嘧草硫醚原药亚慢性经口毒性研究
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摘要
目的在研究嘧草硫醚原药对大鼠的亚慢性经口毒性基础上,初步探讨其作用的靶器官。方法将80只SPF级SD大鼠随机分成4组,雌雄各半,分别用含0、15、60和240 mg/kg嘧草硫醚原药的饲料连续90 d经口喂饲,观察各组动物实验中的临床表现、食物利用率、体重变化情况,实验末期测定相关的血液和尿液学指标、脏器重量及脏器系数、病理组织学变化。结果试验期间,雌雄各剂量组动物活动正常,未见明显中毒体征和异常表现。与相应的对照组相比,中、高剂量组大鼠淋巴细胞百分比(The Ratio of Lymphocyte,LYM%)明显降低,中、高剂量组大鼠的中性粒细胞绝对值百分比(The Absolute Ratio of Neutrophils,GRA%)明显升高。中、高剂量组雄鼠尿素氮(Urinary Nitrogen,BUN)显著升高;中、高剂量组大鼠肌酐(Creatinine,CREA)升高;中、高剂量组雌鼠的白球比(The Albumin and Globulin Ratio,A/G)明显增高;中、高剂量组雌鼠总蛋白(Total Protein,TP)和球蛋白(Globulin,GLB)明显降低。高剂量雌鼠的肝脏重量及肝脏系数明显升高。病理结果显示高剂量组部分动物肾间质有少量炎细胞浸润和肝脏有轻度脂变。结论嘧草硫醚原药对雌、雄SD大鼠亚慢性经口毒性试验的最大无作用剂量(No Observed Adverse Effect Level,NOAEL)分别为11. 8 mg/(kg·bw·d)和11. 2 mg/(kg·bw·d),其长期暴露对动物肝肾具有潜在的毒性作用。
Objective To explore the the subchronic oral toxicity of pyrithiobac-sodium TC in rats and to analyze its target organs preliminarily. Methods A total of 80 SD rats of clean grade were randomly divided into four groups with 10 male and 10 female in each group. The rats in the four pyrithiobac-sodium TC treated groups were respectively fed orally with diet containing pyrithiobac-sodium TC of 0,15,60,and 240 mg/kg for 90 days. The clinical manifestations,food utilization,and body weight changes in each group of animals were observed. At the end of the experiment,relevant blood and urine parameters,organ weight and organ coefficient,and histopathological changes were examined. Results During the period of the experiment,activity of male and female rats in each dose group were normal,and no obvious toxicity symptoms and abnormal performance appeared. Compared with the control group,the ratio of lymphocyte( LYM%) of female and male rats in the medium-and high-dose group decreased significantly. The absolute ratio of neutrophils( GRA%) of female rats in medium-and high-dose group increased obviously. The urinary nitrogen( BUN) of male rats in the medium-and high-dose groups increased significantly. The creatinine( CREA) of female and male rats in the medium-and high-dose group increased. The albumin and globulin ratio( A/G) of female rats in the medium-and high-dose groups decreased. The total protein( TP) and globulin( GLB) of female rats in the medium-and high-dose groups decreased significantly. The liver weight and liver coefficient of female rats in high-dose group increased significantly. For the results of pathological examination,inflammatory cells infiltration in the renal interstitial tissue and mild lipid changes in the liver were found in some rats of high-dose group. Conclusion The no observed adverse effect level( NOAEL) of the subchronic oral toxicity of pyrithiobac-sodium TC in female and male SD rats is 11. 8 mg/( kg·bw·d) and 11. 2 mg/( kg·bw·d) respectively. Long-term exposure to pyrithiobac-sodium TC has toxicity to liver and kidney of rats.
