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ALTEX. 2016;33(4):435-452. doi: 10.14573/altex.1601281. Epub 2016 Jun 21.

Advancing toxicology research using in vivo high throughput toxicology with small fish models.

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Department of Biological Sciences, North Carolina State University, Raleigh, NC, USA.
Center for Human Health and the Environment, North Carolina State University, Raleigh, NC, USA.
Integrated Laboratory Systems, Inc., Research Triangle Park, NC, USA.
National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
Nicholas School of the Environment, Duke University, Durham, NC, USA.
National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, USA.
Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC, USA.
Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, TX, USA.
National Human Genome Research Institute, Bethesda, MD, USA.
Department of Molecular & Biomedical Sciences, University of Maine, Orono, ME, USA.
Graduate School of Biomedical Science and Engineering, University of Maine, Orono, ME, USA.
Division of National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
Department of Environmental & Molecular Toxicology, Oregon State University, Corvallis, OR, USA.


Small freshwater fish models, especially zebrafish, offer advantages over traditional rodent models, including low maintenance and husbandry costs, high fecundity, genetic diversity, physiology similar to that of traditional biomedical models, and reduced animal welfare concerns. The Collaborative Workshop on Aquatic Models and 21st Century Toxicology was held at North Carolina State University on May 5-6, 2014, in Raleigh, North Carolina, USA. Participants discussed the ways in which small fish are being used as models to screen toxicants and understand mechanisms of toxicity. Workshop participants agreed that the lack of standardized protocols is an impediment to broader acceptance of these models, whereas development of standardized protocols, validation, and subsequent regulatory acceptance would facilitate greater usage. Given the advantages and increasing application of small fish models, there was widespread interest in follow-up workshops to review and discuss developments in their use. In this article, we summarize the recommendations formulated by workshop participants to enhance the utility of small fish species in toxicology studies, as well as many of the advances in the field of toxicology that resulted from using small fish species, including advances in developmental toxicology, cardiovascular toxicology, neurotoxicology, and immunotoxicology. We alsoreview many emerging issues that will benefit from using small fish species, especially zebrafish, and new technologies that will enable using these organisms to yield results unprecedented in their information content to better understand how toxicants affect development and health.


21st century toxicology; alternatives; aquatic models

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