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1 Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina
Small amounts of chloroform were identified in the expired air of dogs that had received carbon tetrachloride by inhalation.
Carbon tetrachioride was reduced to chloroform in vitro by homogenates of mouse liver, heart, kidney, lung, brain, and skeletal muscle. The reduction was still carried out but to a lesser extent by liver heated to inactivate enzymes. The reduction of carbon tetrachloride in vitro was also carried out with cysteine, reduced glutathione, ascorbic acid, and cytochrome c.
No methylene chloride could be detected in the expired air of dogs that had received chloroform. Chloroform was reduced to methylene chloride in vitro by mouse liver and by cysteine and ascorbic acid but much more slowly than carbon tetrachloride was reduced.
Even though the replacement of chlorine by hydrogen in carbon tetrachloride and chloroform may occur only to a small extent in vivo, the reaction may have important consequences. It requires acquisition of two electrons from an out-side source. It is suggested that this acquisition of electrons, as well as other undemonstrated but conceivable reactions involving the free radical postulated to be formed by homolytic fission of the carbon-halogen bond, underlie the hepatotoxic effects of alkyl halides.
Submitted on June 5, 1961
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