? TILTON PROJECT One of the most difficult challenges for environmental health is to evaluate hazards from exposure to chemical mixtures. The environmental health science community recognizes a growing need to evaluate toxicity for structurally diverse PAHs and their transformation and breakdown products in complex mixtures, using human-relevant and metabolically competent research models. This Biomedical Science Research Project will assess the toxicity of PAHs in complex mixtures associated with Superfund sites in a 3D human lung model composed of primary human bronchial epithelial cells (HBEC) differentiated at the air-liquid interface. We will quantify the toxicity of PAHs and PAH mixtures targeting lungs via endpoints relevant for multiple exposure routes (inhalation, diet, dermal). We will rely on benchmark dose modeling to identify a threshold response for comparison. We will apply integrated RNAseq and functional proteomics to identify mechanisms by which PAHs exert adverse health outcomes in exposed populations and to identify susceptible individuals in those populations. The overall goal of this project is to understand how individual PAHs contribute to toxicity in mixtures and to establish a relationship between chemical exposure and toxicity. We will apply the outcomes of these studies to assess and communicate human health risk and to evaluate susceptibility for relevant populations. We propose to achieve these aims: 1) quantify the toxicity of PAHs and PAH mixtures in the 3D lung model, 2) assess the role of metabolism on the toxicity of individual PAHs in the 3D human lung model and 3) elucidate the mechanisms of PAH toxicity in the 3D human lung model.

Public Health Relevance

? TILTON PROJECT Critical data gaps exist in understanding toxicity for the broader class of structurally diverse, substituted PAHs along with knowledge of how PAHs contribute to toxicity of mixtures. Our proposal overcomes these critical insufficiencies and addresses stakeholder needs to improve PAH risk assessments. The outcomes of these studies will be used to assess and communicate human health risk and evaluate susceptibility for relevant populations.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
2P42ES016465-11
Application #
9841200
Study Section
Special Emphasis Panel (ZES1)
Project Start
Project End
2025-01-31
Budget Start
2019-12-01
Budget End
2020-11-30
Support Year
11
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Oregon State University
Department
Type
DUNS #
053599908
City
Corvallis
State
OR
Country
United States
Zip Code
97331
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