Evaluation of methods for reconstructing exposures from biomarkers via PBTK models
S.S. Isukapalli1, A.F. Sasso1, M. Okino2, P.G. Georgopoulos1
1Environmental & Occupational Health Sciences Institute, Piscataway, NJ; 2USEPA National Exposure Research Laboratories, Las Vegas, NV
Effective reconstruction of exposures from available biomarker data is an important step in assessing health risks and in understanding strategies for reducing exposures. This is especially true when collection of the corresponding exposure data is resource intensive. One of the approaches for biologically based exposure reconstruction from biomarker data combined with auxiliary exposurerelated data is through the use of Physiologically Based Toxicokinetic (PBTK) models in conjunction with numerical inversion techniques. In this study, a selected subset of recently proposed exposure reconstruction techniques are evaluated through case studies involving representative environmental compounds that span a wide range of half lives. The data for biomarker levels as well as supporting exposure-related data are obtained from the Human Exposure Assessment Survey (NHEXAS). The NHEXAS databases include additional supporting information that can aid in the reconstruction process as well as in the performance evaluation of the exposure reconstruction approaches. The MENTOR-3P system (Modeling ENvironment for TOtal Risk studies with Physiologically-based Pharmacokinetic modeling for Populations) is used for PBTK modeling, along with secondary modeling techniques for improving the computational efficiency of the inversion process. Results from the case studies indicate substantial differences in estimated exposure profiles based on the type of reconstruction method used and on the forward exposure and PBTK models used. The case studies also provide insight into the value of additional information (e.g. study specific data that are collected along with the biomarker data on an "individual by individual" basis), which is important in assessing data needs for future biomonitoring studies.
This work is funded in part by the USEPA through STAR Grant GAD R 832721-010 and Cooperative Agreement CR-83162501. Viewpoints expressed here are the responsibility of the authors and do not necessarily reflect views of the USEPA or its contractors.