caa a22 4500 445879017 CHVBK 20180317145536.0 cr unu---uuuuu 170323e20110501xx s 000 0 eng 10.1007/s11030-010-9268-z doi (NATIONALLICENCE)springer-10.1007/s11030-010-9268-z Oral LD50 toxicity modeling and prediction of per- and polyfluorinated chemicals on rat and mouse [Elektronische Daten] [Barun Bhhatarai, Paola Gramatica] Quantitative structure-activity relationship (QSAR) analyses were performed using the LD50 oral toxicity data of per- and polyfluorinated chemicals (PFCs) on rodents: rat and mouse. PFCs are studied under the EU project CADASTER which uses the available experimental data for prediction and prioritization of toxic chemicals for risk assessment by using the in silico tools. The methodology presented here applies chemometrical analysis on the existing experimental data and predicts the toxicity of new compounds. QSAR analyses were performed on the available 58 mouse and 50 rat LD50 oral data using multiple linear regression (MLR) based on theoretical molecular descriptors selected by genetic algorithm (GA). Training and prediction sets were prepared a priori from available experimental datasets in terms of structure and response. These sets were used to derive statistically robust and predictive (both internally and externally) models. The structural applicability domain (AD) of the models were verified on 376 per- and polyfluorinated chemicals including those in REACH preregistration list. The rat and mouse endpoints were predicted by each model for the studied compounds, and finally 30 compounds, all perfluorinated, were prioritized as most important for experimental toxicity analysis under the project. In addition, cumulative study on compounds within the AD of all four models, including two earlier published models on LC50 rodent analysis was studied and the cumulative toxicity trend was observed using principal component analysis (PCA). The similarities and the differences observed in terms of descriptors and chemical/mechanistic meaning encoded by descriptors to prioritize the most toxic compounds are highlighted. Springer Science+Business Media B.V., 2010 Perfluorinated chemicals nationallicence Oral LD50 nationallicence QSAR nationallicence Toxicity nationallicence Rodents nationallicence REACH nationallicence Bhhatarai Barun QSAR Research Unit in Environmental Chemistry and Ecotoxicology, Department of Structural and Functional Biology (DBSF), University of Insubria, via J.H. Dunant 3, 21100, Varese, Italy aut Gramatica Paola QSAR Research Unit in Environmental Chemistry and Ecotoxicology, Department of Structural and Functional Biology (DBSF), University of Insubria, via J.H. Dunant 3, 21100, Varese, Italy aut Molecular Diversity Springer Netherlands 15/2(2011-05-01), 467-476 1381-1991 15:2<467 2011 15 11030 https://doi.org/10.1007/s11030-010-9268-z text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11030-010-9268-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Bhhatarai Barun QSAR Research Unit in Environmental Chemistry and Ecotoxicology, Department of Structural and Functional Biology (DBSF), University of Insubria, via J.H. Dunant 3, 21100, Varese, Italy aut NATIONALLICENCE 700 1- Gramatica Paola QSAR Research Unit in Environmental Chemistry and Ecotoxicology, Department of Structural and Functional Biology (DBSF), University of Insubria, via J.H. Dunant 3, 21100, Varese, Italy aut NATIONALLICENCE 773 0- Molecular Diversity Springer Netherlands 15/2(2011-05-01), 467-476 1381-1991 15:2<467 2011 15 11030 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer