Predicting the Toxicity of PAHs

Oregon State University, Corvallis OR

Investigators

Linked publications, trials & patents

Abstract

PROJECT SUMMARY – TANGUAY PROJECT Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous contaminants at Superfund sites. The physical proximity of millions of people to PAH contamination challenges regulatory agencies to provide accurate risk assessments in order to protect public health. The potency for a small subset of individual parent PAHs to produce cancer is fairly well understood, but the hazard posed by their numerous environmental derivatives remains unclear. Furthermore, humans always suffer exposure to PAHs in the form of complex mixtures rather than as individual parent PAHs. Persistent alkylated PAHs (a-PAHs) are the most abundant at Superfund sites, but the scientific community has collected little or no toxicity for most alkylated PAHs. In addition to cancer, developmental exposure to PAHs may carry high risk. Recent epidemiological data associate PAH exposures with birth defects, neurobehavioral deficits, and heart disease. During the past funding cycle, we determined that the toxicity of transformed PAHs can exceed that of the parent compounds. Risk assessors desperately need relevant in vivo data to develop comprehensive models for predictive toxicity. The Tanguay Project will link biological responses to PAH structures, uptake, and diagnostic gene expression pathways with their high-throughput zebrafish testing platform and thereby provide rapid feedback to SRP interested parties responsible for risk assessment and remediation. This approach, in one integrated experiment, interrogates all aspects of development and the molecular pathways that underlie it. Through cross-center interactions, we have developed an effective framework to convey this high-impact work to interested parties and to collaborate with populations to reduce their risk. Our overarching hypothesis is that we can learn to predict the toxicity of PAH mixtures based on the structural characteristics, bioactivity profiles, and pathway targets of their PAH components. We will test this hypothesis in four Specific Aims: 1) Determine how the developmental impacts of PAH exposure depend on the composition of PAH mixtures, the chemical structures of environmentally transformed PAHs, and the presence of AHR signaling. 2) Develop diagnostic gene expression pathways for classes of PAHs, determine how those pathways vary as a function of dose, and associate those pathways with specific adverse effects. 3) Discover the external stressors that impact the susceptibility to PAHs. 4) Determine the carcinogenicity of PAHs by conducting long- term zebrafish studies.