IRIS Toxicological Review of Hexachlorocyclopentadiene [and IRIS Summary] (External Review Draft)
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Hexachlorocylopentadiene (HCCPD) is a dense oily liquid with a pungent, unpleasant odor. It is an intermediate in the production of compounds used as dyes, resins, pharmaceuticals, flame retardants, insecticides, and other products. No repeated-exposure human toxicity data exists for HCCPD that do not also involve exposures to other compounds. In animals, the compound adversely affects the histopathology of the tissues along the portal of entry. The RfD of 0.006 mg HCCPD/kg/day was derived from a 13-week subchronic bioassay (Abdo et al., 1984), in which rats and mice exhibited forestomach histopathology. Chronic irritation, manifested as forestomach lesions, in rats and mice was identified as the critical effect. An overall uncertainty factor of 1000 was applied to the BMDL10 to account for the subchronic exposure, extrapolation from rat to human, and intrahuman variability. The RfC of 0.0002 mg/m3 was derived from a 2-year inhalation assay by NTP (1994). Dose-related suppurative inflammation of the nose was observed in mice. An overall uncertainty factor of 100 was used to account for the limited database, extrapolation from mouse to human, and for intrahuman variability. In a 2-year cancer study with rats and mice, no treatment-related neoplastic lesions were observed. Generally, in vitro and in vivo mutagenicity tests have produced negative results. According to the existing Guidelines for Carcinogen Risk Assessment (U.S. EPA, 1986a), HCCPD is most appropriately characterized as a Group E, Evidence of Noncarcinogenicity to Humans, carcinogen. This characterization is based on inadequate data for cancer in humans and evidence of noncarcinogenicity in animals. In accordance with U.S. EPA's Proposed Guidelines for Carcinogen Risk Assessment (U.S. EPA, 1996), HCCPD is not likely to be a human carcinogen.
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