title: Structure-activity relationships for skin sensitization potential: development of structural alerts for use in knowledge-based toxicity prediction systems.
abstract: The development of qualitative structure-activity relationships for the prediction of skin sensitization potential, based on structural alerts (substructures associated with a toxicological mechanism), and suitable for incorporation as rules into a knowledge-based system is described. The structure dependence of the skin sensitization mechanism may be largely defined in terms of the presence or metabolic/nonmetabolic formation of protein reactive functional groups on the test compound and by the physicochemical requirements of significant skin penetration. The proposed structural alerts were tested on a data set of diverse chemicals. The results showed that the alerts have potential as preliminary indicators of skin sensitization potential for a wide range of low molecular weight chemicals.
authors.affiliation: Occupational Medicine and Hygiene Laboratory, Health and Safety Executive, Sheffield, U.K.
authors.forename: M P
authors.initials: MP
authors.lastname: Payne
authors.forename: P T
authors.initials: PT
authors.lastname: Walsh
mesh_terms: D000215:Acylation; D000477:Alkylating Agents / Q000737:chemistry / Q000633:toxicity; D000818:Animals; D001185:Artificial Intelligence; D017449:Dermatitis, Allergic Contact / Q000209:etiology*; D005609:Free Radicals; D006801:Humans; D011506:Proteins / Q000187:drug effects / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000276:immunology; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000378:metabolism; D015262:Xenobiotics / Q000737:chemistry / Q000633:toxicity*
chemical_list: D000477:Alkylating Agents; D005609:Free Radicals; D011506:Proteins; D013438:Sulfhydryl Compounds; D015262:Xenobiotics