{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T03:49:01Z","timestamp":1778212141991,"version":"3.51.4"},"reference-count":43,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T00:00:00Z","timestamp":1605571200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015614","name":"Corteva Agriscience","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015614","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Food and Chemical Toxicology"],"published-print":{"date-parts":[[2021,1]]},"DOI":"10.1016\/j.fct.2020.111869","type":"journal-article","created":{"date-parts":[[2020,11,18]],"date-time":"2020-11-18T12:15:39Z","timestamp":1605701739000},"page":"111869","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":16,"special_numbering":"C","title":["A rat subchronic study transcriptional point of departure estimates a carcinogenicity study apical point of departure"],"prefix":"10.1016","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8135-9730","authenticated-orcid":false,"given":"Enrica","family":"Bianchi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1411-5338","authenticated-orcid":false,"given":"Eduardo","family":"Costa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongyu (June)","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynea","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9736-5211","authenticated-orcid":false,"given":"Jessica","family":"Howell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donna","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7179-7932","authenticated-orcid":false,"given":"Push","family":"Mukerji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anand","family":"Venkatraman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire","family":"Terry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4550-5566","authenticated-orcid":false,"given":"Kamin J.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.fct.2020.111869_bib1","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1177\/019262339602400610","article-title":"A critical appraisal of the value of the mouse cancer bioassay in safety assessment","volume":"24","author":"Alden","year":"1996","journal-title":"Toxicol. Pathol."},{"key":"10.1016\/j.fct.2020.111869_bib2","series-title":"Pronamide: Three Month Dietary Study in Rats","author":"Anderson","year":"1989"},{"key":"10.1016\/j.fct.2020.111869_bib3","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1002\/etc.34","article-title":"Adverse outcome pathways: a conceptual framework to support ecotoxicology research and risk assessment","volume":"29","author":"Ankley","year":"2010","journal-title":"Environ. Toxicol. Chem."},{"key":"10.1016\/j.fct.2020.111869_bib4","series-title":"Kerb Herbicide (Technical, No Clay): 24-Month Dietary Chronic Toxicity\/Carcinogenicity Study in Rats","author":"Bailey","year":"1990"},{"key":"10.1016\/j.fct.2020.111869_bib5","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1093\/toxsci\/kfh293","article-title":"Human carcinogenic risk evaluation, Part V: the national toxicology program vision for assessing the human carcinogenic hazard of chemicals","volume":"82","author":"Bucher","year":"2004","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.fct.2020.111869_bib6","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.yrtph.2019.01.017","article-title":"Chemical carcinogenicity revisited 3: risk assessment of carcinogenic potential based on the current state of knowledge of carcinogenesis in humans","volume":"103","author":"Cohen","year":"2019","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"10.1016\/j.fct.2020.111869_bib7","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1093\/toxsci\/kfh073","article-title":"Evaluating the human relevance of chemically induced animal tumors","volume":"78","author":"Cohen","year":"2004","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.fct.2020.111869_bib8","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1080\/713608371","article-title":"The human relevance of information on carcinogenic modes of action: overview","volume":"33","author":"Cohen","year":"2003","journal-title":"Crit. Rev. Toxicol."},{"key":"10.1016\/j.fct.2020.111869_bib9","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1006\/rtph.1997.1085","article-title":"Carcinogenicity testing and the evaluation of regulatory requirements for pharmaceuticals","volume":"25","author":"Contrera","year":"1997","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"10.1016\/j.fct.2020.111869_bib10","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.taap.2010.10.016","article-title":"Introduction to benchmark dose methods and U.S. EPA's benchmark dose software (BMDS) version 2.1.1","volume":"254","author":"Davis","year":"2011","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.fct.2020.111869_bib11","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1080\/10408440500534370","article-title":"A tiered approach to systemic toxicity testing for agricultural chemical safety assessment","volume":"36","author":"Doe","year":"2006","journal-title":"Crit. Rev. Toxicol."