title: Preservatives in cosmetics: reactivity of allergenic formaldehyde-releasers towards amino acids through breakdown products other than formaldehyde.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  The reactivity of distinctive formaldehyde-releasers towards amino acids is not limited to formaldehyde release.
authors: Laboratoire de Dermatochimie, Institut de Chimie, UMR 7177 CNRS/UdS, Université de Strasbourg, Strasbourg, France.
authors: Mustapha
authors: M
authors: Kireche
authors: Elena
authors: E
authors: Gimenez-Arnau
authors: Jean-Pierre
authors: JP
authors: Lepoittevin
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D000890:Anti-Infective Agents / Q000737:chemistry*; D003358:Cosmetics / Q000009:adverse effects* / Q000737:chemistry*; D017449:Dermatitis, Allergic Contact / Q000209:etiology*; D005557:Formaldehyde / Q000009:adverse effects / Q000737:chemistry; D006801:Humans; D006827:Hydantoins / Q000737:chemistry; D008709:Methenamine / Q000737:chemistry; D011310:Preservatives, Pharmaceutical / Q000737:chemistry*; D011409:Propylene Glycols / Q000737:chemistry
chemical_list: D000596:Amino Acids; D000890:Anti-Infective Agents; D003358:Cosmetics; D006827:Hydantoins; D011310:Preservatives, Pharmaceutical; D011409:Propylene Glycols; D005557:Formaldehyde; C006827:bronopol; C056057:1,3-dimethylol-5,5-dimethylhydantoin; D008709:Methenamine