Allergic contact dermatitis to accelerators in rubber gloves marketed as accelerator‐free

1. Ancona A, Monroy F, Fernández-Diez J. Occupational dermatitis from IPPD in tires. Contact Derm. 1982;8(2):91-94. doi:10.1111/j.16000536.1982.tb04152.x 2. Mariano-Bourin M, Marzouki-Zerouali A, Poreaux C, Schmutz JL, Burszetjn AC. Allergic contact dermatitis caused by a black rubber handbrake handle. Contact Derm. 2020;82(2):124-125. doi:10.1111/cod.13407 3. Navarro-Triviño FJ, Ruiz-Villaverde R. Purpuric contact dermatitis caused by N-isopropyl-N'-phenyl-p-phenylenediamine from a samsung fit strap. Contact Derm. 2020;83(1):68-69. doi:10.1111/ cod.13536 4. Maibach H. Scuba diver facial dermatitis: allergic contact dermatitis to N-isopropyl-N-phenylpara-phenylenediamine. Contact Derm. 1975; 1(5):330. doi:10.1111/j.1600-0536.1975.tb05463.x 5. Fisher AA. Allergic reactions to nonrubber products by testing with rubber mixes. Part III: The black rubber mix. Cutis. 1995;56(5):253-254. 6. Patel K, Nixon R. Allergic contact dermatitis from black rubber in firefighters' masks: a case series. Contact Derm. 2022;86(2):136-137. doi: 10.1111/cod.13993


Correspondence
Richard Brans, Department of Dermatology, Environmental Medicine and Health Theory, University of Osnabrück, Am Finkenhügel 7a, D-49076 Osnabrück, Germany. Email: rbrans@uos.de K E Y W O R D S : accelerator-free, allergic contact dermatitis, carbamates, case report, hand eczema, rubber glove, thiurams, work-related Contact allergies to rubber accelerators used in the production of protective gloves, including thiurams, dithiocarbamates, benzothiazoles, and 1,3-diphenylguanidine are frequent in patients with work-related hand eczema, particularly in cleaning personnel, food handlers and healthcare workers. 1,2 To find suitable protective gloves for these individuals remains a challenge. Accelerator-free rubber gloves might be an alternative. 2 Figure 1A) and a marked and long-lasting positive reaction to the tested nitrile glove (+) which contains dithiocarbamates according to the manufacturer's information ( Figure 1B). A partially work-related F I G U R E 1 Initial patch test at D3 with positive reactions to chromium, thiuram-mix, tetramethylthiuram monosulfide (TMTM), tetraethylthiuram disulfide (TETD), and dipentamethylenethiuram disulfide (DPTD), a doubtful reaction to zinc diethyldithiocarbamate (ZDEC), and a positive reaction to Purple Nitril-Xtra (Halyard Health) (A), positive patch test reaction to Purple Nitril-Xtra (Halyard Health) at D7 (B), positive patch test reaction to SHIELDskin Orange Nitrile 300 (Shield Scientific) and negative patch test reaction to the second selected nitrile glove marketed as accelerator-free at D3 (C). allergic contact dermatitis of the hands due to sensitization to rubber accelerators was diagnosed. Two disposable nitrile gloves marketed as accelerator-free medical gloves were selected for the patient to be used at home and at work. To our surprise, patch testing the patient with these gloves (as described above) led to a positive reaction (+) to SHIELDskin Orange Nitrile 300 (Shield Scientific) at D3 ( Figure 1C).
In a collaboration with the Institution for Statutory Accident Insurance and Prevention in the Healthcare and Welfare Services (BGW) and the Institute for Occupational Safety and Health of the German Social Accident Insurance (IFA), St. Augustin, Germany, a qualitative analysis using methyl tert-butylether extraction and sonication followed by gas chromatography and mass spectrometry (for details see supplement) at the IFA revealed that the analysed two different charges of the glove contained zinc diethyldithiocarbamate, zinc dibutyldithiocarbamate and an unclassified benzothiazole derivate. A selection of six other disposable gloves produced by different manufacturers and all marketed as accelerator-free medical gloves were analysed by the same method.
Rubber accelerators (zinc diethyldithiocarbamate and zinc dibutyldithiocarbamate) were only detected in one other glove (SHIELDskin Extreme Orange Nitrile 300) from the same manufacturer. Moreover, we confirmed the manufacturer's information that the glove Purple Nitril-Xtra (Halyard Health) which had been previously used by the patient, contained zinc diethyldithiocarbamate. The patient was finally equipped with a second protective glove made of polyvinyl chloride.

DISCUSSION
Rubber accelerators are widely used in the production of natural and synthetic rubber gloves. Nowadays, thiurams have mostly been replaced by dithiocarbamates for this purpose. 6,7 However, thiurams and dithiocarbamates constitute a redox pair and are transformed into each other and thiurams are considered a better marker for a thiuram/dithiocarbamate sensitisation when patch tested. 6 Therefore, individuals with sensitization to thiurams are advised to also avoid dithiocarbamates. 3 In response to contact allergies to rubber accelerators, glove manufacturers have developed and marketed accelerator-free gloves. 2 According to European standard EN 455-3, which is mainly used for medical gloves, the absence of a substance may only be declared by the manufacturer if the substance is not used in any part of the manufacturing process. Despite being marketed as accelerator-free, classified as medical device and labelled with EN 455-3, the analysis revealed that the selected 'accelerator-free' glove SHIELDskin Orange Nitrile 300 contained three accelerators of which two were dithiocarbamates, explaining the positive patch test reaction to the glove in our patient. Reassuringly, common accelerators were undetectable with the same analytic methods in all but one of the other analysed gloves marketed as accelerator-free medical gloves. Notably, the only other accelerator-containing glove was produced by the same manufacturer. Upon request, the manufacturer informed us that the gloves are not supposed to contain any thiurams or dithiocarbamates, but cross-contamination could not be excluded as the same manufacturing facilities are used for the production of accelerator-free and accelerator-containing gloves.
We here show that protective gloves classified as medical device and marketed as accelerator-free are not necessarily free of accelerators. As a qualitative and not a quantitative analysis was performed, we cannot comment on the amounts of the detected accelerators.
Even if the 'accelerator-free' glove contains much smaller amounts of accelerators than conventional rubber gloves, this might still cause allergic contact dermatitis in individuals with strong sensitizations to rubber accelerators. Patch testing these gloves prior to use may help to assess individual tolerability even though this cannot exclude

CONFLICT OF INTEREST STATEMENT
There are no conflicts of interest.

SUPPORTING INFORMATION
Additional supporting information can be found online in the Supporting Information section at the end of this article.
How to cite this article: Brans R, Werner S, Obermeyer L,