},{"key":"10.1016\/j.fct.2020.111869_bib12","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.yrtph.2019.01.024","article-title":"Chemical carcinogenicity revisited 2: current knowledge of carcinogenesis shows that categorization as a carcinogen or non-carcinogen is not scientifically credible","volume":"103","author":"Doe","year":"2019","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"10.1016\/j.fct.2020.111869_bib13","series-title":"Triclopyr: 2-Year Dietary Chronic Toxicity-Oncogenicity Study in Fischer 344 Rats","author":"Eisenbrandt","year":"1987"},{"key":"10.1016\/j.fct.2020.111869_bib14","first-page":"195","article-title":"Predicting the carcinogenicity of chemicals in humans from rodent bioassay data","volume":"94","author":"Goodman","year":"1991","journal-title":"Environ. Health Perspect."},{"key":"10.1016\/j.fct.2020.111869_bib15","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1093\/toxsci\/kfaa081","article-title":"Evaluation of 5-day in vivo rat liver and kidney with high-throughput transcriptomics for estimating benchmark doses of apical outcomes","volume":"176","author":"Gwinn","year":"2020","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.fct.2020.111869_bib16","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1080\/10408444.2018.1430121","article-title":"Benchmark dose (BMD) modeling: current practice, issues, and challenges","volume":"48","author":"Haber","year":"2018","journal-title":"Crit. Rev. Toxicol."},{"key":"10.1016\/j.fct.2020.111869_bib17","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1093\/toxsci\/kfaa062","article-title":"A rat liver transcriptomic point of departure predicts a prospective liver or non-liver apical point of departure","volume":"176","author":"Johnson","year":"2020","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.fct.2020.111869_bib18","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1177\/026119290603400117","article-title":"Animal carcinogenicity studies: 1. Poor human predictivity","volume":"34","author":"Knight","year":"2006","journal-title":"Altern Lab Anim"},{"key":"10.1016\/j.fct.2020.111869_bib19","series-title":"Triclopyr: 13-Week Dietary Toxicity Study in Fischer 344 Rats","author":"Landry","year":"1984"},{"key":"10.1016\/j.fct.2020.111869_bib20","doi-asserted-by":"crossref","first-page":"104655","DOI":"10.1016\/j.yrtph.2020.104655","article-title":"Short-term toxicogenomics as an alternative approach to chronic in vivo studies for derivation of points of departure: a case study in the rat with a triazole fungicide","volume":"113","author":"LaRocca","year":"2020","journal-title":"Regul. Toxicol. Pharmacol."},{"issue":"Suppl. 2","key":"10.1016\/j.fct.2020.111869_bib21","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3109\/10408444.2014.910751","article-title":"Human relevance framework for rodent liver tumors induced by the insecticide sulfoxaflor","volume":"44","author":"LeBaron","year":"2014","journal-title":"Crit. Rev. Toxicol."},{"key":"10.1016\/j.fct.2020.111869_bib22","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"10.1016\/j.fct.2020.111869_bib23","series-title":"Analysis of Carcinogenicity Testing for Regulatory Purposes in the European Union","author":"Madia","year":"2016"},{"key":"10.1016\/j.fct.2020.111869_bib24","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1080\/713608373","article-title":"A framework for human relevance analysis of information on carcinogenic modes of action","volume":"33","author":"Meek","year":"2003","journal-title":"Crit. Rev. Toxicol."},{"key":"10.1016\/j.fct.2020.111869_bib25","first-page":"452","article-title":"Guidance document 116 on the conduct and design of chronic toxicity and carcinogenicity studies","volume":"451","author":"Oecd","year":"2014","journal-title":"Supporting Test Guidelines"},{"key":"10.1016\/j.fct.2020.111869_bib26","series-title":"Test No. 451: Carcinogenicity Studies, OECD Guidelines for the Testing of Chemicals","author":"Oecd","year":"2018"},{"key":"10.1016\/j.fct.2020.111869_bib27","series-title":"Test No. 453: Combined Chronic Toxicity\/Carcinogenicity Studies","author":"Oecd","year":"2018"},{"key":"10.1016\/j.fct.2020.111869_bib28","doi-asserted-by":"crossref","first-page":"235","DOI":"10.14573\/altex.1608281","article-title":"Uncertainties of testing methods: what do we (want to) know about carcinogenicity?","volume":"34","author":"Paparella","year":"2017","journal-title":"ALTEX"},{"key":"10.1016\/j.fct.2020.111869_bib29","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1289\/ehp.1002735","article-title":"Moving forward in human cancer risk assessment","volume":"119","author":"Paules","year":"2011","journal-title":"Environ. Health Perspect."