caa a22 4500 378861425 CHVBK 20180305123347.0 cr unu---uuuuu 161128e20030101xx s 000 0 eng 10.1351/pac200375112375 doi (NATIONALLICENCE)gruyter-10.1351/pac200375112375 Regulatory application of SAR/QSAR for priority setting of endocrine disruptors: A perspective [Elektronische Daten] [W. Tong, Hong Fang, H. Hong, Q. Xie, R. Perkins, Jeanne Anson, D. M. Sheehan] Some seven years have passed since the U.S. legislature mandated the EPA to develop and implement a screening and testing program for chemicals that may disrupt the delicate endocrine system. The envisioned EPA program has evolved to incorporate a tiered scheme of in vitro and in vivo assays, and considered QSAR as a viable method to set testing priorities. At the U.S. FDA's National Center for Toxicological Research (NCTR), the Endocrine Disruptor Knowledge Base Project has developed models to predict estrogen and androgen receptor binding. Our approach rationally integrates various QSAR models into a sequential "Four-Phase" scheme according to the strength of each type of model. In four hierarchical phases, models predict the inactive chemicals that are then eliminated from the pool of chemicals to which increasingly precise but more time-consuming models are subsequently applied. Each phase employs different models selected to work complementarily in representing key activity-determining structure features in order to absolutely minimize the rate of false negatives, an outcome we view as paramount for regulatory use. In this paper, the QSAR models developed at NCTR, and particularly how we integrated these models into the "Four-Phase" system will be discussed for a number of datasets, including 58 000 chemicals identified by the U.S. EPA. © 2013 Walter de Gruyter GmbH, Berlin/Boston Tong W. FDA 's National Center for Toxicological Research (NCTR), Jefferson, AR 72079, USA; Logicon ROW Sciences, Jefferson, AR 72079, USA aut Fang Hong FDA 's National Center for Toxicological Research (NCTR), Jefferson, AR 72079, USA; Logicon ROW Sciences, Jefferson, AR 72079, USA aut Hong H. FDA 's National Center for Toxicological Research (NCTR), Jefferson, AR 72079, USA; Logicon ROW Sciences, Jefferson, AR 72079, USA aut Xie Q. FDA 's National Center for Toxicological Research (NCTR), Jefferson, AR 72079, USA; Logicon ROW Sciences, Jefferson, AR 72079, USA aut Perkins R. FDA 's National Center for Toxicological Research (NCTR), Jefferson, AR 72079, USA; Logicon ROW Sciences, Jefferson, AR 72079, USA aut Anson Jeanne FDA 's National Center for Toxicological Research (NCTR), Jefferson, AR 72079, USA; Logicon ROW Sciences, Jefferson, AR 72079, USA aut Sheehan D. M. FDA 's National Center for Toxicological Research (NCTR), Jefferson, AR 72079, USA; Logicon ROW Sciences, Jefferson, AR 72079, USA aut Pure and Applied Chemistry De Gruyter 75/11-12(2003-01-01), 2375-2388 0033-4545 75:11-12<2375 2003 75 pac https://doi.org/10.1351/pac200375112375 text/html Onlinezugriff via DOI 1 research article jats NATIONALLICENCE 856 40 https://doi.org/10.1351/pac200375112375 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Tong W. FDA 's National Center for Toxicological Research (NCTR), Jefferson, AR 72079, USA; Logicon ROW Sciences, Jefferson, AR 72079, USA aut NATIONALLICENCE 700 1- Fang Hong FDA 's National Center for Toxicological Research (NCTR), Jefferson, AR 72079, USA; Logicon ROW Sciences, Jefferson, AR 72079, USA aut NATIONALLICENCE 700 1- Hong H. FDA 's National Center for Toxicological Research (NCTR), Jefferson, AR 72079, USA; Logicon ROW Sciences, Jefferson, AR 72079, USA aut NATIONALLICENCE 700 1- Xie Q. FDA 's National Center for Toxicological Research (NCTR), Jefferson, AR 72079, USA; Logicon ROW Sciences, Jefferson, AR 72079, USA aut NATIONALLICENCE 700 1- Perkins R. FDA 's National Center for Toxicological Research (NCTR), Jefferson, AR 72079, USA; Logicon ROW Sciences, Jefferson, AR 72079, USA aut NATIONALLICENCE 700 1- Anson Jeanne FDA 's National Center for Toxicological Research (NCTR), Jefferson, AR 72079, USA; Logicon ROW Sciences, Jefferson, AR 72079, USA aut NATIONALLICENCE 700 1- Sheehan D. M. FDA 's National Center for Toxicological Research (NCTR), Jefferson, AR 72079, USA; Logicon ROW Sciences, Jefferson, AR 72079, USA aut NATIONALLICENCE 773 0- Pure and Applied Chemistry De Gruyter 75/11-12(2003-01-01), 2375-2388 0033-4545 75:11-12<2375 2003 75 pac CC0 http://creativecommons.org/publicdomain/zero/1.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-gruyter