Dermal uptake study with 4,4′-diphenylmethane diisocyanate led to active sensitization

Background. To investigate the dermal uptake of 4,4'-diphenylmethane diisocyanate (4,4'-MDI), a study was performed in which 2 female volunteers were exposed to 10 and 25 mg, respectively, of 4,4'-MDI by applying 2.0% 4,4'-MDI in petrolatum over areas where the surface concentration corresponded to 800 `mu g/cm(2). Ten days later, they developed eczematous dermatitis at the area of application. Objectives. To investigate whether the dermal application caused active sensitization to 4,4'-MDI. Methods. Chemical analysis of the 4,4'-MDI preparation used in the application and the amount of 4,4'-MDI not absorbed by the skin was performed with liquid chromatography-mass spectrometry. The volunteers were tested with serial dilutions of 4,4'-MDI and the potentially cross-reacting substances 4,4'-diaminodiphenylmethane (4,4'-MDA), p-phenylenediamine (PPD), and dicyclohexylmethane-4,4'-diisocyanate (DMDI). Results. Patch test results suggested that the volunteers were actively sensitized to 4,4'-MDI following the dermal uptake study, as they reacted positively to 4,4'-MDA, a marker for 4,4'-MDI allergy. No positive reactions were seen to PPD or DMDI. Chemical investigation confirmed that the correct concentration had been used for the dermal uptake study, and showed that about 70% of the applied 4,4'-MDI was not absorbed. Conclusions. A dermal uptake study with 4,4'-MDI in 2.0% pet. with an occlusion time of 8 hr induced active sensitization to 4,4'-MDI and subsequently to 4,4'-MDA.