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Grantee Research Project Results

2008 Progress Report: A Rapid In Vivo System for Determining Toxicity of Manufactured Nanomaterials

EPA Grant Number: R833320
Title: A Rapid In Vivo System for Determining Toxicity of Manufactured Nanomaterials
Investigators: Tanguay, Robyn L.
Current Investigators: Tanguay, Robyn L. , Harper, Stacey
Institution: Oregon State University
EPA Project Officer: Hahn, Intaek
Project Period: September 1, 2006 through August 30, 2009
Project Period Covered by this Report: October 1, 2007 through September 30,2008
Project Amount: $400,000
RFA: Exploratory Research: Nanotechnology Research Grants Investigating Environmental and Human Health Effects of Manufactured Nanomaterials: a Joint Research Solicitation-EPA, NSF, NIOSH, NIEHS (2006) RFA Text |  Recipients Lists
Research Category: Nanotechnology , Safer Chemicals

Objective:

Rapid growth of the nanotechnology industry is resulting in increased exposure of humans and the environment to nanomaterials prior to the scientific investigation of potential risks. It is clear that there is a need to develop rapid, relevant, and efficient testing strategies to assess these emerging materials of concern. It is expected that the biological activity of nanomaterials will depend on inherent physicochemical properties not routinely considered in toxicity studies (e.g., particle size and size distribution, agglomeration status, interactions with environmental and biological moieties). A classical toxicokinetic approach would use well-defined, labeled nanomaterials to define each of the above parameters prior to toxicity evaluations. Although this approach is solid, it is perhaps not the most efficient way to assess toxicity of the ever-growing number of novel nanomaterials.

Here we used an alternative approach that utilizes a dynamic whole animal assay to reveal whether a nanomaterial is potentially toxic. It is anticipated that the response will be dependent on toxicokinetic properties, so we propose that those parameters be determined following a “hit” in our in vivo assay. A toxic “hit” in our assay would warrant further testing in other models.

Our hypothesis is that inherent properties of some engineered nanomaterials make them toxic. To test this hypothesis, we specifically proposed to: 1) further develop our zebrafish toxicity assay to define in vivo responses to nanomaterials, 2) define structural properties of nanomaterials that lead to adverse biological consequences, and 3) develop a knowledgebase of Nanomaterial-Biological Interactions to integrate nanotoxicity data.

Progress Summary:

We have now established the embryonic zebrafish model as an ideal biological platform in which to rapidly interrogate the biological activity and toxic potential of nanomaterials. We have made significant progress toward screening nanomaterials and identifying their relative toxic potential using the embryonic zebrafish model.  We have also established the foundational informatics framework for determining dose- or concentration-responses to nanomaterials.  The Nanomaterial-Biological Interactions knowledgebase system is operational and will soon be upgraded to include functional links to other databases on Nanomaterial EHS.

Future Activities:

  • Continue to perform screening-level toxicological evaluations of novel nanomaterials with a focus on discrete libraries of material that are precisely engineered and of high purity.
  • Expand our biological effects evaluations of cellular and molecular level responses.
  • Determine how inherent physicochemical properties of nanomaterial affect uptake and nanoparticle-biological interactions using the NBI knowledgebase.
  • Determine the effects of exposure scenario on biological responses (adverse or beneficial) to nanomaterials.
  • Consolidate the Analytical Hierarchical Process conducted by experts in the field to establish a consensus on the EZ-Metric within the scientific community.
  • Extend metrics to include data derived from additional experimental platforms in order to define a comprehensive metric of nanomaterial-biological interactions CMNBI.
  • Improve web design and establish organizational structure, i.e., features and utilities


Journal Articles on this Report : 5 Displayed | Download in RIS Format

Publications Views
Other project views: All 41 publications 12 publications in selected types All 12 journal articles
Publications
Type Citation Project Document Sources
Journal Article Harper SL, Dahl JA, Maddux BLS, Tanguay RL, Hutchison JE. Proactively designing nanomaterials to enhance performance and minimise hazard. International Journal of Nanotechnology 2008;5(1):124-142. R833320 (2008)
R833320 (Final)
  • Abstract: Inderscience-Abstract
    Exit
  • Journal Article Isaacson CW, Usenko CY, Tanguay RL, Field JA. Quantification of fullerenes by LC/ESI-MS and its application to in vivo toxicity assays. Analytical Chemistry 2007;79(23):9091-9097. R833320 (2008)
    R833320 (Final)
  • Abstract from PubMed
  • Full-text: Tanguay Lab-Full Text PDF
    Exit
  • Abstract: ACS-Abstract
    Exit
  • Other: ACS-Full Text PDF
    Exit
  • Journal Article Truong L, Harper SL, Tanguay RL. Evaluation of embryotoxicity using the zebrafish model. Methods in Molecular Biology 2011;691(Part 6):271-279. R833320 (2008)
    R833320 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Abstract: Springer-Abstract
    Exit
  • Journal Article Usenko CY, Harper SL, Tanguay RL. In vivo evaluation of carbon fullerene toxicity using embryonic zebrafish. Carbon 2007;45(9):1891-1898. R833320 (2008)
    R833320 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Abstract: Science Direct-Abstract
    Exit
  • Journal Article Usenko CY, Harper SL, Tanguay RL. Fullerene C60 exposure elicits an oxidative stress response in embryonic zebrafish. Toxicology and Applied Pharmacology 2008;229(1):44-55. R833320 (2008)
    R833320 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: ScienceDirect-Full Text HTML
    Exit
  • Abstract: ScienceDirect-Abstract
    Exit
  • Other: ScienceDirect-Full Text PDF
    Exit
  • Supplemental Keywords:

    dose-response, teratogen, animal, stressor, toxics, particulates, nanotechnology, nanotoxicology, environmental chemistry, Northwest, Oregon, OR, industry,, Health, Scientific Discipline, PHYSICAL ASPECTS, Health Risk Assessment, Physical Processes, Risk Assessments, Biochemistry, nanomaterials, toxicity assay, exposure, nanoparticle toxicity, nanotechnology

    Relevant Websites:

    Stacey Harper http://www.onami.us/NanoNet/researchers.php?id=26 Exit
    Nanomaterial-Biological Interactions knowledgebase http://oregonstate.edu/nbi/ Exit

    Progress and Final Reports:

    Original Abstract
  • 2007
  • Final Report
  • Top of Page

    The 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.

    Project Research Results

    • Final Report
    • 2007
    • Original Abstract
    41 publications for this project
    12 journal articles for this project

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