Tetrachloroethylene (perchloroethylene) is one of the most widely used chlorinated solvents. It is used in dry cleaning and as a degreaser, and it is a component of water repellents, heat-exchange fluids, grain fumigants, and typewriter correction fluids (Bruckner and Warren, 2001).

There is evidence that tetrachloroethylene is carcinogenic in animals (Bruckner and Warren, 2001). An increased incidence of mononuclear-cell leukemia was observed in male and female Fischer 344 rats exposed to tetrachloroethylene. Renal tubular cell adenomas and adenocarcinomas, which are rare in untreated male rats, were observed in male rats exposed to tetrachloroethylene. Oral exposure of male and female mice to tetrachloroethylene over a lifetime resulted in a dose-dependent increase in the incidence of hepatocellular carcinomas.

Tetrachloroethylene’s ability to cause liver tumors in mice appears to be mediated by trichloroacetic acid, its major metabolite (ATSDR, 1997a). Trichloroacetic acid can induce peroxisome proliferation in mice, which can apparently play a role in liver cancer in B6C3F1 mice (Bull, 2000). Trichloroacetic acid induces peroxisome proliferation to a much lesser extent in rats and does not lead to liver cancer in rats (Bull, 2000). Data indicate that humans are relatively insensitive to peroxisome proliferators (Cattley et al., 1998) and produce only very small amounts of trichloroacetic acid after tetrachloroethylene exposure (ATSDR, 1997a). Therefore, that mechanism of liver carcinogenesis in rodents might not be relevant to humans exposed to tetrachloroethylene (Cattley et al., 1998). Another mechanism proposed to underlie the toxicity of tetrachloroethylene is the production of a reactive epoxide intermediate in the metabolism of tetrachloroethylene to trichloroacetic acid (ATSDR, 1997a).

The renal carcinogenesis observed in a low incidence in male rats may occur, in part, from the conjugation of tetrachloroethylene with glutathione in the liver, followed by the formation of genotoxic metabolites in the kidney by β-lyase (Bruckner and Warren, 2001). That glutathione metabolite is formed in substantially smaller amounts in humans (Volkel et al., 1998). It could, nevertheless, play a role in renal carcinogenesis in humans exposed chronically to very high concentrations of tetrachloroethylene. Another mechanism that might underlie the renal toxicity of tetrachloroethylene in male rats, the accumulation of α-2µ-globulin, is also not relevant to humans, because humans do not produce α-2µ-globulin or related proteins in quantities of concern (Green et al., 1990).


Trichloroethylene is a common environmental contaminant that is used as a degreaser, in textile processing, and as an extraction solvent. Trichloroethylene is found in common consumer products, such as typewriter correction fluids, paint removers and strippers, adhesives, spot removers, and rug-cleaning fluid (Bruckner and Warren, 2001).

Most absorbed trichloroethylene is oxidized by hepatic cytochrome P450s to chloral hydrate, trichloroethanol, and trichloroacetic acid (Bruckner and Warren, 2001). Trichloroethylene when inhaled or ingested has been shown to induce liver cancer in B6C3F1 mice but not in rats. That species difference is thought to be due largely to the greater oxidative metabolism of trichloroethylene in mice than in rats. The carcinogenicity of trichloroethylene is mediated largely by trichloroacetic acid and dichloroacetic acid (a minor metabolite), which are thought to contribute to an increase in liver cancers by

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