{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:03:48Z","timestamp":1791461028594,"version":"4.3.4"},"reference-count":56,"publisher":"American Chemical Society (ACS)","issue":"8","license":[{"start":{"date-parts":[[2017,12,29]],"date-time":"2017-12-29T00:00:00Z","timestamp":1514505600000},"content-version":"vor","delay-in-days":716,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>In ToxCast\u2122 Phase I, the U.S. EPA commissioned screening of 320 pesticides, herbicides, fungicides, and other chemicals in a series of high-throughput assays. The agency also developed a toxicological prioritization tool, ToxPi, to facilitate using ToxCast\u2122 assays to predict biological function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>We asked whether top-scoring PPAR\u03b3 activators identified in ToxCast\u2122 Phase I were genuine PPAR\u03b3 activators and inducers of adipogenesis. Next, we identified ToxCast\u2122 assays that should predict adipogenesis, developed an adipogenesis ToxPi, and asked how well the ToxPi predicted adipogenic activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We used transient transfection to test the ability of ToxCast\u2122 chemicals to modulate PPAR\u03b3 and RXR\u03b1, and differentiation assays employing 3T3-L1 preadipocytes and mouse bone marrow-derived mesenchymal stem cells (mBMSCs) to evaluate the adipogenic capacity of ToxCast\u2122 chemicals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Only 5\/21 of the top scoring ToxCast\u2122 PPAR\u03b3 activators were activators in our assays, 3 were PPAR\u03b3 antagonists, the remainder were inactive. The bona fide PPAR\u03b3 activators we identified induced adipogenesis in 3T3-L1 cells and mBMSCs. Only 7 of the 17 chemicals predicted to be active by the ToxPi promoted adipogenesis, 1 inhibited adipogenesis, and 2 of the 7 predicted negatives were also adipogenic. Of these 9 adipogenic chemicals, 3 activated PPAR\u03b3, and 1 activated RXR\u03b1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>ToxCast\u2122 PPAR\u03b3 and RXR\u03b1 assays do not correlate well with laboratory measurements of PPAR\u03b3 and RXR\u03b1 activity. The adipogenesis ToxPi performed poorly, perhaps due to the performance of ToxCast\u2122 assays. We observed a modest predictive value of ToxCast\u2122 for PPAR\u03b3 and RXR\u03b1 activation and adipogenesis and it is likely that many obesogenic chemicals remain to be identified.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Citation:<\/jats:title>\n                    <jats:p>Janesick AS, Dimastrogiovanni G, Vanek L, Boulos C, Chamorro-Garc\u00eda R, Tang W, Blumberg B. 2016. On the utility of ToxCast\u2122 and ToxPi as methods for identifying new obesogens. Environ Health Perspect 124:1214\u20131226;\u2002http:\/\/dx.doi.org\/10.1289\/ehp.1510352<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1289\/ehp.1510352","type":"journal-article","created":{"date-parts":[[2016,1,12]],"date-time":"2016-01-12T09:41:03Z","timestamp":1452591663000},"page":"1214-1226","source":"Crossref","is-referenced-by-count":84,"title":["On the Utility of ToxCast\u2122 and ToxPi as Methods for Identifying New Obesogens"],"prefix":"10.1021","volume":"124","author":[{"given":"Amanda Shaine","family":"Janesick","sequence":"first","affiliation":[{"name":"Department of Developmental and Cell Biology, University of California, Irvine, Irvine, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Dimastrogiovanni","sequence":"additional","affiliation":[{"name":"Department of Environmental Chemistry, IIQAB-CSIC (Superior Council of Scientific Investigations), Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lenka","family":"Vanek","sequence":"additional","affiliation":[{"name":"Department of Developmental and Cell Biology, University of California, Irvine, Irvine, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christy","family":"Boulos","sequence":"additional","affiliation":[{"name":"Department of Developmental and Cell Biology, University of California, Irvine, Irvine, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Chamorro-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Developmental and Cell Biology, University of California, Irvine, Irvine, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyi","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Developmental and Cell Biology, University of California, Irvine, Irvine, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Blumberg","sequence":"additional","affiliation":[{"name":"Department of Developmental and Cell Biology, University of California, Irvine, Irvine, California, USA"},{"name":"Department of Pharmaceutical Sciences, University of California, Irvine, Irvine, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2016,1,13]]},"reference":[{"key":"2026081810463133200_micit1","article-title":"Data Reduction and Error Analysis for the Physical Sciences.","author":"Bevington PR, Robinson DK","year":"2003"},{"issue":"14","key":"2026081810463133200_micit2","doi-asserted-by":"crossref","first-page":"8804","DOI":"10.1021\/acs.est.5b02641","article-title":"Screening chemicals for estrogen receptor bioactivity using a computational model.","volume":"49","author":"Browne","year":"2015","journal-title":"Environ Sci Technol"},{"issue":"4","key":"2026081810463133200_micit3","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nrm3312","article-title":"Transcriptional integration of metabolism by the nuclear sterol-activated receptors LXR and FXR.","volume":"13","author":"Calkin","year":"2012","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2026081810463133200_micit4","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.coph.2014.10.010","article-title":"Transgenerational effects of obesogens and the obesity epidemic.","volume":"19","author":"Chamorro-Garc\u00eda","year":"2014","journal-title":"Curr Opin Pharmacol"},{"key":"2026081810463133200_micit5","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1289\/ehp.1205063","article-title":"Bisphenol A diglycidyl ether induces adipogenic differentiation of multipotent stromal stem cells through a peroxisome proliferator\u2013activated receptor gamma-independent mechanism.","volume":"120","author":"Chamorro-Garc\u00eda","year":"2012","journal-title":"Environ Health Perspect"},{"key":"2026081810463133200_micit6","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1289\/ehp.1205701","article-title":"Transgenerational inheritance of increased fat depot size, stem cell reprogramming, and hepatic steatosis elicited by prenatal exposure to the obesogen tributyltin in mice.","volume":"121","author":"Chamorro-Garc\u00eda","year":"2013","journal-title":"Environ Health Perspect"},{"issue":"4","key":"2026081810463133200_micit7","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1021\/ci900464s","article-title":"Drug- and lead-likeness, target class, and molecular diversity analysis of 7.9 million commercially available organic compounds provided by 29 suppliers.","volume":"50","author":"Chuprina","year":"2010","journal-title":"J Chem Inf Model"},{"issue":"5865","key":"2026081810463133200_micit8","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1126\/science.1154619","article-title":"Toxicology. 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