阿司匹林丁香酚酯对大鼠的急性毒性研究

试验旨在评价阿司匹林丁香酚酯（aspirin eugenol ester，AEE）对大鼠的急性毒性，了解AEE毒性特点及可能的毒性靶器官，并全面地分析大鼠的致死原因。试验按照改良寇氏法进行，预试验选取50只大鼠，雌雄各半，分为5组，测定绝对致死量（LD₁₀₀）和最大非致死量（LD₀）。根据预试验结果，将80只健康大鼠，雌雄各半，随机平均分为7个药物组（剂量分别为2.62、3.25、4.03、5.00、6.20、7.69和9.53 g/kg）和1个对照组（给予0.5%的羧甲基纤维素钠（CMC-Na）进行正式试验。灌胃给药，观察并记录大鼠给药后的临床症状及体重变化。给药14 d后，统计各剂量组大鼠的死亡时间及总死亡数，并计算AEE的半数致死量（LD₅₀）及其95%可信限。同时对死亡大鼠及时进行剖检，将具有病变的组织用10%的甲醛溶液固定，以进行病理学分析。结果显示，AEE对大鼠口服的LD₅₀是5.95 g/kg，且LD₅₀的95%可信限为5.30~6.68 g/kg。对大鼠的死亡时间进行分析可得出，当口服AEE的剂量大于4.03 g/kg时，其死亡时间主要集中在染毒后的48~96 h内。大鼠染毒后3 d内，体重呈下降趋势，常规饲养第5天开始，大鼠体重可逐渐恢复。病理学检查分析发现，AEE的剂量在5.00 g/kg以上时，对大鼠的肝脏、肾脏和胃肠道有明显损伤。根据外源化学物急性毒性分级（WHO）可知，AEE为实际无毒化合物，AEE对大鼠毒性靶器官主要是肝脏、肾脏和胃肠道。

Acute Toxicity of Aspirin Eugenol Ester on Rats

The acute toxicity study was carried out by intragastric administration in rats to evaluate the toxic characteristics of aspirin eugenol ester (AEE) and target organs and fully analyze the reason of death rats. The experiment was designed in accordance with the method provided by the Kärber arithmetic method. At first, 50 rats (half male and half female)were divided into 5 groups to calculate LD₁₀₀ and LD₀. According to the pre-test results, different doses of AEE (2.62,3.25,4.03,5.00,6.20,7.69 and 9.53 g/kg) and control group of 0.5% CMC-Na were orally administered to 80 rats, half male and half female, divided into 8 groups. After treatment, clinical signs of rats and the change of body weights were observed and recorded. The microscopic pathology of mild damages on organs was conducted. 14 days after adminstration, the death time and total deaths of rats were recorded, and the LD₅₀ and 95% confidence interual of AEE were calculated according to Kärber. Organs were fixed with 10% formaldehyde solution at the end of the experiment. The LD₅₀ of AEE in rats was 5.95 g/kg upon oral administration and its 95% confidence interval calculation was 5.30 to 6.68 g/kg. The death time of rats were centralized at 48 to 96 h after exposing to AEE more than 4.03 g/kg by the analysis of the cumulative mortality-time of AEE in each group. Significant decreases in body weights were noted after treatment of AEE for 3 days, after that body weights gradually grew and recovered at the 5th day. Remarkable damages on livers, kidney and gastrointestinal tract were found at AEE dosage of more than 5.00 g/kg. From the obtained value of LD₅₀>5.00 g/kg, AEE was classified as practically non-toxic compound according to WHO. The target organs of AEE were liver, kidney and gastrointestinal tract.