Mechanism of the microsomal reduction of carbon tetrachloride and halothane

The source of the hydrogen atoms in reduced metabolites of carbon tetrachloride and halothane has been studied. This was approached by measuring deuterium incorporation into chloroform and 2-chloro-1,1,1-trifluoroethane formed as microsomal metabolites of carbon tetrachloride and halothane, respectively, in a medium enriched in deuterium oxide. GC/MS analysis showed no deuterium enrichment of chloroform when hepatic microsomal fractions from control rats were used; however, small increases in enrichment were seen when microsomes from phenobarbitalor benzpyrene-treated rats were employed. No detectable deuterium incorporation into 2-chloro-1,1,1-trifluoroethane was observed. These results suggest that carbanions are not formed as major intermediates and suggest that one-electron transfer reactions predominate in the reductive metabolism of carbon tetrachloride and halothane.