title: An evaluation of selected global (Q)SARs/expert systems for the prediction of skin sensitisation potential.
abstract: Skin sensitisation potential is an endpoint that needs to be assessed within the framework of existing and forthcoming legislation. At present, skin sensitisation hazard is normally identified using in vivo test methods, the favoured approach being the local lymph node assay (LLNA). This method can also provide a measure of relative skin sensitising potency which is essential for assessing and managing human health risks. One potential alternative approach to skin sensitisation hazard identification is the use of (Quantitative) structure activity relationships ((Q)SARs) coupled with appropriate documentation and performance characteristics. This represents a major challenge. Current thinking is that (Q)SARs might best be employed as part of a battery of approaches that collectively provide information on skin sensitisation hazard. A number of (Q)SARs and expert systems have been developed and are described in the literature. Here we focus on three models (TOPKAT, Derek for Windows and TOPS-MODE), and evaluate their performance against a recently published dataset of 211 chemicals. The current strengths and limitations of one of these models is highlighted, together with modifications that could be made to improve its performance. Of the models/expert systems evaluated, none performed sufficiently well to act as a standalone tool for hazard identification.
authors.affiliation: European Chemicals Bureau TP582, IHCP, Joint Research Centre, European Commission, Ispra, Italy. grace.patlewicz@jrc.it
authors.forename: G
authors.initials: G
authors.lastname: Patlewicz
authors.forename: A O
authors.initials: AO
authors.lastname: Aptula
authors.forename: E
authors.initials: E
authors.lastname: Uriarte
authors.forename: D W
authors.initials: DW
authors.lastname: Roberts
authors.forename: P S
authors.initials: PS
authors.lastname: Kern
authors.forename: G F
authors.initials: GF
authors.lastname: Gerberick
authors.forename: I
authors.initials: I
authors.lastname: Kimber
authors.forename: R J
authors.initials: RJ
authors.lastname: Dearman
authors.forename: C A
authors.initials: CA
authors.lastname: Ryan
authors.forename: D A
authors.initials: DA
authors.lastname: Basketter
mesh_terms: D000473:Alkanes / Q000737:chemistry / Q000633:toxicity; D003198:Computer Simulation; D006801:Humans; D007659:Ketones / Q000737:chemistry / Q000633:toxicity; D023441:Local Lymph Node Assay; D008954:Models, Biological; D008956:Models, Chemical; D021281:Quantitative Structure-Activity Relationship; D018570:Risk Assessment / Q000379:methods; D012680:Sensitivity and Specificity; D012882:Skin Tests; D012984:Software
chemical_list: D000473:Alkanes; D007659:Ketones