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
Anderson, Donald S; Silva, Rona M; Lee, Danielle et al. (2015) Persistence of silver nanoparticles in the rat lung: Influence of dose, size, and chemical composition. Nanotoxicology 9:591-602
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
Hopkins, Laurie E; Patchin, Esther S; Chiu, Po-Lin et al. (2014) Nose-to-brain transport of aerosolised quantum dots following acute exposure. Nanotoxicology 8:885-93
Silva, Rona M; Xu, Jingyi; Saiki, Clare et al. (2014) Short versus long silver nanowires: a comparison of in vivo pulmonary effects post instillation. Part Fibre Toxicol 11:52
Silva, Rona M; Doudrick, Kyle; Franzi, Lisa M et al. (2014) Instillation versus inhalation of multiwalled carbon nanotubes: exposure-related health effects, clearance, and the role of particle characteristics. ACS Nano 8:8911-31
Wang, Xiang; Ji, Zhaoxia; Chang, Chong Hyun et al. (2014) Use of coated silver nanoparticles to understand the relationship of particle dissolution and bioavailability to cell and lung toxicological potential. Small 10:385-98
Silva, Rona M; Teesy, Christel; Franzi, Lisa et al. (2013) Biological response to nano-scale titanium dioxide (TiO2): role of particle dose, shape, and retention. J Toxicol Environ Health A 76:953-72