EXECUTIVE SUMMARY

Universal exposure of the population of California to low levels of trichloroacetic acid (TCA) results from its occurrence as a contaminant of drinking water disinfected by chlorination. Other minor occurrences and uses affect a much smaller number of people, but may result in high exposures to those particular individuals. Trichloroacetic acid is a major metabolite of trichloroethylene and tetrachloroethylene (perchloroethylene). These materials are widely used as industrial solvents and (in the case of tetrachloroethylene) in dry cleaning. Secondary exposures to trichloroacetic acid may therefore result from workplace exposures to these compounds, or to local environmental contamination of air or water at sites where they are used. For most exposure situations, TCA and its salts are toxicologically equivalent, since TCA is a strong organic acid that exists principally as the anion in aqueous solutions near neutral pH. TCA caused liver tumors in male and female mice in multiple experiments by the predominant route of human exposure, i.e. drinking water. However, carcinogenicity was not observed in the only carcinogenensis study conducted in the rat. In the mouse TCA acts as a promoter of liver tumors, and promotes foci of altered hepatocytes in both the rat and the mouse. The results of short-term tests for genotoxicity are mainly negative, although there are some marginally positive or equivocal results. Studies in mice have suggested several possible "non-genotoxic" modes of action, although genetic alterations in proto-oncogenes have been observed in TCA-induced tumors. These suggested mechanisms have included effects on peroxisome proliferation, enhanced cell proliferation as a result of receptor-mediated effects or in response to cytotoxicity, and effects on intercellular communication. However, none of these proposed mechanisms has been definitely established as a principal cause of the observed carcinogenicity. Nor have they been shown conclusively to contribute to the carcinogenicity or other toxicity of TCA. There is sufficient evidence of TCA carcinogenicity in animals, based on results in male and female mice. Although the evaluation by the International Agency for Research on Cancer (IARC, 1995) found only limited evidence of carcinogenicity in animals, the data which they considered has since been significantly augmented, including the observation of carcinogenicity in female as well as male mice. The failure to observe carcinogenicity in the one rat study, the negative mutagenicity results in short-term tests, and other mechanistic data raise the possibility of non-genotoxic mechanisms, which might be species-specific.

You will need the free program Adobe Acrobat Reader to view or print PDF files

For questions regarding Proposition 65, please contact the Cynthia Oshita in the Proposition 65 Implementation Program

For help with this web site please contact the Web Mistress