{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T05:23:03Z","timestamp":1791696183444,"version":"4.3.4"},"reference-count":46,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2017,11,1]],"date-time":"2017-11-01T00:00:00Z","timestamp":1509494400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2017,11,1]],"date-time":"2017-11-01T00:00:00Z","timestamp":1509494400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2017,9,3]],"date-time":"2017-09-03T00:00:00Z","timestamp":1504396800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007824","name":"American Chemistry Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007824","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Regulatory Toxicology and Pharmacology"],"published-print":{"date-parts":[[2017,11]]},"DOI":"10.1016\/j.yrtph.2017.08.021","type":"journal-article","created":{"date-parts":[[2017,9,1]],"date-time":"2017-09-01T13:00:52Z","timestamp":1504270852000},"page":"185-196","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":56,"special_numbering":"C","title":["How well can carcinogenicity be predicted by high throughput \u201ccharacteristics of carcinogens\u201d mechanistic data?"],"prefix":"10.1016","volume":"90","author":[{"given":"Richard A.","family":"Becker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Dreier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary K.","family":"Manibusan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis A. (Tony)","family":"Cox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ted W.","family":"Simon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James S.","family":"Bus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.yrtph.2017.08.021_bib1","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.yrtph.2017.02.017","article-title":"Quantitative weight of evidence to assess confidence in alternative modes of action","volume":"86","author":"Becker","year":"2017","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"10.1016\/j.yrtph.2017.08.021_bib2","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1080\/10590501.2013.824188","article-title":"Evaluation of the toxicity forecasting capability of EPA's ToxCast phase I data: can ToxCast in\u00a0vitro assays predict carcinogenicity?","volume":"31","author":"Benigni","year":"2013","journal-title":"J.\u00a0Environ. Sci. Health C Environ. Carcinog. Ecotoxicol. Rev."},{"key":"10.1016\/j.yrtph.2017.08.021_bib3","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1517\/17425255.2014.934670","article-title":"Predicting the carcinogenicity of chemicals with alternative approaches: recent advances","volume":"10","author":"Benigni","year":"2014","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"10.1016\/j.yrtph.2017.08.021_bib4","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1080\/10408440600977677","article-title":"IPCS framework for analyzing the relevance of a cancer mode of action for humans","volume":"36","author":"Boobis","year":"2006","journal-title":"Crit. Rev. Toxicol."},{"key":"10.1016\/j.yrtph.2017.08.021_bib5","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.yrtph.2016.10.014","article-title":"Classification schemes for carcinogenicity based on hazard-identification have become outmoded and serve neither science nor society","volume":"82","author":"Boobis","year":"2016","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"10.1016\/j.yrtph.2017.08.021_bib6","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.yrtph.2017.03.004","article-title":"IARC use of \u201coxidant stress\u201d as key mode of action characteristic for facilitating cancer classification: glyphosate case example illustrating of a lack of robustness in interpretative implementation","volume":"86","author":"Bus","year":"2016","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"10.1016\/j.yrtph.2017.08.021_bib47","article-title":"Use of high-throughput in\u00a0vitro toxicity screening data in cancer hazard evaluations by IARC Monograph Working Groups","author":"Chiu","year":"2017","journal-title":"ALTEX"},{"key":"10.1016\/j.yrtph.2017.08.021_bib7","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.yrtph.2014.05.010","article-title":"Developing scientific confidence in HTS-derived prediction models: lessons learned from an endocrine case study","volume":"69","author":"Cox","year":"2014","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"10.1016\/j.yrtph.2017.08.021_bib8","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.yrtph.2016.02.005","article-title":"How well can in\u00a0vitro data predict in\u00a0vivo effects of chemicals? Rodent carcinogenicity as a case study","volume":"77","author":"Cox","year":"2016","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"10.1016\/j.yrtph.2017.08.021_bib9","doi-asserted-by":"crossref","first-page":"467","DOI":"10.3109\/10408444.2013.807223","article-title":"Advancing human health risk assessment: integrating Recent Advisory Committee recommendations","volume":"43","author":"Dourson","year":"2013","journal-title":"Crit. Rev. Toxicol."