Role of Particle Agglomeration in Nanoparticle ToxicityEPA Grant Number: R832528
Title: Role of Particle Agglomeration in Nanoparticle Toxicity
Investigators: Gordon, Terry , Chen, Lung Chi , Cohen, Beverly S.
Institution: New York University: Nelson Institute of Environmental Medicine -Tuxedo
EPA Project Officer: Hahn, Intaek
Project Period: October 1, 2005 through September 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: Nanotechnology , Health , Safer Chemicals , Health Effects
The objective of this study is to determine the biological consequences of nanoparticle agglomeration. We hypothesize that there will be a difference in the toxicity of fresh (predominantly singlet) vs. aged (predominantly agglomerated) carbon nanoparticles, and in testing this hypothesis we will: 1) measure the agglomeration rate of several types of carbon nanoparticles; 2) identify whether agglomeration is affected by differing exposure conditions including humidity and particle charge; and 3) compare the toxicity of singlet vs. agglomerated particles in mice exposed via the inhalation route. A number of investigators have clearly demonstrated in instillation studies that nanoparticle toxicity is governed, in part, by particle size. Our preliminary studies have demonstrated that freshly formed nanoparticles produce lung injury and inflammation in mice and the extent of adverse effects is influenced by genetic host factors. We will expand upon these findings and identify whether realistic exposure conditions which lead to carbon nanoparticle agglomeration alter the pulmonary response in mice. Particle agglomeration of nanoparticles is known to be influenced by number concentration and other physical factors. Almost all particle agglomeration data has been derived, however, under static conditions whereas occupational exposure to nanoparticles occurs under dynamic conditions. It is critical, therefore, that the influence of agglomeration on nanoparticle toxicity be examined under dynamic conditions.
To test the hypothesis that there is a difference in the toxicity of fresh (predominantly >singlet=) vs. aged (predominantly agglomerated) nanoparticles, we will first establish the agglomeration of freshly generated carbon nanoparticles at various distances (i.e., aging times) downstream from particle generation in a dynamic exposure system. After careful initial characterization of >singlet= and agglomerated particles, inbred mice will be exposed to nanoparticles (generated in an arc furnace) at various stages of particle agglomeration and the lungs will be examined for injury and inflammation. To insure that pulmonary differences in response are due to particle agglomeration, groups of mice will be exposed to >singlet= or agglomerated particles at the same time using the same operating conditions and control of humidity, and particle charge. To determine whether initial findings for a single type of particle composition are applicable to other nanoparticles, we will also generate particles with different amounts of metal content as is found in carbon nanoparticles generated with metal catalysts.
As determined in preliminary studies, we expect that nanoparticle toxicity will be influenced by a variety of exposure conditions including particle size, number, agglomeration state, charge, and composition. By careful characterization of particle agglomeration in a dynamic system, our inhalation toxicity data should provide key information regarding the toxicity of emerging nanoparticle technologies. The data obtained in the proposed animal studies can readily be used for extrapolation to occupational and ambient settings. In summary, the results from this proposal address a number of the research needs identified in this solicitation, including toxicity and exposure assessment.