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Comparison of the Developmental and Acute Neurotoxicity of a Library of Organophosphorus Pesticides Using a Vertebrate Behavioral Assay
Padilla, S., M. Waalkes, J. Hedge, D. Hunter, AND K. Jarema. Comparison of the Developmental and Acute Neurotoxicity of a Library of Organophosphorus Pesticides Using a Vertebrate Behavioral Assay. Society of Toxicology, Baltimore, Maryland, March 12 - 17, 2017.
This work compares the acute toxicity of a pesticide to its developmental toxicity. Although all the chemicals tested are cholinesterase inhibitors and should therefore elicit acute toxicity, it was found at doses so low that they do not cause lethality or morbidity, if the pesticides had an effect, it was usually a developmentally neurotoxic effect rather than an acute effect.
The U.S. Environmental Protection Agency is evaluating methods to screen and prioritize organophosphorus pesticides for neurotoxicity using behavioral tests in an in vivo, vertebrate, medium-throughput model (zebrafish; Danio rerio). Our behavioral testing paradigm assesses the effects of sublethal and subteratogenic concentrations of organophosphorus pesticides in order to compare the developmental vs the neuroactive toxicity potential of each chemical. This 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 (dpf) zebrafish larvae. Each of twenty-seven organophosphorus pesticides at several concentrations (≤ 100 μM nominal concentration) was tested using two different paradigms: (A) by exposing zebrafish embryos/larvae to the pesticide during the first five days of development, followed by 24 hours of depuration and then behavioral testing or (B) tested for their neuroactive potential (i.e., acute toxicity) by assessing the behavior alterations noted after an acute dose in 6 dpf zebrafish larvae. Interestingly, many of the organophosphorus pesticides did not have any effect on locomotor activity when given acutely, but when given developmentally, behavioral changes were noted (e.g., Acephate, Bensulide, Chlorpyrifos, Naled, Tebupirimiphos), while others had no effect when tested for either acute or developmental behavioral effects (e.g., Chlorethoxyfos, Diazoxon, Malathion). These results indicate that, in a developmenting vertebrate model, these chemicals are more likely to produce developmental neurotoxicity, as compared to acute neuroactive changes, at concentrations below those that produce lethality or dysmorphology. This abstract may not necessarily reflect official Agency policy.