Population Physiologically-Based Pharmacokinetic Modeling for the Human Lactational Transfer of PCB 153 with Consideration of Worldwide Human Biomonitoring Results

TitlePopulation Physiologically-Based Pharmacokinetic Modeling for the Human Lactational Transfer of PCB 153 with Consideration of Worldwide Human Biomonitoring Results
Publication TypeJournal Article
Year of Publication2008
AuthorsLaurel E Redding, Michael D Sohn, Thomas E McKone, Shu-Li Wang, Dennis PH Hsieh, Raymond SH Yang
JournalEnvironmental Health Perspectives
Volume116
Issue12
Pagination1629-1634
Keywordsbayesian inference, body burden, Environmental Chemistry, Exposure and Risk Group, human milk biomonitoring, indoor environment department, lactational transfer, pcb 153, physiologically-based pharmacokinetic modeling, pollutant fate and transport modeling, poly-chlorinated biphenyls, reverse dosimetry
Abstract

We developed a physiologically based pharmacokinetic model of PCB 153 in women, and predict its transfer via lactation to infants. The model is the first human, population-scale lactational model for PCB 153. Data in the literature provided estimates for model development and for performance assessment. Physiological parameters were taken from a cohort in Taiwan and from reference values in the literature. We estimated partition coefficients based on chemical structure and the lipid content in various body tissues. Using exposure data in Japan, we predicted acquired body burden of PCB 153 at an average childbearing age of 25 years and compare predictions to measurements from studies in multiple countries. Forward-model predictions agree well with human biomonitoring measurements, as represented by summary statistics and uncertainty estimates. The modelsuccessfully describes the range of possible PCB 153 dispositions in maternal milk,suggesting a promising option for back estimating doses for various populations. One example of reverse dosimetry modeling was attempted using our PBPK model for possible exposure scenarios in Canadian Inuits who had the highest level of PCB 153 in their milk in the world.