噻唑膦原药对大鼠的亚慢性毒性作用

摘要

目的：研究90 d摄入噻唑膦原药对大鼠的亚慢性毒性作用，确定其最大无作用剂量，为安全生产及慢性毒性实验提供剂量参考。方法将80只SD大鼠（雌雄各半）按体重随机分为4组，分别为噻唑膦原药0.8 mg／kg体重组、4.0 mg／kg体重组、20.0 mg／kg体重和正常对照组。在实验结束后处死实验大鼠，同时检测血清生化、体重、尿常规和脏器系数等指标，并对结果进行统计学处理。结果高剂量组雄、雌性大鼠体质量增长缓慢，雄性大鼠高剂量组甘油三酯（TG）、胆碱酯酶（CHE）明显低于对照组，雌性大鼠高剂量组碱性磷酸酶（ALP）明显高于对照组，雌性大鼠高剂量组总蛋白（ TP）、白蛋白（ ALB）、总胆红素（ TBIL）、肌酐（ CREA）、血糖（ GLU）、胆碱酯酶（CHE）明显低于对照组；雄、雌性大鼠尿胆红素（BIL）、比重（SG）、尿蛋白（PRO）的阳性率与对照组相比有显著性差异；雄性大鼠高剂量组脑、肺、肾、肾上腺、睾丸的脏器重量系数明显高于对照组，雌性大鼠高剂量组脑、肺、肾的脏器重量系数明显高于对照组，高剂量组的卵巢子宫的脏器重量系数明显低于对照组（ P＜0.05，P＜0.01）。结论噻唑膦原药对雄、雌性大鼠90经口染毒剂量为20.0 mg／kg 体重及以上时，对大鼠有毒性效应；90天喂养噻唑膦原药对大鼠最大无作用剂量为4 mg／kg 体重。%Objective To study the toxicity of fosthiazate feeding for 90 days in rats, and to determine the maximal non-effective dose of fosthiazate , in order to provide the reference dose for safety in production and chronic toxicity experiment.Methods A total of 80 SD rats ( half female and half male ) were randomly divided into 4 groups, respectively:0.8 mg/kg· bw· d group, 4.0 mg/kg· bw· d group, 20.0 mg/kg· bw· d group, and normal control group .The rats were sacrificed to determine the indices including serum biochemical parameters , body weight , routine urine test and organ coefficients after the end of the experiment , and the results were statistically analyzed .Results In the high dose group, the body weight gain was slowed in male and female rats .The TG and CHE in the high dose group of male rats and the TP, ALB, CREA, GLU, and CHE in the high dose group of female rats were significantly lower than those of normal control group.The ALP in the high dose group of female rats was higher than that of the normal control group .The positive rates of BIL, SG, and PRO in both male and female rats had significant differences compared with those of normal control group.The organ coefficients of brain , lung, kidney, adrenal, and testis of male rats, and the organ coefficients of brain , lung, and kidney of female rats in the high dose group were significantly higher than those of the normal control group .The ovaries and uterus in the female rats of high dose group were significantly lower than those of normal control group ( P<0.05,P<0.01).Conclusions The oral dose of fosthiazate at 4.0 mg/kg· bw· d fed for 90 days and above cause toxic effects on rats , and its maximal non-effect dose of long-term intake of low-dose fosthiazate on rats is 4 mg/kg· bw· d.