Sensitizing Capacities and Cross-Reactivity Patterns of Some Diisocyanates and Amines Using the Guinea-Pig Maximization Test. Can p-phenylenediamine be Used as a Marker for Diisocyanate Contact Allergy?

Haneen Hamada*, Erik Zimerson, Magnus Bruze, Marléne Isaksson, Malin Engfeldt
Department of Occupational and Environmental Dermatology, Lund University, Skåne University Hospital, Malmö, Sweden

© 2017 Hamada et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: ( This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Occupational and Environmental Dermatology, Lund University, Skåne University Hospital, Jan Waldenströms gata 18, 205 02 Malmö, Sweden; Tel: +46(0)40331759; E-mail:



Isocyanates are mainly considered respiratory allergens but can also cause contact allergy. Diphenylmethane-4,4′-diamine (4,4′-MDA) has been considered a marker for diphenylmethane-4,4′-diisocyanate (4,4′-MDI) contact allergy. Furthermore, overrepresentation of positive patch-test reactions to p-phenylenediamine (PPD) in 4,4′-MDA positive patients have been reported.


To investigate the sensitizing capacities of toluene-2,4-diisocyanate (2,4-TDI) and PPD and the cross-reactivity of 4,4′-MDA, 2,4-TDI, dicyclohexylmethane-4,4′-diamine (4,4′-DMDA), dicyclohexylmethane-4,4′-diisocyanate (4,4′-DMDI), 4,4′-MDI and PPD.


The Guinea Pig Maximization Test (GPMT) was used.


PPD was shown to be a strong sensitizer (p<0.001). Animals sensitized to PPD showed cross-reactivity to 4,4′-MDA (p<0.001). Animals sensitized to 4,4′-MDA did not show cross-reactivity to PPD. 8 animals sensitized to 2,4-TDI were sacrificed due to toxic reactions at the induction site and could thus not be fully evaluated.


PPD was shown to be a strong sensitizer. However, it cannot be used as a marker for isocyanate contact allergy. On the other hand, positive reactions to 4,4′-MDA could indicate a PPD allergy. The intradermal induction concentration of 2,4-TDI (0.70% w/v) can induce strong local toxic reactions in guinea-pigs and should be lowered.

Keywords: Guinea Pig Maximization Test, PPD, Cross-reactivity, Sensitization, Diphenylmethane-4,4′-diamine, 4,4′-MDA.