Risk assessment of isocycloseram: resistance development in Plutella xylostella and selective toxicity to the predatory stink bug Arma chinensis

Abstract BACKGROUND Isocycloseram is a novel isoxazoline insecticide targeting the γ‐aminobutyric acid (GABA)‐gated chloride channel (GABAR). It exhibits high efficacy against Lepidopteran pests like Plutella xylostella but is safe to natural enemies. However, the risk of isocycloseram resistance in P. xylostella and the mechanisms underlying its selective action between P. xylostella and its natural enemy, Arma chinensis , remain unknown. RESULTS In this study, the resistance risk of P. xylostella to isocycloseram was assessed. After 16 generation selections, P. xylotella developed 32.0‐fold resistance with a realized heritability ( h 2 ) of 0.452. The isocycloseram resistant strain also showed 4.4‐fold cross‐resistance to abamectin but remained susceptible to endosulfan, broflanilide, cyproflanilide, and chlorantraniliprole. Furthermore, isocycloseram was found to be highly toxic to P. xylostella but safe to A. chinensis . The specific activities of esterases, glutathione S‐transferases, and cytochrome P450 O ‐demethylation enzymes in A. chinensis were significantly higher than those in P. xylostella when induced by isocycloseram. In addition, molecular docking demonstrated that isocycloseram binds more strongly to PxGABAR (−9.44 kcal mol −1 ) than to AcGABAR (−8.06 kcal mol −1 ). CONCLUSION Plutella xylostella has a high risk of developing resistance to isocycloseram. The elevated activity of detoxification enzymes in A. chinensis and reduced binding affinity of AcGABAR to isocycloseram may contribute to the selective toxicity of isocycloseram between P. xylostella and A. chinensis . These findings lay a foundation for the scientific application of isocycloseram in pest control and natural enemy conservation. © 2026 Society of Chemical Industry.