Acetone-induced potentiation of trihalomethane toxicity in male rats

The acute hepato- and nephrotoxic potentials of two trihalomethane water contaminants, bromodichloromethane (BrCHCl2) and dibromochloromethane (Br2CHCl), were determined in male Sprague-Dawley rats. Br2CHCl possessed a greater hepatotoxic and lethal potential than BrCHCl2. However, both Br2CHCl and BrCHCl2 were weak hepatotoxicants as compared to a related trihalomethane, CHCl3. Br2CHCl and BrCHCl2 did not produce liver injury until near-lethal dosages were administered. Neither trihalomethane appeared to produce appreciable kidney injury during the 24-h challenge period. Pretreatment of rats with acetone (15 mmol/kg, p.o.) markedly potentiated the hepatotoxic response to BrCHCl2 and Br2CHCl. The potentiated response observed with acetone plus BrCHCl2 or Br2CHCl was equal to or greater than that observed with acetone plus an approximately equimolar dosage of CHCl3. That is, acetone appeared to convert these weak hepatotoxicants into strong hepatotoxicants.