Trichloroethylene (TCE) exposure has been associated with increased risk of liver and
kidney cancer in both laboratory animal and epidemiologic studies. The U.S. Environmental Protection Agency 2001 draft TCE risk assessment concluded that it is difficult to determine which TCE metabolites may be responsible for these effects, the key events involved in their modes of action (MOAs) , and the relevance of these MOAs to humans. In this article, which is part of a mini-monograph on key issues in the health risk assessment of TCE, we present a review of recently published scientific literature examining the effects of TCE metabolites in the context of the preceding questions. Studies of the TCE metabolites
dichloroacetic acid (DCA) ,
trichloroacetic acid (TCA) , and
chloral hydrate suggest that both DCA and TCA are involved in TCE-induced liver
tumorigenesis and that many DCA effects are consistent with conditions that increase the risk of
liver cancer in humans. Studies of S-(1,2-dichlorovinyl) -
l-cysteine have revealed a number of different possible cell signaling effects that may be related to kidney
tumorigenesis at lower concentrations than those leading to cytotoxicity. Recent studies of
trichloroethanol exploring an alternative hypothesis for kidney
tumorigenesis have failed to establish the formation of
formate as a key event for TCE-induced kidney
tumors. Overall, although MOAs and key events for TCE-induced liver and kidney
tumors have yet to be definitively established, these results support the likelihood that toxicity is due to multiple metabolites through several MOAs, none of which appear to be irrelevant to humans.