Using a physiologically based pharmacokinetic model to link urinary biomarker concentrations to dietary exposure of perchlorate

Exposure to perchlorate is widespread in the United States and many studies have attempted to character the perchlorate exposure by estimating the average daily intakes of perchlorate. These approaches provided population-based estimates, but did not provide individual-level exposure estimates. Until recently, exposure activity database such as CSFII, TDS and NHANES become available and provide opportunities to evaluate the individual-level exposure to chemical using exposure surveillance dataset. In this study, we use perchlorate as an example to investigate the usefulness of urinary biomarker data for predicting exposures at the individual level. Specifically, two analyses were conducted: (1) using data from a controlled human study to examine the ability of a physiologically based pharmacokinetic (PBPK) model to predict perchlorate concentrations in single-spot and cumulative urine samples; and (2) using biomarker data from a population-based study and a PBPK model to demonstrate the challenges in linking urinary biomarker concentrations to intake doses for individuals. Results showed that the modeling approach was able to characterize the distribution of biomarker concentrations at the population level, but predicting the exposure-biomarker relationship for individuals was much more difficult. The type of information needed to reduce the uncertainty in estimating intake doses, for individuals, based on biomarker measurements is discussed.