In silico predictions of absorption of MDI substances after dermal or inhalation exposures to support a category based read-across assessment

Publication: Regul Toxicol Pharmacol
Software: GastroPlus®
Division: Simulations Plus


Methylenediphenyl diisocyanate (MDI) substances used polyurethane production can range from their simplest monomeric forms (e.g., 4,4′-MDI) to mixtures of the monomers with various homologues, homopolymer, and prepolymer derivatives. The relative dermal or inhalation absorption of 39 constituents of these substances in human were predicted using the GastroPlus® program.

Predicted dermal uptake and absorption of the three MDI monomers from an acetone vehicle was 84–86% and 1.4–1.5%, respectively, with lower uptake and absorption predicted for the higher MW analogs. Lower absorption was predicted from exposures in a more lipophilic vehicle (1-octanol).

Modeled inhalation exposures afforded the highest pulmonary absorption for the MDI monomers (38–54%), with 3–27% for the MW range of 381–751, and <0.1% for the remaining, higher MW derivatives. Predicted oral absorption, representing mucociliary transport, ranged from 5 to 10% for the MDI monomers, 10–25% for constituents of MW 381–751, and ≤3% for constituents with MW > 900.

These in silico evaluations should be useful in category-based, worst-case, Read-Across assessments for MDI monomers and modified MDI substances for potential systemic effects. Predictions of appreciable mucociliary transport may also be useful to address data gaps in oral toxicity testing for this category of compounds.

By Michael Bartels, William van Osdol, Maxime Le Merdy, Anne Chappelle, Adam Kuhl, Robert West