Effects of commonly used pesticides and their mixtures on the upper airway epithelium using porcine organoid-derived models.

Airborne pesticide contamination can result in widespread respiratory exposure particularly among agricultural workers, yet its impact on respiratory health remains poorly understood. In this study, we assessed the effects of ten commonly used pesticides and the synergist piperonyl butoxide, individually and in mixtures, on the viability of porcine proximal airway epithelial organoid-derived monolayers. Eight of the eleven compounds reduced cell viability, with pendimethalin, glyphosate, cyprodinil and piperonyl butoxide inducing pronounced effects at low concentrations. Mixture exposure caused stronger reductions in viability than individual compounds, consistent with additive toxicity. Transcriptomic analysis of seven selected compounds revealed alterations in pathways related to epithelial barrier integrity, immune signalling, and mucociliary function. These findings indicate that pesticide exposure of the upper airway may impair airway epithelial function and could contribute to respiratory dysfunction, highlighting the need to incorporate inhalation exposure and mixture effects in pesticide risk assessment. Moreover, this study provides a basis for the development of physiologically relevant models and targeted assays to evaluate respiratory effects of environmental pesticide mixtures.