Evaluation of PM2.5 Oxidative Potential (OP) as a proxy for the aerosol toxicity

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Small airborne dust particles smaller than 2.5 micrometers in size (known as PM2.5) are widely recognized as detrimental to human health. The mass concentrations of PM2.5 in outdoor air are highly regulated in developed nations. Exposure to high concentrations of PM2.5 can cause various health problems including decreased lung function, aggravated asthma, and premature death in people with heart or lung disease. To date, the mechanisms by which these particles induce toxicity in humans are not well understood. Recent work has focused on the ability of PM2.5 to damage cells through the production of oxidants. However, the correlation between the oxidative potential (OP) and toxicity of PM2.5 has not been explored. The goal of this project is to address this knowledge gap. To achieve this goal, the PI will measure the OP of a large number of samples of PM2.5 collected across many polluted sites around the world. Both statistical and mechanistic approaches will be utilized to unravel the role of PM2.5 OP in inducing cellular toxicity. The successful completion of this project will benefit society through the development of new fundamental knowledge to identify and target the most toxic sources of PM2.5. Further benefits to society will be achieved through student research training and public outreach. This will include the recruitment and mentoring of undergraduate students from under-represented groups along with the development of virtual labs and tutorial materials on PM2.5 toxicity for public dissemination during meetings of the GeoHealth section of the American Geophysical Union (AGU). Numerous epidemiological studies have shown strong linkages between PM2.5 concentrations and human diseases related to respiratory and cardiovascular systems. However, the spatiotemporal variability in the strengths of these associations suggests that bulk PM2.5 mass concentration is not the best surrogate of aerosol toxicity. Recent investigations have indicated that the capability of ambient PM2.5 to generate oxidants – known as oxidative potential (OP), might be a more relevant indicator of toxicity than PM2.5 mass concentration in outdoor air. However, the relationships between particle OP, cellular toxicity, and health endpoints have remained elusive. The goal of this project is to advance our fundamental understanding of the relationships between the OP of ambient PM2.5 and their cellular toxicity. To achieve this goal, the PI will compare the results of OP assays with observed cellular toxicity of a large number of PM2.5 samples collected from many countries across the world. The novel approach of exposing antioxidant-enriched cells to ambient PM2.5 samples will provide the most direct evidence for assessing the role of particle-driven oxidant generation in inducing cellular toxicity. Comparison of this approach to well-established chemical assays will allow the assessment of how induced toxicity is related to measured particle OP. Successful completion of this project has potential for transformative impact in air pollution management through the development of new knowledge and insight that will enable the use of particle OP as a proxy for aerosol toxicity.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.