Development of a Screening Tool for Nanotoxicology

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Proposal Title: Development of a Screening Tool for NanotoxicologyPrincipal Investigator: Valerie Leppert Institution: University of California - MercedProposal No: CBET- 0854574 This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).A model is proposed for the respiratory toxicity of ambient and engineered nanophases based on production of reactive oxygen species (ROS) from the reaction of surface transition metal impurities with components of the lung extracellular lining fluid (ELF), and subsequent lipid peroxidation and production of inflammatory mediators. The proposed research will seek to verify the model and investigate the role of particle characteristics and dose. Specific objectives include determination of the effect of particle size, shape, surface transition metals, and dose on respiratory toxicity and/or the alveolar macrophase respiratory burst; and determination of whether hydrogen peroxide production and/or lipid peroxidation products are involved in the mechanism through which trace metals at sub-lethal concentrations are involved in the production of inflammatory and fibrogenic mediators. Complete characterization of the nanophases investigated is essential in order to understand the mechanisms at work in respiratory toxicity, and this will be accomplished by ICP-MS, and scanning and transmission electron microscopy in concert with high spatial-resolution electron energy-loss and energy-dispersive X-ray spectroscopy. Following confirmation of the model, an in vitro screening assay for macrophage inflammatory mediator production that could be used to predict lung inflammation caused by naturally occurring and engineering particles will be investigated. Phases that will be investigated include ambient silica, synthetic silica, titanium dioxide, and SWCNTs. The proposed activities will contribute to several educational and outreach objectives. Research results from the proposed work will be presented in nanotechnology and air pollution lectures given by the PI and co-PI in UC Merced?s General Education Core Courses (these course are required for all UC Merced students). A student Engineering Service Learning team that the PI mentors will also incorporate results from the research into nanotechnology exhibits that the team designs for the Castle Science and Technology Center. CSTC is a local science discovery museum that most middle school students in Merced and surrounding counties visit (the population of the area is ~50% Hispanic). New capabilities in hard-soft electron microscopy at UC Merced?s Imaging and Microscopy Facility will be utilized for the proposed work, and new microscopy techniques developed in the course of the proposed work will be disseminated in the electron microscopy courses that the PI teaches. In addition, the PI and co-PI will incorporate undergraduate students in the proposed research through the NSF NSEC Center Of Integrated Nanomechanical Systems program that UCM participates in. UC Merced, a Hispanic Service Institution, is the 10th and newest campus of the University of California, with a ~50% minority student population. The PIs are committed to the engagement of underrepresented and nontraditional students in science and engineering research and education