精异丙甲草胺原药的毒性实验观察

Observation on Toxicity Experiment of S-metolachlor

目的了解受试样品精异丙甲草胺原药的毒性特点,取得该样品亚慢性经口的最大无作用剂量参数,为安全生产及慢性毒性实验提供剂量参考依据。方法依据GB 15670-1995《农药登记毒理学试验方法》对其进行了为期90 d的毒性实验,依据《化学品毒性鉴定规范》进行仓鼠肺细胞基因突变试验和仓鼠肺细胞染色体畸变试验。结果受检样品精异丙甲草胺不诱发培养的哺乳动物细胞染色体畸变,体外哺乳动物细胞基因突变试验结果为阴性。在整个染毒期间,高剂量组雄、雌性大鼠周平均体重从第2周开始至实验结束,中剂量组雄、雌性大鼠周平均体重从第6周开始至实验结束均明显低于对照组(P<0.01),高剂量组雄性大鼠的胆红素(B IL)明显高于对照组(P<0.01),高剂量组雌性大鼠的天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)明显高于对照组(P<0.05),高剂量组雄性大鼠,中、高剂量组雌性大鼠甘油三酯(TG)明显低于对照组(P<0.05),提示受检样品对大鼠肝功能酯类代谢有一定影响;高剂量组雄、雌性大鼠肝脏器系数明显高于对照组(P<0.01),且高剂量组大鼠动物肝脏肝细胞轻度水肿,与对照组比较有明显差异。表明高剂量受检样品对大鼠肝脏有一定影响。结论受检样品精异丙甲草胺不诱发培养的哺乳动物细胞染色体畸变,对培养的哺乳动物细胞不诱发基因突变。精异丙甲草胺原药对雄、雌性大鼠经口染毒剂量为158.0和632.0 mg/(kg.d)及以上时,对大鼠有毒性效应。精异丙甲草胺原药对大鼠亚慢性经口毒性最大无作用剂量雄、雌性均为31.6 mg/(kg.d)。

[ Objective] To identify the toxicity characteristics and maximal non-effect dose of s-metolachlor active compound by oral, and provide reference for maintaining safety in production and chronic toxicity test. [ Methods] According to GB 15670 - 1995 ＂ Test Methods of Toxicity for Pesticide Registration＂, 90 days toxicity experiment of s-metolachlor was performed. C, ene mutation test and chromosome aberration test of hamster lung ceil was based on＂ Identification Standards for Toxicity of Chemicals＂. [ Results] S- metolachlor did not induced chromosome aberration in mammalian ceils, in vitro chromosome aberration test result was negative. During the test, the weight of high dosage rats which from 2 weeks and the weight of middle dosage rats which from 6 week to experiment end were obviously lower than that of rots in control group （ P 〈 0.01 ）. The BIL value of high dosage male rats was higher than that of control group （ P 〈 0. 05 ）. The AST and ALP value of high dosage female rats was higher than that of control group （ P 〈 0.05 ）, the value of TG in high dosage male rats and in high and middle dosage female rats was significantly lower than that of control group （P 〈 0.05 ） which suggested that the tested sample had a certain influence on metabolism esters of rat liver. Coefficient of liver of high dose group male and female rats were significantly higher than that of controls（ P 〈0.01 ）, and hepatocytes with mild edema appeared in high dose group, the difference was significant, compared with control group. It indicated that high dose s-metolaehlor had a certain effect on rat liver. [ Conclusion] S-metolaehlor did not induced chromosome aberration and gene mutation in mammalian cells. When administration dose of s-metolaehlor is at or over 158.0 and 632.0 mg/（ kg. d） by oral, it has toxic effect on rats. Maximal non-effect dose of s-metolachlor active compound by oral is 31.6 mg/（ kg. d） for both male and female rats .