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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。
The physiological and pharmacokinetic (PBTK) model was used to simulate the distribution and metabolic process of DDVP in rats after oral ingestion, in order to explore a reasonable method for evaluating the risk of exposure to dichlorvos. The PBTK model includes a total of 4 atrioventricular: liver, kidney, full perfusion chamber and inadequate perfusion chamber, the rate of change of concentration of dichlorvos in each room using the mass conservation differential equation. According to the Euler numerical method, toxicokinetic data of rats after oral ingestion of dichlorvos were simulated, and the liver and blood were respectively predicted after oral ingestion of 10, 25 and 50 mg / kg bw of dichlorvos In the concentration of dichlorvos changes in blood and acetylcholinesterase activity curve. In order to verify the accuracy of this method, the simulated changes in the concentration of dichlorvos in rats after oral ingestion of 35 mg / kg bw of dichlorvos, and the change of acetylcholinesterase activity in blood after oral ingestion of 10 mg / kg bw of dichlorvos The simulated values are compared with the experimental values in the literature. The results show that there is no significant difference between the simulated values and the experimental values. Therefore, it is considered that the PBTK model can be used to estimate the in vivo toxicokinetic data of rats after oral ingestion of dichlorvos, which provides a convenient way to evaluate the internal dose of exposure of harmful substances in human body.