Toxicity and metabolism of trichloroethylene in rat hepatocytes.

Trichloroethylene (TCE) hepatotoxicity is controversial. The present study was designed to investigate the mechanism of TCE hepatotoxicity. The toxicity of equimolar concentrations (5.7 mM) of TCE and its two major metabolites, trichloroacetic acid (TCA) and trichloroethanol (TCL), was determined. TCE cell viability was dose- and time-dependent. Enzyme leakage correlated with decrease in cell viability; significantly increased leakage started at 1.9 mM treatment. 5.7 mM TCA or TCL was not toxic compared with the same dose of TCE. Hepatocytes isolated from phenobarbital pretreated rats exhibited no significant alteration in toxicity parameters when exposed to 1.9 and 5.7 mM concentrations of TCE. While the phenobarbital pretreatment increased the rate of metabolism of TCE. The present study suggests that TCE toxicity occurs before the formation of TCA and TCL.