Prediction and analysis of acute fish toxicity of pesticides to the rainbow trout using 2D-QSAR

The acute toxicity in the rainbow trout (Oncorhynchus mykiss) was analyzed and predicted using quantitative structure-activity relationships (QSAR). The aquatic toxicity, 96h LC50 (median lethal concentration) of 275 organic pesticides, was obtained from EU-funded project DEMETRA. Prediction models were derived from 558 2D molecular descriptors, calculated in PreADMET. The linear (multiple linear regression) and nonlinear (support vector machine and artificial neural network) learning methods were optimized by taking into account the statistical parameters between the experimental and predicted pLC50. After preprocessing, population based forward selection were used to select the best subsets of descriptors in the learning methods including 5-fold cross-validation procedure. The support vector machine model was used as the best model (R 2 CV= 0.677, RMSECV= 0.887, MSECV= 0.674) and also correctly classified 87% for the training set according to EU regulation criteria. The MLR model could describe the structural characteristics of toxic chemicals and interaction with lipid membrane of fish. All the developed models were validated by 5 fold cross-validation and Yscrambling test.