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Assessing the Developmental Neurotoxicity of 27 Organophosphorus Pesticides Using a Zebrafish Behavioral Assay
Waalkes, M., D. Hunter, K. Jarema, W. Mundy, AND S. Padilla. Assessing the Developmental Neurotoxicity of 27 Organophosphorus Pesticides Using a Zebrafish Behavioral Assay. SETAC North America, Orlando, FL, November 06 - 10, 2016.
The U.S. Environmental Protection Agency is developing methods to screen chemicals for Developmental Neurotoxicity. Twenty-seven organophosphorus pesticides have been tested for developmental neurotoxicity in the developing zebrafish. There was a wide range of responses, with some of the pesticides testing negative, but with others producing developmental neurotoxicity at low concentrations. These data may be used by the Program Offices to inform their regulation of these pesticides.
Assessing the Developmental Neurotoxicity of 27 Organophosphorus Pesticides Using a Zebrafish Behavioral Assay, Waalkes, M., Hunter, D.L., Jarema, K., Mundy, W., and S. Padilla. The U.S. Environmental Protection Agency is evaluating methods to screen and prioritize organophosphorus pesticides for developmental neurotoxicity. As such, we are exploring a behavioral testing paradigm that can assess the effects of sublethal and subteratogenic concentrations of developmental neurotoxicants on zebrafish (Danio rerio). This in vivo assay quantifies the locomotor response to light stimuli under tandem light and dark conditions in a 96-well plate using a video tracking system on 6 day post fertilization zebrafish larvae. Each of twenty-seven organophosphorus pesticides was tested for their developmental neurotoxic potential by exposing zebrafish embryos/larvae to the pesticide at several concentrations (≤ 100 μM nominal concentration) during the first five days of development, followed by 24 hours of depuration and then behavioral testing. Approximately 22% of the chemicals (Acephate, Dichlorvos, Diazoxon, Bensulide,Tribufos, Tebupirimfos) did not produce any behavioral changes after developmental exposure, while many (Malaoxon Fosthiazate, Dimethoate, Dicrotophos, Ethoprop, Malathion, Naled, Diazinon, Methamidophos, Terbufos, Trichlorfon, Phorate, Pirimiphos-methyl, Profenofos, Z-Tetrachlorvinphos, Chlorpyrifos, Coumaphos, Phosmet, Omethoate) produced changes in swimming activity . Some of the latter group (Diazinon, Omethoate, Pirimiphos-methyl, Profenofos, Terbuphos) were particularly potent for developmental neurotoxicity, showing behavioral alterations at doses 2 to 3 orders of magnitude below the developmental concentrations that produced death or dysmorphology. These results indicate that some of these organophosphorus pesticides may elicit neurodevelopmental toxic effects in zebrafish at concentrations below those that produce lethality or dysmorphology. This abstract may not necessarily reflect official Agency policy.