By:Leusch, FDL (Leusch, Frederic D. L.)^[ 1 ] ; Neale, PA (Neale, Peta A.)^[ 1 ] ; Busetti, F (Busetti, Francesco)^[ 2,3 ] ; Card, M (Card, Marcella)^[ 4,9 ] ; Humpage, A (Humpage, Andrew)^[ 5 ] ; Orbell, JD (Orbell, John D.)^[ 6 ] ; Ridgway, HF (Ridgway, Harry F.)^[ 7 ] ; Stewart, MB (Stewart, Matthew B.)^[ 6 ] ; van de Merwe, JP (van de Merwe, Jason P.)^[ 1 ] ; Escher, BI (Escher, Beate, I)^[ 1,4,8 ]

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Pharmaceuticals and personal care products (PPCPs) and endocrine disrupting compounds (EDCs) are frequently detected in drinking water sources. This raises concerns about the formation of potentially more toxic transformation products (TPs) after drinking water disinfection. This study applied a combination of computational and experimental methods to investigate the biological activity of eight EDCs and PPCPs commonly detected in source waters (acetaminophen, bisphenol A, carbamazepine, estrone, 17 alpha-ahinylestradiol, gemfibrozil, naproxen and triclosan) before and after disinfection. Using a Stepped Forced Molecular Dynamics (SFMD) method, we detected 911 unique TPs, 36% of which have been previously reported in the scientific literature. We calculated the likelihood that TPs would cause damage to biomolecules or DNA relative to the parent compound based on lipophilicity and the occurrence of structural alerts, and applied two Quantitative Structure-Activity Relationship (QSAR) tools to predict toxicity via receptor-mediated effects. In parallel, batch experiments were performed with three disinfectants, chlorine, chlorine dioxide and chloramine. After solid-phase extraction, the resulting TP mixtures were analyzed by chemical analysis and a battery of eleven in vitro bioassays covering a variety of endpoints. The laboratory results were in good agreement with the predictions. Overall, the combination of computational and experimental chemistry and toxicity methods used in this study suggest that disinfection of the studied EDCs and PPCPs will produce a large number of TPs, which are unlikely to increase specific toxicity (e.g., endocrine activity), but may result in increased reactive and non-specific toxicity. (C) 2018 Elsevier B.V. All rights reserved.