论文部分内容阅读
目的观察胸腺法新中2种杂质的急性毒性和大鼠30 d喂养的亚慢性毒性。方法采用最大耐受量法观察2种杂质对NIH小鼠的急性毒性;连续30 d皮下注射观察2种杂质对SD大鼠的亚慢性毒性,每种杂质均设置高、中、低3个剂量组(分别为人体暴露量的100、50和25倍),对照组为灭菌注射用水,对一般生理指标、血液学、血液生化和组织病理学进行检查。结果 2种杂质在最大给药浓度及给药容量条件下均未导致小鼠死亡,且14 d内给药组与对照组小鼠的摄食量、体重均无显著性差异。大鼠连续30 d给药后,与相应对照组比较有显著性差异的项目有:杂质1的天冬氨酸转氨酶(AST)、尿素氮(BUN)、肝脏的脏器系数;杂质2的胸腺的脏器系数,但上述指标的改变无剂量依赖性,雌雄大鼠表现不一致,且在实验室正常参考值范围内。组织病理学结果显示各脏器均无与受试物相关的明显异常病变。结论急性毒性试验与大鼠30 d喂养试验结果表明胸腺法新中2种杂质均无毒性。
Objective To observe the acute toxicity of two kinds of impurities in thymus and the subchronic toxicity of 30-day feeding in rats. Methods The maximum tolerated dose was used to observe the acute toxicity of two kinds of impurities to NIH mice. The subchronic toxicity of two kinds of impurities to SD rats was observed by subcutaneous injection for 30 days. Each dose of high, medium and low dose (100, 50 and 25 times of body exposure, respectively). The control group was sterile water for injection. The general physiological indices, hematology, blood biochemistry and histopathology were examined. Results The results showed that the two kinds of impurities did not cause the death of mice at the maximum drug concentration and administration volume. There was no significant difference in the food intake and body weight between the two groups within 14 days. After administration for 30 days in a row, the significant differences compared with the corresponding control group were aspartate aminotransferase (AST), blood urea nitrogen (BUN), liver organ coefficient; impurity thymus However, the changes of the above indexes were not dose-dependent, the performance of male and female rats was inconsistent, and it was within the normal laboratory reference value. Histopathology showed no visceral abnormalities in each organ associated with the test substance. Conclusion The results of acute toxicity test and 30-day feeding test in rats showed that the two kinds of impurities in thymus were non-toxic.