Cellular and signaling mechanisms of cyantraniliprole toxicity in the nontarget organism Bombyx mori

The extensive agricultural use of cyantraniliprole has led to its increasing detection as an environmental residue, raising concerns over sublethal effects on nontarget organisms. Nevertheless, the ecotoxicological consequences of environmentally relevant sublethal exposure remain poorly characterized. Here, we investigated sublethal toxicity of cyantraniliprole in the silkworm Bombyx mori. Sublethal exposure preferentially impaired the midgut, the primary site of dietary xenobiotic contact, and stimulated marked oxidative and detoxification stress. Transcriptomic profiling revealed coordinated changes in autophagy- and apoptosis-associated genes. These transcriptional changes were corroborated at the protein level by increased lipidation of autophagy-related protein 8 (ATG8), accelerated degradation of sequestosome 1 (SQSTM1), and activation of interleukin-1β converting enzyme (ICE), indicating a dose-dependent engagement of autophagic and apoptotic pathways, consistent with ultrastructural changes. At the signaling level, cyantraniliprole exposure was associated with the disruption of stress-integration pathways, characterized by the suppression of phosphorylated protein kinase B signaling and activation of phosphorylated AMP-activated protein kinase and phosphorylated mitogen-activated protein kinase. These results demonstrate that sublethal cyantraniliprole toxicity in B. mori is initiated by oxidative and detoxification stress, which converges to activate integrated autophagic and apoptotic programs. Altogether, this study extends diamide Insecticide hazard assessment beyond canonical neurotoxicity by revealing the disruption of conserved cellular homeostasis as a critical dimension of sublethal ecological risk.