served after 2 weeks of exposure at 1,000 ppm and then after 4-8 weeks of exposure at concentrations as low as 10 ppm (Sharma and Gehring 1979).

VC is a well-established genotoxicant, having been investigated in a variety of test systems, including in vitro studies of bacteria, fungi, and mammalian cells and in vitro studies of rodents and humans (ATSDR 2006). It has been shown to be mutagenic, and its mutagenicity is enhanced with metabolic activation; this suggests that one of its metabolites is more mutagenic than VC (CalEPA 2000a; ATSDR 2006).

VC has been shown to cause cancer in multiple organs and multiple species when inhaled or ingested (IARC 1979; EPA 2000; ATSDR 2006). The association between VC and hepatic angiosarcomas in the epidemiologic literature is supported by similar findings in mice (e.g., Drew et al. 1983), rats (e.g., Feron et al. 1981; Maltoni et al. 1981; Drew et al. 1983; Bi et al. 1985), and hamsters (e.g., Drew et al. 1983). Tumors in rats were found after oral exposure at concentrations as low as 1.7 mg/kg per day.

Other cancers found in rats were Zymbal-gland tumors, mammary-gland tumors, neuroblastomas, and lung tumors (Feron et al. 1981; Maltoni et al. 1981; Drew et al. 1983; Til et al. 1991). Mice exposed by inhalation developed lung tumors, mammary-gland tumors, and angiosarcomas and adenocarcinomas in various sites (Drew et al. 1983). Hamsters also developed hemangiosarcomas, mammary-gland carcinomas, gastric adenocarcinomas, and skin carcinomas (Drew et al. 1983). Some studies have shown that younger rats are more susceptible to the carcinogenicity of VC (Drew et al. 1983; Maltoni and Cotti 1988).