Preservatives in cosmetics: reactivity of allergenic formaldehyde-releasers towards amino acids through breakdown products other than formaldehyde.

Compounds slowly releasing formaldehyde, the so-called formaldehyde-releasers, are commonly employed as preservatives in cosmetics instead of free formaldehyde, which is a strong skin sensitizer. It has been long accepted that formaldehyde-releaser sensitization is attributable to released formaldehyde. However, clinical studies show the existence of patients allergic to formaldehyde-releasers but not to formaldehyde itself. To prove that, for certain formaldehyde-releasers, reactive intermediates other than formaldehyde could be involved in the formation of the hapten-protein antigenic complex, a key step of the sensitization process, thus explaining their sensitizing potential. DMDM hydantoin, 2-bromo-2-nitropropane-1,3-diol and methenamine were synthesized, (13) C-labelled at the position(s) precursor of formaldehyde. Their reactivity towards amino acids was followed by one-dimensional and two-dimensional (13) C-nuclear magnetic resonance. Many adducts formed by reacting formaldehyde-releasers with amino acids resulted from a direct interaction of the releaser or from reaction of a breakdown product, and not from a reaction involving simply released formaldehyde. DMDM hydantoin was reactive per se, and 2-bromo-2-nitropropane-1,3-diol and methenamine decomposed in water, producing bromoethanol and diaminomethane, respectively, which were reactive towards some of the amino acids tested. The reactivity of distinctive formaldehyde-releasers towards amino acids is not limited to formaldehyde release.