Metabolism of Carbon Tetrachloride and Chloroform by the Rat

Abstract

Eighteen hours after intraduodenal administration of C 14 Cl 4 , 85% had been excreted in the expired air unaltered and 1% had been converted to C 14 O 2 . After administration of C 14 HCl 3 , 70% had appeared in the expired air unchanged and 4% as C 14 O 2 . Liver slices also formed CO 2 more rapidly from CHCl 3 than from CCl 4 . The metabolism of CCl 4 and CHCl 3 is greatly diminished if the tissues are homogenized. The production of CO 2 from chloromethanes by liver slices is stimulated by citrate and acetate, inhibited by iodoacetate, fluoride arsenate, cyanide and by acid, alkali or heat treatment of the liver slices. Succinate stimulated the metabolism only of CCl 4 , not of CHCl 3 . Neither reduced glutathione nor cysteine increases CO 2 production from CCl 4 . Some CCl 4 is converted to CHCl 3 in vivo and in vitro. No evidence of the formation of other chloromethanes from either CHCl 3 or CCl 4 was obtained. It is concluded that CCl 4 and CHCl 3 are converted to CO 2 by enzyme-catalyzed reactions and that CHCl 3 probably is an intermediate in the metabolism of CCl 4 .