Predictive Dosimetry and Metabolism Core

Oregon State University, Corvallis OR

Investigators

Linked publications, trials & patents

Abstract

SUMMARY – PREDICTIVE DOSIMETRY AND METABOLISM CORE The mission of the OSU Superfund Research Center is to identify polycyclic aromatic hydrocarbons (PAHs) in the environment, to characterize their toxicity, to specify concentrations of PAHs found in the environmental that pose no threat to human health, and to identify safe, sustainable techniques for remediating PAH- contaminated sites. Modern methods to assess chemical hazards and risks to human health require a robust understanding of chemical dosimetry to translate laboratory-based measurements to real-world exposures. The Predictive Dosimetry and Metabolism Core (PDMC) will provide OSU Superfund Research Center investigators with tools and predictions of PAH dosimetry, enabling them to compare results across model systems and to translate experimental observations to real-world human exposures. The PDMC will develop and apply novel tools to assess risks to human health presented by PAHs found at Superfund Sites. The PDMC will rely on in silico tools, many unique to PNNL, to predict PAH metabolites, chemical properties, mutagenicity, aryl hydrocarbon receptor (AhR) binding, and synergistic toxicity of PAH mixtures. The PDMC will measure rates of PAH metabolism and identify PAH metabolites via a reference-free approach with liquid chromatography ion mobility mass spectrometry (LC-IMS-MS/MS). The PDMC will develop computational models to predict PAH dosimetry in zebrafish and in human lung cell culture systems and to extend the predictions to human populations via physiologically based pharmacokinetic (PBPK) modeling. Tools and predictions provided by the PDMC will enable the research of the OSU Superfund Research Center to maximize its impact on the risk assessment of Superfund Sites.