摘要
目的应用基准剂量法评价特丁净亚慢性毒性阈值,并与NOAEL法进行对比。方法特丁净大鼠亚慢性毒性试验设0、320mg/kg、970mg/kg、2900mg/kg饲料4个剂量组,根据与对照组比较结果及剂量-反应(效应)关系确定有害效应观察终点,再从中选择敏感终点,确定NOAEL值。基准剂量计算采用EPA的BMDS软件。结果雄性大鼠的有害效应观察终点为脑脏体系数、肝脏体系数、HGB(血红蛋白)、HCT(血细胞比容),敏感终点为肝脏体系数;雌性大鼠的有害效应观察终点有脑脏体系数、肝脏体系数、肾脏体系数、RBC(红细胞)、HGB、HCT,敏感终点为脑脏体系数、肾脏体系数、RBC、HGB、HCT。雌雄大鼠NOAEL均在低剂量组。结论特丁净大鼠亚慢性毒性雄性大鼠的BMDL值为31.44mg/kg·d^-1,大于NOAEL(27.01±1.65)mg/kg·d^-1,雌性大鼠的BMDL值为25.29mg/kg·d^-1,小于NOAEL(31.61±2.04)mg/kg·d^-1。
Objective To evaluate the subchronic threshold dose of terbutym using benchmark dose approach and to compare with no observed adverse effect level(NOAEL) method. Methods The studies on subchronic toxicity of terbutyrn, were divided into four groups and administrated with 0,320mg/kg,970mg/kg and 2900mg/kg feedstuff for each rat, respectively. Observed endpoints of adverse effect were established according to the results comparing with the control group and the dose-effect(response) relationship. The sensitive end-point and the NOAEL were established. Benchmark dose was calculated by EPA's BMD software.Results Observed end-point of adverse effect of male rats included the coefficients of brain/body and liver/body, HGB,HCT, the sensitive end-point was the coefficient of liver/body. Observed end-points of adverse effect of female rats included the coefficients of brain/body, liver/body and kidney/body,RBC,HGB and HCT. The sensitive end-points were the coefficients of brain/body and kidney/body, RBC,HGB and HCT. Conclusion The benchmark dose level(BMDL) of terbutryn of male rats was 31.44mg/kg· d^-1,higher than the NOAEL of (27.01±1.65)mg/kg· d^-1.The BMDL of female was 25.29 mg/kg· d^-1,lower than the NOAEL of(31.61±2.04)mg/kg· d^-1.