Chemical and Clinical Studies of Isocyanate Contact Allergy with focus on diphenylmethane diisocyanate

Abstract: Isocyanates are highly reactive compounds used in the production of polyurethane. Exposure to isocyanates is mainly associated with respiratory disorders, but may also result in allergic contact dermatitis. Reports describing contact allergy to isocyanates are few in number and it has been considered a rare phenomenon. In the present study it is shown that the low frequency of reported cases could partly be explained by weaknesses in the method used to detect contact allergy arising from isocyanates, i.e. patch testing with the commercially available isocyanate series. These series generally comprise petrolatum preparations of the four diisocyanates diphenylmethane-4,4'-diisocyanate (4,4'-MDI), 2,4-toluene diisocyanate (2,4-TDI), 1,6-hexamethylene diisocyanate (1,6-HDI) and isophorone diisocyanate (IPDI), as well as two corresponding amines, 4,4'-diaminodiphenylmethane (4,4'-MDA) and isophorone diamine (IPDA). The following results are reported in the thesis. (i) Chemical analyses of isocyanate series obtained from four American and nine European patch testing departments showed that patch test preparations of 2,4-TDI, 1,6-HDI and IPDI contained the declared concentrations, but the concentration of 4,4'-MDI was generally so low that patch testing with it could not be considered reliable. (ii) A stability study showed that preparations of technical grade MDI, i.e. polymeric MDI (PMDI), were more stable and more homogeneous than preparations of pure 4,4'-MDI during the course of a year. (iii) A patch test study revealed that PMDIs rendered as many positive reactions as 4,4'-MDI, (iv) that positive reactions to 4,4'-MDI and PMDI appear late, i.e. after day 3 and sometimes also after day 7, and (v) that the amine 4,4'-MDA is a good marker for 4,4'-MDI contact allergy. In order to optimize patch testing with isocyanates it is thus recommended that patients be tested with their own work products containing technical grade isocyanates since they better reflect the possible allergens that patients are in fact exposed to. It is not yet known if the isomers presently used in commercial preparations are the most potent allergens in technical grade products or if there are other monomers and/or oligomers that cause skin problems. When contact allergy to MDI is suspected patients can also be tested with 4,4'-MDA since it is a marker for 4,4'-MDI contact allergy. Isocyanate patch tests should be read on day 3 or 4 as well as on day 7.