The goal of this program is to systematically explore the influence of physicochemical properties of size,composition, surface lability as well as charge, density, and activity of engineered nanomaterials (ENMs).The goal of this project is to define the effect of these physical/chemical properties on how ENMs interactwith the intact organism, including specific target organs and specific cell types within the target organs. Wewill focus one ofthe major classes of ENMs, the high aspect ratio nanomaterials (HARNMs), including singlewall carbon nanotubes (SWNTs) and nanowires (NWs) of various lengths. The importance of size (diameterand length) and coatings (silica as one example) to affect toxicity, retention and translocation will beassessed. HARNM with differing physical/chemical property described above will be employed in a series ofsystematic examinations of absorption and distribution following inhalation/ingestion experiments. Primaryand secondary target organ responses will be monitored, and the influence of HARNM exposure In a modelof allergy will be assessed. The overall hypothesis Is that differences in composition, size, diameter andsurface coating of HARNMs will modulate the in vivo uptake, distribution and biologic effects of HARNMs in arat model. This hypothesis will be addressed in four specific aims that will determine the effect of HARNMon 1) deposition, retention and distribution to various organs; 2) respiratory system cytotoxicity, inflammationand airway remodeling; 3) oxidative stress in the respiratory system; and 4) exacerbation of ainwayhyperresposiveness in a sensitive model. We will address these aims using a transdisciplinary approachthat combines inhalation toxicology, chemistry, histopathology, high resolution imaging and novelmethodologies developed at UC Davis that uniquely position us to successfully address the biological effectsof these materials. The long term goal is to identify features of these materials that reduce their toxicity andbiological effects.
;To develop and evaluate techniques and approaches to assess the potential disease burden associated withexposures to ENMs. The goal of Project 2 is to define exposure effects of high aspect ratio nanomaterials(single walled carbon nanotubes and nanowires) in an in vivo inhalation model that includes airwayshyperresonsiveness.
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