敌敌畏生理毒物代谢动力学模型的建立  

Physiologically based toxicokinetic model for dichlorvos in Rattus norregicus

作　　者：梁颖[1,2] 刘敏[2] 丁莹[2] 张留娟 刘贤金[1] 

机构地区：[1]江苏省农业科学院江苏省食品质量安全重点实验室,南京210014 [2]江苏省农业科学院农业部农产品质量安全控制技术与标准重点实验室,南京210014

出　　处：《农药学学报》2015年第1期35-40,共6页Chinese Journal of Pesticide Science

基　　金：国家自然科学基金(31201356);江苏省农业自主创新项目[cx(13)3087];江苏省自然科学基金(BK20130701)

摘　　要：利用生理毒物代谢动力学(PBTK)模型,对大鼠经口摄入敌敌畏后其在体内分布及转化代谢过程进行模拟,旨在探寻评价敌敌畏饮食暴露风险的合理方法。该PBTK模型共包括4个房室:肝脏、肾脏、充分灌注室和不充分灌注室,各房室内敌敌畏的浓度变化率采用质量守恒微分方程表示。根据欧拉数值计算方法,对大鼠经口摄入敌敌畏后的毒物代谢动力学数据进行模拟,分别预测了大鼠经口摄入10、25和50 mg/kg b.w.的敌敌畏后,肝脏和血液中敌敌畏浓度变化以及血液中乙酰胆碱酯酶活性变化的曲线。为验证该方法的准确性,将大鼠经口摄入35 mg/kg b.w.敌敌畏后血液中敌敌畏的浓度变化模拟值,以及经口摄入10 mg/kg b.w.敌敌畏后血液中乙酰胆碱酯酶活性变化的模拟值与文献的实验测量值进行了比较,结果显示,模拟值与实验值之间不存在显著性差异。因此认为,利用该PBTK模型可以估测大鼠经口摄入敌敌畏后的体内生理毒物代谢动力学数据,为评估人体的有害物质暴露内剂量数据提供了便捷途径。A physiologically based toxicokinetic（PBTK） model was applied to simulate the process of absorption, distribution and metabolism of dichlorvos in Rattus norregicus＇ body after oral ingestion. The PBTK model for dichlorvos contained four compartments： liver, kidney, rapidly perfused tissues and slowly perfused tissues. The change rate of dichlorvos concentration in the compartments was described by the mass balance differential equation. The toxicokinetic data were simulated according to Euler＇s method of numerical integration. The concentrations of dichlorvos in the liver and blood and the changing of AChE activity in blood were predicted after exposing to 10, 25 and 50 mg/kg b. w. dichlorvos. In order to validate this method, the simulation values and experimental values of the dichlorvos concentration in Rattus norregicus＇ blood following oral ingestion of 35 mg/kg b.w. dichlorvos was compared, the blood AChE activity changing in Rattus norregicus following oral ingestion of 10 mg/kg b. w. dichlorvos was also compared. It was found that the simulation results obtained had no significant difference with the experimental values. The results suggested that PBTK model could predict the toxicokinetics of oral ingestion of dichlorvos in Rattus norregicus, and provided a new route for assessing the deliverated dose of human being exposed to hazards.

关 键 词：敌敌畏 生理毒物代谢动力学模型 大鼠 欧拉数值法 经口摄入 

分 类 号：S481.1[农业科学—农药学] S482.3[农业科学—植物保护]