title: Possible origin of the skin sensitization potential of isoeugenol and related compounds. (I). Preliminary studies of potential reaction mechanisms.
abstract: Although many simple chemicals can give rise to the phenomenon of allergic contact dermatitis, it is rare that the mechanism of reaction between the chemical hapten and skin protein is known. A further complication is that metabolic processes may produce substantial changes to a chemical penetrating skin. Thus the skin contactant may be regarded as a prohapten which will give rise to the true hapten in vivo. In this study, the possible reaction mechanisms for a number of related simple aromatic chemicals have been investigated. The approach taken was to evaluate potential reaction mechanisms by assessing the degree to which chemicals could cross-react in sensitization tests. By careful choice of chemicals, it was then possible to confirm (or reject) options. Using this approach, a number of reaction schemes were investigated for eugenol, isoeugenol, dihydroeugenol, anethole and several related chemicals. The patterns of sensitization obtained and the cross-reactions observed indicated clearly that electrophile/nucleophile interactions were unlikely to provide a complete explanation of the sensitization processes. Eugenol and isoeugenol are not mutually cross-reactive, yet both cross-reacted with dihydroeugenol. Examination of the possible reaction mechanisms allows the speculation that eugenol reacts in part via a phenolic radical mechanism, whilst isoeugenol reacts largely via formation of an orthoquinone. Both reaction mechanisms are proposed for dihydroeugenol.
authors.affiliation: Unilever Environmental Safety Laboratory, Sharnbrook, Bedford, UK.
authors.forename: M D
authors.initials: MD
authors.lastname: Barratt
authors.forename: D A
authors.initials: DA
authors.lastname: Basketter
mesh_terms: D000081248:Allylbenzene Derivatives; D000818:Animals; D000840:Anisoles / Q000737:chemistry / Q000276:immunology; D003429:Cross Reactions; D005054:Eugenol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000276:immunology; D006168:Guinea Pigs; D012867:Skin / Q000276:immunology*
chemical_list: D000081248:Allylbenzene Derivatives; D000840:Anisoles; D005054:Eugenol; C036643:isoeugenol; C006578:anethole