title: Dermal uptake study with 4,4'-diphenylmethane diisocyanate led to active sensitization.
abstract: 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 µg/cm(2) . Ten days later, they developed eczematous dermatitis at the area of application.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Occupational and Enviromental Dermatology, Skåne University Hospital, Lund University, 205 02 Malmö, Sweden. haneen.hamada@gmail.com
authors.forename: Haneen
authors.initials: H
authors.lastname: Hamada
authors.forename: Marléene
authors.initials: M
authors.lastname: Isaksson
authors.forename: Magnus
authors.initials: M
authors.lastname: Bruze
authors.forename: Malin
authors.initials: M
authors.lastname: Engfeldt
authors.forename: Ingrid
authors.initials: I
authors.lastname: Liljelind
authors.forename: Sara
authors.initials: S
authors.lastname: Axelsson
authors.forename: Bo
authors.initials: B
authors.lastname: Jönsson
authors.forename: Håkan
authors.initials: H
authors.lastname: Tinnerberg
authors.forename: Erik
authors.initials: E
authors.lastname: Zimerson
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000814:Aniline Compounds / Q000009:adverse effects* / Q000737:chemistry; D017449:Dermatitis, Allergic Contact / Q000175:diagnosis / Q000209:etiology*; D004485:Eczema / Q000139:chemically induced* / Q000175:diagnosis; D005260:Female; D006801:Humans; D017953:Isocyanates / Q000009:adverse effects* / Q000737:chemistry; D010328:Patch Tests; D010577:Petrolatum / Q000737:chemistry*; D012869:Skin Absorption; D013997:Time Factors; D055815:Young Adult; D001559:Benzhydryl Compounds
chemical_list: D000814:Aniline Compounds; D017953:Isocyanates; D010577:Petrolatum; C005969:4,4'-diphenylmethane diisocyanate; D001559:Benzhydryl Compounds; C009505:4,4'-diaminodiphenylmethane