A species comparison of chloral hydrate metabolism in blood and liver.
Chloral hydrate (CH), [302-17-0], is a human sedative useful in premature infants. No current epidemiological study supports increased cancer risk. CH is also a rodent toxicant and a P450-derived metabolite of trichloroethylene (TRI). P450 induction increases TRI toxicity in rodents. 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 liver and blood of the rat, mouse, and human. Both TCA and TCOH are formed 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-fold lower than for TCA formation in these species. Clearance values for TCOH are higher than for TCA. These data support TCOH as the first major metabolite of TRI and CH in vivo.
Lipscomb
J C
JC
Armstrong Laboratory, Wright-Patterson Air Force Base, Ohio 45433-7400, USA. JLipscomb@AL.WPAFB.AF.MIL
Mahle
D A
DA
Brashear
W T
WT
Garrett
C M
CM
D000818:Animals; D001711:Biotransformation; D002697:Chloral Hydrate / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D004912:Erythrocytes / Q000378:metabolism; D006801:Humans; D006993:Hypnotics and Sedatives / Q000378:metabolism; D007231:Infant, Newborn; D007234:Infant, Premature; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013045:Species Specificity
D006993:Hypnotics and Sedatives; D009243:NAD; D002697:Chloral Hydrate