Bogen K T, McKone T E
Environmental Sciences Division, Lawrence Livermore National Laboratory, Livermore, California 94550.
Risk Anal. 1988 Dec;8(4):509-20. doi: 10.1111/j.1539-6924.1988.tb01191.x.
Physiologically based pharmacokinetic (PBPK) models describing the uptake, metabolism, and excretion of xenobiotic compounds are now proposed for use in regulatory health-risk assessments. In this study we investigate the extent of PCE metabolism arising from domestic respiratory exposure to tetrachloroethylene (PCE) from ground water, as predicted using a PBPK model. Indoor exposure patterns we use as input to the PBPK model are realistic ones generated from a three-compartment model describing volatilization of PCE from domestic water into household air. Values we use for the metabolic parameters of the PBPK model are estimated from data on urinary metabolites in workers exposed to PCE. It is shown that for respiratory PCE exposure due to typical levels of PCE in ground water, use of time-weighted average air concentrations with a steady-state PBPK model yields estimates of total metabolized PCE similar to those obtained using completely dynamic modeling, despite considerable uncertainty in key exposure- and metabolic-model parameters. These findings suggest that, for PCE, risk estimation taking pharmacokinetics into account may be accomplished using a simple analytic approach.
描述外源化合物吸收、代谢和排泄的基于生理学的药代动力学（PBPK）模型现被提议用于监管健康风险评估。在本研究中，我们调查了如使用PBPK模型所预测的，家庭呼吸暴露于来自地下水的四氯乙烯（PCE）所导致的PCE代谢程度。我们用作PBPK模型输入的室内暴露模式是由一个三室模型生成的实际模式，该模型描述了PCE从生活用水挥发到室内空气中的情况。我们用于PBPK模型代谢参数的值是根据接触PCE的工人尿液代谢物数据估算得出的。结果表明，对于因地下水中典型PCE水平导致的呼吸性PCE暴露，使用稳态PBPK模型的时间加权平均空气浓度得出的总代谢PCE估算值与使用完全动态模型得出的估算值相似，尽管关键暴露和代谢模型参数存在相当大的不确定性。这些发现表明，对于PCE，考虑药代动力学的风险估计可以使用简单的分析方法来完成。
