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Applying the Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) Tool to Gain Insight on Diamide Insecticide Toxicity Across Species
Citation:
Jensen, M., L. Glimsdal, A. Johnson, E. Stacy, K. Santana Rodriguez, K. Mattingly, D. Villeneuve, J. Hockett, B. Blackwell, J. Cavallin, AND C. LaLone. Applying the Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) Tool to Gain Insight on Diamide Insecticide Toxicity Across Species. Midwest SETAC 31st Annual Scientific Meeting, La Crosse, WI, April 11 - 12, 2024. https://doi.org/10.23645/epacomptox.27055195
Impact/Purpose:
Due to the abundance of chemicals being produced, testing their potential impact on the environment and human health is critically important. As more and more chemicals are produced, we need to find methods to test their toxicity that are efficient, cost-effective, and reduce the use of animals. Computational tools are being developed that can predict the impact of these chemicals. These tools evaluate the similarity of biological targets, such as proteins, across the diversity of species. Because chemicals bind to these proteins to cause an adverse event, the tools can predict whether each species will be affected by the chemical of interest. Pesticides are chemicals that are used to control insect populations. We can use the computational tools to predict if this class of chemicals would impact other insects and animals that the chemicals were not designed to harm and confirm the predictions with focused toxicity testing. The work described here focused on the effects of chlorantraniliprole, a diamide insecticide used to control pest insects. Predictions from computational approaches were used to inform follow-up acute toxicity studies using Daphnia magna, Daphnia pulex, Pimephales promelas, and Danio rerio. Multiple endpoints were studied upon exposure to the pesticide including survival, mobility, and gene expression. Results showed that the Daphnia species tested are susceptible to CHL, while the larval fish species were less susceptible.
Description:
Diamide insecticides, including chlorantraniliprole (CHL), cyantraniliprole (CYAN), and flubendiamide (FLU), act on the ryanodine receptor (RyR) to control lepidopteran agricultural pests. This class of insecticides has been increasing in popularity over the past decade, with CHL rising to be one of the most widely used insecticides in the world. As its use has increased, a few pest species have developed resistance mutations, including I4790M in the diamondback moth (Plutella xylostella), where pests possessing the methionine residue have increased resistance to CHL. Because the taxonomic coverage is limited in toxicity data for CHL, this study aimed to address data gaps by applying both traditional toxicity test methods and the US Environmental Protection Agency’s Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool. The SeqAPASS tool evaluates the conservation of protein targets across thousands of species to make chemical susceptibility predictions. Here, the RyR was queried in the SeqAPASS tool to generate susceptibility predictions for CHL, including for species that will never be tested empirically. The predictions were then used to inform aquatic toxicity tests on Daphnia magna, Daphnia pulex, Pimephales promelas, and Danio rerio. Even though both Daphnia species contain a methionine residue in the position of the I4790M resistance mutation, both D. magna and D. pulex were found to be sensitive to CHL at environmentally relevant concentrations, while the fish species were not sensitive. The SeqAPASS results showed that many other species are predicted to be susceptible to CHL, including beneficial pollinators such as Apis and non-Apis bees and other Lepidoptera. Overall, this study presents a case example of how SeqAPASS results can be used in combination with toxicity data to fill knowledge gaps in toxicity data across species and increase confidence in predictive approaches. Importantly, it demonstrates how SeqAPASS can be used as a screening approach that could prioritize both chemicals and species for toxicity testing. The views expressed in this work are those of the authors and do not necessarily reflect the views or policies of the US EPA.
URLs/Downloads:
DOI: Applying the Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) Tool to Gain Insight on Diamide Insecticide Toxicity Across Species
APPLYING THE SEQAPASS TOOL TO GAIN INSIGHT ON DIAMIDE INSECTICIDE TOXICITY ACROSS SPECIES- 508.PDF (PDF, NA pp, 3929.609 KB, about PDF)