ACUTE ALTERATION OF CHLOROFORM-INDUCED HEPATOTOXICITY AND NEPHROTOXICITY BY MIREX AND KEPONE

Previous investigations have suggested that production of ketosis in laboratory animals by administration of exogenous ketones, alcohols which are metabolized to ketones, or production of diabetic ketosis potentiates halogenated hydrocarbon toxicity. To test this hypothesis, two structurally related compounds, mirex and Kepone (a ketone), were selected and their ability to modify CHCl3-induced hepato- and nephrotoxicity determined. Mirex (10, 50, or 250 mg/kg) or Kepone (50 mg/kg) were administered (po) to male Swiss-Webster mice. After 18 hr a challenge dose of CHCl3 (0.1 ml/kg, po) was administered. Liver and kidney damage were determined 24 hr later, using plasma glutamic-pyruvic transaminase (GPT) and ornithine carbamyl transferase (OCT) activity, blood urea nitrogen (BUN) content, and altered renal cortical slice accumulation of p-aminohippurate (PAH) and tetraethylammonium (TEA) ion. Mirex alone did not produce signs of toxicity at any dose but produced hepatomegaly at 50 and 250 mg/kg. Kepone alone was similarly without toxic effect. CHCl3 alone increased GPT and decreased kidney slice ion uptake. Pretreatment with mirex did not markedly alter the hepato- and nephrotoxic effects of CHCl3. In contrast, Kepone pretreatment potentiated CHCl3 hepatotoxicity and may have increased CHCl3-induced kidney damage. These results indicate that Kepone ingestion may increase the sensitivity of the liver and kidney to CHCl3 toxicity. © 1979.