In vivo-in vitro comparison of acute respiratory tract toxicity using human 3D airway epithelial models and human A549 and murine 3T3 monolayer cell systems

► In vitro systems reflect inhalation toxicity aspects relating to cells/endpoints. ► To predict inhalation toxicity, 3D models were not superior to monolayer cultures. ► Prediction models distinguishing toxic from non-toxic substances were satisfactory. ► Mediocre prediction of 4-level hazard classes was best for respiratory irritants. ► Hazard categories are based upon scientific evidence and political decisions.