Chidgey M A, Kennedy J F, Caldwell J
Food Chem Toxicol. 1987 Jul;25(7):521-5. doi: 10.1016/0278-6915(87)90203-1.
[methylene-14C]Benzyl acetate was applied over an area of 6.25, 12 or 18 cm2 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 the 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 less than 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/cm2) 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 less than 4% of the administered dose and levels in all the organs examined were lower at 24 than at 6 hr.
将[14C-甲基]乙酸苄酯以100、250和500mg/kg的剂量水平，分别涂抹于6.25、12或18cm2面积的雄性Fischer 344大鼠剃毛后的背部，并用封闭敷料覆盖。化合物以纯物质形式或溶于乙醇的50%（v/v）溶液形式给药。6小时后去除敷料，用乙醇清洗剃毛区域，并对敷料和清洗液进行14C计数。从治疗开始收集72小时的尿液和粪便，通过放射性薄层色谱法和高效液相色谱法分析尿液代谢产物。给予纯化合物后，从给药部位回收了相当比例的剂量（28 - 48%），在0 - 24小时尿液中吸收并排泄的比例相似（28 - 46%）。在所有情况下，0 - 24小时尿液中14C的排泄量约占吸收的14C的95%，放射性的总回收率为79 - 84%，实验结束时 carcass 中剂量的含量低于2%。通过尿液中代谢产物的回收率评估，每单位皮肤面积乙酸苄酯的吸收程度随皮肤表面测试化合物浓度（mg/cm2）的增加而升高。当剂量以50%乙醇溶液给药时，局部应用乙酸苄酯的吸收情况基本相同。在所有情况下，主要的尿液代谢产物是马尿酸（约占尿液14C的95%），同时还有少量的苯甲酰葡萄糖醛酸、苯甲酸和苄基巯基尿酸。将5mg[14C-甲基]乙酸苄酯/kg以1%（v/v）乙醇溶液局部涂抹于大鼠后，在6小时和24小时检查组织中14C的分布。所有 carcass 中的放射性低于给药剂量的4%，所有检查器官中的水平在24小时时低于6小时。 （注：“carcass”在文中可能是一个特定的医学相关术语，但不太明确具体含义，这里直接保留英文未翻译）
