{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:43:05Z","timestamp":1790714585258,"version":"4.1.0"},"reference-count":33,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2014,12,1]],"date-time":"2014-12-01T00:00:00Z","timestamp":1417392000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Regulatory Toxicology and Pharmacology"],"published-print":{"date-parts":[[2014,12]]},"DOI":"10.1016\/j.yrtph.2014.09.011","type":"journal-article","created":{"date-parts":[[2014,10,9]],"date-time":"2014-10-09T07:12:26Z","timestamp":1412838746000},"page":"648-658","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":53,"title":["Liver tumor formation in female rat induced by fluopyram is mediated by CAR\/PXR nuclear receptor activation"],"prefix":"10.1016","volume":"70","author":[{"given":"H.","family":"Tinwell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Rouqui\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Schorsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Geter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Wason","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Bars","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"Pt 2","key":"10.1016\/j.yrtph.2014.09.011_b0005","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1042\/bj3060473","article-title":"Identification and characterization of DNA elements implicated in the regulation of CYP4A1 transcription","volume":"306","author":"Aldridge","year":"1995","journal-title":"Biochem. J."},{"key":"10.1016\/j.yrtph.2014.09.011_b0010","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1124\/dmd.105.008185","article-title":"Cytochrome P450 gene induction in rats ex vivo assessed by quantitative real-time reverse transcriptase-polymerase chain reaction (TaqMan)","volume":"34","author":"Baldwin","year":"2006","journal-title":"Drug Metab. Dispos."},{"key":"10.1016\/j.yrtph.2014.09.011_b0015","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/0278-6915(93)90225-N","article-title":"Hepatic peroxisome proliferation in rodents and its significance for humans","volume":"31","author":"Bentley","year":"1993","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.yrtph.2014.09.011_b0020","doi-asserted-by":"crossref","first-page":"3337","DOI":"10.1016\/0006-2952(85)90355-7","article-title":"Ethoxy-, pentoxy- and benzyloxyphenoxazones and homologues: a series of substrates to distinguish between different induced cytochromes P-450","volume":"34","author":"Burke","year":"1985","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.yrtph.2014.09.011_b0030","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1177\/0192623310363813","article-title":"Evaluation of possible carcinogenic risk to humans based on liver tumors in rodent assays: the two-year bioassay is no longer necessary","volume":"38","author":"Cohen","year":"2010","journal-title":"Toxicol. Pathol."},{"issue":"2","key":"10.1016\/j.yrtph.2014.09.011_b0035","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/S0014-5793(98)00246-4","article-title":"Phenobarbital induces cytochrome P4501A2 hnRNA, mRNA and protein in the liver of C57BL\/6J wild type and aryl hydrocarbon receptor knock-out mice","volume":"425","author":"Corcos","year":"1998","journal-title":"FEBS Lett."},{"key":"10.1016\/j.yrtph.2014.09.011_b0040","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/0300-483X(77)90049-X","article-title":"Long-term studies in chemically induced liver enlargement in the rat. I. Sustained induction of microsomal enzymes with absence of liver damage on feeding phenobarbitone or butylated hydroxytoluene","volume":"7","author":"Crampton","year":"1977","journal-title":"Toxicology"},{"issue":"1","key":"10.1016\/j.yrtph.2014.09.011_b0045","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1093\/toxsci\/kfp006","article-title":"Mode of action analysis for the synthetic pyrethroid metofluthrin-induced rat liver tumors: evidence for hepatic CYP2B induction and hepatocyte proliferation","volume":"108","author":"Deguchi","year":"2009","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.yrtph.2014.09.011_b0050","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1080\/00401706.1964.10490181","article-title":"Multiple comparisons using rank sums","volume":"6","author":"Dunn","year":"1964","journal-title":"Technometrics"},{"key":"10.1016\/j.yrtph.2014.09.011_b0055","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1080\/01621459.1955.10501294","article-title":"A multiple comparison procedure for comparing several treatments with a control","volume":"50","author":"Dunnett","year":"1955","journal-title":"J. Am. Stat. Assoc."