title: Definition of the applicability domains of knowledge-based predictive toxicology expert systems by using a structural fragment-based approach.
abstract: The applicability domain of a (quantitative) structure-activity relationship ([Q]SAR) must be defined, if a model is to be used successfully for toxicity prediction, particularly for regulatory purposes. Previous efforts to set guidelines on the definition of applicability domains have often been biased toward quantitative, rather than qualitative, models. As a result, novel techniques are still required to define the applicability domains of structural alert models and knowledge-based systems. By using Derek for Windows as an example, this study defined the domain for the skin sensitisation structural alert rule-base. This was achieved by fragmenting the molecules within a training set of compounds, then searching the fragments for those created from a test compound. This novel method was able to highlight test chemicals which differed from those in the training set. The information was then used to designate chemicals as being either within or outside the domain of applicability for the structural alert on which that training set was based.
authors.affiliation: School of Pharmacy and Chemistry, Liverpool John Moores University, Liverpool, UK. c.m.ellison@2007.ljmu.ac.uk
authors.forename: Claire M
authors.initials: CM
authors.lastname: Ellison
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Enoch
authors.forename: Mark Td
authors.initials: MT
authors.lastname: Cronin
authors.forename: Judith C
authors.initials: JC
authors.lastname: Madden
authors.forename: Philip
authors.initials: P
authors.lastname: Judson
mesh_terms: D000826:Animal Testing Alternatives / Q000379:methods; D005103:Expert Systems; D006801:Humans; D008956:Models, Chemical; D021281:Quantitative Structure-Activity Relationship; D023422:Skin Irritancy Tests / Q000379:methods; D018675:Toxicity Tests / Q000379:methods; D014116:Toxicology / Q000379:methods*