Use of a Physiologically Based Pharmacokinetic Model to Identify Exposures Consistent With Human Biomonitoring Data for Chloroform

Abstract

Biomonitoring data provide evidence of human exposure to environmental chemicals by quantifying the chemical or its metabolite in a biological matrix. To better understand the correlation between biomonitoring data and environmental exposure, physiologically based pharmacokinetic (PBPK) modeling can be of use. The objective of this study was to use a combined PBPK model with an exposure model for showering to estimate the intake concentrations of chloroform based on measured blood and exhaled breath concentrations of chloroform. First, the predictive ability of the combined model was evaluated with three published studies describing exhaled breath and blood concentrations in people exposed to chloroform under controlled showering events. Following that, a plausible exposure regimen was defined combining inhalation, ingestion, and dermal exposures associated with residential use of water containing typical concentrations of chloroform to simulate blood and exhaled breath concentrations of chloroform. Simulation results showed that inhalation and dermal exposure could contribute substantially to total chloroform exposure. Next, sensitivity analysis and Monte Carlo analysis were performed to investigate the sources of variability in model output. The variability in exposure conditions (e.g., shower duration) was shown to contribute more than the variability in pharmacokinetics (e.g., body weight) to the predicted variability in blood and exhaled breath concentrations of chloroform. Lastly, the model was used in a reverse dosimetry approach to estimate distributions of exposure consistent with concentrations of chloroform measured in human blood and exhaled breath.

The authors thank George Petrov, Erin Knight, and Jessica Rubis for their help in the early phases of the research. We thank Drs. Susan Borghoff and Teresa Leavens for their valuable consultations, comments, and reviews. The modeling work was supported by the Chlorine Chemistry Council.

The U.S. Environmental Protection Agency through its Office of Research and Development conducted and collaborated in the research described here. It has been subjected to agency review and approved for publication.

The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official views of the Centers for Disease Control and Prevention.