An innovative strategy for the selection of compounds with a similar toxicological mode of action was proposed in the study of chemical mixtures (PREDICT EU-Research Project). A representation of chemical structures for phenylureas and triazines by different molecular descriptors allowed a preliminary exploration of similarity based on Principal Components Analysis (PCA), MultiDimensional Scaling (MDS) and Hierarchical Cluster. The use of Genetic Algorithm to select the most relevant molecular descriptors in modeling toxicity data makes it possible to both develop good predictive QSAR toxicity models, and select the most similar phenylureas and triazines.
P.Gramatica et al. Chemosphere, 2001, 42, 873.
A proposal of new water quality objectives (WQO) for EEC priority List 1 (76/464/EEC) was realized by QSAR models and chemometric analysis of toxicity data.
M.Vighi, P.Gramatica, et al. Ecotox and Environ Safety, 2001, 49, 206.
The Duluth data set of toxicity data on Pimephales promelas was recently studied by the author group: new statistically validated MLR models were developed to predict the aquatic toxicity of chemicals classified according to their Mode Of Action (MOA). Also, a unique general model for Direct Toxicity Prediction (DTP model) was developed to propose a predictive tool with a wide applicability domain, applicable independently of a priori knowledge of the MOA of chemicals. Similarly, new QSAR models for esters’ aquatic toxicity and a ranking for cumulative end-points were proposed.
E.Papa et al., J. Chem. Inf. Model 2005, 45,1256; Chemosphere 2005, Vol 58, 559.
In the EU-FP7 Project CADASTER toxicity of perfluorinated chemicals (PFCs) is studied: oral and inhalation rat and mouse toxicity have been modeled with the principal aim to select priority PFCs for experimental tests.
B. Bhatarai and P. Gramatica, Chem. Res. Toxicol., 2010, 23, 528; Mol. Div., 2011, 15, 467.
Similarly, oral acute toxicity and cytotoxic activity of fragrance materials in rodents for fragrances have been modeled:
E. Papa et al. SAR QSAR Environ Res., 2009, 20, 767.
The aquatic ecotoxicity (on Daphnia , algae and fish) of various classes of pollutants were studied and predicted to prioritize the most dangerous and propose QSAR approach for a priori safer alternatives’ design: benzotriazoles and Personal Care Products in CADASTER project and recently pharmaceuticals.
An Aquatic Toxicity Index (ATI), based on PCA of the 3 ecotoxicity, is proposed and modelled by QSAR.
Some interspecies models for the reduction of fish tests predicting the fish toxicity from Daphnia data are also published.
P.Gramatica et al. Mol. Inf., 2012, 31, 817. S.Cassani et al. ATLA, 2013, 41, 49; J. Haz. Mat, 2013, 258-259, 50. P. Gramatica, A. Sangion, Environ Int. 2016, 95, 131. A. Sangion, P.Gramatica, SAR QSAR Environ Res, 2016, P. Gramatica et al. Green Chem, 2016, 18 (16), 4315-4572 [selected for COVER]