Determination of the solubility of 2,4’-methylene diphenyl diisocyanate (MDI) in Elendt M4 medium at 295 K

The aqueous solubility of a substance is a critical physicochemical property for designing environmental fate and toxicity tests. The hydrophobic nature and water-reactivity of aromatic diisocyanates constitute significant challenges to determining their aqueous solubility: the establishment of a steady-state equilibrium cannot readily be observed because substance composition and the dissolution process are variable and dynamic. Criteria developed in a previous publication were applied in this work to determine the solubility of 2,4’-methylene diphenyl diisocyanate (MDI) in Elendt M4 medium in the presence of 0.001% (10 μL/L) acetonitrile as a co-solvent. The value at 295 ± 2 K was 11.7 μg/L with a confidence interval of 9.9–13.6 μg/L. The availability of an experimental value for the first time allows for revision of the quantitative structure-activity relationship estimation tools, which – for lack of experimental data – currently predict solubilities (much) in excess of 1 mg/L. In addition, the low solubility enables and necessitates developing testing scenarios that are at the same time realistic compared to the potential exposure scenarios and consistent with the physical-chemical properties of methylene diphenyl diisocyanate and its derivatives.