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Functional Assays and Alternative Species: Using Larval Zebrafish in Developmental Neurotoxicity Screening
Citation:
PADILLA, S. J. Functional Assays and Alternative Species: Using Larval Zebrafish in Developmental Neurotoxicity Screening. Presented at Developmental Neurotoxicity 3 (DNT3) International conference, Varese, ITALY, May 10 - 13, 2011.
Impact/Purpose:
We have designed a behavioral testing paradigm capable of assessing the effects of sublethal and subteratogenic concentrations of developmental neurotoxicants.
Description:
The U.S. Environmental Protection Agency is developing and evaluating methods to screen and prioritize large numbers of chemicals for developmental toxicity. Towards this goal, we are exploring methods to detect developmental neurotoxicants in very young larval zebrafish. We have designed a behavioral testing paradigm capable of assessing the effects of sublethal and subteratogenic concentrations of developmental neurotoxicants. The behavioral approach simultaneously tests individual larval zebrafish under both light and dark conditions in a 96-well plate using a video tracking system. By controlling the duration and intensity of light, we are able to assess visual threshold, changes in locomotion during light-dark transitions, and adaptation to both light and dark during approximately 1 hour of testing. The testing format allows evaluation of large numbers of larvae, chemicals and chemical concentrations. Using this paradigm we have tested a training set of chemicals (n=12) that are either known or generally considered positive or negative controls for producing developmental neurotoxicity in mammals. We have found that many developmentally neurotoxic compounds (e.g., valproate, d-amphetamine) perturb "behavior at subteratogenic doses, while many developmentally non-neurotoxic compounds (e.g., glyphosphate, omeprazole, saccharin and d-sorbitol) do not. Exposure to developmental neurotoxicants may alter the overall level of activity in light and dark conditions and/or the pattern of activity. Therefore, results from the training set indicate that careful behavioral evaluation of zebrafish larvae may be able to identify mammalian developmental neurotoxicants. This abstract may not necessarily reflect official Agency policy.