Liao Kai H, Tan Yu-Mei, Clewell Harvey J
Center for Human Health Assessment, CIIT at the Hammer Institute for Health Sciences, 6 Davis Drive, Research Triangle Park, NC, USA.
Risk Anal. 2007 Oct;27(5):1223-36. doi: 10.1111/j.1539-6924.2007.00964.x.
A screening approach is developed for volatile organic compounds (VOCs) to estimate exposures that correspond to levels measured in fluids and/or tissues in human biomonitoring studies. The approach makes use of a generic physiologically-based pharmacokinetic (PBPK) model coupled with exposure pattern characterization, Monte Carlo analysis, and quantitative structure property relationships (QSPRs). QSPRs are used for VOCs with minimal data to develop chemical-specific parameters needed for the PBPK model. The PBPK model is capable of simulating VOC kinetics following multiple routes of exposure, such as oral exposure via water ingestion and inhalation exposure during shower events. Using published human biomonitoring data of trichloroethylene (TCE), the generic model is evaluated to determine how well it estimates TCE concentrations in blood based on the known drinking water concentrations. In addition, Monte Carlo analysis is conducted to characterize the impact of the following factors: (1) uncertainties in the QSPR-estimated chemical-specific parameters; (2) variability in physiological parameters; and (3) variability in exposure patterns. The results indicate that uncertainty in chemical-specific parameters makes only a minor contribution to the overall variability and uncertainty in the predicted TCE concentrations in blood. The model is used in a reverse dosimetry approach to derive estimates of TCE concentrations in drinking water based on given measurements of TCE in blood, for comparison to the U.S. EPA's Maximum Contaminant Level in drinking water. This example demonstrates how a reverse dosimetry approach can be used to facilitate interpretation of human biomonitoring data in a health risk context by deriving external exposures that are consistent with a biomonitoring data set, thereby permitting comparison with health-based exposure guidelines.
开发了一种针对挥发性有机化合物（VOCs）的筛查方法，以估算与人体生物监测研究中在体液和/或组织中测量的水平相对应的暴露量。该方法利用了一个通用的基于生理的药代动力学（PBPK）模型，结合暴露模式表征、蒙特卡罗分析和定量结构-性质关系（QSPR）。对于数据极少的VOCs，使用QSPR来开发PBPK模型所需的化学特异性参数。PBPK模型能够模拟多种暴露途径后的VOC动力学，例如通过饮水摄入的口服暴露和淋浴期间的吸入暴露。利用已发表的三氯乙烯（TCE）人体生物监测数据，对通用模型进行评估，以确定其根据已知的饮用水浓度估算血液中TCE浓度的能力。此外，进行蒙特卡罗分析以表征以下因素的影响：（1）QSPR估算的化学特异性参数的不确定性；（2）生理参数的变异性；（3）暴露模式的变异性。结果表明，化学特异性参数的不确定性对预测血液中TCE浓度的总体变异性和不确定性贡献较小。该模型用于反向剂量测定法，根据血液中TCE的给定测量值推导饮用水中TCE浓度的估算值，以便与美国环境保护局（U.S. EPA）饮用水中的最大污染物水平进行比较。这个例子展示了如何通过推导与生物监测数据集一致的外部暴露量，利用反向剂量测定法在健康风险背景下促进对人体生物监测数据的解释，从而允许与基于健康的暴露指南进行比较。
