DEUTERIUM-ISOTOPE EFFECT IN BIOACTIVATION AND HEPATOTOXICITY OF CHLOROFORM

Cytochrome P-450 appears to catalyze the in vitro formation of phosgene (COCl2) from chloroform (CHCl3) in rat liver microsomes, since this reaction is NADPH dependent and inhibited by carbon monoxide and SKF 525-A. Moreover, the cleavage of the C-H bond appears to be the rate-determining step in this process since deuterium labeled chloroform (CDCl3) is biotransformed into COCl2 slower than is CHCl3. CDCl3 was also less hepatotoxic than CHCl3 suggesting that a similar pathway of metabolism is responsible for the hepatotoxic properties of chloroform. © 1978.