Objective To explore the the subchronic oral toxicity of pyrithiobac-sodium TC in rats and to analyze its target organs preliminarily. Methods A total of 80 SD rats of clean grade were randomly divided into four groups with 10 male and 10 female in each group. The rats in the four pyrithiobac-sodium TC treated groups were respectively fed orally with diet containing pyrithiobac-sodium TC of 0,15,60,and 240 mg/kg for 90 days. The clinical manifestations,food utilization,and body weight changes in each group of animals were observed. At the end of the experiment,relevant blood and urine parameters,organ weight and organ coefficient,and histopathological changes were examined. Results During the period of the experiment,activity of male and female rats in each dose group were normal,and no obvious toxicity symptoms and abnormal performance appeared. Compared with the control group,the ratio of lymphocyte( LYM%) of female and male rats in the medium-and high-dose group decreased significantly. The absolute ratio of neutrophils( GRA%) of female rats in medium-and high-dose group increased obviously. The urinary nitrogen( BUN) of male rats in the medium-and high-dose groups increased significantly. The creatinine( CREA) of female and male rats in the medium-and high-dose group increased. The albumin and globulin ratio( A/G) of female rats in the medium-and high-dose groups decreased. The total protein( TP) and globulin( GLB) of female rats in the medium-and high-dose groups decreased significantly. The liver weight and liver coefficient of female rats in high-dose group increased significantly. For the results of pathological examination,inflammatory cells infiltration in the renal interstitial tissue and mild lipid changes in the liver were found in some rats of high-dose group. Conclusion The no observed adverse effect level( NOAEL) of the subchronic oral toxicity of pyrithiobac-sodium TC in female and male SD rats is 11. 8 mg/( kg·bw·d) and 11. 2 mg/( kg·bw·d) respectively. Long-term exposure to pyrithiobac-sodium TC has toxicity to liver and kidney of rats.
引文
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[10] PETRUSHEVSKA G,KOSTADINOVA-KUNOVSKA S,JOVANOVIC R,et al. Immunohistochemical study of the inflammatory infiltrate and the proliferative index in the tubulointerstitium in human glomerulonephritis[J]. Bantao Journal,2012,10(1):13-20.
[11]孟令仪,张晶莹,吴晓刚,等.对Wistar大鼠30 d喂养试验血液学及血生化指标参考值的研究[J].医学动物防制,2017,33(12):1282-1285.
[12] NEETU,TYAGI R. Toxicological observations in the liver of Channa punctatus(Bloch)related to its total protein synthesis[J]. Biochemical&Cellular Archives,2011,11(2):367-372.
[13]曾明,钟才高,廖春华,等.杀螟丹对大鼠的亚慢性经口毒性研究[J].毒理学杂志,2006,20(3):199-200.
[14]汪建良,纪磊,岑江杰,等.氯胺嘧草醚原药亚慢性经口毒性试验[J].农药,2015,54(4):286-288.
[2]武云龙.嘧草硫醚除草剂及二芳基硫醚的合成方法研究[D].济南:山东大学,2008.
[3]吴本林,张黎辉,李波,等.嘧草硫醚除草剂:中国,102742575A[P]. 2012.
[4]李美,高兴祥,高宗军,等.嘧草硫醚对棉花的安全性及除草生物活性测定[J].农药,2009,48(7):538-541.
[5]黄健,蒋建勋,杜明伟,等.黄河流域棉区北部机采棉田恶性杂草的化学防除研究[J].中国棉花,2017,60(11):12-19.
[6]胡雄飞,张丽娜,熊志军.不同年龄SD大鼠肝脏功能及组织形态学探讨[J].医学动物防制,2016,32(8):848-849.
[7]吴晓刚,孟令仪,隋自洁.人参亚慢性毒性试验中末期大鼠血液学变化的比较研究[J].中国实用医药,2016,11(33):193-194.
[8] DONG YS,YIN JY,CHEN Z,et al. Establishment and application of the normal reference values of organ masses and organ/body coefficients in SD rats[J]. Military Medical Sciences,2012,36(5):351-353.
[9]余晓巍,杨秀鸿,吴军,等.粉唑醇原药的亚慢性经口毒性研究[J].实用预防医学,2017,24(9):1040-1043.
[10] PETRUSHEVSKA G,KOSTADINOVA-KUNOVSKA S,JOVANOVIC R,et al. Immunohistochemical study of the inflammatory infiltrate and the proliferative index in the tubulointerstitium in human glomerulonephritis[J]. Bantao Journal,2012,10(1):13-20.
[11]孟令仪,张晶莹,吴晓刚,等.对Wistar大鼠30 d喂养试验血液学及血生化指标参考值的研究[J].医学动物防制,2017,33(12):1282-1285.
[12] NEETU,TYAGI R. Toxicological observations in the liver of Channa punctatus(Bloch)related to its total protein synthesis[J]. Biochemical&Cellular Archives,2011,11(2):367-372.
[13]曾明,钟才高,廖春华,等.杀螟丹对大鼠的亚慢性经口毒性研究[J].毒理学杂志,2006,20(3):199-200.
[14]汪建良,纪磊,岑江杰,等.氯胺嘧草醚原药亚慢性经口毒性试验[J].农药,2015,54(4):286-288.