A SPECIES COMPARISON OF CHLORAL HYDRATE METABOLISM IN BLOOD AND LIVER

Chloral hydrate (CH), [302-17-0], is a human sedative useful in premat ure infants. No current epidemiological study supports increased cance r risk. CH is also a rodent toxicant and a P450-derived metabolite of trichloroethylene (TRI). P450 induction increases TRI toxicity in rode nts. CH is very rapidly metabolized to trichloroacetic acid (TCA) and trichloroethanol (TCOH). Because TCA mediates some responses following TRI exposure, we assessed the metabolism of CH to TCA and TCOH by liv er and blood of the rat, mouse, and human. Both TCA and TCOH are forme d in blood and liver. The constants for hepatic TCA and TCOH formation are presented. The K-m for hepatic TCOH formation is at least ten-fol d lower than for TCA formation in these species. Clearance values for TCOH are higher than for TCA. These data support TCOH as the first maj or metabolite of TRI and CH in vivo. (C) 1996 Academic Press, Inc.