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Assessing the Developmental Toxicity and Developmental Neurotoxicity of 26 Organophosphorus Pesticides Using a Zebrafish (Danio rerio) Larval Assay
Citation:
Padilla, S., M. Waalkes, D. Hunter, J. Hedge, AND K. Jarema. Assessing the Developmental Toxicity and Developmental Neurotoxicity of 26 Organophosphorus Pesticides Using a Zebrafish (Danio rerio) Larval Assay. Society of Toxicology, Baltimore, Maryland, March 10 - 14, 2019.
Impact/Purpose:
The U.S. Environmental Protection Agency is evaluating methods to screen and prioritize organophosphorus (OP) pesticides for developmental toxicity and developmental neurotoxicity. Testing each of 26 OP pesticides in developing zebrafish, we found that not all OP pesticides had the same toxicity profile. Some were not toxic at all while others showed selective neurodevelopmental toxicity.
Description:
The U.S. Environmental Protection Agency is evaluating methods to screen and prioritize organophosphorus (OP) pesticides for developmental toxicity and developmental neurotoxicity (DNT). One of those methods uses larval zebrafish. Developmental toxicity in zebrafish embryos/larvae is defined as lethality, non-hatching, or dysmorphology (e.g. curved body axis, edema, non-inflation of swim bladder). DNT is defined as behavioral alterations in the light/dark locomotor assay, in which the locomotor response to light stimuli under tandem light and dark conditions in a 96-well plate is quantified using a video tracking system on 6 day post fertilization zebrafish larvae. Twenty-six OP pesticides were tested for their developmental toxicity and DNT potential by exposing zebrafish embryos/larvae to the pesticide at several concentrations (≤ 100 μM nominal concentration) during the first five days of development (daily renewal of chemical), followed by 24 hours of depuration. Behavioral testing was conducted at six days after fertilization followed by a visual assessment of the larvae for lethality, hatching status, and dysmorphology. Behavior was only analyzed for normal animals. Five of the pesticides produced no effect in either assay: Chlorethoxyfos, Dimethoate, Fosthiazate, Methamidophos, and Trichlorfon. Slightly more than half (14/26) of the OP pesticides were developmentally toxic, and half (13/26) were neurodevelopmentally toxic to the developing zebrafish. Six of the OP pesticides (Profenofos, Acephate, Coumaphos, Dicrotophos, Ethoprop, and Terbufos) showed significant specificity for DNT in that they were neurodevelopmentally toxic to the zebrafish larvae at doses ≥ 3 orders of magnitude below the doses that elicited death or dysmorphology. These results indicate that some of these OP pesticides could affect brain development in zebrafish at concentrations below toxic levels for embryos. This abstract may not necessarily reflect official Agency policy.