Effect of subchronic corn oil gavage on the acute toxicity of orally administered bromodichloromethane.
Bromodichloromethane (BDCM) is a by-product of water chlorination and is the second most common trihalomethane (THM) in finished drinking water. It has been reported that delivery of THMs in corn oil can influence the site and magnitude of toxic and carcinogenic responses in rodents, perhaps by inducing metabolizing enzymes or altering tissue composition. To determine if corn oil influences the acute toxicity of BDCM, adult male F-344 rats were pretreated 5 days/week for 6 weeks with oral doses of corn oil or water at a volume of 5 ml/kg. Following pretreatment, animals were gavaged with a single dose of 0, 200 or 400 mg BDCM/kg in 10% Emulphor. Urine was collected at timed intervals over a 48-h period following BDCM administration. Rats were sacrificed at this time and organs and blood removed. Urine and serum were analyzed for indicators of toxicity. Corn oil pretreatment did not enhance the acute hepato- or nephrotoxicity of BDCM, suggesting that vehicle effects noted in previous THM toxicity and carcinogenicity studies are more likely due to pharmacokinetic differences between administration in corn oil and aqueous gavage vehicles than to altered tissue composition or physiological changes.
Lilly
P D
PD
Curriculum in Toxicology, University of North Carolina at Chapel Hill 27599, USA.
Simmons
J E
JE
Pegram
R A
RA
D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D003314:Corn Oil / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005618:Fresh Water; D006846:Hydrocarbons, Halogenated / Q000008:administration & dosage / Q000633:toxicity* / Q000652:urine; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D013194:Staining and Labeling; D016707:Tissue Fixation; D022882:Trihalomethanes; D014874:Water Pollutants, Chemical / Q000008:administration & dosage / Q000633:toxicity*; D018508:Water Purification
D015415:Biomarkers; D006846:Hydrocarbons, Halogenated; D022882:Trihalomethanes; D014874:Water Pollutants, Chemical; C025191:bromodichloromethane; D003314:Corn Oil; D003577:Cytochrome P-450 Enzyme System