},{"key":"10.1016\/j.yrtph.2014.09.011_b0060","doi-asserted-by":"crossref","first-page":"64","DOI":"10.3109\/10408444.2013.835786","article-title":"Mode of action and human relevance analysis for nuclear receptor-mediated liver toxicity: a case study with phenobarbital as a model constitutive androstane receptor (CAR) activator","volume":"44","author":"Elcombe","year":"2013","journal-title":"Crit. Rev. Toxicol."},{"key":"10.1016\/j.yrtph.2014.09.011_b0065","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1080\/01926230590888324","article-title":"Classification of proliferative hepatocellular lesions in harlan sprague\u2013dawley rats chronically exposed to dioxin-like compounds","volume":"33","author":"Hailey","year":"2005","journal-title":"Toxicol. Pathol."},{"key":"10.1016\/j.yrtph.2014.09.011_b0070","first-page":"2946","article-title":"Roles of cytochrome P-450 enzymes in chemical carcinogenesis and cancer chemotherapy","volume":"48","author":"Guengerich","year":"1988","journal-title":"Cancer Res."},{"key":"10.1016\/j.yrtph.2014.09.011_b0075","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1093\/toxsci\/kfj001","article-title":"Mode of action in relevance of rodent liver tumors to human cancer risk","volume":"89","author":"Holsapple","year":"2006","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.yrtph.2014.09.011_b0080","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1093\/toxsci\/64.2.192","article-title":"Reversibility and persistence of di-2-ethylhexyl phthalate (DEHP)-and phenobarbital induced hepatocellular changes in rodents","volume":"64","author":"Isenberg","year":"2001","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.yrtph.2014.09.011_b0085","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.taap.2013.09.016","article-title":"Mode of action of ethyl tertiary-butyl ether hepatotumorigenicity in the rat: evidence for a role of oxidative stress via activation of CAR, PXR and PPAR signaling pathways","volume":"273","author":"Kakehashi","year":"2013","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.yrtph.2014.09.011_b0090","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.reprotox.2003.10.012","article-title":"Evaluation of the rodent Hershberger assay using three reference endocrine disrupters (androgen and antiandrogens)","volume":"18","author":"Kennel","year":"2004","journal-title":"Reprod. Toxicol."},{"key":"10.1016\/j.yrtph.2014.09.011_b0095","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1016\/0006-2952(78)90144-2","article-title":"The effect of prolonged sodium phenobarbitone treatment on hepatic xenobiotic metabolism and the urinary excretion of metabolites of the d-glucuronic acid pathway in the rat","volume":"27","author":"Lake","year":"1978","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.yrtph.2014.09.011_b0100","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.taap.2013.04.009","article-title":"An integrated approach for prospectively investigating a mode-of-action for rodent liver effects","volume":"270","author":"LeBaron","year":"2013","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.yrtph.2014.09.011_b0105","series-title":"Levene Test in Biometry","author":"Sokal","year":"1981"},{"key":"10.1016\/j.yrtph.2014.09.011_b0110","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1093\/toxsci\/kfr099","article-title":"A molecular and phenotypic integrative approach to identify a no-effect dose level for antiandrogen-induced testicular toxicity","volume":"122","author":"Ludwig","year":"2011","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.yrtph.2014.09.011_b0115","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1007\/s11095-005-9571-z","article-title":"A mechanism-based integrated pharmacokinetic enzyme model describing the time course and magnitude of phenobarbital-mediated enzyme induction in the rat","volume":"23","author":"Magnusson","year":"2006","journal-title":"Pharm. Res."},{"key":"10.1016\/j.yrtph.2014.09.011_b0120","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1177\/0192623310373778","article-title":"Hepatic enzyme induction: histopathology","volume":"38","author":"Maronpot","year":"2010","journal-title":"Toxicol. Pathol."