For definition of Groups, see Preamble Evaluation.
Supplement 7: (1987) (p. 220)
Hexachlorocyclohexane [mixed isomers]
CAS No.:
Chem. Abstr. Name: 1,2,3,4,5,6-Hexachlorocyclohexane
Hexachlorocyclohexane [a-isomer]
CAS No.:
Chem. Abstr. Name: 1a,2a,3b,4a,5b,6a-Hexachlorocyclohexane
Hexachlorocyclohexane [b-isomer]
CAS No.:
Chem. Abstr. Name: 1a,2b,3a,4b,5a,6b-Hexachlorocyclohexane
Lindane
CAS No.:
Chem. Abstr. Name: 1a,2a,3b,4a,5a,6b-Hexachlorocyclohexane
Hexachlorocyclohexane [d-isomer]
CAS No.:
Chem. Abstr. Name: 1a,2a,3a,4b,5a,6b-Hexachlorocyclohexane
Hexachlorocyclohexane [e-isomer]
CAS No.:
Chem. Abstr. Name: 1a,2a,3a,4b,5b,6b-Hexachlorocyclohexane
Hexachlorocyclohexane [z-isomer]
CAS No.:
Chem. Abstr. Name: 1a,2a,3a,4a,5a,6a-Hexachlorocyclohexane
Hexachlorocyclohexane [h-isomer]
CAS No.:
Chem. Abstr. Name: 1a,2a,3a,4a,5b,6b-Hexachlorocyclohexane
Hexachlorocyclohexane [q-isomer]
CAS No.:
Chem. Abstr. Name: 1a,2a,3a,4a,5a,6b-
A. Evidence for carcinogenicity to humans (inadequate for hexachlorocyclohexanes)
Four cases of leukaemia were reported in men exposed to g-hexachlorocyclohexane (lindane) with or without other chemicals [ref: 1,2]. Cases of aplastic anaemia have also been associated with exposure to this compound [ref: 1]. Mean tissue levels of hexachlorocyclohexanes were reported to be elevated in two of three studies of autopsy patients; in one of these, in four liver cancer patients, the level of the b-isomer was abnormally high [ref: 3-5]. Mean serum levels of b-hexachlorocyclohexane were not appreciably higher in four cancer patients than in three controls [ref: 6]. Exposure to g-hexachlorocyclohexane was recorded in case-control studies of soft-tissue sarcomas and of lymphomas [ref: 7,8] but was insufficiently frequent for any conclusion to be drawn. An increase in lung cancer mortality was observed in agricultural workers who had used hexachlorocyclohexane (unspecified) and a variety of other pesticides and herbicides (standardized mortality ratio, 180 [95% confidence interval, 140-240]) [ref: 9].
B. Evidence for carcinogenicity to animals (sufficient for technical-grade and for the a isomer; limited for the b and for the g isomers)
Technical-grade, a- and b-hexachlorocyclohexane and the g isomer (lindane) produced liver tumours in mice when administered orally [ref: 1,10,11]; the technical grade also produced lymphoreticular neoplasms [ref: 10]. In two studies in rats, an increased incidence of liver tumours was observed with the a isomer [ref: 1,12], and in one study in rats a few thyroid tumours were observed with the g isomer [ref: 1]; other studies in rats [ref: 11,13-15] were considered to be inadequate. Studies in hamsters [ref: 11] and dogs [ref: 16] were also inadequate. Technical-grade hexachlorocyclohexane and the g isomer were tested inadequately by skin application in mice [ref: 1,10]. a-Hexachlorocyclohexane enhanced the incidence of liver neoplasms induced in rats by N-nitrosodiethylamine [ref: 12].
C. Other relevant data
In a single study, chromosomal aberrations were not found in workers involved in the production of g-hexachlorocyclohexane (lindane) [ref: 17].
Technical-grade hexachlorocyclohexane, but not g- hexachlorocyclohexane, induced dominant lethal mutations in mice; chromosomal aberrations were not found in bone-marrow cells of mice exposed to technical-grade or g-hexachlorocyclohexane in vivo. g-Hexachlorocyclohexane did not induce unscheduled DNA synthesis in human cells in vitro and did not induce micronuclei or chromosomal aberrations in cultured rodent cells; it induced DNA strand breaks but not unscheduled DNA synthesis. It inhibited intercellular communication in Chinese hamster V79 cells. It did not induce sex-linked recessive lethal mutations in Drosophila. a- Hexachlorocyclohexane was not mutagenic to yeast, but the gamma isomer induced gene conversion. Neither g- nor b-hexachlorocyclohexane was mutagenic to bacteria, and a- and b-hexachlorocyclohexane did not cause DNA damage in bacteria [ref: 17].
