Acute Renal and Hepatic Toxicity of Bromodichloromethane (BDCM) in F-344 Rats Following Administration in Different Dosing Vehicles

BDCM, a water disinfection byproduct, was administered by gavage at 0, 200, and 400 mg/kg in either corn oil or 10% Emulphor to 90-day-old F-344 male rats. Urine was collected from 0-6, 6-12, 12-24, 24-36, and 36-48 hours. Animals were killed at 24 or 48 hr, and serum collected. In the high dose groups for both vehicles after 48 hours, significant increases were observed in serum aspartate aminotransferase (AST), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), cholesterol and bile acids. At the apparent time of peak hepatotoxicity (48 hours), 400 mg BDCM/kg caused significantly greater elevations in AST, creatinine, and bile acids when administered in corn oil than in 10% Emulphor. Significant interactions between dose and vehicle of administration were noted for serum enzymes AST, ALK, and LDH, indicating that vehicle differences observed in BDCM hepatotoxicity may be dose dependent. At 200 mg/kg, the only significant response of a serum enzyme was a slight increase in LDH following aqueous administration of BDCM. In contrast to the virtual lack of effects on liver function enzymes at 200 mg/kg, urinary enzymes were dramatically elevated at the low dose in both vehicles. At 24 hours, BDCM increased urine ALT (33%), AST (390%), LDH (300%), and alkaline phosphatase (ALK) (230%) in the low dose corn oil group with respective increases of 75%, 590%, 540%, and 380% in the 10% Emulphor group. Significant vehicle differences were noted for urinary AST and total protein at the 200 mg/kg dose after 36 hours and glucose at the high dose level at 48 hours. Significant interactions between BDCM dose and dosing vehicle were observed for urinary AST, LDH, and total protein at 36 hours post-gavage and total protein at 24 hours, suggesting again that vehicle effects noted in BDCM nephrotoxicity may be dependent on dose. At 400 mg/kg, the time to peak nephrotoxicity appeared greater with corn oil than with the aqueous vehicle. These data suggest that BDCM is more acutely hepatotoxic when administered in corn oil than in an aqueous vehicle and further suggest that the kidney may be a more sensitive indicator of BDCM toxicity than the liver.Master of Science in Public Healt