Grantee Research Project Results
2005 Progress Report: Physical and Chemical Determinants of Nanofiber/Nanotube Toxicity
EPA Grant Number: R831719Title: Physical and Chemical Determinants of Nanofiber/Nanotube Toxicity
Investigators: Hurt, Robert H. , Kane, Agnes B.
Institution: Brown University
EPA Project Officer: Hahn, Intaek
Project Period: August 1, 2004 through July 31, 2007
Project Period Covered by this Report: August 1, 2004 through July 31, 2005
Project Amount: $335,000
RFA: Exploratory Research to Anticipate Future Environmental Issues: Impacts of Manufactured Nanomaterials on Human Health and the Environment (2003) RFA Text | Recipients Lists
Research Category: Nanotechnology , Safer Chemicals , Human Health
Objective:
Tubular and fibrous materials play a very special role in emerging nanotechnologies, but may show asbestos-like toxicity in humans upon inhalation. For asbestos fibers, it is known that both surface-reactive transition metals and fibrous geometry are major determinants of toxicity. Most commercial nanotubes/fibers are complex materials containing transition metal catalysts or residues and exhibiting complex distributions of length and diameter, as well as variability in defect density and surface functional groups. The objective of this research project is to carry out a carefully designed parametric study of the physical and chemical factors that underlie nanofiber/tube toxicity, in which the effects of shape, size, surface chemistry, and metal content are carefully isolated by special synthesis techniques developed at Brown University.
Progress Summary:
Year 1 of the project was devoted to the study of iron effects in carbon nanotube toxicity. Most commercial nanotubes samples contain significant quantities of residual metal catalyst, and iron is the single most common element used in nanotube catalyst formulations. Iron is hypothesized to play a role in asbestos toxicity as a redox catalyst that generates reactive oxygen species capable of damaging lipid membranes and DNA. A major question in carbon nanotube toxicology is whether the partially encapsulated iron residues show a similar bioactivity, i.e., whether free iron can be mobilized from the material surfaces under physiological conditions to initiate radical production through redox cycling in solution. To address this question the following tasks were carried out in Year 1:
- Synthesis of a fibrous carbon nanomaterial of ultra-high purity as a model for studying cell/fiber (tube) interactions in the absence of iron.
- Doping of well-defined, accessible zero-valent iron nanoparticles on the same carbon nanofiber surfaces using in situ reduction of iron nitrate.
- Acquisition and processing of a commercial multiwall carbon nanotube sample set including as-produced, purified, purified and oxidized, and purified and mechanically damaged samples. The last two samples simulate possible material damage and iron re-exposure during handling by nanomaterial users.
- Detailed materials characterization of the model nanofibers and commercial multiwall nanotube sample sets using scanning electron microscopy, high resolution transmission electron microscopy, electron diffraction, X-Ray diffraction, and Mossbauer spectroscopy. Multiple tests are particularly important to interpret the toxicity data as the iron in carbon nanotubes is complex, both in chemical form and in its mode of association with carbon.
- Development and application of four nanotoxicity assays: (1) quantitative Fe-mobilization under physiologically relevant conditions; (2) percentage of single-strand breaks in plasmid DNA; (3) viability of murine macrophages incubated with carbon nanotubes/fibers; and (4) morphology of murine macrophages by electron microscopy following interaction with carbon nanotubes/fibers.
During Year 1, these four assays were developed and applied to both the model and commercial nanomaterial set and used to evaluate cytoxicity of the various materials and to reveal the underlying mechanisms with emphasis on iron effects. This research is nearly complete and a draft publication is in preparation. The larger goal of this research project is to identify the proper purification and processing procedures to minimize or eliminate toxicity concerns in carbon nanotubes.
Future Activities:
As the project moves into its second year, the group is establishing reproducibility and confidence limits on the three main quantitative endpoints that were the focus of our Year 1 work: iron (Fe)-mobilization, plasmid DNA single-strand breaks, and viability (cell death) of murine macrophages. An archival publication on Fe effects in nanotube/nanofiber toxicity will be submitted as the reproducibility and accuracy of the endpoints has been firmly established.
Having developed and validated a set of molecular and cellular assays for iron effects, we plan to continue work in this area by applying the same assays to a larger suite of Fe-containing nanomaterials including single-wall carbon nanotubes, additional multi-wall tube samples, and several types of iron-based magnetic nanoparticles. We also have begun to examine the issues surrounding the potential toxicity of nickel residues, the second most common metal in nanotube growth catalysts. Principal Investigators Hurt and Kane also will serve as editors for a special edition of the journal Carbon. This special edition will focus on the toxicology of new carbon nanomaterials and it will be published in 2006.
Journal Articles:
No journal articles submitted with this report: View all 24 publications for this projectSupplemental Keywords:
health effects, human health, carcinogen, cellular, toxics, particulates, metals, oxidants, environmentally conscious manufacturing, nanotechnology, engineering, pathology, industry, health, sustainable industry/business, biochemistry, environmental chemistry, environmental engineering, health risk assessment, risk assessments, sustainable environment, technology for sustainable environment, asbestos like toxicity, biochemical research, carbon fullerene, engineered nanomaterials, exposure, genotoxins, human exposure, human health risk, nanofiber, nanofibers, nanotechnology, nanotube toxicity,, RFA, Health, Scientific Discipline, Sustainable Industry/Business, Sustainable Environment, Environmental Chemistry, Health Risk Assessment, Technology for Sustainable Environment, Risk Assessments, Biochemistry, nanofibers, nanotechnology, nanotube toxicity, carbon fullerene, exposure, particle exposure, human exposure, engineered nanomaterials, asbestos like toxicity, nanofiber, biochemical research, human health riskRelevant Websites:
http://www.engin.brown.edu/Facilities/LINC/ Exit
Progress 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.