title: Consensus QSAR Related to Global or MOA Models: Application to Acute Toxicity for Fish.
abstract: Under REACH legislation, alternative methods (in silico or in vitro) like QSAR (Quantitative Structure-Activity Relationships) models are expected to play a significant role. QSARs are based on the assumption that substances with similar chemical structures may have the same biological activities. However, identification of chemical classes could be problematic because chemicals often exhibit different chemical moieties, thereby confounding efforts to achieve a meaningful classification. This publication is focus on the notion of global model with the integration of a recent genetic algorithm for the generation of QSAR models. Starting from three datasets (EPAFHM, ECBHPV, AQUIRE), prediction of acute toxicity for fish (Pimephales promelas) with a global consensus model was carried out leading to very interesting statistics. The integration of the notion of Mode of Action was the second point of this study. A Bayesian classification associated to the genetic algorithm for consensus models was created leading to a good estimation of toxicity associated to derivatives with nonspecific MOA.
authors.affiliation: Centre d'Etudes et de Recherche sur le Médicament de Normandie, UPRES EA4258 FR CNRS INC3M, Université de Caen, Basse-Normandie, U.F.R. des Sciences Pharmaceutiques, Boulevard Becquerel, 14032 Caen Cedex, France tel: (33)2-31-56-68-20, fax: (33)2-31-56-68-03.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Lozano
authors.affiliation: Centre d'Etudes et de Recherche sur le Médicament de Normandie, UPRES EA4258 FR CNRS INC3M, Université de Caen, Basse-Normandie, U.F.R. des Sciences Pharmaceutiques, Boulevard Becquerel, 14032 Caen Cedex, France tel: (33)2-31-56-68-20, fax: (33)2-31-56-68-03.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Halm-Lemeille
authors.affiliation: Centre d'Etudes et de Recherche sur le Médicament de Normandie, UPRES EA4258 FR CNRS INC3M, Université de Caen, Basse-Normandie, U.F.R. des Sciences Pharmaceutiques, Boulevard Becquerel, 14032 Caen Cedex, France tel: (33)2-31-56-68-20, fax: (33)2-31-56-68-03.
authors.forename: Alban
authors.initials: A
authors.lastname: Lepailleur
authors.affiliation: Centre d'Etudes et de Recherche sur le Médicament de Normandie, UPRES EA4258 FR CNRS INC3M, Université de Caen, Basse-Normandie, U.F.R. des Sciences Pharmaceutiques, Boulevard Becquerel, 14032 Caen Cedex, France tel: (33)2-31-56-68-20, fax: (33)2-31-56-68-03.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Rault
authors.affiliation: Centre d'Etudes et de Recherche sur le Médicament de Normandie, UPRES EA4258 FR CNRS INC3M, Université de Caen, Basse-Normandie, U.F.R. des Sciences Pharmaceutiques, Boulevard Becquerel, 14032 Caen Cedex, France tel: (33)2-31-56-68-20, fax: (33)2-31-56-68-03. ronan.bureau@unicaen.fr.
authors.forename: Ronan
authors.initials: R
authors.lastname: Bureau
keywords: Bayesian classification; Ecotoxicity; Genetic algorithm; Mode of action; QSAR