Formaldehyde is a common cause of contact allergy. In Europe, 2–3% of patients suspected of contact dermatitis have positive patch test reactions, and in the USA prevalence rates of sensitization of 8–9% are reported in this selected group of patients. Allergic contact dermatitis caused by formaldehyde is often chronic, presumably because it is difficult to avoid exposure to the allergen completely. Indeed, formaldehyde may be found in many cosmetics, toiletries, household products such as washing and cleaning agents and in a great number of industrial applications including adhesives, paints, lacquers and metalworking fluids. Often, the products are not preserved with formaldehyde itself, but with agents that release formaldehyde under usage conditions, the so-called formaldehyde-releasers (or formaldehyde donors). Well-known examples are quaternium-15, imidazolidinyl urea, diazolidinyl urea, DMDM hydantoin and 2-bromo-2-nitropropane-1,3-diol, preservatives frequently used in cosmetic products. Industrial products such as metalworking fluids frequently contain formaldehyde donors, such as the Bioban® product range of biocides and tris(N-hydroxyethyl) hexahydrotriazine (better known by its trade name Grotan® BK). Other products containing and releasing formaldehyde are the formaldehyde resins including urea formaldehyde and melamine formaldehyde resins. These were formerly used extensively as textile finishes and caused dermatitis from clothing in formaldehyde-sensitive individuals due to their high content of free formaldehyde. The finishes used currently by the clothing manufacturers release far less free formaldehyde, but are even today reported as causes of clothing allergic contact dermatitis.
Lists of formaldehyde-releasers have been published in articles and recent textbooks (1–8). Such lists are commonly handed out to patients allergic to formaldehyde with the instruction to avoid contact with these chemicals and products containing them. However, for most formaldehyde-releasers, the current understanding of their relationship to formaldehyde allergy appears to be limited and mainly based on patch test studies. Thus, it is often assumed that concomitant positive patch test reactions to formaldehyde and a releaser or to two or more releasers are caused by allergy to formaldehyde, though definite proof of this is often lacking (9–11). Whether it is really necessary to avoid all formaldehyde-releasing preservatives in patients allergic to formaldehyde is largely unknown. Indeed, only with a few compounds such as diazolidinyl urea (12) and imidazolidinyl urea (13), have experimental use test exposure studies have been performed in patients allergic to formaldehyde. Some authors have suggested that for formaldehyde-sensitive patients, it is sufficient to avoid only those formaldehyde-releasers that, in addition to formaldehyde, also elicited a positive patch test reaction (14). Others, however, think that it is prudent for formaldehyde-sensitive subjects to recommend avoidance of products containing any releaser (15–17).
The purpose of this study is to review the literature on the formaldehyde-releasers and their relationship to formaldehyde sensitivity with emphasis on (i) frequency of sensitization, (ii) patch test
relationship to formaldehyde and other formaldehyde-releasers, (iii) the relevance of positive patch test reactions, (iv) the amount of formaldehyde released by the various chemicals and, consequently, (v) the risk they pose for individuals allergic to formaldehyde. Do we have adequate knowledge to give formaldehyde allergic patients proper advice on avoidance of formaldehyde-releasers?
This review is presented as a series. In this article, formaldehyde sensitivity is reviewed, an inventory of the formaldehyde-releasers is presented and the frequency of their presence in various product categories is summarized. In other parts, formaldehyde-releasers commonly used in cosmetic products are discussed, formaldehyde in textile finishes is considered, and finally releasers in industrial products, notably metalworking fluids, and miscellaneous releasers are reviewed.