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 interact with the intact organism, including specific target organs and specific cell types within the target organs. We will focus one ofthe major classes of ENMs, the high aspect ratio nanomaterials (HARNMs), including single wall carbon nanotubes (SWNTs) and nanowires (NWs) of various lengths. The importance of size (diameter and length) and coatings (silica as one example) to affect toxicity, retention and translocation will be assessed. HARNM with differing physical/chemical property described above will be employed in a series of systematic examinations of absorption and distribution following inhalation/ingestion experiments. Primary and secondary target organ responses will be monitored, and the influence of HARNM exposure In a model of allergy will be assessed. The overall hypothesis Is that differences in composition, size, diameter and surface coating of HARNMs will modulate the in vivo uptake, distribution and biologic effects of HARNMs in a rat model. This hypothesis will be addressed in four specific aims that will determine the effect of HARNM on 1) deposition, retention and distribution to various organs;2) respiratory system cytotoxicity, inflammation and airway remodeling;3) oxidative stress in the respiratory system;and 4) exacerbation of ainway hyperresposiveness in a sensitive model. We will address these aims using a transdisciplinary approach that combines inhalation toxicology, chemistry, histopathology, high resolution imaging and novel methodologies developed at UC Davis that uniquely position us to successfully address the biological effects of these materials. The long term goal is to identify features of these materials that reduce their toxicity and biological effects.

Public Health Relevance

; To develop and evaluate techniques and approaches to assess the potential disease burden associated with exposures 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 airways hyperresonsiveness.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01ES020127-05
Application #
8663596
Study Section
Special Emphasis Panel (ZES1-SET-V (03))
Program Officer
Nadadur, Srikanth
Project Start
2010-09-27
Project End
2015-04-30
Budget Start
2014-05-01
Budget End
2015-04-30
Support Year
5
Fiscal Year
2014
Total Cost
$483,061
Indirect Cost
$165,315
Name
University of California Davis
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Holland, Nathan A; Thompson, Leslie C; Vidanapathirana, Achini K et al. (2016) Impact of pulmonary exposure to gold core silver nanoparticles of different size and capping agents on cardiovascular injury. Part Fibre Toxicol 13:48
Patchin, Esther Shin; Anderson, Donald S; Silva, Rona M et al. (2016) Size-Dependent Deposition, Translocation, and Microglial Activation of Inhaled Silver Nanoparticles in the Rodent Nose and Brain. Environ Health Perspect 124:1870-1875
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Anderson, Donald S; Patchin, Esther S; Silva, Rona M et al. (2015) Influence of particle size on persistence and clearance of aerosolized silver nanoparticles in the rat lung. Toxicol Sci 144:366-81
Davidson, R Andrew; Anderson, Donald S; Van Winkle, Laura S et al. (2015) Evolution of silver nanoparticles in the rat lung investigated by X-ray absorption spectroscopy. J Phys Chem A 119:281-9
Liu, Ying X; Karsai, Arpad; Anderson, Donald S et al. (2015) Single-Cell Mechanics Provides an Effective Means To Probe in Vivo Interactions between Alveolar Macrophages and Silver Nanoparticles. J Phys Chem B 119:15118-29

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