Metabolism of trichloroethylene in B6C3F1 mouse and human liver slices.

摘要

Human and B6C3F1 mouse liver tissue was exposed to trichloroethylene (TCE) to determine metabolic rate constants. Using a novel volatile exposure system based on precision-cut tissue explants, TCE biometabolism was measured by appearance of a major oxidative product trichloroacetic acid (TCA). TCE metabolic rate was linear in this system to 150 minutes, allowing calculation of Michaelis-Menten kinetic parameters, Km and Vmax. Both human and mouse liver explants tolerated exposure to TCE up to 750 microM without evidence of cytotoxicity. Km values for mouse and human tissue were 215 and 30.6 microM TCE, respectively, and Vmax estimates were 6.14 and 0.47 ng TCA produced per mg protein*min-1, mouse and human, respectively. These results are consistent with other reports in describing the greater capacity of mice to metabolize TCE. Metabolic differences such as these must be considered when interpreting the implications of TCE-induced toxicity in rodent models for human health assessment.