Linking PAH Exposure to Health Outcomes Using Human Primary In Vitro Respiratory Model

Oregon State University, Corvallis OR

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Abstract

PROJECT SUMMARY – TILTON PROJECT One of the most difficult challenges for environmental health assessment is to evaluate hazards from exposure to chemical mixtures. The environmental health science community recognizes polycyclic aromatic hydrocarbons (PAHs) as a re-emerging class of environmental pollutants due to their persistence and prominence in mixtures of concern; however, little data exists for structurally diverse PAHs and their transformation and breakdown products in complex mixtures. In particular, alkylated PAHs (a-PAHs) appear abundantly in environmental samples from multiple sources, including petrochemicals associated with Superfund sites and thermal decomposition of organic matter. To assess risk to relevant populations, it is important to understand how PAHs contribute to toxicity in mixtures using human-relevant and metabolically competent research models and to establish a relationship between chemical exposure and toxicity. This Biomedical Science Research Project will rely on a 3D human lung model composed of primary human bronchial epithelial cells differentiated at the air-liquid interface to assess the toxicity of PAHs in complex mixtures associated with multi-source exposures near Superfund sites. To quantify the toxicity of PAHs in lungs, we will measure the threshold response using benchmark dose modeling and identify the mechanisms by which PAHs exert adverse health outcomes in exposed populations. The overall goals of this project are to assess the toxicity of novel PAHs alone and in mixtures from combined sources of exposure near Superfund sites, to advance organotypic models for improving extrapolation and risk assessment from in vitro systems, and to understand risk for toxicity in susceptible individuals. We will apply the outcomes of these studies to assess and communicate human health risks, including to vulnerable populations. We propose to achieve these aims: 1) quantify toxicity of novel substituted PAHs as components of multi-source exposures in the 3D human lung model, 2) assess chemical drivers of in vitro toxicity from complex mixtures linked to in vivo exposures via effects-directed analysis, and 3) identify endpoints that predict PAH toxicity in susceptible individuals in order to assess toxicity from combined risk factors.