氰戊菊酯生理毒物代谢动力学模型的建立
Physiologically Based Toxicokinetic Model for Fenvalerate in Mice
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摘要: 利用生理毒物代谢动力学(PBTK)对小鼠静脉注射农药氰戊菊酯后,氰戊菊酯在体内分布转化代谢过程进行模拟,为评价农药暴露风险提供依据。小鼠静脉注射氰戊菊酯的PBTK模型构建分为5个房室:肝脏、肺、肾脏、充分灌注室和不充分灌注室,各房室内氰戊菊酯的浓度变化率由质量守恒微分方程表示。根据欧拉数值计算方法,对小鼠静脉注射氰戊菊酯后的毒物代谢动力学数据进行模拟。结果模拟预测了小鼠静脉注射0.5 mg·kg-1、2.5 mg·kg-1、10 mg·kg-1氰戊菊酯后血液、肝脏和肺中氰戊菊酯浓度变化曲线。为验证该模型的准确性,对小鼠静脉注射0.77 mg·kg-1氰戊菊酯后血液、肝脏和肺中氰戊菊酯的浓度值变化模拟值与前人的实验测量值进行比较,结果显示模拟值与实验值之间不存在显著性差异。因此利用该方法可以估测小鼠静脉注射氰戊菊酯的毒物代谢动力学数据,为评估农药暴露体内剂量数据提供了便利途径。
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关键词:
- 氰戊菊酯 /
- 生理毒物代谢动力学模型 /
- 小鼠 /
- 欧拉数值法 /
- 静脉注射
Abstract: The physiologically based toxicokinetic (PBTK) model was developed to simulate the process of absorption, distribution and metabolism of fenvalerate in mice's body after intravenous injection. The PBTK model for fenvalerate contains five compartments:liver, lung, kidney, rapidly perfused tissues and slowly perfused tissues. The change rate of the amount of fenvalerate in the compartments could be described by the mass balance differential equation. The toxicokinetic data were simulated according to Euler's method of numerical integration. The concentrations of fenvalerate in the liver, lung and blood were obtained for exposing to 0.5 mg·kg-1, 2.5 mg·kg-1, 10mg·kg-1 fenvalerate. The simulation results were validated by comparing them with experimental measurements. It was found that the simulation results obtained were very close to experimental results. This method could predict the toxicokinetics of injectionof fenvalerate in mice. By this model, the internal doses of organism exposed to hazards could be estimated providing a new route for assessing the hazards.-
Key words:
- fenvalerate /
- physiologically based toxicokinetic model /
- mice /
- Euler's method /
- injection
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