Engineered nanomaterials are being used or are being proposed for use in a large number of commercial products. Because of their highly diverse physical and chemical characteristics, and their small size, concerns have been raised regarding their potential to cause harm to human health or the environment. One important class of ENMs are quantum dots (Qdots) which are luminexcent semiconductor nanocrystals composed of heavy metal cores (e.g. CdSe, CdTe, HgTe) with cap and coating structures that vary greatly, depending upon the characteristics required for various applications. Certain characteristics are known to be determinants for the interaction of nanoparticles with cells and tissues, including shape, size, hydrophobieity, and surface charge. Because of the highly variable nature of these and other engineered nanomaterials, it will be nonetheless difficult to predict their toxicity. Modern advances in genomics, epigenetics and bioinformatics, and the availability of multiple strains of inbred mice with well characterized polymorphisms and regulatory sequences have made it possible to map and predict toxicity pathways for many toxic substances including nanomaterials. The research proposed herein will utilize in vitro and in vivo models of airway exposure to aerosolized quantum dot nanoparticles to 1) define the physical and chemical characteristics that govern their absorption, distribution, metabolism, excretion and toxicity;2) using multiple inbred strains of mice, map toxicity pathways associated with these characteristics;and 3) incorporate the information that is obtained from these in vitro and in vivo models into a risk assessment paradigm that will be used to predict nanomaterial toxicity to humans. Such information will not only define which physical and chemical characteristics are important for the adverse biological effects of quantum dots, but will also simultaneously advance the fields of nanomaterial toxicology and functional epigenomics. These advances can then be used in safe design and manufacturing of nanomaterials so as to maximize their utility for many applications.

Public Health Relevance

Engineered nanomaterials may have certain characteristics that make them unsafe. The research proposed here will utilize modern genetic technologies to define the physical and chemical characteristics of engineered nanomaterials that impart adverse biological responses. This information will utimately be used to inform safer design and manufacturing of engineered nanomaterials.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19ES019545-05
Application #
8675247
Study Section
Special Emphasis Panel (ZES1-SET-V)
Project Start
Project End
Budget Start
2014-05-01
Budget End
2015-04-30
Support Year
5
Fiscal Year
2014
Total Cost
$340,055
Indirect Cost
$122,071
Name
University of Washington
Department
Type
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
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