TOXICITY OF BROMODICHLOROMETHANE IN FEMALE RATS AND MICE AFTER REPEATED ORAL DOSING

The carcinogenic water disinfection byproduct, bromodichloromethane (B DCM), produces renal and hepatic toxicity in rodents in acute and subc hronic studies. In the present investigation, female rats and mice (n = 6) were dosed daily for 5 consecutive days with BDCM (dissolved in a n aqueous, 10% Emulphor solution) by gavage, Rats received 75, 150 and 300 mg BDCM/kg body weight/day and mice received 75 and 150 mg BDCM/k g body weight/day. Two rats in the 300 mg/kg/day treatment group died on day 5. On day 6, the animals were sacrificed and serum samples were taken for analysis of indicators of hepatic and renal toxicity, Liver s and kidneys were excised and samples taken for histopathological eva luation. Portions of the livers were also utilized to produce microsom es for analysis of cytochrome P450 enzyme activities and total P450 co ntent. Total hepatic cytochrome P450 was decreased in rats dosed with 150 and 300 mg BDCM/kg body weight/day, but was not significantly affe cted in BDCM-treated mice. Serum lactate (LDH) and sorbitol (SDH) dehy drogenase, aspartate aminotransferase (AST), creatinine and blood urea nitrogen were increased above those of controls in rats dosed with 30 0 mg BDCM/kg/day. These data suggested that hepatic and renal damage h ad occurred in this treatment group. This was confirmed by histopathol ogical analyses which revealed that lesions occurred in both hepatic a nd renal tissues from rats dosed with 150 and 300 mg BDCM/kg/day. The hepatic lesions were centrilobular and primarily consisted of vacuolar degeneration. The hepatotoxicity indicators alanine aminotransferase (ALT) and SDH were increased in mice dosed with 150 mg BDCM/kg/day. Ho wever, no histopathological lesions were observed in these animals. Th is study shows that BDCM is both hepatotoxic and nephrotoxic to female rats after repeated dosing, but is only weakly hepatotoxic to female mice at the administered doses. Also, reduced activities of hepatic cy tochrome P450 were observed in rats, but not mice. These species diffe rences in toxicity and xenobiotic metabolizing enzyme inhibition cause d by BDCM suggest that an understanding of the mechanism of toxicity o f this compound will be critical when extrapolating rodent toxicity da ta to humans for this environmental pollutant.