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Title: Comparative hazard analysis and toxicological modeling of diverse nanomaterials using the embryonic zebrafish (EZ) metric of toxicity

The integration of rapid assays, large data sets, informatics and modeling can overcome current barriers in understanding nanomaterial structure-toxicity relationships by providing a weight-of-the-evidence mechanism to generate hazard rankings for nanomaterials. Here we present the use of a rapid, low-cost assay to perform screening-level toxicity evaluations of nanomaterials in vivo. Calculated EZ Metric scores, a combined measure of morbidity and mortality, were established at realistic exposure levels and used to develop a predictive model of nanomaterial toxicity. Hazard ranking and clustering analysis of 68 diverse nanomaterials revealed distinct patterns of toxicity related to both core composition and outermost surface chemistry of nanomaterials. The resulting clusters guided the development of a predictive model of gold nanoparticle toxicity to embryonic zebrafish. In addition, our findings suggest that risk assessments based on the size and core composition of nanomaterials alone may be wholly inappropriate, especially when considering complex engineered nanomaterials. These findings reveal the need to expeditiously increase the availability of quantitative measures of nanomaterial hazard and broaden the sharing of that data and knowledge to support predictive modeling. In addition, research should continue to focus on methodologies for developing predictive models of nanomaterial hazard based on sub-lethal responses to low dose exposures.
 [1] ;  [2] ;  [2] ;  [2] ;  [3] ;  [2] ;  [4] ;  [1]
  1. Oregon State Univ., Corvallis, OR (United States)
  2. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
  3. Intelligent Automation, Inc., Rockville, MD (United States)
  4. Oswaldo Cruz Foundation, Recife (Brazil)
Publication Date:
OSTI Identifier:
Report Number(s):
Journal ID: ISSN 1388-0764; TRN: US1500797
Grant/Contract Number:
Accepted Manuscript
Journal Name:
Journal of Nanoparticle Research
Additional Journal Information:
Journal Volume: 17; Journal Issue: 6; Journal ID: ISSN 1388-0764
Tsinghua University Press
Research Org:
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
Sponsoring Org:
Country of Publication:
United States
77 NANOSCIENCE AND NANOTECHNOLOGY nanoparticle; zebrafish; toxicity; surface chemistry; nanotechnology; toxicology; informatics