Poor correlation between stated and found concentrations of diphenylmethane‐4,4′‐diisocyanate (4,4′‐MDI) in petrolatum patch‐test preparations

Abstract

Diphenylmethane diisocyanate (MDI) is widely used in its polymeric form in the manufacturing of polyurethane products. Previous reports on MDI-related contact allergy have shown a pattern, where patients seem to react to their own MDI-based work material but not to commercial patch-test preparations, which contain 4,4'-MDI. Therefore, we performed chemical analyses of 14 commercial test preparations of 4,4'-MDI obtained from 8 European and 4 American dermatology departments as well as 2 preparations from 2 major European suppliers of patch-test allergens. A new method for monitoring 4,4'-MDI in petrolatum preparations was developed and the determination of 4,4'-MDI as the MDI-dibutylamine derivative using liquid chromatography-mass spectrometry was performed. None of the preparations obtained from the dermatology departments contained more than 12% of the concentration stated on the label. In most cases, 4,4'-MDI content was only a few percentages or less of the concentration stated. 7 of the 14 preparations were analysed before the expiry date. Yet, only 1 of them, a preparation directly obtained from the supplier, came close to the concentration stated on the label. Thus, using these preparations, patients will be tested with a lower concentration than intended, leading to possible false-negative reactions.

4,4′‐Methylene diphenyl diisocyanate (MDI) [101‐68‐8] and “polymeric” MDI (PMDI) [9016‐87‐9] [MAK Value Documentation, 2008]

“…Of 179 patients with suspected occupational contact dermatitis who were investigated between 1991 and 1996 using the patch test (2% MDI in petrolatum), none reacted . One publication reports that MDI concentrations in commercial patch test preparations are often too low, so that falsenegative results in the patch tests are conceivable (Frick et al 2004). …”

Occupational allergic and irritant contact dermatitis in workers exposed to polyurethane foam

“…Regarding positive patch test reactions caused by MDA, it should be noted that they are relatively often seen (even in 2-4% of the patients tested), but their relevance is not always clear [28]. MDA may be used as a hardener of epoxy resins, an antioxidant of rubber products and in the production of synthetic textile fibers [13].…”

“…Frick et al found poor correlation between the specified and true concentrations of 4,4'-MDI in petrolatum patch test preparations from 8 European and 4 American dermatology departments, which were found to contain no more than 12% of the concentrations specified in the label. The use of these preparations might have led to possible falsenegative reactions [28]. In the Finnish Institute of Occupational Medicine, an in-house test substance, containing 4,4'-MDI, MDI triisocyanate and 2,4'-MDI proved to be superior to commercial preparations of MDI [4].…”

Allergologische Diagnostik und aktuelle Allergene in der Berufsdermatologie

“…Diisocyanate, die Grundstoffe von Polyurethan-Harzen, haben nicht nur atemwegssensibilisierende, sondern auch hautsensibilisierende Eigenschaften. Aufgrund ihrer hohen Reaktivität ist ihre Stabilität in Epikutantestzubereitungen gering, sodass der Test ohne Weiteres falschnegativ ausfallen kann [20,21]. Angesichts der großen Vielfalt der möglichen beruflichen Exposition hat die DKG beschlossen, keine Testreihe für Maler und Lackierer zusammenzustellen.…”