Dermal absorption of 4,4'-methylene diphenyl diisocyanate (MDI) using human skin preparations.

4,4'-Methylene diphenyl diisocyanate (MDI) is a reactive diisocyanate used in polyurethane production. Despite potential occupational skin contact, quantitative data on dermal uptake in humans is limited. The dermal absorption and distribution of MDI across human abdominal split‑thickness skin was measured in a flow‑through system according to the OECD test guideline no. 428. [14C]MDI was topically applied as a single 10 mg/cm² neat dose to the skin (n = 8). Exposure was terminated after 8 hours by skin washing, while receptor sampling continued for 16 hours. The amounts of MDI in the receptor fractions, dermis, epidermis, stratum corneum (20 tape strips) and the skin washing fluids were quantified by liquid scintillation counting. The mean total recovery of radioactivity was 94.82% for precise mass balance calculations. The mean dislodgeable fraction, calculated as the sum of skin washes and donor chamber washing, accounted for 94.52% of the applied dose. The total amount recovered in tape strips plus remaining skin was below 0.30% per skin preparation, with the first two tape strips accounting for 0.22% of the applied dose. The mean absorbed dose in the receptor fluid was 0.0003% of the applied dose. [14C]MDI shows negligible dermal absorption into the receptor compartment; radiolabel is largely removable by washing after 8 hours of exposure time with only trace skin‑associated residues, indicating rapid skin immobilization due to reactive isocyanate groups. For pure MDI, these human‑skin data support risk assessments focusing on skin‑mediated hazards such as sensitization rather than systemic toxicity associated with systemic availability.