From Source to Dose: Modeling Human Exposure to Poly- and Perfluoroalkyl Substances

Abstract

Poly- and Perfluoroalkyl Substances (PFASs) are a class of synthetic organic chemicals that have been in production since 1950s. They are detectable in virtually all Americans. Exposure to some PFASs have been linked to a suite of adverse health outcomes including developmental, metabolic and immunotoxic effects. Elucidating the origin of contamination and the relative importance of exposure pathways is critical for designing effective public health interventions to reduce exposure and prevent adverse health outcomes. Pathways for human exposure to these compounds include marine foods, drinking water and consumer goods. Several recent drinking water PFAS contamination has drown nationwide attention. This thesis links environmental sources and human exposure to understand the role of environment in the overall exposure and health risks related to PFASs. Chapter 1 of this thesis reviews the current science on PFAS sources, exposure pathways and health concerns. This introductory section leverages information from both peer-reviewed literature and regulatory docket files to present a comprehensive overview. Chapter 2 presents a spatial analysis on the latest nationwide drinking water PFAS occurrence data to establish the link between point sources and drinking water contamination. This work reveals the prevalence of drinking water PFAS contamination in the nation, and highlights the substantial data gap for a third of the country. Chapter 3 extends the link from drinking water to human plasma concentrations. By leveraging unique samples from a large U.S-based cohort study, Nurses’ Health Study, and applying both statistical and mechanistic models, I found that drinking water can be important exposure pathway even for the general population living far away from the point sources. I also quantified the relative importance of drinking water to overall human exposure, which has implications for current risk assessment practice and drinking water health advisory levels. Chapter 4 completes the loop around exposure source and human exposure by fingerprinting major exposure source based on the serum PFAS profiles. I identified effective tracers for exposure from marine foods and consumer products. I also discussed methodological considerations of using this approach. Chapter 5 summarizes all the work presented in this thesis and makes recommendations for future research. My thesis shows the increasing importance of environmental sources for PFAS exposure as these compounds are being phased out in consumer products. Risk assessment needs to incorporate temporal changes, interindividual variability and source information to be effective and health protective.