Chloral Hydrate and Trichloroethanol Metabolism in B6C3F1 Mouse Liver Slices

摘要

Chloral hydrate (CH) and trichloroethanol (TCOH) are two major metabolites of the common groundwater pollutant trichloroethylene (TCE). TCE is presently regulated based on its ability to induce hepatocellular carcinomas in B6C3F1 mice, a species and strain specific effect that has been linked to differences in metabolism. Present whole animal exposure estimates of TCE degradation capacity make tissue specific rate calculations problematic. We determined B6C3F1 mouse liver-tissue rate constants for two initial TCE metabolites, chloral hydrate (CH) and trichloroethanol (TCOH), using a precision cut tissue explant system. The generally proposed metabolic scheme of TCE to CH, TCOH and subsequent metabolites was investigated. Metabolic rate constants (Vmax) of 274 nmoles CH removed/mg protein*min-1 and 20 nmoles TCOH removed/mg protein*min-l were calculated. The results of the study confirm that CH is metabolized to trichloroacetic acid (TCA) and TCOH, and that TCOH can form CH via a 'reverse' pathway.