Determination of Aggregate and Cumulative Exposures of Perfluorinated Compounds Consistent with Biomarkers of the Compounds Using Simulation Modeling of Exposure and Pharmacokinetics

EPA Grant Number: R833450
Title: Determination of Aggregate and Cumulative Exposures of Perfluorinated Compounds Consistent with Biomarkers of the Compounds Using Simulation Modeling of Exposure and Pharmacokinetics
Investigators: Chaisson, Christine , Andersen, Melvin E. , Clewell, Harvey , Franklin, Claire A. , Jayjock, Michael , Krewski, Daniel , Mathis, Eric T. , Ramsay, Tim , Tan, Yu-Mei , Tedder, Douglas R.
Institution: The LifeLine Group, Inc. , Center for Human Health Assessment CIIT Centers for Health Research , University of Ottawa’s Institute for Population Health
EPA Project Officer: Pascual, Pasky
Project Period: May 1, 2007 through May 1, 2010
Project Amount: $749,991
RFA: Interpretation of Biomarkers Using Physiologically Based Pharmacokinetic Modeling (2006) RFA Text |  Recipients Lists
Research Category: Health Effects , Health

Description:

This project will perform research on linking exposure and PBPK models as a method for characterizing the relationship between exposures and biomarker levels of two perfluorinated compounds, perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS). The resulting model will then be used to test the hypothesis that the known sources of perfluorinated compounds can explain the observed variation in serum levels of the compounds with age, gender, and ethnicity. The method has the potential to provide significant quantitative insight on the exposures and doses associated with observed levels of the compounds.

Objective:

To develop a novel method that relates the cumulative exposures to known sources of perfluorinated compounds to the observed levels of PFOA and PFOS in serum. Subsequently, to use this method to investigate if known sources of PFOA and PFOS are adequate to explain observed serum levels in the U.S population.

Approach:

The method will be created by 1) developing PBPK models of PFOA and PFOS in humans and 2) integrating the PBPK models with models of interindividual variation in physiology and longitudinal exposures to develop a model that simulates the relationship between sources and PFOA and PFOS serum levels in surveyed populations. The proposed approach builds on the strengths of the members of the project team. The program will be used in a forward direction to determine if the reported co-occurrences of plasma levels for the compounds can be modeled from the available exposure information on the two compounds. The program will also be used in reverse to characterize the exposures that are consistent with specific biomarker levels (reverse dosimetry).

Expected Results:

The result of the project will advance the field of biomarker analysis by providing a quantitative method for linking observed biomarker levels to doses and exposures from specific sources. A unique aspect of the work is that it will link multiple biomarkers (PFOA and PFOS) measured in one individual to multiple concurrent sources of exposure for multiple compounds (cumulative exposures). These findings will be relevant to the determination of the sources of current and historic exposures and could help support future risk assessment and risk mitigation decisions for the compounds. The methodology developed here can be applied to other fluorinated compounds and has relevance for the evaluation of other persistent chemicals.

Supplemental Keywords:

Monte Carlo, PBPK, perfluorinated compounds, exposure, simulation, longitudinal,, RFA, Health, Scientific Discipline, Environmental Chemistry, Health Risk Assessment, Endocrine Disruptors - Environmental Exposure & Risk, Risk Assessments, endocrine disruptors, Biochemistry, Biology, Endocrine Disruptors - Human Health, neurotoxic, bioindicator, thyroid toxicants, exposure studies, dose response, developmental biology, human growth and development, toxicity, hormone production, assessment technology, ecological risk assessment model, human health risk