Jc. Lipscomb et al., A SPECIES COMPARISON OF CHLORAL HYDRATE METABOLISM IN BLOOD AND LIVER, Biochemical and biophysical research communications, 227(2), 1996, pp. 340-350
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.