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

Objectives: 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. Materials/Methods: DMDM hydantoin, 2-bromo-2-nitropropane-1,3-diol and methenamine were synthesized, 13C-labelled at the position(s) precursor of formaldehyde. Their reactivity towards amino acids was followed by one-dimensional and two-dimensional 13C-nuclear magnetic resonance. Results: 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. Conclusion: The reactivity of distinctive formaldehyde-releasers towards amino acids is not limited to formaldehyde release.