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

Abstract

Chloroform (CHCI₃) produces renal and hepatic damage in humans and experimental animals. Deuterium‐labeled chloroform (CDCI₃) has been reported to be less hepatotoxic than CHCI₃ in rats. However, this isotope effect has not been determined in other species or in extrahepatic tissues. In this investigation, the effect of deuterium substitution on the nephrotoxicity and hepatotoxicity of CHCI₃ was quantified in male ICR mice. Renal and hepatic damage were determined 24 h after administration of various doses of CHCI₃ or CDCI₃. Liver damage was estimated by measuring serum glutamic‐pyruvic transaminase (SGPT) activity. Nephrotoxicity was evaluated by measuring blood urea nitrogen (BUN) and in vitro renal cortical accumulation of p‐aminohip‐purate (PAH) and tetraethylammonium (TEA). Dose‐related hepatotoxicity and nephrotoxicity were observed after administration of CHCI₃ and CDCI₃. CDCI₃ produced less liver damage than CHCI₃ in mice, suggesting that mouse liver metabolizes CHCI₃ by the same mechanism as rat liver. CDCI₃ was also less toxic to kidneys than CHCI₃, suggesting that the kidney may metabolize CHCI₃ in the same marineras the liver.