Metabolism of Chloroform—II. A Sex Difference in the Metabolism of [14C]Chloroform in Mice

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Abstract
1. Chloroform (60 mg/kg), administered orally in olive oil to male and female mice of the CF/LF, CBA and C57 Black Strains, was metabolized to CO2 to an extent of 80%, the remainder being unchanged. 2. The general pattern of distribution of chloroform was shown by auto-radiography. Strain differences in distribution were not marked but the amount of radioactivity appearing in the renal cortex in males was much greater than for females. The males of the CBA strain had the greatest amount in the kidney. A sex difference was also noted in the amount of radioactivity in the liver where higher values for the females were seen. 3. The renal metabolite is bound to the tissues and has not been identified. 4. Testosterone treatment of female mice resulted in a greater concentration of radioactivity in the renal cortex but stilbestrol treatment in males did not reverse the pattern of distribution. Castration reduced the amount of renal cortical radioactivity in males; this was uninfluenced by stilbestrol but restored to normal with testosterone. Testosterone seems therefore to play an important part in the kidney metabolism of chloroform. 5. It is concluded, in view of the sex differences and overall metabolism, that the mouse is an unsuitable species for interpreting the toxicity of chloroform with respect to man.