},{"key":"10.1016\/j.yrtph.2014.09.011_b0130","first-page":"7415","article-title":"Increased cell division as a cause of human cancer","volume":"50","author":"Preston-Martin","year":"1990","journal-title":"Cancer Res."},{"key":"10.1016\/j.yrtph.2014.09.011_b0135","doi-asserted-by":"crossref","first-page":"97","DOI":"10.3109\/10408447409079856","article-title":"Induction of liver growth by xenobiotic compounds and other stimuli","volume":"3","author":"Schulte-Hermann","year":"1974","journal-title":"CRC Crit. Rev. Toxicol."},{"key":"10.1016\/j.yrtph.2014.09.011_b0140","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1006\/rtph.2001.1493","article-title":"IPCS conceptual framework for evaluating a mode of action for chemical carcinogenesis","volume":"34","author":"Sonich-Mullin","year":"2001","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"10.1016\/j.yrtph.2014.09.011_b0145","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.taap.2006.08.011","article-title":"In vitro screening of 200 pesticides for agonistic activity via mouse peroxisome proliferator-activated receptor (PPAR)alpha and PPARgamma and quantitative analysis of in vivo induction pathway","volume":"217","author":"Takeuchi","year":"2006","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.yrtph.2014.09.011_b0150","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1124\/mol.61.1.1","article-title":"Diverse roles of the nuclear orphan receptor CAR in regulating hepatic genes in response to phenobarbital","volume":"61","author":"Ueda","year":"2002","journal-title":"Mol. Pharmacol."},{"key":"10.1016\/j.yrtph.2014.09.011_b0155","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1080\/01480540802390825","article-title":"Temporal evaluation of CYP mRNA in mice administered with prototypical P450 inducers: comparison with conventional protein\/enzyme methods","volume":"31","author":"Wang","year":"2008","journal-title":"Drug Chem. Toxicol."},{"key":"10.1016\/j.yrtph.2014.09.011_b0160","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1038\/35038112","article-title":"The nuclear receptor CAR mediates specific xenobiotic induction of drug metabolism","volume":"407","author":"Wei","year":"2000","journal-title":"Nature"},{"key":"10.1016\/j.yrtph.2014.09.011_b0165","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/0163-7258(96)00067-8","article-title":"Phenobarbital mechanistic data and risk assessment: enzyme induction, enhanced cell proliferation, and tumor promotion","volume":"71","author":"Whysner","year":"1996","journal-title":"Pharmacol. Ther."},{"key":"10.1016\/j.yrtph.2014.09.011_b0170","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1093\/toxsci\/kfp007","article-title":"Case study: an evaluation of the human relevance of the synthetic pyrethroid metofluthrin-induced liver tumors in rats based on mode of action","volume":"108","author":"Yamada","year":"2009","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.yrtph.2014.09.011_b0175","doi-asserted-by":"crossref","first-page":"7197","DOI":"10.1158\/0008-5472.CAN-04-1459","article-title":"The orphan nuclear receptor constitutive active\/androstane receptor is essential for liver tumor promotion by phenobarbital in mice","volume":"64","author":"Yamamoto","year":"2004","journal-title":"Cancer Res."}],"container-title":["Regulatory Toxicology and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0273230014002165?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0273230014002165?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2020,8,25]],"date-time":"2020-08-25T16:42:20Z","timestamp":1598373740000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0273230014002165"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,12]]},"references-count":33,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2014,12]]}},"alternative-id":["S0273230014002165"],"URL":"https:\/\/doi.org\/10.1016\/j.yrtph.2014.09.011","relation":{},"ISSN":["0273-2300"],"issn-type":[{"value":"0273-2300","type":"print"}],"subject":[],"published":{"date-parts":[[2014,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Liver tumor formation in female rat induced by fluopyram is mediated by CAR\/PXR nuclear receptor activation","name":"articletitle","label":"Article Title"},{"value":"Regulatory Toxicology and Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.yrtph.2014.09.011","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2014 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}