Nephrotoxicity and hepatotoxicity of chloroform in mice: Effect of deuterium substitution

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Abstract
CHCl3 produces renal and hepatic damage in humans and experimental animals. Deuterium-labeled chloroform (CDCl3) was reported to be less hepatotoxic than CHCl3 in rats. This isotope effect was not determined in other species or in extrahepatic tissues. The effect of deuterium substitution on the nephrotoxicity and hepatotoxicity of CHCl3 was quantified in male ICR mice. Renal and hepatic damage were determined 24 h after administration of various doses of CHCl3 or CDCl3. Liver damage was estimated by measuring serum glutamic-pyruvic transaminase (SGPT) activity. Nephrotoxicity was evaluated by measuring blood urea N (BUN) and in vitro renal cortical accumulation of p-aminohippurate (PAH) and tetraethylammonium (TEA). Dose-related hepatotoxicity and nephrotoxicity were observed after administration of CHCl3 and CDCl3. CDCl3 produced less liver damage than CHCl3 in mice, suggesting that mouse liver metabolized CHCl3 by the same mechanism as rat liver. CDCl3 was also less toxic to kidneys than CHCl3, suggesting that the kidney may metabolize CHCl3 in the same manner as the liver.