Grantee Research Project Results
Final Report: Chemical Fate, Biopersistance, and Toxicology of Inhaled Carbonaceous Nanoscale Materials
EPA Grant Number: R832527Title: Chemical Fate, Biopersistance, and Toxicology of Inhaled Carbonaceous Nanoscale Materials
Investigators: McDonald, Jacob D. , Seagrave, Jean Clare , VanderWal, Randall L. , Gigliotti, Andrew
Institution: Lovelace Biomedical & Environmental Research Institute , NASA-Glenn
EPA Project Officer: Hahn, Intaek
Project Period: December 1, 2005 through November 30, 2008
Project Amount: $350,000
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:
Our work is focused on aerosol delivery of nanomaterials to enable an assessment of their potential hazard if encountered in the environment or workplace. The primary focus is on carbonaceous materials used in the nanotechnology industry, specifically C60 fullerenes and carbon nanotubes. The objective was to develop inhalation atmospheres to deliver these materials to rodents for assessment of inhalation toxicity and biological fate.
The hypotheses of the program were that: 1) The toxicity of inhaled carbon nanotubes and fullerenes, due to their relative non-reactive surface chemistry, is low relative to crystalline silica when administered by inhalation; 2) The preferential carbon nanotube toxicity observed (in prior studies) by instillation is an artifact of dose and dose administration technique; 3) fullerenes and carbon nanotubes are not completely eliminated from the nasal or lung regions after inhalation exposure.
Fullerene exposures to rodents are conducted with C60 nanofullerene aerosols generated by a sublimation/condensation approach. Animals are exposed by nose-only inhalation to as much as 1 mg/m3 particle mass, which provides aerosol size at approximately 20 nm. Rodents are evaluated for toxicity by inflammatory indicators in the lung and tissue distribution/elimination is assessed with a developed LC/MS/MS method.
Carbon nanotube exposures are conducted primarily with multi-walled carbon nanotube aerosols that are generated with a jet mill. Animals are exposed by whole-body inhalation to as much as 5 mg/m3 particle mass, which provides aerosol size at approximately 100-300 nm by number and 0.7-1.8 microns by mass. Composition is assessed by a number of techniques to evaluate morphology, purity, surface area, surface chemistry. Inhalation toxicity includes pulmonary inflammation/pathology and systemic immune function.
Summary/Accomplishments (Outputs/Outcomes):
In the past year we have shown initial carbon disposition after fullerene inhalation reveals limited systemic adsorption and clearance from the lung is slow. However, the presence of the fullerene in the lungs does not illicit any overt toxicity. We have shown that inhalation delivery of multi-walled carbon nanotubes shows less pulmonary pathology than has been reported by instillation. We are currently conducting follow-on research to further evaluate these findings in relationship to the type of tube utilized, the species used (mouse versus rat), and the time to progression of pulmonary pathology. We have observed suppression of immune function measured in splenocytes of animals exposed to nanotubes. Current work is focused on evaluating the mechanism of this response, which appears to be mediated throuth signaling in the lung that may traverse through the COX-2 pathway.
Journal Articles on this Report : 1 Displayed | Download in RIS Format
| Other project views: | All 2 publications | 1 publications in selected types | All 1 journal articles |
|---|
| Type | Citation | ||
|---|---|---|---|
|
|
Mitchell LA, Gao J, Vander Wal R, Gigliotti A, Burchiel SW, McDonald JD. Pulmonary and systemic immune response to inhaled multiwalled carbon nanotubes. Toxicological Sciences 2007;100(1):203-214. |
R832527 (Final) |
Exit Exit |
Supplemental Keywords:
nanoparticles, inhalation, pulmonary toxicity, biological disposition, particle size, particle surface area, health effects, , ENVIRONMENTAL MANAGEMENT, Scientific Discipline, Health, Risk Assessment, Risk Assessments, Health Risk Assessment, Biochemistry, exposure assessment, biochemical research, fate and transport, inhalation toxicology, bioaccumulation, human health risk, metal oxide nanoscale materials, toxicology
, Health, Scientific Discipline, ENVIRONMENTAL MANAGEMENT, Health Risk Assessment, Risk Assessments, Biology, Biochemistry, Risk Assessment, animal model, bioaccumulation, fate and transport, inhalation toxicology, toxicology, metal oxide nanoscale materials, human health risk, biochemical research
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.