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目的研究虱螨脲原药主要亚慢性经口毒性作用,取得虱螨脲原药亚慢性经口的最大无作用剂量和最小有作用剂量参数,初步确定毒作用的靶器官。方法采用经口喂饲法染毒,设3个染毒剂量组和1个空白对照组,雌、雄各半,分别用含500、2 000和8 000 mg/kg虱螨脲原药的加药饲料对大鼠连续经口喂饲染毒90 d,观察动物的一般表现、体重、进食量,试验结束时进行血常规、尿常规、血生化指标、脏器重量、脏器系数以及病理组织学检查。结果血常规检查结果显示,中、高剂量组雌鼠白细胞计数(WBC)降低(P<0.05和0.01),雄鼠白细胞计数(WBC)、淋巴细胞比例(LYM)降低(P<0.01)、中性粒细胞比例(MON)增高(P<0.01),高剂量组雄鼠单核细胞(GRA)比例明显增高(P<0.05);血液生化检查结果显示,高剂量组雌鼠尿素氮(BUN)、肌酐(CREA)升高(P<0.01),中、高剂量组雄鼠总胆固醇(CHO)、尿素氮(BUN)增高(P<0.01);脏器系数检查结果显示,中、高剂量组雌鼠肝体比值增高(P<0.05和0.01),雄鼠肝体比值增高(P<0.01),睾丸及睾丸体重比值降低(P<0.05);病理组织学检查结果显示,中、高剂量组雄鼠睾丸曲精小管生精上皮变性、坏死或消失、睾丸萎缩、间质增生,睾丸病变发生率增高(P<0.05);高剂量组雄鼠肝脏脂肪变性发生率增加(P<0.01);各剂量组尿常规检查结果显示与对照组比较,差异无统计学意义(P>0.05)。低剂量组雌、雄鼠各项指标与其对照组相比,均未见明显差异或有临床意义的改变。结论虱螨脲原药对大鼠的血液、肝、肾、生殖器官、神经系统具有毒性作用。其对SD大鼠亚慢性(90 d)经口毒性的最大无作用剂量雌、雄分别为为41.4和37.9 mg/kg、最小有作用剂量雌、雄分别为为152.0和147.8 mg/kg。
Objective To study the main subchronic oral toxicity of lutropine drug and obtain the maximum effective dose and minimum effective dose of sub-chronic oral administration of lufenuron and determine the target organ of toxicity. Methods The animals were orally inoculated with three dose groups and one blank control group. Female and male mice were treated with 500, 2 000 and 8 000 mg / kg bafeufloxacin The rats were continuously orally administered with the drug for 90 days to observe the general performance, body weight and food intake of the animals. Blood routine test, urine routine test, blood biochemical test, organ weight, organ coefficient and histopathology School inspection. Results The results of routine blood tests showed that the white blood cell count (WBC) and the white blood cell count (WBC) and the lymphocyte ratio (LYM) of the male and female rats decreased significantly (P <0.01 and P <0.01) (P <0.01), and the proportion of monocytes (GRA) in male rats in high dose group increased significantly (P <0.05). The result of blood biochemical test showed that the levels of BUN, (P <0.01). The levels of total cholesterol (CHO) and blood urea nitrogen (BUN) were increased in middle and high dose groups (P <0.01). The results of organ coefficient test showed that middle and high dose groups The ratio of liver to body increased (P <0.05 and 0.01), the ratio of liver and body increased (P <0.01) and the ratio of testicular and testicular weight decreased (P <0.05). The results of histopathological examination showed that the medium and high dose groups The testicular seminiferous tubule degeneration, necrosis or disappearance, testicular atrophy, interstitial hyperplasia and testicular lesions increased in male testicular seminiferous tubules (P <0.05). The incidence of hepatic steatosis increased in high dose group (P <0.01). Urine routine examination results of each dose group showed no significant difference compared with the control group (P> 0.05). Low-dose group of female and male rats compared with the control group, no significant differences or clinically significant changes. Conclusion Lumbricus drug has a toxic effect on the blood, liver, kidney, reproductive organs and nervous system in rats. The maximal non-active dose of sub-chronic (90 d) oral toxicity to SD rats was 41.4 and 37.9 mg / kg, respectively. The minimum effective dose was 152.0 and 147.8 mg / kg, respectively.