Under what conditions is trichloroethylene likely to be a carcinogen in humans?

Exposures to trichloroethylene (TCE) induce several types of cancer in expe rimental animals. TCE is metabolized in the body to multiple compounds, sev eral of which are carcinogenic at relatively high doses in rodents. Risk as sessments can be pursued with any one of the animal cancer endpoints after consideration of their relevance for humans exposed at low environmental co ncentrations. Among the TCE metabolites, dichloroacetic acid (DCA), trichlo roacetic acid (TCA), chloral hydrate (CHL), and 1,2-dichlorovinylcysteine ( DCVC) are each considered carcinogenic in rodents. Two of these, DCA and CH L, are used therapeutically in humans, while a third, TCA, has metabolic ef fects similar to compounds used therapeutically in humans to reduce lipid c oncentrations in blood. Each of these three compounds produces biological r esponses that are expected in humans. However, these biological responses, although they serve as precursors for tumor formation in rodents, are not e xpected to lead to tumors in humans at any environmentally relevant exposur e situations. 1,2-DCVC, formed by a minor pathway of TCE metabolism, is fur ther metabolized in kidney to a reactive thioketene. Of the observed animal carcinogenic responses, only the kidney tumors from the DCVC pathway are c onsidered relevant as predictors of human cancer. Factors that increase TCE metabolism to glutathione conjugates or predispose humans to kidney damage should increase risks posed to workers from high-concentration exposures t o TCE. Based on our knowledge of the cytotoxic and mutagenic modes of actio n expected for these active metabolite(s), a nonlinear cancer risk assessme nt approach is recommended to be used with the kidney tumor data to assess the human risks of TCE.