基于生理毒代动力学模型对氯乙烯暴露后人体内剂量的求解

Solution of Internal Doses for Inhaled Vinyl Chloride by Physiologically Based Toxicokinetic (PBTK) Model

目的通过利用生理毒代动力学(PBTK)模型对吸入职业性有害物质氯乙烯后,人体内的分布转化代谢过程进行模拟,为评价职业有害因素暴露提供依据。方法吸入氯乙烯的PBTK模型包括5个房室:气体交换室(肺)、脂肪、充分灌注室、不充分灌注室和肝脏,各房室内化学物的浓度变化率由质量守恒微分方程表达。将模型公式和参数输入Excel电子表格,根据Euler数值计算方法,对人体吸入氯乙烯后的毒物代谢动力学数据进行模拟。结果模拟预测了成人连续6 h暴露于100 ppm氯乙烯后肝脏中氯乙烯浓度、静脉血中氯乙烯浓度和肝脏中氯乙烯代谢量的经时变化曲线。此外,为了验证求解方法的准确性,我们分别对暴露于59 ppm和261 ppm氯乙烯7.5 h后成人呼出气中氯乙烯的浓度值进行了模拟,将所得结果与前人的实验测量值和模拟软件预测值进行比较,发现3组结果十分接近。结论利用本文方法可以估计吸入氯乙烯的人体毒代动力学数据,不需要编程基础,是一种简便实用且经济的工具。PBTK模型为估计职业有害物质暴露后的人体内剂量数据提供了一种新的途径。

Objective To simulate the process of absorption, distribution and metabolism of vinyl chloride in the body after inhaling by physiologically based toxieokinetic （PBTK） model and to provide a criterion for occupational exposure assessment. Methods The PBTK model for vinyl chloride contains five compartments： gas exchange compartment （lung）, fat, fully perfused tissues, slowly perfused tissues and liver. The change rate of the amount of vinyl chloride in the compartments could be described by the mass balance differential equation. The toxicokinetic data were simulated by keying the model equations and parameter values into Excel spreadsheets, and solving the differential equations according to Euler＇s method of numerical integration. Results The concentration of vinyl chloride in the liver and mixed venous blood, and the amount metabolized in the liver of human exposed to 100 ppm for 6 hours were obtained. The simulation results by the suggested method were validated by comparing them with experimental measurements. It was found that the simulation results obtained using simulation software（Simusolv）of three groups were very close. Conclusions This method could predict the toxicokinetics of inhaled vinyl chloride in human body and do not need programming languages. It is a convenient, economical and practical tool. By this model, the internal doses of human exposed to occupational hazards could be estimated providing a new route for assessing the occupational hazards.