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Studies of the Variables Affecting Behavior of Larval Zebrafish for Developmental Neurotoxicity Testing*
Citation:
PADILLA, S. J. Studies of the Variables Affecting Behavior of Larval Zebrafish for Developmental Neurotoxicity Testing*. Presented at Oklahoma State University, Stillwater, OK, November 19, 2010.
Impact/Purpose:
We are exploring methods to screen for developmentally neurotoxic chemicals using zebrafish behavior at 6 days of age. The behavioral paradigm simultaneously tests larval zebrafish under both light and dark conditions in a 96-well plate using a video tracking system.
Description:
The U.S. Environmental Protection Agency is evaluating methods to screen and prioritize large numbers of chemicals for developmental toxicity. We are exploring methods to screen for developmentally neurotoxic chemicals using zebrafish behavior at 6 days of age. The behavioral paradigm simultaneously tests 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 1.5 hours of testing. The testing format allows evaluation of large numbers of larvae, chemicals and chemical concentrations. We have found that many chemicals that are toxic to the developing mammalian nervous system ( e.g., valproate, d-amphetamine) perturb larval zebrafish behavior, while many non-developmentally neurotoxic compounds (e.g., acetaminophen, saccharin) do not. Additionally, we have found that many variables affect the level or pattern of locomotor activity including age of the larvae, lighting conditions during development, size of the well, time of day that behavior is tested, presence of malformations, and housing conditions (individually, in groups) during development. Zebrafish larval behavior on day 6 using a microtiter plate format may be an ideal endpoint for screening developmentally neurotoxic chemicals, but it is imperative that many test variables be carefully specified and controlled. This is an abstract of a proposed presentation: the information does not necessarily reflect EPA policy.