Abstract
<title>Abstract</title> <p>Background Inhalation of combined pesticide formulations can occur during preparation and application and may contribute to respiratory toxicity. Nurinol contains chlorpyrifos (organophosphate) and cypermethrin (type II pyrethroid), agents with distinct but potentially convergent mechanisms of lung injury. Quantitative data on time-dependent airway and parenchymal remodeling after repeated inhalation of such mixtures are limited. Aim To characterize acute and repeated inhalation toxicity of Nurinol in rabbits and to quantify lung remodeling with and without antioxidant intervention using digital morphometry. Methods Adult male rabbits were assigned to five groups: control; 30-day exposure; 30-day plus alpha-lipoic acid (ALA); 120-day exposure; 120-day plus ALA. Acute lethality across six dose levels was analyzed by probit regression to derive LD₁₆/LD₅₀/LD₉₀. Repeated exposures were conducted twice daily for 10 minutes at 0.75×LD₅₀ in a sealed aerosol chamber. ALA (9 mg/kg/day) was administered orally in intervention groups. Lungs were fixed, paraffin-embedded, H&E-stained, whole-slide scanned, and analyzed using QuPath and ImageJ. Primary endpoints were terminal bronchiole lumen area, bronchiole wall thickness, mean alveolar diameter, alveolar septal thickness, and capillary diameter. Results Probit analysis yielded LD₅₀ ≈289 mg/kg. Repeated inhalation produced progressive remodeling. At 30 vs 120 days (vs control), terminal bronchiole lumen area decreased by ~ 19% and ~ 35%; bronchiole wall thickness increased by ~ 29% and ~ 57%; alveolar diameter decreased by ~ 24% and ~ 37%; septal thickness increased by ~ 103% and ~ 214%; and capillary diameter increased by ~ 82% and ~ 45%. ALA partially normalized measures, with greater effect at 30 days. Conclusions Nurinol inhalation induces dose-dependent lethality and marked, time-dependent bronchiolar–alveolar remodeling consistent with transition from inflammatory to fibrosis-like changes. ALA mitigates early injury but incompletely reverses established structural remodeling.</p>