Grantee Research Project Results
2006 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, 2005 through July 31, 2006
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 , Human Health , Safer Chemicals
Objective:
Carbon nanotubes (CNTs) and related fibrous materials play a very special role in emerging nanotechnologies. The young nanotoxicology literature contains conflicting reports on the biological response to carbon nanotubes, and we hypothesize that some of the variability is due to real sample-to-sample differences in material properties. Most commercial nanotubes or nanofibers 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 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 especially metals content are carefully isolated by special synthesis techniques developed at Brown University.
Progress Summary:
During the second project year we completed a study of iron effects on the biological response to CNTs and initiated a parallel study of nickel effects. Almost all commercial nanotube samples contain significant quantities of residual catalyst, and iron and nickel are the two most common elements used in nanotube catalyst formulations. Iron is hypothesized to play a role in the toxicity of ambient particulate matter and some types of asbestos fibers acting as a redox catalyst that generates reactive oxygen species capable of damaging lipid membranes and DNA. Nickel, found in some types of respirable particles, is a known human carcinogen that binds to histone proteins and causes increased DNA condensation and gene silencing. Nickel cation, if it reaches the cell interior, can also deactivate hydroxylation pathways for the transcription factor HIF1alpha and lead to hypoxia signaling. The overall goal of this research thrust is to assess the importance of metals’ contributions to CNT toxicity and to identify the proper purification and processing procedures to minimize or eliminate this health risk.
For both metals, the known molecular toxicity mechanisms involve the soluble cation, and a key question therefore is whether the particulate metals embedded in CNTs are released as metal cations into physiological fluids at toxicologically relevant concentrations. During Year 2, we carried out the following activities to address this key issue:
- Measured the release of soluble iron from a large panel of commercial Fe-containing nanotube samples, both as-produced and “purified” by commercial vendors.
- Measured the effect of processing conditions on iron release including partial oxidation, mechanical grinding, sonication, and sample aging under atmospheric conditions, which leads to nanoscale iron oxidation.
- Characterized the redox activity of the released iron by an acellular assay that measures single strand breaks in plasmid DNA.
- Prepared a manuscript on the bioavailability and redox activity of CNT iron (currently under review for archival publication).
- Assembled a separate sample bank of Ni-containing single wall CNT samples and measured soluble Ni release as a function of pH, dissolved oxygen, and presence of solutes in cell culture media.
- Studied the effect of common post-processing steps on CNT nickel release including oxidation, bath and probe sonication, and acid washing.
- Studied the uptake of CNT-derived nickel into human lung epithelial cells and compared the uptake to nickel chloride as a reference soluble nickel form.
- Compiled a draft manuscript on nickel bioavailability for submission to an archival scientific journal in Project Year 3.
This work, when completed, will provide a basis for assessing the role of metals in CNT toxicity. It also should lead to practical guidelines for minimizing nanotube health risk through intelligent metals management during nanotube synthesis, processing, handling, and purification.
Future Activities:
As the project moves into its third and final year, we are extending the iron studies to a larger suite of Fe-containing nanomaterials, including several types of iron-based magnetic nanoparticles, using the bioavailability and DNA break assays we have validated during Years 1 and 2. A major effort will be devoted to further studies of nickel effects. We seek to understand the cellular transport pathways and the molecular toxicity mechanisms induced by nanotube-derived Ni in human lung epithelial cells. Having completed a comprehensive study of CNT-nickel bioavailability in 2006, we now have sufficient understanding of these complex C/Ni mixtures, and the techniques for biologically relevant materials characterization needed to properly investigate and understand the cellular response to Ni-containing nanotubes. We will attempt to determine the intracellular location of nickel following incubation with nanotubes using fluorescent nickel-binding probes, and will measure the expression of HIF1alpha responsible for hypoxia signaling as an important step in Ni-induced carcinogenesis. Finally, we will use the last project year to explore methods for detoxifying nanotubes through targeted removal of the bioavailable portion of the total metal, making use of our new understanding of metal location, form, and release behavior in physiological fluids.
Journal Articles on this Report : 1 Displayed | Download in RIS Format
| Other project views: | All 24 publications | 7 publications in selected types | All 7 journal articles |
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Hurt RH, Monthioux M, Kane A. Toxicology of carbon nanomaterials: status, trends, and perspectives on the special issue. Carbon 2006;44(6):1028-1033. |
R831719 (2006) R831719 (Final) |
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Supplemental 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,, Sustainable Industry/Business, RFA, Health, Scientific Discipline, Technology for Sustainable Environment, Health Risk Assessment, Risk Assessments, Sustainable Environment, Environmental Chemistry, Biochemistry, human exposure, nanotube toxicity, engineered nanomaterials, nanotechnology, nanofiber, exposure, nanofibers, asbestos like toxicity, human health risk, genotoxins, particle exposure, biochemical researchRelevant Websites:
http://www.engin.brown.edu/Facilities/LINC/ Exit
http://www.brown.edu/Administration/EHS/nanosafety/ 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.