Allyl acetate (AAC), allyl alcohol (AAL), and acrolein (ACR) are used in the manufacture of detergents, plastics, pharmaceuticals, and chemicals and as agricultural agents. A metabolic relationship exists between these chemicals in which allyl acetate is metabolized to allyl alcohol and subsequently to the highly reactive, alpha,beta-unsaturated aldehyde, acrolein. Due to the weaker reactivity of the protoxicants, allyl acetate and allyl alcohol, relative to acrolien we hypothesized the protoxicants would attain greater systemic exposure and therefore deliver higher doses of acrolein to the internal organs. By extension, the higher systemic exposure to acrolein we hypothesized should lead to more internal organ toxicity in the allyl acetate and allyl alcohol treated animals relative to those treated with acrolein. To address our hypothesis we compared the range of toxicities produced by all three chemicals in male and female Fischer 344/N rats and B6C3F1 mice exposed 5 days a week for 3 months by gavage in 0.5% methylcellulose. Rats (10/group) were dosed with 0-100mg/kg allyl acetate, 0-25mg/kg allyl alcohol, or 0-10mg/kg acrolein. Mice (10/group) were dosed with 0-125mg/kg allyl acetate, 0-50mg/kg allyl alcohol, or 0-20mg/kg acrolein. The highest dose of allyl acetate and acrolein decreased survival in both mice and rats. The primary target organ for the toxicity of all three chemicals in both species and sexes was the forestomach; squamous epithelial hyperplasia was observed following exposure to each chemical. In both species the highest allyl acetate dose group exhibited forestomach epithelium necrosis and hemorrhage and the highest dose of acrolein led to glandular stomach hemorrhage. Liver histopathology was the most apparent with allyl acetate, was also observed with allyl alcohol, but was not observed with acrolein. All chemicals had effects on the hematopoietic system with allyl acetate having the most pronounced effect. When dosed at quantities limited by toxicity, allyl acetate and allyl alcohol produce higher levels of urinary mercapturic acids than the minimally toxic dose of acrolein. This observation is likely due to biotransformation of allyl acetate and ally alcohol to acrolein that occurs after absorption and suggests that these chemicals are protoxicants that increase systemic exposure of acrolein. Increased systemic exposure to acrolein is likely responsible for the differences in hepatic toxicological profile observed with these chemicals.

中文翻译：

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乙酸烯丙酯，烯丙醇和丙烯醛的90天毒性对比研究。

乙酸烯丙酯（AAC），烯丙醇（AAL）和丙烯醛（ACR）用于制造洗涤剂，塑料，药物和化学药品以及用作农业制剂。这些化学物质之间存在代谢关系，其中乙酸烯丙酯被代谢为烯丙醇，随后被代谢为高反应性的α，β-不饱和醛，丙烯醛。相对于丙烯醛，由于前毒素，乙酸烯丙酯和烯丙醇的反应性较弱，我们假设前毒素会获得更大的全身暴露量，因此会向内部器官输送更高剂量的丙烯醛。进一步地，相对于用丙烯醛处理的动物，我们假设较高的全身暴露于丙烯醛的系统应导致乙酸烯丙酯和烯丙醇处理的动物体内器官毒性更高。为了解决我们的假设，我们比较了三种化学物质对雄性和雌性Fischer 344 / N大鼠和每周6天连续3天暴露于0.5％甲基纤维素的B6C3F1小鼠连续3个月产生的毒性范围。给大鼠（10只/组）给药0-100mg / kg乙酸烯丙酯，0-25mg / kg烯丙醇或0-10mg / kg丙烯醛。给小鼠（10只/组）给药0-125mg / kg乙酸烯丙酯，0-50mg / kg烯丙醇或0-20mg / kg丙烯醛。最高剂量的乙酸烯丙酯和丙烯醛会降低小鼠和大鼠的存活率。这三种化学物质在物种和性别上均具有毒性，其主要目标器官是香oma。接触每种化学物质后观察到鳞状上皮增生。在这两个物种中，乙酸烯丙酯最高剂量组均表现出前胃上皮坏死和出血，而最高剂量的丙烯醛则导致胃腺出血。乙酸烯丙酯最明显的是肝脏组织病理学，烯丙醇也可观察到，但丙烯醛则未观察到。所有化学品均对造血系统有影响，其中乙酸烯丙酯的影响最为明显。当受毒性限制的剂量给药时，乙酸烯丙酯和烯丙醇比最低毒性剂量的丙烯醛产生更高水平的尿巯基酸。该观察结果很可能是由于乙酸烯丙酯和烯丙醇在吸收后发生了生物转化为丙烯醛的现象，这表明这些化学物质是会增加丙烯醛全身暴露量的前毒素。