Citation:

Jarema, K., D. Hunter, B. Hill, J. Olin, K. Britton, M. Waalkes, AND S. Padilla. Developmental Neurotoxicity and Behavioral Screening in Larval Zebrafish with a Comparison to Other Published Results. Toxics. MDPI, Basel, Switzerland, 10(5):256, (2022). https://doi.org/10.3390/toxics10050256

Impact/Purpose:

In this publication we have tested a relatively large group of chemicals for developmental neurotoxicity potential using a zebrafish behavioral assay and compared our results to publications using the same chemicals and employing a similar experimental design. There appears to be considerable variability within the literature regarding larval zebrafish behavioral alterations after developmental exposure to some of the chemicals. This comparison also allowed identification of some chemicals that are consistent positives and negatives across publications, and prompts us to identify ways to improve the experimental design and interpretation of the assay that we conduct in our own laboratory. As a step toward data transparency and inter-laboratory collaboration, we have included all of our raw behavioral data to allow exploration of the data by other investigators and to encourage more zebrafish behavioral data sharing in the future. Manuscript from Behavioral Screen for Developmental neurotoxicity in zebrafish. This product will complete testing of a 60 chemical DNT reference set in a behavioral assay for zebrafish. It will complete testing of this set of chemicals in all of the EPA NAMs for DNT, and allow for comparisons to be made across the different assays and evaluation of the EPA DNT NAMs.  

Description:

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.

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