},{"key":"10.1016\/j.fct.2020.111869_bib30","series-title":"BMDExpress 2: Enhanced Transcriptomic Dose-Response Analysis Workflow","author":"Phillips","year":"2018"},{"issue":"Suppl. 2","key":"10.1016\/j.fct.2020.111869_bib31","doi-asserted-by":"crossref","first-page":"25","DOI":"10.3109\/10408444.2014.910750","article-title":"Mode-of-action and human relevance framework analysis for rat Leydig cell tumors associated with sulfoxaflor","volume":"44","author":"Rasoulpour","year":"2014","journal-title":"Crit. Rev. Toxicol."},{"key":"10.1016\/j.fct.2020.111869_bib32","series-title":"Pronamide (Propyzamide): 18-month Oncogenicity Study in CD-1 Mice","author":"Stebbins","year":"2004"},{"key":"10.1016\/j.fct.2020.111869_bib33","series-title":"XR-777: 90 Day Dietary Toxicity Study in F344\/DuCrl Rats","author":"Stebbins","year":"2012"},{"key":"10.1016\/j.fct.2020.111869_bib34","series-title":"XDE-777: Two-Year Dietary Chronic Toxicity\/Carcinogenicity Study in F344\/DuCrl Rats","author":"Stebbins","year":"2014"},{"key":"10.1016\/j.fct.2020.111869_bib36","series-title":"XDE-777: 18-month Dietary Oncogenicity Study in Crl:CD1(ICR)mice","author":"Thomas","year":"2013"},{"key":"10.1016\/j.fct.2020.111869_bib37","series-title":"XDE-208: Oncogenicity Study in Crl:CD1(ICR) Mice","author":"Thomas J","year":"2013"},{"key":"10.1016\/j.fct.2020.111869_bib35","series-title":"XDE-208: Two-Year Chronic Toxicity\/Oncogenicity Study in F344\/DuCrl Rats","author":"Stebbins","year":"2010"},{"key":"10.1016\/j.fct.2020.111869_bib38","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1093\/toxsci\/kfq355","article-title":"Application of transcriptional benchmark dose values in quantitative cancer and noncancer risk assessment","volume":"120","author":"Thomas","year":"2011","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.fct.2020.111869_bib39","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.mrgentox.2012.01.007","article-title":"Integrating pathway-based transcriptomic data into quantitative chemical risk assessment: a five chemical case study","volume":"746","author":"Thomas","year":"2012","journal-title":"Mutat. Res."},{"key":"10.1016\/j.fct.2020.111869_bib40","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1093\/toxsci\/kft094","article-title":"Temporal concordance between apical and transcriptional points of departure for chemical risk assessment","volume":"134","author":"Thomas","year":"2013","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.fct.2020.111869_bib41","series-title":"Triclopyr: 22-month Oral Chronic Toxicity and Oncogenicity Study in Mice","author":"Tsuda","year":"1987"},{"key":"10.1016\/j.fct.2020.111869_bib43","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1093\/toxsci\/kfy050","article-title":"Availability, quality, and relevance of toxicogenomics data for human health risk assessment: a scoping review of the literature on trihalomethanes","volume":"163","author":"Vachon","year":"2018","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.fct.2020.111869_bib44","series-title":"XR-208: 90-Day Dietary Toxicity Study in F344\/DuCrl Rats with a 28-Day Recovery in F344\/DuCrl Rats","author":"Yano","year":"2009"}],"container-title":["Food and Chemical Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0278691520307596?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0278691520307596?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T22:06:07Z","timestamp":1759529167000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0278691520307596"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":43,"alternative-id":["S0278691520307596"],"URL":"https:\/\/doi.org\/10.1016\/j.fct.2020.111869","relation":{},"ISSN":["0278-6915"],"issn-type":[{"value":"0278-6915","type":"print"}],"subject":[],"published":{"date-parts":[[2021,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"A rat subchronic study transcriptional point of departure estimates a carcinogenicity study apical point of departure","name":"articletitle","label":"Article Title"},{"value":"Food and Chemical Toxicology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.fct.2020.111869","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 The Authors. Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"111869"}}