},{"key":"10.1016\/j.yrtph.2017.08.021_bib10","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.taap.2017.01.020","article-title":"Improving the international agency for research on Cancer's consideration of mechanistic evidence","volume":"319","author":"Goodman","year":"2017","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.yrtph.2017.08.021_bib11","series-title":"Systematic Identification of the Mechanistic Evidence for Cancer Hazard Assessment: Experience of the IARC Monographs Programme","author":"Guyton","year":"2015"},{"key":"10.1016\/j.yrtph.2017.08.021_bib13","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0092-8674(00)81683-9","article-title":"The hallmarks of cancer","volume":"100","author":"Hanahan","year":"2000","journal-title":"Cell"},{"key":"10.1016\/j.yrtph.2017.08.021_bib14","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: the next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"10.1016\/j.yrtph.2017.08.021_bib15","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1093\/toxsci\/kfw195","article-title":"Editor's highlight: negative predictors of carcinogenicity for environmental chemicals","volume":"155","author":"Hill","year":"2017","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.yrtph.2017.08.021_bib16","volume":"me 112","author":"IARC (International Agency for Research on Cancer)","year":"2017"},{"key":"10.1016\/j.yrtph.2017.08.021_bib17","volume":"vol. 110","author":"IARC","year":"2016"},{"key":"10.1016\/j.yrtph.2017.08.021_bib18","volume":"vol. 113","author":"IARC","year":"2016"},{"key":"10.1016\/j.yrtph.2017.08.021_bib19","series-title":"Preamble","author":"IARC","year":"2016"},{"key":"10.1016\/j.yrtph.2017.08.021_bib20","series-title":"Evaluation of Biomarkers and Surrogate Endpoints in Chronic Disease","author":"Institute of Medicine (IOM)","year":"2010"},{"key":"10.1016\/j.yrtph.2017.08.021_bib21","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1093\/toxsci\/kfw092","article-title":"Editor's highlight: analysis of the effects of cell stress and cytotoxicity on in\u00a0vitro assay activity across a diverse chemical and assay space","volume":"vol. 152","author":"Judson","year":"2016","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.yrtph.2017.08.021_bib22","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1093\/toxsci\/kfs285","article-title":"In\u00a0vitro perturbations of targets in cancer hallmark processes predict rodent chemical carcinogenesis","volume":"131","author":"Kleinstreuer","year":"2013","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.yrtph.2017.08.021_bib23","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1093\/toxsci\/kfv236","article-title":"Dose and effect thresholds for early key events in a PPARalpha-mediated mode of action","volume":"149","author":"Lake","year":"2016","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.yrtph.2017.08.021_bib24","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1002\/etc.3805","article-title":"Advancing the adverse outcome pathway framework-An international horizon scanning approach","volume":"36","author":"LaLone","year":"2017","journal-title":"Environ. Toxicol. Chem."},{"key":"10.1016\/j.yrtph.2017.08.021_bib25","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/S1470-2045(13)70104-9","article-title":"Carcinogenicity of polychlorinated biphenyls and polybrominated biphenyls","volume":"4","author":"Lauby-Secretan","year":"2013","journal-title":"Lancet Oncol1"},{"key":"10.1016\/j.yrtph.2017.08.021_bib26","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.1007\/s11356-015-4829-4","article-title":"Use of mechanistic data in the IARC evaluations of the carcinogenicity of polychlorinated biphenyls and related compounds","volume":"23","author":"Lauby-Secretan","year":"2016","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"10.1016\/j.yrtph.2017.08.021_bib27","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/S1470-2045(15)00081-9","article-title":"Carcinogenicity of lindane, DDT, and 2,4-dichlorophenoxyacetic acid","volume":"16","author":"Loomis","year":"2015","journal-title":"Lancet Oncol."},{"key":"10.1016\/j.yrtph.2017.08.021_bib28","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1093\/carcin\/bgr297","article-title":"Current understanding of the mechanism of benzene-induced leukemia in humans: implications for risk assessment","volume":"33","author":"McHale","year":"2012","journal-title":"Carcinogenesis"},{"key":"10.1016\/j.yrtph.2017.08.021_bib29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/jat.2949","article-title":"New developments in the evolution and application of the WHO\/IPCS framework on mode of action\/species concordance analysis","volume":"34","author":"Meek","year":"2013","journal-title":"J.\u00a0Appl. Toxicol."},{"key":"10.1016\/j.yrtph.2017.08.021_bib30","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1002\/jat.2984","article-title":"Mode of action human relevance (species concordance) framework: evolution of the Bradford Hill considerations and comparative analysis of weight of evidence","volume":"34","author":"Meek","year":"2014","journal-title":"J.\u00a0Appl. Toxicol."