For definition of Groups, see Preamble Evaluation.
Supplement 7: (1987) (p. 152)
CAS No.: 67-66-3
Chem. Abstr. Name: Trichloromethane
A. Evidence for carcinogenicity to humans (inadequate)
Two studies of trihalomethane levels in drinking-water supplies and community-based rates of cancer mortality have been reported. Correlations were found between these levels and various site-specific cancer mortality rates, especially those for bladder cancer, but also those for cancers of the rectum/large intestine, brain and kidney and lymphoma [ref: 1,2]. In one study in which trihalomethane levels in drinking-water at place of residence were compared directly for 395 matched pairs of female teachers with regard to colorectal cancer, no association with trihalomethane exposure was observed [ref: 3]. A mortality study of anaesthesiologists who worked at the time chloroform was used provided no significant information [ref: 4].
Several investigations have attempted to assess the effects of trihalomethanes in drinking-water indirectly by comparing risks of cancers at various sites with extent of chlorination. Although excesses of some cancers have been found, it is not possible to evaluate any effect of chloroform from such studies [ref: 5-16].
B. Evidence for carcinogenicity to animals (sufficient)
Chloroform produced benign and malignant tumours of the liver and kidney in mice following oral gavage [ref: 17,18]. Administration in drinking-water to female mice did not increase the incidence of liver tumours [ref: 19]. Administration of chloroform to rats by gavage or in drinking-water increased the incidences of kidney [ref: 17,19] and thyroid tumours [ref: 17] and of neoplastic nodules of the liver [ref: 20]. Chloroform was tested inadequately by subcutaneous and intraperitoneal injection in mice [ref: 17]. A study by oral administration in dogs gave negative results [ref: 21]. Oral administration of chloroform did not enhance the incidences of liver and lung tumours induced in mice by intraperitoneal injection of N-ethyl-N-nitrosourea [ref: 22], but it enhanced the incidence of liver preneoplastic foci in rats treated with a single dose of N-nitrosodiethylamine [ref: 23].
C. Other relevant data
No adequate data were available on the genetic and related effects of chloroform in humans.
Chloroform did not induce micronuclei in bone-marrow cells of mice or DNA damage in liver or kidney cells of rats treated in vivo. It did not induce chromosomal aberrations, sister chromatid exchanges or unscheduled DNA synthesis in human lymphocytes in vitro. Chloroform enhanced virus-induced cell transformation of Syrian hamster embryo cells. It did not induce sister chromatid exchanges or mutation in Chinese hamster cells or DNA damage in rat hepatocytes in vitro. Chloroform did not induce sex-linked recessive lethal mutations in Drosophila or aneuploidy, mutation or somatic segregation in Aspergillus. Chloroform induced DNA damage but not mutation, aneuploidy, mitotic recombination or gene conversion in Saccharomyces cerevisiae, whereas mutation, mitotic recombination and gene conversion were induced in S. cerevisiae under conditions in which endogenous levels of cytochrome P450 were enhanced. Chloroform did not induce mutation or DNA damage in bacteria [ref: 24].
Chloroform is possibly carcinogenic to humans (Group 2B).
For definition of the italicized terms, see Preamble Evaluation.
Subsequent evaluation: Vol. 73 (1999)
Also see previous evaluations: Vol. 1 (1972); Vol. 20 (1979)
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2. Cantor, K.P., Hoover, R., Mason, T.J., McCabe, L.J. (1978) Association of cancer mortality with halomethanes in drinking water. J. natl Cancer Inst., 61, 979-985
3. Lawrence, C.E., Taylor, P.R., Trock, B.J. & Reilly, A.A. (1984) Trihalomethanes in drinking water and human colorectal cancer. J. natl Cancer Inst., 72, 563-568
4. Linde, H.W. & Mesnick, P.S. (1980) Causes of Death of Anesthesiologists from the Chloroform Era (PB 80-125172 (EPA/600/1-79-043)), Springfield VA, National Technical Information Service
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7. Craun, G.F. (1985) Epidemiologic studies of organic micropollutants in drinking water. Sci. total Environ., 47, 461-472
8. DeRouen, T.A. & Diem, J.E. (1977) Relationships between cancer mortality in Louisiana drinking-water source and other possible causative agents. In: Hiatt, H.H., Watson, J.D. & Winsten, J.A., eds, Origins of Human Cancer, Book A, Incidence of Cancer in Humans, Cold Spring Harbor, NY, CSH Press, pp. 331-345
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11. Brenniman, G.R., Vasilomanolakis-Lagos, J., Amsel, J., Namekata, T. & Wolff, A.H. (1980) Case-control study of cancer deaths in Illinois communities served by chlorinated or nonchlorinated water. In: Jolly, R.J., Brungs, W.A., Cumming, R.B. & Jacobs, V.A., eds, Water Chlorination, Environmental Impact and Health Effects, Vol. 3, Ann Arbor, MI, Ann Arbor Science, pp. 1043-1057
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14. Young, T.B., Kanarek, M.S. & Tsiatis, A.A. (1981) Epidemiologic study of drinking water chlorination and Wisconsin female cancer mortality. J. natl Cancer Inst., 67, 1191-1198
15. Kanarek, M.S. & Young, T.B. (1982) Drinking water treatment and risk of cancer death in Wisconsin. Environ. Health Perspect., 46, 179-186
16. Wilkins, J.R., III & Comstock, G.W. (1981) Source of drinking water at home and site-specific cancer incidence in Washington county, Maryland. Am. J. Epidemiol., 114, 178-190
17. IARC Monographs, 20, 401-427, 1979
18. Roe, F.J.C., Palmer, A.K., Worden, A.N. & Van Abbé, N.J. (1979) Safety evaluation of toothpaste containing chloroform. I. Long-term studies in mice. J. environ. Pathol. Toxicol., 2, 799-819
19. Jorgenson, T.A., Meierhenry, E.F., Rushbrook, C.J., Bull, R.J. & Robinson, M. (1985) Carcinogenicity of chloroform in drinking water to male Osborne-Mendel rats and female B6C3F1 mice. Fundam. appl. Toxicol., 5, 760-769
20. Tumasonis, C.F., McMartin, D.N. & Bush, B. (1985) Lifetime toxicity of chloroform and bromodichloromethane when administered over a lifetime in rats. Ecotoxicol. environ. Saf., 9, 233-240
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22. Pereira, M.A., Knutsen, G.L. & Herren-Freund, S.L. (1985) Effect of subsequent treatment of chloroform or phenobarbital on the incidence of liver and lung tumors initiated by ethylnitrosourea in 15 day old mice. Carcinogenesis, 6, 203-207
23. Deml, E. & Oesterle, D. (1985) Dose-dependent promoting activity of chloroform in rat liver foci bioassay. Cancer Lett., 29, 59-63
24. IARC Monographs, Suppl. 6, 155-158, 1987
See Also: Chloroform (CHEMINFO) Chloroform (EHC 163, 1994) Chloroform (IARC Summary & Evaluation, Volume 1, 1972) Chloroform (IARC Summary & Evaluation, Volume 20, 1979) Chloroform (ICSC) Chloroform (PIM 121)