Overall evaluation
Hexacyclohexanes are possibly carcinogenic to humans (Group 2B).
For definition of the italicized terms, see Preamble Evaluation.
Also see previous evaluations: Vol. 5 (1974); Vol. 20 (1979)
References
1. IARC Monographs, 20, 195-239, 1979
2. Sidi, Y., Kiltchevsky, E., Shaklai, M. & Pinkhas, J. (1983) Acute myeloblastic leukemia and insecticide. N.Y. State J. Med., 83, 161
3. Hoffman, W.S., Adler, H., Fishbein, W.I. & Bauer, F.C. (1967) Relation of pesticide concentrations in fat to pathological changes in tissues. Arch. environ. Health, 15, 758-765
4. Radomski, J.L., Deichmann, W.B., Clizer, E.E. & Rey, A. (1968) Pesticide concentrations in the liver, brain and adipose tissue of terminal hospital patients. Food Cosmet. Toxicol., 6, 209-220
5. Kasai, A., Asanuma, S. & Nakamura, S. (1972) Studies on organochlorine pesticide residues in human organs. Part III (Jpn.). Nippon Noson Igakkai Zasshi, 21, 296-297
6. Caldwell, G.G., Cannon, S.B., Pratt, C.B. & Arthur, R.D. (1981) Serum pesticide levels in patients with childhood colorectal carcinoma. Cancer, 48, 774-778
7. Eriksson, M., Hardell, L., Berg, N.O., Möller, T. & Axelson, O. (1981) Soft-tissue sarcomas and exposure to chemical substances: a case-referent study. Br. J. ind. Med., 38, 27-33
8. Hardell, L., Eriksson, M., Lenner, P. & Lundgren, E. (1981) Malignant lymphoma and exposure to chemicals, especially organic solvents, chlorophenols and phenoxy acids: a case-control study. Br. J. Cancer, 43, 169-176
9. Barthel, E. (1981) Increased risk of lung cancer in pesticide-exposed male agricultural workers. J. Toxicol. environ. Health, 8, 1027-1040
10. Kashyap, S.K., Nigam, S.K., Gupta, R.C., Karnik, A.B. & Chatterjee, S.K. (1979) Carcinogenicity of hexachlorocyclohexane (BHC) in pure inbred Swiss mice. J. environ. Sci. Health, B14, 305-318
11. Munir, K.M., Soman, C.S. & Bhide, S.V. (1983) Hexachlorocyclohexane-induced tumorigenicity in mice under different experimental conditions. Tumori, 69, 383-386
12. Schulte-Hermann, R. & Parzefall, W. (1981) Failure to discriminate initiation from promotion of liver tumors in a long-term study with the phenobarbital-type inducer a-hexachlorocyclohexane and the role of sustained stimulation of hepatic growth and monooxygenases. Cancer Res., 41, 4140-4146
13. Angsubhakorn, S., Bhamarapravati, N., Romruen, K., Sahaphong, S. & Thamavit, W. (1977) Alpha benzene hexachloride inhibition of aflatoxin B1-induced hepatocellular carcinoma. A preliminary report. Experientia, 34, 1069-1970
14. Hiasa, Y., Ohshima, M., Ohmori, T. & Murata, Y. (1978) Effect of a-benzene hexachloride on 2-fluorenylacetamide carcinogenesis in rats. Gann, 69, 423-426
15. Angsubhakorn, S., Bhamarapravati, N., Romruen, K., Sahaphong, S., Thamavit, W. & Miyamoto, M. (1981) Further study of alpha benzene hexachloride inhibition of aflatoxin B1 hepatocarcinogenesis in rats. Br. J. Cancer, 43, 881-883
16. Rivett, K.F., Chesterman, H., Kellett, D.N., Newman, A.J. & Worden, A.N. (1978) Effects of feeding lindane to dogs for periods of up to 2 years. Toxicology, 9, 273-289
17. IARC Monographs, Suppl. 6, 333-335, 1987
Synonyms for Hexachlorocyclohexane [mixed isomers]
Synonyms for Hexachlorocyclohexane [b-isomer]
Synonyms for Hexachlorocyclohexane [d-isomer]
Synonyms for Hexachlorocyclohexane [e-isomer]
Synonyms for Hexachlorocyclohexane [z-isomer]
Synonym for Hexachlorocyclohexane [q-isomer]
See Also:
Toxicological Abbreviations