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目的研究长期低剂量摄入氟磺唑草胺原药对大鼠的毒性作用,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。方法依据氟磺唑草胺原药急性经口LD50的1/125、1/25和1/5将80只SD大鼠,雌雄各半,按体重随机分为4组,分别为氟磺唑草胺原药11.76 mg/kg·bw·d组、58.80 mg/kg·bw·d组、294.00 mg/kg·bw·d和正常对照组。在90 d喂养结束后隔夜禁食并处死实验大鼠,同时检测血液学、血清生化、体重和脏器系数等指标,并对结果进行统计学处理。结果氟磺唑草胺原药引起雄性大鼠高剂量组的ALT、ALP、TBIL和BUN明显高于对照组,高剂量组的CHOL及中、高剂量组的TG明显低于对照组,雌性大鼠高剂量组的TP、ALB、CHE明显低于对照组,高剂量组雄、雌性大鼠WBC明显高于对照组,高剂量组雄、雌性大鼠RBC明显低于对照组,中、高剂量组雄性大鼠和高剂量组雌性大鼠HGB明显低于对照组,高剂量组雌性大鼠白细胞分类中淋巴细胞明显高于对照组、中性粒细胞明显低于对照组,雄性大鼠高剂量组脑、心、肺、肝、睾丸及中、高剂量组脾、肾的脏体比系数明显高于对照组,雌性大鼠高剂量组心、脾及中、高剂量组脑、肺的脏体比系数明显高于对照组(P<0.05,P<0.01)。结论氟磺唑草胺原药对雄、雌性大鼠经口亚慢性染毒剂量为58.80 mg/kg·bw·d及以上时,对大鼠有毒性效应;90 d喂养氟磺唑草胺原药对大鼠最大无作用剂量为11.76 mg/kg·bw·d。
Objective To study the long-term low-dose intake of fluconazole in rats virulence, to determine the maximum non-effect dose, for safe production and chronic toxicity experiments to provide dose reference. Methods Eighty SD rats were randomly divided into 4 groups according to their body weight, and were divided into 4 groups according to 1 / 125,1 / 25 and 1/5 of the acute oral LD50 of fluconazole. The original amines 11.76 mg / kg · bw · d group, 58.80 mg / kg · bw · d group, 294.00 mg / kg · bw · d and the normal control group. After 90 days of feeding, rats were fasted overnight and sacrificed. At the same time, hematology, serum biochemistry, body weight and organ coefficient were measured and the results were statistically analyzed. Results The levels of ALT, ALP, TBIL and BUN in the high dose group of fluconazole were significantly higher than those in the control group. The CHOL in the high dose group and TG in the middle and high dose group were significantly lower than those in the control group Compared with control group, the WBC of male and female rats in high-dose group were significantly higher than that in control group. The RBC of male and female rats in high-dose group were significantly lower than those in control group. The middle and high dose The levels of HGB in male rats in high dose group and those in high dose group were significantly lower than those in control group. The numbers of lymphocytes in leucocyte of high dose group were significantly higher than those in control group, the neutrophils were significantly lower than those in control group, The ratio of viscera of spleen and kidney in group of brain, heart, lung, liver, testes and medium and high dose was significantly higher than that of control group. The content of heart and spleen in high dose group and brain and lung of middle and high dose group Body coefficient was significantly higher than the control group (P <0.05, P <0.01). Conclusion The results showed that the original dose of fluconazole was toxic to rats when administered subcutaneously at a dose of 58.80 mg / kg · bw · d to male and female rats. The maximum no dose of the drug in rats was 11.76 mg / kg · bw · d.