PMID- 26069453 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240323 IS - 1388-0764 (Print) IS - 1572-896X (Electronic) IS - 1388-0764 (Linking) VI - 17 IP - 6 DP - 2015 TI - Comparative hazard analysis and toxicological modeling of diverse nanomaterials using the embryonic zebrafish (EZ) metric of toxicity. PG - 250 LID - 250 AB - The integration of rapid assays, large datasets, 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 in developing embryonic zebrafish, were established at realistic exposure levels and used to develop a hazard ranking of diverse nanomaterial toxicity. Hazard ranking and clustering analysis of 68 diverse nanomaterials revealed distinct patterns of toxicity related to both the core composition and outermost surface chemistry of nanomaterials. The resulting clusters guided the development of a surface chemistry-based model of gold nanoparticle toxicity. 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. Research should continue to focus on methodologies for determining nanomaterial hazard based on multiple sub-lethal responses following realistic, low-dose exposures, thus increasing the availability of quantitative measures of nanomaterial hazard to support the development of nanoparticle structure-activity relationships. FAU - Harper, Bryan AU - Harper B AD - Oregon State University, 1007 ALS Building, Corvallis, OR 97331 USA. FAU - Thomas, Dennis AU - Thomas D AD - Pacific Northwest National Laboratory, Richland, WA USA. FAU - Chikkagoudar, Satish AU - Chikkagoudar S AD - Pacific Northwest National Laboratory, Richland, WA USA. FAU - Baker, Nathan AU - Baker N AD - Pacific Northwest National Laboratory, Richland, WA USA. FAU - Tang, Kaizhi AU - Tang K AD - Intelligent Automation, Inc., Rockville, MD USA. FAU - Heredia-Langner, Alejandro AU - Heredia-Langner A AD - Pacific Northwest National Laboratory, Richland, WA USA. FAU - Lins, Roberto AU - Lins R AD - CPqAM, Oswaldo Cruz Foundation, FIOCRUZ-PE, Recife, PE 50.740-465 Brazil. FAU - Harper, Stacey AU - Harper S AD - Oregon State University, 1007 ALS Building, Corvallis, OR 97331 USA. LA - eng GR - P30 ES000210/ES/NIEHS NIH HHS/United States GR - R01 ES016896/ES/NIEHS NIH HHS/United States GR - R01 ES017552/ES/NIEHS NIH HHS/United States GR - U01 NS073457/NS/NINDS NIH HHS/United States PT - Journal Article DEP - 20150604 PL - Netherlands TA - J Nanopart Res JT - Journal of nanoparticle research : an interdisciplinary forum for nanoscale science and technology JID - 101088075 PMC - PMC4454819 OTO - NOTNLM OT - Informatics OT - Nanoparticle OT - Surface chemistry OT - Toxicity OT - Zebrafish EDAT- 2015/06/13 06:00 MHDA- 2015/06/13 06:01 PMCR- 2015/06/04 CRDT- 2015/06/13 06:00 PHST- 2014/05/30 00:00 [received] PHST- 2015/05/26 00:00 [accepted] PHST- 2015/06/13 06:00 [entrez] PHST- 2015/06/13 06:00 [pubmed] PHST- 2015/06/13 06:01 [medline] PHST- 2015/06/04 00:00 [pmc-release] AID - 3051 [pii] AID - 10.1007/s11051-015-3051-0 [doi] PST - ppublish SO - J Nanopart Res. 2015;17(6):250. doi: 10.1007/s11051-015-3051-0. Epub 2015 Jun 4.