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Integration of In Silico New Approach Methods (NAMs) to Guide Focused Testing and Inform Pesticide Toxicity Across Species – Case Study with Chlorantraniliprole
Citation:
Jensen, M., L. Glimsdal, A. Johnson, E. Stacy, K. Santana Rodriguez, K. Mattingly, Dan Villeneuve, R. Hockett, B. Blackwell, J. Cavallin, AND C. Lalone. Integration of In Silico New Approach Methods (NAMs) to Guide Focused Testing and Inform Pesticide Toxicity Across Species – Case Study with Chlorantraniliprole. Society of Environmental Toxicology and Chemistry (SETAC) North America 44th Annual Meeting, Louisville, KY, November 12 - 16, 2023. https://doi.org/10.23645/epacomptox.29271500
Impact/Purpose:
Presentation to the Society of Environmental Toxicology and Chemistry (SETAC) North American Annual Meeting November 2023. 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:
Emphasis has widely been placed on utilizing New Approach Methods (NAMs) and predictive approaches in chemical toxicity evaluations to conserve resources, generate data faster, and reduce the use of animals. Advancements in bioinformatics have led to the development of in silico NAMs for addressing species extrapolation, including the U.S. EPA’s Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool. The SeqAPASS tool evaluates conservation of protein targets to make chemical susceptibility predictions across thousands of species, including species that will never be tested empirically. Many NAMs are relatively new; therefore, case examples that demonstrate the applicability of the tools through the strategic combination of existing and new knowledge are needed to help build support for their use in generating predictions. Here, a study focusing on chlorantraniliprole (CHL), a diamide insecticide, is described. Diamide insecticides, which act on ryanodine receptors (RyRs), have been gaining popularity for control of lepidopteran agricultural pests. However, there are knowledge gaps regarding their toxicity across species, and detectable concentrations of these chemicals have been found in the environment. We used the SeqAPASS tool to generate susceptibility predictions after querying the RyR. Predictions 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 CHL including survival, mobility, and RyR gene expression. Results showed that the Daphnia species tested are susceptible to CHL, while the larval fish species were less susceptible, which can be explained in part by their RyR sequence similarity when compared to known targeted pest insects. Together, SeqAPASS evaluations combined with existing toxicity data can inform targeted toxicity testing to gain insight into cross-species chemical susceptibility while increasing confidence in predictive approaches. 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: Integration of In Silico New Approach Methods (NAMs) to Guide Focused Testing and Inform Pesticide Toxicity Across Species – Case Study with Chlorantraniliprole
SETAC POSTER 2023 MJENSEN_FINAL.PDF (PDF, NA pp, 1006.595 KB, about PDF)