Reconstructing population exposures from dose biomarkers: inhalation of trichloroethylene (TCE) as a case study

Physiologically based pharmacokinetic (PBPK) modeling is a well-established toxicological tool designed to relate exposure to a target tissue dose. The emergence of federal and state programs for environmental health tracking and the availability of exposure monitoring through biomarkers creates the opportunity to apply PBPK models to estimate exposures to environmental contaminants from urine, blood, and tissue samples. However, reconstructing exposures for large populations is complicated by often having too few biomarker samples, large uncertainties about exposures, and large interindividual variability. In this paper, we use an illustrative case study to identify some of these difficulties, and for a process for confronting them by reconstructing population-scale exposures using Bayesian inference. The application consists of interpreting biomarker data from eight adult males with controlled exposures to trichloroethylene (TCE) as if the biomarkers were random samples from a large population with unknown exposure conditions. The TCE concentrations in blood from the individuals fell into two distinctly different groups even though the individuals were simultaneously in a single exposure chamber. We successfully reconstructed the exposure scenarios for both subgroups - although the reconstruction of one subgroup is different than what is believed to be the true experimental conditions. We were however unable to predict with high certainty the concentration of TCE in air.