{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T22:04:48Z","timestamp":1775253888284,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,10,19]],"date-time":"2018-10-19T00:00:00Z","timestamp":1539907200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004341","name":"The Dow Chemical Company","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100004341","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environ and Mol Mutagen"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:p>\n                    The\n                    <jats:italic>Pig\u2010a<\/jats:italic>\n                    assay is an emerging and promising\n                    <jats:italic>in vivo<\/jats:italic>\n                    method to determine mutagenic potential of chemicals. Since its development in 2008, remarkable progress has been made in harmonizing and characterizing the test procedures, primarily using known mutagenic chemicals. The purpose of the present study was to evaluate specificity of the\n                    <jats:italic>Pig\u2010a<\/jats:italic>\n                    assay using two nongenotoxic and well\u2010characterized rodent liver carcinogens, phenobarbital and clofibrate, in male F344\/DuCrl rats. Daily oral administration of phenobarbital or clofibrate at established hepatotoxic doses for 28 days resulted in substantial hepatic alterations, however, did not increase the frequency of\n                    <jats:italic>Pig\u2010a<\/jats:italic>\n                    mutation markers (RET\n                    <jats:sup>CD59\u2010<\/jats:sup>\n                    and RBC\n                    <jats:sup>CD59\u2010<\/jats:sup>\n                    ) compared to vehicle control or pre\u2010exposure (Day \u22125) mutant frequencies. These results are consistent with the existing literature on the nonmutagenic mode of action (MoA) of phenobarbital and clofibrate liver tumors. The present study contributes to the limited, but expanding evidence on the specificity of the\n                    <jats:italic>Pig\u2010a<\/jats:italic>\n                    assay and further for the investigations of carcinogenic MoAs,\n                    <jats:italic>i.e<\/jats:italic>\n                    ., mutagenic or nonmutagenic potential of chemicals. Environ. Mol. Mutagen. 60:42\u201346, 2019. \u00a9 2018 Wiley Periodicals, Inc.\n                  <\/jats:p>","DOI":"10.1002\/em.22232","type":"journal-article","created":{"date-parts":[[2018,10,19]],"date-time":"2018-10-19T04:50:51Z","timestamp":1539924651000},"page":"42-46","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pilot studies evaluating the nongenotoxic rodent carcinogens phenobarbital and clofibrate in the rat\n                    <i>Pig\u2010a<\/i>\n                    assay"],"prefix":"10.1002","volume":"60","author":[{"given":"Zhiying","family":"Ji","sequence":"first","affiliation":[{"name":"Toxicology and Environmental Research and Consulting The Dow Chemical Company Midland Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raja S.","family":"Settivari","sequence":"additional","affiliation":[{"name":"Toxicology and Environmental Research and Consulting The Dow Chemical Company Midland Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew J.","family":"LeBaron","sequence":"additional","affiliation":[{"name":"Toxicology and Environmental Research and Consulting The Dow Chemical Company Midland Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,10,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477-3163-3-7"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.20379"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.20686"},{"issue":"1","key":"e_1_2_8_5_1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S0022-3565(25)30738-X","article-title":"Clofibrate and clofibric acid: comparison of the metabolic disposition in rats and dogs","volume":"200","author":"Cayen MN","year":"1977","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3109\/10408444.2013.835784"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrgentox.2011.01.009"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfs258"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.21846"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.20671"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.20627"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3109\/10408444.2013.835786"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfu014"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/mutage\/gev005"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrgentox.2014.09.007"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.21863"},{"key":"e_1_2_8_17_1","first-page":"391","article-title":"Monographs on the Evaluation of Carcinogenic Risks to Humans","volume":"66","author":"IARC","year":"1996","journal-title":"Clofibrate"},{"key":"e_1_2_8_18_1","first-page":"161","article-title":"Monographs on the Evaluation of Carcinogenic Risks to Humans","volume":"79","author":"IARC","year":"2001","journal-title":"Phenobarbital and its Sodium Salt"},{"issue":"1","key":"e_1_2_8_19_1","first-page":"S76","article-title":"Utilizing the Pig\u2010a Assay to Assess in vivo Mutagenicity in an Integrated Testing Strategy and Comparing Pig\u2010a to the TGR mutation Assay","volume":"56","author":"Ji Z","year":"2015","journal-title":"Environmental and Molecular Mutagenesis"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.2131\/jts.37.943"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.20691"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.20614"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2017.05.013"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.20414"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.20413"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrgentox.2008.08.011"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.20687"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.20692"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrgentox.2015.01.002"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.21709"},{"key":"e_1_2_8_31_1","unstructured":"WHO.2015. 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