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Studies of the Variables Affecting Behavior of Larval Zebrafish for Developmental Neurotoxicity Testing
Citation:
PADILLA, S. J., D. L. HUNTER, B. K. PADNOS, S. Frady, AND R. C. MACPHAIL. Studies of the Variables Affecting Behavior of Larval Zebrafish for Developmental Neurotoxicity Testing. Presented at Society of Toxicology (SOT) Annual meeting, Washington, DC, March 06 - 10, 2011.
Impact/Purpose:
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 detect developmentally neurotoxic chemicals using zebrafish behavior at 6 days of age.
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 detect developmentally neurotoxic chemicals using zebrafish behavior at 6 days of age. The behavioral paradigm 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 1.5 hours of testing. The testing format allows evaluation of large numbers of larvae, chemicals and chemical concentrations. We have found that many developmentally neurotoxic compounds ( e.g., valproate, d-amphetamine) perturb behavior, while many developmentally non-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, size of the well, time of day that behavior is tested, and the presence of malformations. Some other variables, however, do not appear to affect larval behavior including type of rearing solution (10% Hank's vs. 1:3 Danieau vs 60 mg/kg Instant Ocean vs 1x and 1:10 x EPA Moderately Hard Water). Zebrafish larval behavior 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 ofa proposed presentation: the information does not necessarily reflect EPA