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The primary objective of this work was to compare PODs based on high-throughput predictions of bioactivity, exposure predictions, and traditional hazard information for 448 chemicals. PODs derived from new approach methodologies (NAMs) were obtained for this comparison using the 50th (PODNAM, 50) and the 95th (PODNAM, 95) percentile credible interval estimates for the steady-state plasma concentration used in in vitro to in vivo extrapolation of administered equivalent doses. Of the 448 substances, 89% had a PODNAM, 95 that was less than the traditional POD (PODtraditional) value. For the 48 substances for which PODtraditional &amp;lt; PODNAM, 95, the PODNAM and PODtraditional were typically within a factor of 10 of each other, and there was an enrichment of chemical structural features associated with organophosphate and carbamate insecticides. When PODtraditional &amp;lt; PODNAM, 95, it did not appear to result from an enrichment of PODtraditional based on a particular study type (eg, developmental, reproductive, and chronic studies). Bioactivity:exposure ratios, useful for identification of substances with potential priority, demonstrated that high-throughput exposure predictions were greater than the PODNAM, 95 for 11 substances. When compared with threshold of toxicological concern (TTC) values, the PODNAM, 95 was greater than the corresponding TTC value 90% of the time. This work demonstrates the feasibility, and continuing challenges, of using in vitro bioactivity as a protective estimate of POD in screening-level assessments via a case study.<\/jats:p>","DOI":"10.1093\/toxsci\/kfz201","type":"journal-article","created":{"date-parts":[[2019,9,13]],"date-time":"2019-09-13T19:31:01Z","timestamp":1568403061000},"page":"202-225","source":"Crossref","is-referenced-by-count":227,"title":["Utility of In Vitro Bioactivity as a Lower Bound Estimate of In Vivo Adverse Effect Levels and in Risk-Based Prioritization"],"prefix":"10.1093","volume":"173","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2710-1691","authenticated-orcid":false,"given":"Katie","family":"Paul Friedman","sequence":"first","affiliation":[{"name":"National Center for Computational Toxicology, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC, 27711"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Gagne","sequence":"additional","affiliation":[{"name":"Healthy Environments and Consumer Safety Branch, Health Canada, Government of Canada, Ottawa, Ontario, Canada, K1A0K9"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lit-Hsin","family":"Loo","sequence":"additional","affiliation":[{"name":"Innovations in Food and Chemical Safety Programme and Bioinformatics Institute, Agency for Science, Technology and Research, Singapore, 138671, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiotis","family":"Karamertzanis","sequence":"additional","affiliation":[{"name":"Computational Assessment Unit, European Chemicals Agency, European Chemicals Agency Annankatu 18, P.O. Box 400, FI-00121 Helsinki, Uusimaa, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Netzeva","sequence":"additional","affiliation":[{"name":"Computational Assessment Unit, European Chemicals Agency, European Chemicals Agency Annankatu 18, P.O. Box 400, FI-00121 Helsinki, Uusimaa, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Sobanski","sequence":"additional","affiliation":[{"name":"Computational Assessment Unit, European Chemicals Agency, European Chemicals Agency Annankatu 18, P.O. Box 400, FI-00121 Helsinki, Uusimaa, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill A","family":"Franzosa","sequence":"additional","affiliation":[{"name":"National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC, 27711"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann M","family":"Richard","sequence":"additional","affiliation":[{"name":"National Center for Computational Toxicology, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC, 27711"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan R","family":"Lougee","sequence":"additional","affiliation":[{"name":"National Center for Computational Toxicology, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC, 27711"},{"name":"Oak Ridge Institute for Science and Education, U.S. Department of Energy, Oak Ridge, TN 37831, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Gissi","sequence":"additional","affiliation":[{"name":"Computational Assessment Unit, European Chemicals Agency, European Chemicals Agency Annankatu 18, P.O. Box 400, FI-00121 Helsinki, Uusimaa, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Ying Joey","family":"Lee","sequence":"additional","affiliation":[{"name":"Innovations in Food and Chemical Safety Programme and Bioinformatics Institute, Agency for Science, Technology and Research, Singapore, 138671, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Angrish","sequence":"additional","affiliation":[{"name":"National Center for Environmental Assessment, Office of Research and Development, US Environmental Protection Agency, Washington, DC, 20004 and Research Triangle Park, NC 27711"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Lou","family":"Dorne","sequence":"additional","affiliation":[{"name":"Scientific Committee and Emerging Risks Unit Department of Risk Assessment and Scientific Assistance, Via Carlo Magno 1A, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stiven","family":"Foster","sequence":"additional","affiliation":[{"name":"Office of Land and Emergency Management, U.S. Environmental Protection Agency, Washington, DC, 20004"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Raffaele","sequence":"additional","affiliation":[{"name":"Office of Land and Emergency Management, U.S. Environmental Protection Agency, Washington, DC, 20004"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Bahadori","sequence":"additional","affiliation":[{"name":"Oak Ridge Institute for Science and Education, U.S. Department of Energy, Oak Ridge, TN 37831, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen R","family":"Gwinn","sequence":"additional","affiliation":[{"name":"National Center for Computational Toxicology, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC, 27711"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Lambert","sequence":"additional","affiliation":[{"name":"National Center for Computational Toxicology, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC, 27711"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurice","family":"Whelan","sequence":"additional","affiliation":[{"name":"European Commission, Joint Research Centre (JRC), Via Enrico Fermi, 2749, I - 21027 Ispra, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Rasenberg","sequence":"additional","affiliation":[{"name":"Computational Assessment Unit, European Chemicals Agency, European Chemicals Agency Annankatu 18, P.O. 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