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 toxicokineti cs of benzyl acetate were studied in male F344 rats and B6C3F(1) mice. Benzyl acetate was rapidly hydrolysed to benzyl alcohol and then oxid ized 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. Resu lts show that although the daily doses of benzyl acetate are comparabl e, bolus gavage administration effectively saturated the benzoic add e limination pathway whereas dosed feed administration did not. In contr ast, hippuric acid plasma concentrations were similar after both gavag e and dosed feed administration due to the depletion of the glycine su pply pool. Study results could explain the different toxicity and carc inogenicity responses of benzyl acetate observed in 2-yr chronic gavag e and dosed feed studies.