丙烯腈类性激素作用的整体动物筛检试验  

Uterotrophic and Hershberber Assays for Acrylonitrile in Rats

作　　者：王宁[1] 荣顺兴[1] 朱菊一[1] 黄简抒[2] 周元陵[2] 金泰廙[1] 

机构地区：[1]复旦大学公共卫生学院公共卫生安全国家教委重点实验室,上海200032 [2]复旦大学附属金山医院职防科,上海200540

出　　处：《环境与职业医学》2005年第5期408-412,共5页Journal of Environmental and Occupational Medicine

摘　　要：[目的]研究丙烯腈(AN)的类性激素样作用。[方法]①采用经典大鼠子宫增重方法测试丙烯腈的类雌激素样作用,对去卵巢SD大鼠皮下注射剂量分别为0、10、15、25、40、60 mg/kg受试物丙烯腈,每天一次、连续3天;同时皮下注射剂量为0.001 mg/kg雌二醇玉米油溶液为阳性对照组。最后一次给药24 h后,将大鼠麻醉后取血并处死,观察受试动物子宫湿重、干重、肝重、肾重等指标。②研究丙烯腈的抗雄激素作用。采用OECD推荐的内分泌干扰体内筛检实验方法(Hershberger试验),对雄性去势大鼠皮下注射剂量为0.4 mg/kg 体重丙酸睾酮,同时经口灌胃剂量分别为0,10,20,30,40, 50 mg/kg体重的受试物丙烯腈以及25 mg/kg体重的阳性参照物氟他胺(flutamide,FLU),每天一次,连续10天。最后一次给药24h后,将大鼠麻醉后取血并处死,观察受试动物前列腺、精囊腺、阴茎、肛提肌/球体海绵体肌、尿道球腺等附性腺组织(sex accessory tissue,SAT)重量和肝重、肾重等指标。[结果] ①子宫增重实验:丙烯腈各剂量组大鼠子宫干重、湿重与溶剂对照组无显著差异(P>0.05),阳性对照组与溶剂对照组及丙烯腈各剂量组比较,子宫干重、湿重差异存在显著性(P<0.05)。②Hershberger试验:丙烯腈各剂量组与阴性对照组相比,SAT重量差异无显著性(P>0.05),阳性对照组(FLU) 与阴性对照组相比,SAT重量差别具有显著性(P<0.05)。丙烯腈各剂量组肝、肾重量与阴性对照组差别无显著性(P>0.05), 提示受试动物无明显系统毒性。[结论]采用子宫增重测试和Hershberger体内筛检试验来发现丙烯腈具有类性激素作用。[ Objective ] To assess the estrogenic and anti-androgenic effects of acrylonitrile （AN） by in-vivo uterotrophic and Hershberger assays proposed by the OECD. [ Methods ] For the uterotrophic assay, AN was injected subcutaneously at the doses of 0, 10, 15, 25, 40 and 60mg/kg to 56-day-old ovariectomized rats for 3 days. In some rats, 17β-estradiol （EE） was also injected subcutaneously at a dose of 0.001 mg/kg as a positive control group. For the Hershberger assay, AN was administered orally at doses of 0, 10, 20, 30, 40 and 50 mg/kg to 56-day-old castrated rats for 10 days. 0.4 mg/kg testosterone propionate （TP） was also administered by subcutaneous injection after the administration of AN. In some rats, flutamide （FLU） was also administered orally at a dose of 25 mg/kg as the reference chemical for anti-vandrogenicity. [ Results ] For the uterotrophic assay, there were essentially no differences in the uterine wet or blotted weights between the control and any of the AN-treated groups. For the Hershberger assay,the weights of the accessory sex organs of the castrated rats showed no significant differences between the oil plus TP-treated group and any of the AN plus TP-treated groups. [ Conclusion ] These findings suggest that AN dose not have any endocrine-disrupting properties in in-vivo screening tests.

关 键 词：丙烯腈 子宫增重实验 Hershberger试验 雌二醇 丙酸睾酮 

分 类 号：R114[医药卫生—卫生毒理学]