PARENT SESSION

1F - QSAR
Poster Hall
8:30 AM - Tuesday, 29 April 2003
Chair: Schüürmann, G.¹, ¹
Co-chair: Verhaar, H.J.M.², Cronin, M.³, ^{2 3}

(TUP/47) QSAR Prediction of Aquatic Toxicity of Esters.

Gramatica, Paola¹, Battaini, Francesca¹, Papa, Ester¹, ¹ QSAR and Environmental Chemistry Research Unit - University of Insubria, Varese, VA, Italy

ABSTRACT- Esters are an important class of industrial chemicals, for which the EU-Directive White Paper on a strategy for a future Community Policy for Chemicals requires toxicity data by, at the latest, the end of 2005. The object of the study was to develop QSAR models to rapidly predict the aquatic toxicity of esters. Unfortunately the experimental toxicity data are not known for a large number of these compounds or, if known, the data are not all homogeneous, hindering an accurate and comparable evaluation of the toxicological behaviour of the considered compounds. Different theoretical molecular descriptors (1D-constitutional, 2D-topological, and different 3D-descriptors) are calculated by the DRAGON software. The Genetic Algorithm (GA-Variable Subset Selection) is used to select the more relevant molecular descriptors in the modelling by Ordinary Least Squares (OLS) regression. The studied end-points are: LC50 in Pimephales promelas, EC50 in Daphnia magna and in seaweed, IGC50 in Entosiphon sulcatum and chronic toxicity in Daphnia magna . The best models were validated for their predictive performance using leave-one-out (Q² LOO=70-90%), leave-many-out (30% of perturbation, Q² LMO=70-90%) and the scrambling of the responses. The models were not all externally validated owing to the small dimension (14-30) of the studied sets. The reliability of the predictions was always checked by the leverage approach in order to verify the chemical domain of the models. A PCA model, based on four acute toxicity end-points, has been proposed to evaluate the trend of aquatic toxicity for the studied esters. The PC1 score is also modelled by theoretical molecular descriptors (Q² LOO=89%, Q² LMO=88%): this last model can be used as an evaluative method for screening esters according to their aquatic toxicity, just starting from their molecular structure.

Key words: esters, QSAR, toxicity, external validation