARC Summary & Evaluation, Volume 79, 2001)