Structure-function Relationships in Engineered Nanomaterial ToxicityEPA Grant Number: R832536
Title: Structure-function Relationships in Engineered Nanomaterial Toxicity
Investigators: Colvin, Vicki L.
Institution: Rice University
EPA Project Officer: Karn, Barbara
Project Period: December 1, 2005 through November 30, 2008
Project Amount: $375,000
RFA: Exploratory Research: Nanotechnology Research Grants Investigating Environmental and Human Health Effects of Manufactured Nanomaterials: A Joint Research Solicitation - EPA, NSF, NIOSH (2005) RFA Text | Recipients Lists
Research Category: Health , Safer Chemicals , Health Effects , Nanotechnology
As nanotechnology develops into a mature industry the environmental and health effects of its core materials are of increasing importance. A significant challenge for this area of research is that for every class of engineered nanoparticle (nanotubes, metal nanocrystals) there are literally thousands of possible samples with various sizes, surfaces and shapes. This huge parameter space cannot be narrowed by focusing only on commercial materials, as few systems are in commerce at this point. Indeed, most nanotechnology companies are optimizing and evaluating hundreds of material prototypes for possible commercial use. In such a climate, all stakeholders benefit from an understanding of how fundamental nanoparticle characteristics (e.g. surface chemistry, size, shape) control their biological effects.
This aim is the overarching objective of this proposal, which stated another way, will provide the first structure-function relationships for nanoparticle toxicology. This information benefits industry in that it will suggest material modifications that may produce systems with minimal environmental and health impact. It also benefits regulators by not only indicating whether information on one nanoparticle type can be used to predict the properties of a related material, but also by setting a framework for evaluating newly developed nanoparticle variants. Finally, a correlation between biological effects and nanoparticle structure will enable the development of chemical methods to alter more toxic nanomaterial species into less toxic materials upon disposal.
To realize these structure-function relationships requires that we develop new analytical tools as well as evaluate material datasets with systematic changes in fundamental properties. Our specific objectives are 1) to expand the characterization of nanoparticle structure in biological media and 2) to characterize the effects of nanoparticles on cell function. This data will be used to test the hypothesis that nanoparticle structure (e.g. size and shape) controls directly cytotoxicity. A secondary hypothesis is that of the four major materials parameters in engineered nanoparticles (size, shape, composition and surface) surface will be the most important in governing cellular effects. These hypotheses will be tested in several major classes of nanoparticles.
This work exploits recent advances in nanochemistry which allow for the production of highly size and surface controlled nanoparticles from a variety of materials. These model systems provide the systematic variations in nanoparticle ‘structure’ required for structure-function relationships. Our model systems will include engineered carbon nanoparticles, both C60 and single-walled carbon nanotubes; up to eight distinct sizes of nanoscale iron oxides; and a wide variety of nanoscale titania with varying surface coatings. All of these materials have been reported to generate oxygen radicals under some circumstances; thus we expect to correlate our ‘structures’ with the acute cellular toxicity in three human cell lines. This overarching objective is strongly supported by ongoing efforts to expand the characterization of nanoparticle structure directly in biological media (objective #1). Additionally, structure-function trends are made much more general if they can be rationalized by some basic mechanism. Thus, objective #2 aims to both characterize nanoparticle-cell interactions as well as put forward a mechanism to explain any observed acute toxicity.
The introduction of a new class of materials into consumer products will require information about the potential behavior and risks these systems pose to the environment and people. Risk management will be improved with the information provided in this grant particularly in that we will establish structure-function relationships for several major classes of nanomaterials.