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Prioritizing Compounds for Developmental Neurotoxicity Based on an Early Developmental Model for Zebrafish: Can Zebrafish Be Used to Identify Developmentally Neurotoxic Chemicals?
Citation:
Padilla, S. Prioritizing Compounds for Developmental Neurotoxicity Based on an Early Developmental Model for Zebrafish: Can Zebrafish Be Used to Identify Developmentally Neurotoxic Chemicals? National Toxicology Program Developmental Neurotoxicity Workshop, Research Triangle Park, North Carolina, September 26 - 28, 2017.
Impact/Purpose:
The U.S. Environmental Protection Agency is evaluating methods to screen and prioritize chemicals for developmental neurotoxicity. We are exploring behavioral methods using zebrafish by designing a behavioral testing paradigm capable of assessing the effects of sublethal and sub-teratogenic concentrations of developmental neurotoxicants. We have tested a set of chemicals that are considered positive or negative controls for eliciting developmental neurotoxicity in mammals. We have found that many developmentally neurotoxic compounds perturb behavior at sub-teratogenic doses, while many developmentally non-neurotoxic compounds do not perturb behavior. Therefore, careful evaluation of zebrafish larval behavior may be able to identify some mammalian developmental neurotoxicants.
Description:
The U.S. Environmental Protection Agency is evaluating methods to screen and prioritize chemicals for developmental neurotoxicity. We are exploring behavioral methods using zebrafish by designing a behavioral testing paradigm capable of assessing the effects of sublethal and sub-teratogenic concentrations of developmental neurotoxicants. The behavioral paradigm simultaneously tests 96 individual 6 day old zebrafish under both light and dark conditions in a multiwell plate using a video tracking system. By controlling the duration and intensity of light, we are able to assess changes in locomotion during light-dark transitions, and adaptation to both light and dark. This format allows evaluation of large numbers of larvae, chemicals and concentrations. Using this paradigm, we have tested a set of chemicals that are considered positive or negative controls for eliciting developmental neurotoxicity in mammals. We have found that many developmentally neurotoxic compounds perturb behavior at sub-teratogenic doses, while many developmentally non-neurotoxic compounds do not perturb behavior. Exposure to developmental neurotoxicants may alter the overall level of activity in light and dark conditions and/or the pattern of activity. Therefore, results showed that careful behavioral evaluation of zebrafish larvae may be able to identify some mammalian developmental neurotoxicants. This abstract may not necessarily reflect official Agency policy.