title: Skin sensitization of epoxyaldehydes: importance of conjugation.
abstract: Structure-activity relationship (SAR) models are important tools for predicting the skin sensitization potential of new compounds without animal testing. In compounds possessing a structural alert (aldehyde) and an activation alert (double bond), it is important to consider bioactivation/autoxidation (e.g., epoxidation). In the present study, we have explored a series of aldehydes with regard to contact allergy. The chemical reactivity of these 6 aldehydes toward a model hexapeptide was investigated, and their skin sensitization potencies were evaluated using the local lymph node assay (LLNA). Overall, we observed a similar trend for the in vitro reactivity and the in vivo sensitization potency for the structural analogues in this study. The highly reactive conjugated aldehydes (α,β-unsaturated aldehydes and 2,3-epoxyaldehydes) are sensitizing moieties, while nonconjugated aldehydes and nonterminal aliphatic epoxides show low reactivity and low sensitization potency. Our data show the importance of not only double bond conjugation to aldehyde but also epoxide-aldehyde conjugation. The observations indicate that the formation of nonconjugated epoxides by bioactivation or autoxidation is not sufficient to significantly increase the sensitization potency of weakly sensitizing parent compounds.
authors.affiliation: Department of Chemistry and Molecular Biology, Dermatochemistry and Skin Allergy, University of Gothenburg , SE-412 96 Gothenburg, Sweden. tamara.delaine@chem.gu.se
authors.forename: Tamara
authors.initials: T
authors.lastname: Delaine
authors.forename: Lina
authors.initials: L
authors.lastname: Hagvall
authors.forename: Johanna
authors.initials: J
authors.lastname: Rudbäck
authors.forename: Kristina
authors.initials: K
authors.lastname: Luthman
authors.forename: Ann-Therese
authors.initials: AT
authors.lastname: Karlberg
mesh_terms: D000447:Aldehydes / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*; D000485:Allergens / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D017449:Dermatitis, Allergic Contact / Q000209:etiology*; D004852:Epoxy Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*; D005260:Female; D023441:Local Lymph Node Assay; D051379:Mice; D008808:Mice, Inbred CBA
chemical_list: D000447:Aldehydes; D000485:Allergens; D004852:Epoxy Compounds