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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 assess the distribution of occupational harmful substances by using the model of physiological toxicokinetics (PBTK) to simulate the metabolic process of inhalation and inhalation of occupational harmful substances vinyl chloride in human body. Methods The PBTK model of inhaled VCG consisted of five compartments: gas exchange chamber (lung), fat, well perfusion chamber, inadequate perfusion chamber and liver. The rate of change of concentration in each room was expressed by conservation of mass differential equation. The model formulas and parameters were input into the Excel spreadsheet. According to the Euler numerical method, the toxicokine-kinetic data of human body inhaled with vinyl chloride were simulated. Results Simulations predicted changes in the concentration of vinyl chloride in the liver, the concentration of vinyl chloride in venous blood, and the amount of vinyl chloride in the liver after exposure to 100 ppm vinyl chloride for 6 h in adults. In addition, in order to verify the accuracy of the solution, we simulated the concentrations of vinyl chloride in adult exhaled breaths exposed to 59 ppm and 261 ppm of vinyl chloride for 7.5 h, respectively. The results obtained were compared with the previous experimental measurements and simulations Software predicted values were compared and found that the three groups of results are very close. Conclusions The human toxicity data for the inhalation of vinyl chloride can be estimated using this method without any programming basis and is a simple, practical and economical tool. The PBTK model provides a new way to estimate human dose data after occupational exposure to occupational hazards.