},{"key":"10.1016\/j.yrtph.2017.08.021_bib31","series-title":"Users' Handbook Supplement to the Guidance Document for Developing and Assessing Adverse Outcome Pathways. OECD Series on Adverse Outcome Pathways, No. 1","author":"OECD","year":"2016"},{"key":"10.1016\/j.yrtph.2017.08.021_bib32","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.yrtph.2015.02.011","article-title":"Proposing a scientific confidence framework to help support the application of adverse outcome pathways for regulatory purposes","volume":"71","author":"Patlewicz","year":"2015","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"10.1016\/j.yrtph.2017.08.021_bib33","unstructured":"Predictive Analytics Toolkit (PAT). 2017. http:\/\/cox-associates.com\/patkit\/[accessed 15 May 2017]."},{"key":"10.1016\/j.yrtph.2017.08.021_bib34","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1289\/ehp.1409029","article-title":"Using ToxCast data to reconstruct dynamic cell state trajectories and estimate toxicological points of departure","volume":"124","author":"Shah","year":"2016","journal-title":"Environ. Health Perspect."},{"issue":"6","key":"10.1016\/j.yrtph.2017.08.021_bib35","doi-asserted-by":"crossref","first-page":"e0127952","DOI":"10.1371\/journal.pone.0127952","article-title":"A\u00a0model for aryl hydrocarbon receptor-activated gene expression shows potency and efficacy changes and predicts squelching due to competition for transcription co-activators","volume":"10","author":"Simon","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.yrtph.2017.08.021_bib36","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.taap.2004.06.019","article-title":"Dose-dependent transitions in mechanisms of toxicity","volume":"201","author":"Slikker","year":"2004","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.yrtph.2017.08.021_bib37","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1289\/ehp.1509912","article-title":"Key characteristics of carcinogens as a basis for organizing data on mechanisms of carcinogenesis","volume":"124","author":"Smith","year":"2016","journal-title":"Environ. Health Perspect."},{"key":"10.1016\/j.yrtph.2017.08.021_bib38","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.2017.08.021_bib39","series-title":"Biometry: the Principles and Practices of Statistics in Biological Research","author":"Sokal","year":"1981"},{"key":"10.1016\/j.yrtph.2017.08.021_bib40","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1093\/toxsci\/kfs159","article-title":"A\u00a0comprehensive statistical analysis of predicting in\u00a0vivo hazard using high-throughput in\u00a0vitro screening","volume":"128","author":"Thomas","year":"2012","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.yrtph.2017.08.021_bib41","author":"United States Environmental Protection Agency (USEPA)"},{"key":"10.1016\/j.yrtph.2017.08.021_bib42","series-title":"Systematic Review Relating to Mechanistic Data: what Is Really Needed, and How Can it Be Efficiently Applied?","author":"United States Environmental Protection Agency (USEPA)","year":"2015"},{"key":"10.1016\/j.yrtph.2017.08.021_bib43","series-title":"Annual Cancer Report. Chemicals Evaluated for Carcinogenic Potential, Office of Pesticide Programs","author":"United States Environmental Protection Agency (USEPA)","year":"2016"},{"key":"10.1016\/j.yrtph.2017.08.021_bib44","series-title":"External Review Draft, Toxicological Review of Ethyl Tertiary Butyl Ether","author":"United States Environmental Protection Agency (USEPA)","year":"2017"},{"issue":"13","key":"10.1016\/j.yrtph.2017.08.021_bib45","first-page":"1","article-title":"Application of the adverse outcome pathway (AOP) concept to structure the available in\u00a0vivo and in\u00a0vitro mechanistic data for allergic sensitization to food proteins","volume":"7","author":"van Bilsen","year":"2017","journal-title":"Clin. Transl. Allergy"},{"key":"10.1016\/j.yrtph.2017.08.021_bib46","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1289\/ehp.1408244","article-title":"Molecular signaling network motifs provide a mechanistic basis for cellular threshold responses","volume":"122","author":"Zhang","year":"2014","journal-title":"Environ. Health Perspect."}],"container-title":["Regulatory Toxicology and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0273230017302714?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0273230017302714?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T18:02:46Z","timestamp":1762365766000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0273230017302714"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11]]},"references-count":46,"alternative-id":["S0273230017302714"],"URL":"https:\/\/doi.org\/10.1016\/j.yrtph.2017.08.021","relation":{},"ISSN":["0273-2300"],"issn-type":[{"value":"0273-2300","type":"print"}],"subject":[],"published":{"date-parts":[[2017,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"How well can carcinogenicity be predicted by high throughput \u201ccharacteristics of carcinogens\u201d mechanistic data?","name":"articletitle","label":"Article Title"},{"value":"Regulatory Toxicology and Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.yrtph.2017.08.021","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2017 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}