QSAR models for predicting acute toxicity of pesticides in rainbow trout using the CORAL software and EFSA's OpenFoodTox database

Abstract

Optimal (flexible) descriptors were used to establish quantitative structure - activity relationships (QSAR) for toxicity of pesticides (n=116) towards rainbow trout. A heterogeneous set of hundreds of pesticides has been used, taken from the EFSA's chemical Hazards Database: OpenFoodTox. Optimal descriptors are preparing from simplified molecular input-line entry system (SMILES). So-called, correlation weights of different fragments of SMILES are calculating by the Monte Carlo optimization procedure where correlation coefficient between endpoint and optimal descriptor plays role of the target function. Having maximum of the correlation coefficient for the training set, one can suggest that the optimal descriptor calculated with these correlation weights can correlate with endpoint for external validation set. This approach was checked up with three different distributions into the training (≈85%) set and external validation (≈15%) set. The statistical characteristics of these models are (i) for training set correlation coefficient (r²) ranges 0.72-0.81, and root mean squared error (RMSE) ranges 0.54-1.25; (ii) for external (validation) set r² ranges 0.74-0.84; and RMSE ranges 0.64-0.75. Computational experiments have shown that presence of chlorine, fluorine, sulfur, and aromatic fragments is promoter of increase for the toxicity.

Keywords: CORAL software; Monte Carlo method; OECD; QSAR; Rainbow trout; Toxicity.