Network toxicological mechanism analysis of pyrethroid insecticides-induced chronic respiratory system damage in humans

Household pyrethroid insecticides are products frequently encountered in daily human life, such as mosquito and cockroach control agents. While generally regarded as safe with low toxicity and minimal impact on humans, growing evidence indicates their chronic adverse effects on the human respiratory system cannot be overlooked. This study employed network toxicology and molecular docking techniques to investigate six common active ingredients of household pyrethroid insecticides (Theta-Cypermethrin, Transfluthrin, Cyphenothrin, Prallethrin, Dimefluthrin, Imiprothrin). Results demonstrated significant respiratory toxicity for all six pyrethroids. Analysis revealed 226 overlapping targets between the pyrethroid target repository and the chronic respiratory disease (CRDs) target database. Protein-protein interaction (PPI) analysis identified four core toxicity targets: AKT1, SRC, STAT3, and EGFR. Molecular docking studies confirmed high-affinity binding between pyrethroids and these targets. These targets are critically involved in inflammation and tumorigenesis pathways. Through integrated network toxicology and molecular docking, this research preliminarily elucidates multiple potential targets and mechanisms by which pyrethroids may induce CRDs (including chronic obstructive pulmonary disease, asthma, and pulmonary fibrosis). Additionally, findings suggest these compounds pose risks beyond the respiratory system, with neurotoxicity and carcinogenicity also warranting significant attention.