title: Using In Silico Tools in a Weight of Evidence Approach to Aid Toxicological Assessment.
abstract: Integrated testing strategies are an important and useful approach to reduce animal usage in toxicity testing. Increased usage of integrated testing strategies is foreseen in current chemical legislation, e.g. REACH. Skin sensitisation is a well studied endpoint and many in silico models have been developed for the prediction of the skin sensitising potential of chemicals. This paper discusses the use of the OECD (Q)SAR Application Toolbox, Derek for Windows, the CAESAR global model and SMARTS rules for reactivity within a weight of evidence approach to predict skin sensitisation. Conclusions drawn from a weight of evidence approach can be used within an integrated testing strategy to reduce the requirement for in vivo tests. Using all four models in this manner enabled 76% of the conclusive predictions made regarding the test data to be in agreement with the observed toxicities. In addition, using all four models in conjunction identified areas where further information is required, as confounding results were produced. The actual data requirements for an integrated testing strategy are discussed along with what considerations need to be made for the remaining compounds that were misclassified or for which the programs contradicted one another and a definitive conclusion could not be reached.
authors.affiliation: School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, UK fax: 0151 231 2170.
authors.forename: Claire M
authors.initials: CM
authors.lastname: Ellison
authors.affiliation: School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, UK fax: 0151 231 2170.
authors.forename: Judith C
authors.initials: JC
authors.lastname: Madden
authors.affiliation: Lhasa Limited, 22-23 Blenheim Terrace, Woodhouse Lane, Leeds, LS2 9HD, UK.
authors.forename: Philip
authors.initials: P
authors.lastname: Judson
authors.affiliation: School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, UK fax: 0151 231 2170. m.t.cronin@ljmu.ac.uk.
authors.forename: Mark T D
authors.initials: MT
authors.lastname: Cronin
keywords: Integrated testing strategies; REACH; Skin sensitisation; Structure-activity relationships; Toxicology; Weight of evidence