and Département de santé environnementale et santé au travail, Faculté de Médecine, Université de Montréal, Chaire en analyse des risques toxicologiques pour l'humain, Montreal (Quebec)Canada.
Toxicol Mech Methods. 2004;15(1):33-52. doi: 10.1080/15376520490446392.
Abstract A multi-compartment kinetic model was developed to describe the kinetics of parathion and its metabolites, p-nitrophenol (p-NP) and alkyl phosphates (AP), in order to assess worker exposure and health risks. Model compartments represent body burdens and excreta of parathion and its metabolites; to minimize the number of compartments and free parameters, regrouping was carried out on the basis of the time scales of the kinetic processes involved. Burden variations in time were described mathematically by differential equations that ensure conservation of mass on a mole basis. Model parameter values were determined from statistical fits to published in vivo kinetic data in humans. Except for the dermal absorption fraction and absorption rate, which are known to be subject to wide intra- and inter-individual variability, a single set of parameter values for the internal body kinetics enabled the model to simulate accurately the available kinetic data. For dermal exposure to parathion, with a typical absorption rate of 0.085 h(-1), model simulations show that it takes 20 h to recover half of the total amounts of p-NP eventually excreted in urine and 30 h for the AP. The model can be used to estimate the dose of parathion absorbed under different exposure routes and temporal scenarios, based on measurements of amounts of metabolites accumulated in urine over given time periods. Using the above dose-excreta links and the human no-observed-effect level for parathion reported in the literature for the inhibition of cholinesterase activities, biological reference values are proposed in the form of specific amounts of urinary metabolites excreted over chosen time periods.
摘要 为了评估工人的暴露水平和健康风险，建立了一个多室动力学模型来描述对硫磷及其代谢物对硝基酚（p-NP）和烷基磷酸酯（AP）的动力学。模型室代表对硫磷及其代谢物的体内负担和排泄物；为了尽量减少室和自由参数的数量，根据所涉及的动力学过程的时间尺度进行了分组。通过确保在摩尔基础上质量守恒的微分方程来描述时间上的负荷变化。模型参数值是根据人体体内动力学的已发表动力学数据的统计拟合确定的。除了已知具有广泛个体内和个体间变异性的皮肤吸收分数和吸收速率外，内部身体动力学的单一参数值集使模型能够准确模拟可用的动力学数据。对于对硫磷的皮肤暴露，典型的吸收速率为 0.085 h(-1)，模型模拟表明，尿液中最终排泄的 p-NP 的总量的一半需要 20 小时才能恢复，AP 需要 30 小时。该模型可以根据在给定时间段内尿液中代谢物积累量的测量，来估计不同暴露途径和时间情况下吸收的对硫磷剂量。利用上述剂量-排泄物关系以及文献中报道的对硫磷抑制胆碱酯酶活性的无观察效应水平，以在选定时间段内排泄的特定量的尿液代谢物的形式提出了生物参考值。
