Grantee Research Project Results
2007 Progress Report: Role of Particle Agglomeration in Nanoparticle Toxicity
EPA Grant Number: R832528Title: Role of Particle Agglomeration in Nanoparticle Toxicity
Investigators: Gordon, Terry , Chen, Lung Chi , Cohen, Beverly S.
Institution: New York University Medical Center Allied Hlth Ed
EPA Project Officer: Hahn, Intaek
Project Period: October 1, 2005 through September 30, 2008
Project Period Covered by this Report: October 1, 2006 through September 30,2007
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 , Safer Chemicals
Objective:
The objective of this study was to determine whether agglomeration of nanoparticles affected their physicochemcial characteristics and therefore their toxicity. We hypothesized that that there would be a difference in the toxicity of freshly generated vs. aged nanoparticles. In testing this hypothesis, we: 1) measured the agglomeration rate of several types of nanoparticles; 2) identified whether agglomeration and associated toxicity was affected by differing exposure conditions including temperature, humidity, and particle charge; and 3) compared the toxicity of singlet vs. agglomerated particles in mice exposed via the inhalation route.
Progress Summary:
Aim I: To measure the agglomeration rate of carbon nanoparticles under dynamic exposure conditions. Carbon and metal nanoparticles will be generated with an arc furnace and the agglomeration rate will be established for each particle type.
Aim I was completed. Carbon nanoparticles freshly generated by the arc method were approximately 10 to 15 nm in count median diameter (CMD) whereas aging of these particles resulted in a count median diameter that varied between 150 to 250 nm in different experiments. Nanoparticles which were freshly generated from pure zinc or copper electrodes had a CMD similar to carbon nanoparticles.
Aim II. To identify the extent to which agglomeration is affected by altering physical exposure conditions such as humidity and particle charge.
To examine the effect of particle charge on nanoparticle toxicity, carbon nanoparticles were generated at 5 mg/m3 and mice were exposed to the non-modified nanoparticles or nanoparticles which were passed through a Americium particle neutralizer. The particle neutralizer had no effect on particle toxicity as seen by equal inflammation which was observed in mice exposed to the non-modified and the neutralized nanoparticles (Figure 1). To examine whether relative humidity affected either particle agglomeration or toxicity, additional groups of animals were exposed to fresh carbon nanoparticles that were delivered to the nose-only exposure chamber under conditions of either 15% or 85% relative humidity. Neither particle size nor toxicity was different between these 2 extremes of exposure chamber humidity (Figure 2).
Aim III. To compare the toxicity of ‘singlet’ vs. agglomerated particles in mice exposed via the inhalation route. Acute lung injury and inflammation will be studied in mice exposed to fresh (predominantly ‘singlet’) or aged (predominantly agglomerated) carbon nanoparticles. Conditions studied in Aims I and II will be varied to examine the influence of particle composition, humidity, and charge on carbon nanoparticle agglomeration and toxicity.
Aims I and II demonstrated that neither charge nor relative humidity extremes affected the toxicity of freshly generated carbon nanoparticles. Therefore, the studies proposed in Aim III were conducted using the particle charge state which naturally occurred in particles generated by the arc method and a relative humidity of 30-50%.
Inbred BALB/c mice were exposed to fresh and aged carbon nanoparticles generated by the arc method. Freshly generated carbon nanoparticles (11-60 nm CMD range) produced a significantly greater increase in neutrophils in lavage fluid compared to carbon nanoparticles aged approximately 3 minutes (190-250 nm) (see 2.5 and 5 mg/m3 data in Figure 3). There was little difference, however, in total protein concentrations in the lavage fluid of mice exposed to fresh vs. aged carbon nanoparticles (Figure 4). Thus, freshly generated carbon nanoparticles were present predominantly as singlets and produced greater inflammation (increased neutrophils (PMNs)) but not lung injury (total protein concentration).
Key Personnel: There were no changes in key personnel.
Journal Articles:
No journal articles submitted with this report: View all 4 publications for this projectSupplemental Keywords:
nanoparticles, particle charge, age, mice, genetic susceptibility, Health, Scientific Discipline, ENVIRONMENTAL MANAGEMENT, Health Risk Assessment, Risk Assessments, Biochemistry, Risk Assessment, lung injury, nanochemistry, animal model, bioavailability, carbon fullerene, nanotechnology, nanomaterials, animal bioassays, nanoparticle toxicity, analysis of chemical exposureProgress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.