Computational new approach methods guide focused testing and enhance understanding of chlorantraniliprole toxicity across species

作者：Marissa A Jensen-Brickley, Leah Glimsdal, Abigail Johnson, Emma Stacy, Kelvin Santana Rodriguez, Kali Z. Mattingly, Daniel L. Villeneuve, Russ Hockett, Brett R. Blackwell, Jenna E. Cavallin, Carlie A. LaLone · 发表于：Environmental Toxicology and Chemistry · 年份：2025 · DOI：10.1093/etojnl/vgae057 · 被引用次数：5 · 研究领域：Pesticide Residue Analysis and Safety、Pharmacogenetics and Drug Metabolism、Analytical Chemistry and Chromatography

Diamide insecticides, specifically chlorantraniliprole (CHL), have been rising in popularity over the past decade, becoming one of the most widely used insecticide classes globally. These insecticides target the ryanodine receptor (RyR), primarily for control of lepidopteran agricultural pests. Field studies have revealed that some lepidopteran species have developed mutations where a methionine in a particular position (e.g., I4790M) increases resistance to CHL. The toxicity data for CHL across species is limited, as is the case for many chemicals, which creates an opportunity to apply both traditional toxicity test methods and new approach methods (NAMs) to address data gaps. Here, the U.S. Environmental Protection Agency's Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool was used to query the RyR to generate susceptibility predictions for species exposed to CHL to fill those data gaps. These SeqAPASS results generated testable hypotheses that were used to guide focused acute aquatic toxicity studies using Daphnia magna, Daphnia pulex, Pimephales promelas, and Danio rerio. The fish species were not sensitive to CHL, whereas D. magna and D. pulex were found to be sensitive to CHL at environmentally relevant concentrations, despite having the methionine residue in the position of the I4790M resistance mutation. Additional SeqAPASS results showed that many other species, including beneficial pollinators and Lepidoptera, are predicted as likely suscep...