Studies on benzyl acetate. III. The percutaneous absorption and disposition of [ Methylene- 14C]benzyl acetate in the rat

Abstract

[ methylene- 14C]Benzyl acetate was applied over an area of 6.25, 12 or 18 cm 2 to the shaved backs of male Fischer 344 rats under an occlusive dressing at dose levels of 100, 250 and 500 mg/kg. The compound was administered either as the neat substance or as a 50% (v/v) solution in ethanol. After 6 hr the dressing was removed, the shaven area was washed with ethanol and the dressing and washings were counted for 14C. Urine and faeces were collected for 72 hr from the start of treatment and urinary metabolites were assayed by radio-TLC and HPLC. Following administration of the neat compound, a significant proportion of the dose was recovered from the application site (28–48%) and a similar proportion (28–46%) was absorbed and excreted in 0–24-hr urine. Excretion of 14C in the urine over 0–24 hr accounted for c. 95% of absorbed 14C in all cases, and total recovery of radioactivity was 79–84% with <2% of the dose present in the carcass at the end of the experiments. The extent of absorption of benzyl acetate per unit area of skin, as assessed by the recovery of its metabolites in urine, rose with increasing concentration (mg/cm 2) of the test compound on the skin. The absorption of topically applied benzyl acetate was essentially the same when the dose was administered in a 50% ethanolic solution. In all cases, the major urinary metabolite was hippuric acid ( c. 95% of urinary 14C), together with much smaller amounts of benzoyl glucuronide, benzoic acid and benzylmercapturic acid. The distribution of 14C in the tissues was examined 6 and 24 hr after the topical application of 5 mg [ methylene- 14C]benzyl acetate/kg as a 1% (v/v) solution in ethanol to rats. Radioactivity in all carcasses was < 4% of the administered dose and levels in all the organs examined were lower at 24 than at 6 hr.