caa a22 4500 37886193X CHVBK 20180305123348.0 cr unu---uuuuu 161128e20030101xx s 000 0 eng 10.1351/pac200375112389 doi (NATIONALLICENCE)gruyter-10.1351/pac200375112389 QSAR prioritization of chemical inventories for endocrine disruptor testing [Elektronische Daten] [P. Schmieder, Ovanes Mekenyan, Steven Bradbury, G. Veith] Binding affinity between chemicals and the estrogen receptor (ER) serves as an indicator of the potential to cause endocrine disruption through this receptor-mediated endocrine pathway. Estimating ER-binding affinity is, therefore, one strategic approach to reducing the costs of screening chemicals for potential risks of endocrine disruption. While measuring ER binding with in vitro assays may be the first choice in prioritizing chemicals for additional in vitro or in vivo estrogenicity testing, the time and costs associated with screening thousands of chemicals is prohibitive. Recent advances in 3D modeling of the reactivity of flexible structures make in silico methods for estimating ER binding possible. One technique, the common reactivity pattern (COREPA) approach, was applied to development of reactivity patterns for ER relative binding affinity based on global nucleophilicity, interatomic distances between nucleophilic sites, and local electron donor capability of the nucleophilic sites. The reactivity patterns provided descriptor profiles for order-of-magnitude RBA ranges of training set chemicals. An exploratory expert system was subsequently developed to predict RBA and rank chemicals with respect to potential estrogenicity. A strategy is presented for extending initial exploratory 3D QSAR models beyond current training sets to increase applicability to more diverse structures in large chemical inventories. © 2013 Walter de Gruyter GmbH, Berlin/Boston Schmieder P. U.S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Mid- Continent Ecology Division, 6201 Congdon Blvd., Duluth, MN 55804, USA; Laboratory of Mathematical Chemistry, University "Prof. As. Zlatarov ”, 8010 Bourgas, Bulgaria; U.S. Environmental Protection Agency, Office of Pesticide Programs, Environmental Fate and Effects Division, Washington, DC 20460, USA aut Mekenyan Ovanes U.S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Mid- Continent Ecology Division, 6201 Congdon Blvd., Duluth, MN 55804, USA; Laboratory of Mathematical Chemistry, University "Prof. As. Zlatarov ”, 8010 Bourgas, Bulgaria; U.S. Environmental Protection Agency, Office of Pesticide Programs, Environmental Fate and Effects Division, Washington, DC 20460, USA aut Bradbury Steven U.S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Mid- Continent Ecology Division, 6201 Congdon Blvd., Duluth, MN 55804, USA; Laboratory of Mathematical Chemistry, University "Prof. As. Zlatarov ”, 8010 Bourgas, Bulgaria; U.S. Environmental Protection Agency, Office of Pesticide Programs, Environmental Fate and Effects Division, Washington, DC 20460, USA aut Veith G. U.S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Mid- Continent Ecology Division, 6201 Congdon Blvd., Duluth, MN 55804, USA; Laboratory of Mathematical Chemistry, University "Prof. As. Zlatarov ”, 8010 Bourgas, Bulgaria; U.S. Environmental Protection Agency, Office of Pesticide Programs, Environmental Fate and Effects Division, Washington, DC 20460, USA aut Pure and Applied Chemistry De Gruyter 75/11-12(2003-01-01), 2389-2396 0033-4545 75:11-12<2389 2003 75 pac https://doi.org/10.1351/pac200375112389 text/html Onlinezugriff via DOI 1 research article jats NATIONALLICENCE 856 40 https://doi.org/10.1351/pac200375112389 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Schmieder P. U.S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Mid- Continent Ecology Division, 6201 Congdon Blvd., Duluth, MN 55804, USA; Laboratory of Mathematical Chemistry, University "Prof. As. Zlatarov ”, 8010 Bourgas, Bulgaria; U.S. Environmental Protection Agency, Office of Pesticide Programs, Environmental Fate and Effects Division, Washington, DC 20460, USA aut NATIONALLICENCE 700 1- Mekenyan Ovanes U.S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Mid- Continent Ecology Division, 6201 Congdon Blvd., Duluth, MN 55804, USA; Laboratory of Mathematical Chemistry, University "Prof. As. Zlatarov ”, 8010 Bourgas, Bulgaria; U.S. Environmental Protection Agency, Office of Pesticide Programs, Environmental Fate and Effects Division, Washington, DC 20460, USA aut NATIONALLICENCE 700 1- Bradbury Steven U.S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Mid- Continent Ecology Division, 6201 Congdon Blvd., Duluth, MN 55804, USA; Laboratory of Mathematical Chemistry, University "Prof. As. Zlatarov ”, 8010 Bourgas, Bulgaria; U.S. Environmental Protection Agency, Office of Pesticide Programs, Environmental Fate and Effects Division, Washington, DC 20460, USA aut NATIONALLICENCE 700 1- Veith G. U.S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Mid- Continent Ecology Division, 6201 Congdon Blvd., Duluth, MN 55804, USA; Laboratory of Mathematical Chemistry, University "Prof. As. Zlatarov ”, 8010 Bourgas, Bulgaria; U.S. Environmental Protection Agency, Office of Pesticide Programs, Environmental Fate and Effects Division, Washington, DC 20460, USA aut NATIONALLICENCE 773 0- Pure and Applied Chemistry De Gruyter 75/11-12(2003-01-01), 2389-2396 0033-4545 75:11-12<2389 2003 75 pac CC0 http://creativecommons.org/publicdomain/zero/1.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-gruyter