title: Skin sensitization: reaction mechanistic applicability domains for structure-activity relationships.
abstract: The prediction of skin sensitization potential with minimum animal testing is currently of great importance in light of forthcoming legislation. A number of structure-activity relationships for skin sensitization have been published over the years, but their applicability has often been limited to structural classes. The concept of an applicability domain for a quantitative structure-activity relationship [(Q)SAR] is increasingly being viewed as key for the predictive application of (Q)SARs. This is particularly the case for skin sensitization if more widely applicable SARs are to be developed. In this paper, we analyze a recently published chemical data set for skin sensitization, apply reaction mechanistic criteria to domain classification, and evaluate the structure-activity trends observed within each of these mechanistic domains.
authors.affiliation: SEAC, Unilever Colworth, Sharnbrook, Bedford, MK44 1LQ, England. nora.aptula@unilever.com
authors.forename: Aynur O
authors.initials: AO
authors.lastname: Aptula
authors.forename: Grace
authors.initials: G
authors.lastname: Patlewicz
authors.forename: David W
authors.initials: DW
authors.lastname: Roberts
mesh_terms: D000215:Acylation; D000485:Allergens; D003432:Cross-Linking Reagents / Q000737:chemistry; D005557:Formaldehyde / Q000737:chemistry; D005976:Glutaral / Q000737:chemistry; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D012545:Schiff Bases / Q000737:chemistry; D012867:Skin / Q000187:drug effects*
chemical_list: D000485:Allergens; D003432:Cross-Linking Reagents; D012545:Schiff Bases; D005557:Formaldehyde; D005976:Glutaral