VOL.: 71 (1999) (p. 603)
Chem. Abstr. Name: (Chloromethyl)oxirane
Exposure to epichlorohydrin may occur during the production and use of resins, glycerine and propylene-based rubbers and its use as a solvent. It has been detected at low levels in water.
5.2 Human carcinogenicity data
The risk of cancer has been investigated among four populations exposed to epichlorohydrin. In one cohort study, an excess of lung cancer was observed among the small number of workers employed in the production of epichlorohydrin. A nested case–control study within this population found a weak association between epichlorohydrin and lung cancer but risk was not related to level of exposure. In another nested case–control study based on the same cohort, a weak association with central nervous system tumours was observed which appeared to be related to the level of exposure. A small excess of lung cancer was observed in another cohort, but in a third no excess of cancer was observed. In a case–control study of lung cancer nested within a further cohort of chemical workers, a significantly decreased risk of lung cancer was associated with epichlorohydrin exposure. All results were based on relatively small numbers.
5.3 Animal carcinogenicity data
Epichlorohydrin was tested in rats by oral administration, inducing papillomas and carcinomas of the forestomach, and by inhalation, inducing papillomas and carcinomas of the nasal cavity. It was also tested in mice by skin application and by subcutaneous and intraperitoneal injection; it gave negative results after continuous skin painting but was active as an initiator on skin. It produced local sarcomas after subcutaneous injection and was active in a mouse-lung tumour bioassay by intraperitoneal injection.
5.4 Other relevant data
Epichlorohydrin is itself a reactive epoxide and is metabolized by binding to glutathione and by hydration via epoxide hydrolase. The same haemoglobin adduct has been detected in humans and rats. In man, epichlorohydrin causes local damage upon contact exposure. In rodents, toxicity to kidneys, liver and forestomach has been observed. After inhalation, the most sensitive target organ is the nasal turbinates. Epichlorohydrin induces genetic damage in most bacterial and mammalian tests in vitro or in vivo, not requiring the presence of a metabolic activation system.
There is inadequate evidence in humans for the carcinogenicity of epichlorohydrin.
There is sufficient evidence in experimental animals for the carcinogenicity of epichlorohydrin.
Epichlorohydrin is probably carcinogenic to humans (Group 2A).
In making the overall evaluation, the Working Group took into consideration the known chemical reactivity of epichlorohydrin and its direct activity in a wide range of genetic tests.For definition of the italicized terms, see Preamble Evaluation.
Previous evaluations: Vol. 11 (1976); Suppl. 7
See Also: Toxicological Abbreviations Epichlorohydrin (EHC 33, 1984) Epichlorohydrin (HSG 8, 1987) Epichlorohydrin (ICSC)