Effects of gavage versus dosed feed administration on the toxicokinetics of benzyl acetate in rats and mice.
Effects of gavage versus dosed feed administration on the toxicokinetics of benzyl acetate were studied in male F344 rats and B6C3F1 mice. Benzyl acetate was rapidly hydrolysed to benzyl alcohol and then oxidized to benzoic acid. After gavage administration of benzyl acetate in corn oil at 500 mg/kg (rats) and 1000 mg/kg (mice), high benzoic acid plasma concentrations were observed. In contrast, much lower benzoic acid plasma concentrations were found after dosed feed administration at about 615 mg/kg/day for rats and about 850 mg/kg/day for mice. Results show that although the daily doses of benzyl acetate are comparable, bolus gavage administration effectively saturated the benzoic acid elimination pathway whereas dosed feed administration did not. In contrast, hippuric acid plasma concentrations were similar after both gavage and dosed feed administration due to the depletion of the glycine supply pool. Study results could explain the different toxicity and carcinogenicity responses of benzyl acetate observed in 2-yr chronic gavage and dosed feed studies.
Yuan
J H
JH
National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709.
Goehl
T J
TJ
Abdo
K
K
Clark
J
J
Espinosa
O
O
Bugge
C
C
Garcia
D
D
D000284:Administration, Oral; D000395:Air Pollutants, Occupational / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D001565:Benzoates / Q000097:blood; D019817:Benzoic Acid; D019905:Benzyl Alcohol; D001592:Benzyl Alcohols / Q000097:blood / Q000378:metabolism; D001593:Benzyl Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D002273:Carcinogens / Q000378:metabolism / Q000633:toxicity; D002851:Chromatography, High Pressure Liquid; D003198:Computer Simulation; D003314:Corn Oil; D005998:Glycine / Q000378:metabolism; D006626:Hippurates / Q000097:blood; D006868:Hydrolysis; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D010084:Oxidation-Reduction; D051381:Rats; D011916:Rats, Inbred F344
D000395:Air Pollutants, Occupational; D001565:Benzoates; D001592:Benzyl Alcohols; D001593:Benzyl Compounds; D002273:Carcinogens; D006626:Hippurates; C046412:benzyl acetate; D003314:Corn Oil; D019817:Benzoic Acid; D019905:Benzyl Alcohol; C030514:hippuric acid; D005998:Glycine