A Bayesian population PBPK model for multiroute chloroform exposure

Abstract

A Bayesian hierarchical model was developed to estimate the parameters in a physiologically based pharmacokinetic (PBPK) model for chloroform using prior information and biomarker data from different exposure pathways. In particular, the model provides a quantitative description of the changes in physiological parameters associated with hot-water bath and showering scenarios. Through Bayesian inference, uncertainties in the PBPK parameters were reduced from the prior distributions. Prediction of biomarker data with the calibrated PBPK model was improved by the calibration. The posterior results indicate that blood flow rates varied under two different exposure scenarios, with a two-fold increase of the skin's blood flow rate predicted in the hot-bath scenario. This result highlights the importance of considering scenario-specific parameters in PBPK modeling. To demonstrate the application of a probability approach in toxicological assessment, results from the posterior distributions from this calibrated model were used to predict target tissue dose based on the rate of chloroform metabolized in liver. This study demonstrates the use of the Bayesian approach to optimize PBPK model parameters for typical household exposure scenarios.