METABOLISM OF CARBON TETRACHLORIDE AND CHLOROFORM BY THE RAT

¹ Department of Biochemistry, McGill University, Montreal, Quebec, Canada

Eighteen hours after intraduodenal administration of C¹⁴Cl₄, 85% had been excreted in the expired air unaltered and 1% had been converted to C¹⁴O₂. After administration of C¹⁴HCl₃, 70% had appeared in the expired air unchanged and 4% as C¹⁴O₂. Liver slices also formed CO₂ more rapidly from CHCl₃ than from CCl₄. The metabolism of CCl₄ and CHCl₃ is greatly diminished if the tissues are homogenized. The production of CO₂ 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 CCl₄, not of CHCl₃. Neither reduced glutathione nor cysteine increases CO₂ production from CCl₄.

Some CCl₄ is converted to CHCl₃ in vivo and in vitro. No evidence of the formation of other chloromethanes from either CHCl₃ or CCl₄ was obtained. It is concluded that CCl₄ and CHCl₃ are converted to CO₂ by enzyme-catalyzed reactions and that CHCl₃ probably is an intermediate in the metabolism of CCl₄.