Interrelating the acute and chronic mode of action of inhaled methylenediphenyl diisocyanate (MDI) in rats assisted by computational toxicology

► Polymeric MDI aerosol has extensively been studied to interrelate acute and chronic pulmonary irritation. ► Acute lung irritation by polymeric MDI is 1-order of magnitude less that than of monomeric MDI. ► Cumulative and acute threshold mode of actions have been debated. ► This study compared to use PBPK modeling to predict pulmonary toxicity. ► This analysis concludes that long-term effects depend on the acute irritation threshold.