Developmental Neurotoxicity and Behavioral Screening in Larval Zebrafish with a Comparison to Other Published Results
Kimberly A. Jarema,
Deborah L. Hunter,
Bridgett N. Hill,
Jeanene K. Olin,
Katy N. Britton,
Matthew R. Waalkes,
Stephanie Padilla
Affiliations
Kimberly A. Jarema
Center for Public Health and Environmental Assessment, Immediate Office, Program Operations Staff, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA
Deborah L. Hunter
Center for Computational Toxicology and Exposure, Biomolecular and Computational Toxicology Division, Rapid Assay Development Branch, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA
Bridgett N. Hill
ORISE Research Participation Program Hosted by EPA, Center for Computational Toxicology and Exposure, Biomolecular and Computational Toxicology Division, Rapid Assay Development Branch, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA
Jeanene K. Olin
Center for Computational Toxicology and Exposure, Biomolecular and Computational Toxicology Division, Rapid Assay Development Branch, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA
Katy N. Britton
ORAU Research Participation Program Hosted by EPA, Center for Computational Toxicology and Exposure, Biomolecular and Computational Toxicology Division, Rapid Assay Development Branch, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA
Matthew R. Waalkes
ORISE Research Participation Program Hosted by EPA, National Health and Environmental Effects Research Laboratory, Integrated Systems Toxicology Division, Genetic and Cellular Toxicology Branch, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA
Stephanie Padilla
Center for Computational Toxicology and Exposure, Biomolecular and Computational Toxicology Division, Rapid Assay Development Branch, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA
With the abundance of chemicals in the environment that could potentially cause neurodevelopmental deficits, there is a need for rapid testing and chemical screening assays. This study evaluated the developmental toxicity and behavioral effects of 61 chemicals in zebrafish (Danio rerio) larvae using a behavioral Light/Dark assay. Larvae (n = 16–24 per concentration) were exposed to each chemical (0.0001–120 μM) during development and locomotor activity was assessed. Approximately half of the chemicals (n = 30) did not show any gross developmental toxicity (i.e., mortality, dysmorphology or non-hatching) at the highest concentration tested. Twelve of the 31 chemicals that did elicit developmental toxicity were toxic at the highest concentration only, and thirteen chemicals were developmentally toxic at concentrations of 10 µM or lower. Eleven chemicals caused behavioral effects; four chemicals (6-aminonicotinamide, cyclophosphamide, paraquat, phenobarbital) altered behavior in the absence of developmental toxicity. In addition to screening a library of chemicals for developmental neurotoxicity, we also compared our findings with previously published results for those chemicals. Our comparison revealed a general lack of standardized reporting of experimental details, and it also helped identify some chemicals that appear to be consistent positives and negatives across multiple laboratories.
