Dose-dependent vehicle differences in the acute toxicity of bromodichloromethane.
Bromodichloromethane (BDCM) is a disinfection by-product of drinking water chlorination and is the second most common trihalomethane (THM) in finished drinking water. THMs have generally been administered to experimental animals in corn oil, rather than drinking water, which can influence the site and magnitude of toxicity. To examine the effects of gavage vehicle on the acute renal and hepatic toxicity of orally administered BDCM, 95-day-old male F344 rats were given single doses of 0, 200, or 400 mg BDCM/kg in corn oil or an aqueous 10% Emulphor solution. Activities of serum hepatoxicity indicators were significantly greater 48 hr after administration of 400 mg BDCM/kg in corn oil compared to the aqueous vehicle, but delivery of the low dose in either dosing vehicle had little effect on serum enzymes. In contrast, significant elevations in urinary renal toxicity indicators were noted at 200 and 400 mg BDCM/kg in both vehicles after 24 hr, indicating that the kidney is more sensitive to low doses of BDCM than the liver. Significantly greater increases were observed in urinary indicators after delivery of 200 mg BDCM/kg in 10% Emulphor compared to corn oil. However, administration of the high dose in corn oil resulted in greater nephrotoxicity than in the aqueous vehicle. Significant interactions between vehicle of administration and BDCM dose observed for both urinary and serum parameters further indicate that vehicle differences noted in BDCM acute toxicity are dose dependent. This observation may be due to pharmacokinetic differences in gastrointestinal rates of absorption of BDCM from corn oil as compared to an aqueous solution.
Department of Environmental Sciences and Engineering, University of North Carolina-Chapel Hill.
P D
PD
Lilly
J E
JE
Simmons
R A
RA
Pegram
D000284:Administration, Oral; D000818:Animals; D003314:Corn Oil / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D006846:Hydrocarbons, Halogenated / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D014677:Pharmaceutical Vehicles / Q000633:toxicity*; D010938:Plant Oils / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D022882:Trihalomethanes
D006846:Hydrocarbons, Halogenated; D014677:Pharmaceutical Vehicles; D010938:Plant Oils; D022882:Trihalomethanes; C025191:bromodichloromethane; D003314:Corn Oil