title: Assessment of in silico models for acute aquatic toxicity towards fish under REACH regulation.
abstract: We evaluated the performance of eight QSAR in silico modelling packages (ACD/ToxSuite™, ADMET Predictor™, DEMETRA, ECOSAR, TerraQSAR™, Toxicity Estimation Software Tool, TOPKAT™ and VEGA) for acute aquatic toxicity towards two species of fish: Fathead Minnow and Rainbow Trout. For the Fathead Minnow, we compared model predictions for 567 substances with the corresponding experimental values for 96-h median lethal concentrations (LC50). Some models gave good results, with r2up to 0.85. We also classified the predictions of all the models into four toxicity classes defined by CLP. This permitted us to assess other parameters, such as the percentage of correct predictions for each class. Then we used a set of 351 substances with toxicity data towards Rainbow Trout (96-h LC50). In this case the predictability was unacceptable for all the in silico models. The calculated r2gave poor correlations (≤0.53). Another analysis was performed according to chemical classes and for mode of action. In the first case, all the classes show a high percentage of correct predictions, in the second case only narcotics and polar narcotics were predicted with good confidence. The results indicate the possibility of using in silico methods to estimate aquatic toxicity within REACH regulation, after careful evaluation.
authors.affiliation: a Department of Environmental Health Sciences , IRCCS Istituto di Ricerche Farmacologiche Mario Negri , Milan , Italy.
authors.forename: C I
authors.initials: CI
authors.lastname: Cappelli
authors.affiliation: a Department of Environmental Health Sciences , IRCCS Istituto di Ricerche Farmacologiche Mario Negri , Milan , Italy.
authors.forename: A
authors.initials: A
authors.lastname: Cassano
authors.affiliation: a Department of Environmental Health Sciences , IRCCS Istituto di Ricerche Farmacologiche Mario Negri , Milan , Italy.
authors.forename: A
authors.initials: A
authors.lastname: Golbamaki
authors.affiliation: a Department of Environmental Health Sciences , IRCCS Istituto di Ricerche Farmacologiche Mario Negri , Milan , Italy.
authors.forename: Y
authors.initials: Y
authors.lastname: Moggio
authors.affiliation: a Department of Environmental Health Sciences , IRCCS Istituto di Ricerche Farmacologiche Mario Negri , Milan , Italy.
authors.forename: A
authors.initials: A
authors.lastname: Lombardo
authors.affiliation: b Health and Environment Department , Istituto Superiore di Sanità , Rome , Italy.
authors.forename: M
authors.initials: M
authors.lastname: Colafranceschi
authors.affiliation: a Department of Environmental Health Sciences , IRCCS Istituto di Ricerche Farmacologiche Mario Negri , Milan , Italy.
authors.forename: E
authors.initials: E
authors.lastname: Benfenati
keywords: CLP; QSAR; REACH; applicability domain; fish acute toxicity