VOL.: 79 (2001) (p. 411)
Chem. Abstr. Name: 1,2,4,5,6,7,8,8-Octachloro-2,3,3a,4,7,7a-hexahydro-4,7-methano-1H-indene
Chem. Abstr. Name: (1a ,2a ,3aa ,4b ,7b ,7aa )-1,2,4,5,6,7,8,8-Octachloro-2,3,3a,4,7,7a-hexahydro-
Chem. Abstr. Name: (1a ,2b ,3aa ,4b ,7b ,7aa)-1,2,4,5,6,7,8,8-Octachloro-2,3,3a,4,7,7a-
Chem. Abstr. Name: 1,4,5,6,7,8,8-Heptachloro-3a,4,7,7a-tetrahydro-4,7-methano-1H-indene
Chem. Abstr. Name: (1aa ,1bb ,2a ,5a ,5ab ,6b ,6aa )-2,3,4,5,6,7,7eptachloro-1a,1b,5,5a,6,6a-hexahydro-
5.1 Exposure data
Chlordane and heptachlor are structurally related organochlorine insecticides; the technical-grade product of each contains about 10–20% of the other compound. They have been used since the 1950s for termite control, on agricultural crops, on lawns, on livestock and for other purposes. Their use has currently been banned or severely restricted in many countries. In these countries, human exposure is still possible owing to their persistence in the environment and their consequent occurrence in meat, fish and other fat-containing foodstuffs, but the mean daily intake has probably decreased.
5.2 Human carcinogenicity data
Several cohort studies, with different inclusion criteria and lengths of follow-up, have been conducted to investigate the mortality of workers at two plants in the USA, one producing chlordane and the other heptachlor and endrin. The workers were also exposed to other chemicals. Although no excess was seen in the rate of mortality from all cancers, some, but not all, of the studies showed a slight excess of lung cancer. A similar small excess of mortality from lung cancer was observed in two cohorts of pesticide applicators in the USA; however, when the analyses were limited to the workers more likely to be exposed to chlordane, the mortality rate for lung cancer was lower than in the overall cohort.
A number of case–control studies were conducted to investigate the risks for cancers of the lymphohaematopoietic system, breast and a few other sites in relation to exposure to chlordane. These studies differed widely in size and methods and in exposure assessment, which was either reported by the subjects themselves (or proxy respondents) or estimated from measures of the concentrations of chlordane metabolites in samples of fat tissue or blood. The populations studied also varied widely, some studies including higher proportions of farmers, who are occupationally exposed to pesticides, while the subjects in others (including most studies of women) had no occupational exposure to chlordane. In most studies, exposure to many other organochlorine or other types of pesticides was also assessed. Four case–control studies of non-Hodgkin lymphoma showed a consistent but modest increase in the risk associated with exposure to chlordane, although it was almost impossible to separate the effect of chlordane from those related to farming per se or to exposure to other pesticides. One case–control study each of hairy-cell leukaemia, leukaemia not otherwise specified, soft-tissue sarcoma and multiple myeloma yielded no notable results with respect to chlordane. No association with chlordane concentrations in blood or fat tissue was found in six of seven case–_control studies of breast cancer conducted in Denmark and North America, in two of which blood samples were collected prospectively, or in one study on endometrial cancer conducted in Sweden. No clear pattern emerged in a study of pancreatic cancer in the USA, while a small study of brain cancer in children showed elevated risks associated with termite control treatment, also in comparison with children with cancer of the lymphohaematopoietic system.
5.3 Animal carcinogenicity data
Chlordane, technical-grade chlordane, heptachlor, technical-grade heptachlor, heptachlor epoxide and a mixture of heptachlor and heptachlor epoxide have been tested for carcinogenicity by oral administration in several strains of mice and rats. In the studies in mice, increased incidences of hepatocellular neoplasms (including carcinomas) were seen in both males and females. Increased incidences of thyroid follicular-cell adenomas and carcinomas were seen in one study each with chlordane and technical-grade heptachlor in rats. In a third study in rats, technical-grade chlordane marginally increased the incidence of liver adenomas in male rats. In initiation–_promotion studies in mice, administration of chlordane or heptachlor after N-nitrosodiethylamine resulted in increased incidences of hepatocellular tumours.
5.4 Other relevant data
Chlordane is primarily metabolized to oxychlordane and to a minor extent may also be dehydrochlorinated to heptachlor. Heptachlor, which is also a component of technical-grade chlordane, is biotransformed to its epoxide. Subsequent dechlorination reactions lead to hydroxylated compounds, which are excreted primarily as glucuronides. Minor metabolites include heptachlor and heptachlor epoxide.
Accidental or intentional exposure to chlordane has resulted in signs of neurotoxicity and, in some cases, death. In experimental animals, the toxic effects of chlordane on the liver include lipid peroxidation and cell proliferation secondary to cytotoxicity. In the thyroid, chlordane has been shown to decrease thyroxine concentrations in rats. Both chlordane and heptachlor induce hepatic and gonadal microsomal oxidative enzymes and also steroid hormone metabolism.
Chlordane and heptachlor are toxic to reproduction and development in mice, rats and mink. Pre- and postnatal exposures to chlordane affected the development of the immune system in rodents. Impaired cell-mediated immunity after prenatal exposure to chlordane has been observed in female BALB/c mice.
No data were available on the genetic and related effects of chlordane or heptachlor in humans. Both compounds inhibited gap-junctional intercellular communication and induced gene mutations in rodent cells. Likewise, both compounds induced unscheduled DNA synthesis in human fibroblasts but not in rodent hepatocytes. Chlordane induced DNA damage in liver cells of rats treated in vivo, but heptachlor did not induce mutations in hepatocytes of lacI transgenic mice treated in vivo. Neither chlordane nor heptachlor caused dominant lethal mutation in mice. Neither chlordane nor heptachlor was mutagenic to bacteria, and only chlordane damaged bacterial or plasmid DNA.
There is inadequate evidence in humans for the carcinogenicity of chlordane and heptachlor.
There is sufficient evidence in experimental animals for the carcinogenicity of chlordane and of heptachlor.
Chlordane and heptachlor are possibly carcinogenic to humans (Group 2B).For definition of the italicized terms, see Preamble Evaluation.
Previous evaluations: Chlordane: Vol. 20 (1979) (p. 45); Chlordane/Heptachlor: Suppl. 7 (1987) (p. 146); Vol. 53 (1991)
See Also: Toxicological Abbreviations Chlordane and Heptachlor (IARC Summary & Evaluation, Volume 53, 1991)