粉唑醇原药的亚慢性经口毒性研究
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摘要
目的研究粉唑醇原药亚慢性经口毒性作用,初步分析染毒后对大鼠血液、肝和肾功能的影响。方法按照GB15670-1995《农药登记毒理学试验方法》的要求进行实验,将80只清洁级SD大鼠按体重随机分成4组,每组20只,雌雄各半。分别用含37.5、150和600 mg/kg粉唑醇的饲料连续喂饲染毒90 d。观察各组大鼠的临床表现、摄食量、体重,实验结束时测定相关血液学指标、血液生化学指标、脏器重量、脏器系数及病理组织学改变。结果雌鼠各组实际染毒剂量分别为2.8、12.2、47.2 mg/kg,雄鼠各组实际染毒剂量分别为2.8、11.3、47.1 mg/kg。试验期间,各剂量组雌、雄鼠活动、进食、饮水基本正常,未见明显中毒表现。与相应对照组相比,高剂量组雄鼠白细胞计数(WBC)显著降低。中、高剂量组大鼠尿素氮(BUN)和肌酐(CREA)显著升高,高剂量组雌鼠总胆红素(TBIL)升高;中、高剂量组雌鼠天冬氨酸氨基转换酶(AST)和乳酸脱氢酶(LDH)显著升高;各剂量组雌、雄鼠各脏器重量和脏器系数与对照组相比差异均无统计学意义(P>0.05)或无生物学意义。大体解剖未见明显异常,粉唑醇原药未引起SD大鼠各脏器病理性改变。结论粉唑醇原药长期暴露对大鼠的血液、肝、肾具有毒性作用和潜在的致病风险。其对雌、雄SD大鼠亚慢性经口毒性试验的最大无作用剂量均为2.8 mg/(kg bw·d)。
Objective To explore the subchronic oral toxicity of flutriafol TC,and to preliminarily analyze its effects on the blood system,liver and kidney functions of rats.Methods The experiment was performed according to the requirement of Toxicological Test Methods of Pesticides for Registration(GB15670-1995).80 SD rats of clean grade were randomly divided into four groups based on their body weight,with 10 male and 10 femele rats in each group.The rats in the three flutriafol TC treated groups were respectively fed with diet containing flutriafol TC 37.5,150 and 600 mg/kg for 90 days.The clinical manifestations,food consumption and body weight of rats in each group were observed.Haematological parameters,clinical chemistry parameters,organ weight,organ coefficients and histopathological changes were examined at the end of the experiment.Results The actual doses of flutriafol TC taken by female rats in the three dose groups were 2.8,12.2,and 47.2mg/kg respectively,and by male rats were 2.8,11.3 and 47.1 mg/kg.During the period of the experiment,activity,food and water consumption of male and female rats in each dose group were normal,and no obvious toxicity symptoms appeared.Compared with the control group,WBC of male rats in the high-dose group decreased significantly.Blood urea nitrogen(BUN) and creatinine(CREA) of rats in the medium-and high-dose groups increased significantly.Total bilirubin(TBIL) of female rats in the high-dose group increased obviously.Aspartate amino-transferase(AST) and lactic dehydrogenase(LDH) of female rats in the medium-and high-dose groups increased significantly.No statistically significant difference or biological significance was found in organ weight and organ coefficients of male and females rats between each dose group and the control group(P>0.05).General anatomy indicated that no meaningful pathological changes induced by flutriafol TC were observed.Conclusions Long-term exposure to flutriafol TC has toxicity and potential pathogenic risk to the blood system,liver and kidney functions of rats.The maximum non-effect level of flutriafol TC is 2.8 mg/(kg bw·d) in female and male rats.
Objective To explore the subchronic oral toxicity of flutriafol TC,and to preliminarily analyze its effects on the blood system,liver and kidney functions of rats.Methods The experiment was performed according to the requirement of Toxicological Test Methods of Pesticides for Registration(GB15670-1995).80 SD rats of clean grade were randomly divided into four groups based on their body weight,with 10 male and 10 femele rats in each group.The rats in the three flutriafol TC treated groups were respectively fed with diet containing flutriafol TC 37.5,150 and 600 mg/kg for 90 days.The clinical manifestations,food consumption and body weight of rats in each group were observed.Haematological parameters,clinical chemistry parameters,organ weight,organ coefficients and histopathological changes were examined at the end of the experiment.Results The actual doses of flutriafol TC taken by female rats in the three dose groups were 2.8,12.2,and 47.2mg/kg respectively,and by male rats were 2.8,11.3 and 47.1 mg/kg.During the period of the experiment,activity,food and water consumption of male and female rats in each dose group were normal,and no obvious toxicity symptoms appeared.Compared with the control group,WBC of male rats in the high-dose group decreased significantly.Blood urea nitrogen(BUN) and creatinine(CREA) of rats in the medium-and high-dose groups increased significantly.Total bilirubin(TBIL) of female rats in the high-dose group increased obviously.Aspartate amino-transferase(AST) and lactic dehydrogenase(LDH) of female rats in the medium-and high-dose groups increased significantly.No statistically significant difference or biological significance was found in organ weight and organ coefficients of male and females rats between each dose group and the control group(P>0.05).General anatomy indicated that no meaningful pathological changes induced by flutriafol TC were observed.Conclusions Long-term exposure to flutriafol TC has toxicity and potential pathogenic risk to the blood system,liver and kidney functions of rats.The maximum non-effect level of flutriafol TC is 2.8 mg/(kg bw·d) in female and male rats.
引文
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[5]Xu C,Liu Q,Huan F,et al.Changes in gut microbiota may be early signs of liver toxicity induced by epoxiconazole in rats[J].Chemotherapy,2014,60(2):135-142.