{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:52:55Z","timestamp":1791247975159,"version":"4.1.0"},"reference-count":73,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cigarettes induce oxidative stress and DNA damage, processes that contribute to cardiovascular and pulmonary disease. High content screening (HCS) is an increasingly valuable tool for comparative toxicology because it enables simultaneous quantification of multiple mechanistic endpoints at single\u2010cell resolution. In this study, HCS was used to compare the biological activity of extracts from reference cigarette 1R6F smoke and aerosol extracts from one heated tobacco product and two electronic vapour products in human coronary artery endothelial cells and bronchial epithelial cells. Endpoints included reactive oxygen species generation, glutathione depletion, \u03b3H2AX induction as a marker of DNA double\u2010strand break signalling and NRF2 translocation as an indicator of oxidative stress signalling. 1R6F cigarette smoke extract showed the highest cytotoxic and genotoxic responses, whereas the selected HTP and EVP aerosol extracts generally showed lower potency, with higher minimum effective concentrations across several endpoints under the tested conditions.\n                    <jats:italic>N<\/jats:italic>\n                    \u2010acetylcysteine (NAC) attenuated several responses, supporting oxidative stress as an important contributor to the observed cellular effects. Overall, under the tested in\u00a0vitro conditions, extracts from the selected HTP and EVP products showed lower potency across several oxidative stress\u2010, genotoxicity\u2010 and cytotoxicity\u2010associated endpoints than 1R6F cigarette smoke extract. These findings support product\u2010specific comparative in\u00a0vitro bioactivity assessment but do not directly establish reduced human health risk, product safety or clinical harm reduction. The study extends previous HCS work by integrating potency\u2010based comparisons, mechanistic interrogation using NAC and cross\u2010tissue evaluation.\n                  <\/jats:p>","DOI":"10.1002\/jat.70448","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:07:01Z","timestamp":1791245221000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["High\u2010Content Screening Comparison of 1R6F Cigarette Smoke Extract and Selected Heated Tobacco and Electronic Vapour Product Aerosol Extracts in Endothelial and Bronchial Epithelial Cell Models"],"prefix":"10.1002","author":[{"given":"Edgar Trelles","family":"Sticken","sequence":"first","affiliation":[{"name":"Reemtsma Cigarettenfabriken GmbH, an Imperial Brands PLC Company  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2018-6577","authenticated-orcid":false,"given":"Konstantinos","family":"Papikinos","sequence":"additional","affiliation":[{"name":"Group Science and Regulatory Affairs Imperial Brands PLC  Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"Chapman","sequence":"additional","affiliation":[{"name":"Group Science and Regulatory Affairs Imperial Brands PLC  Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Wieczorek","sequence":"additional","affiliation":[{"name":"Reemtsma Cigarettenfabriken GmbH, an Imperial Brands PLC Company  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah Jean","family":"Pour","sequence":"additional","affiliation":[{"name":"Reemtsma Cigarettenfabriken GmbH, an Imperial Brands PLC Company  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torge","family":"Evenburg","sequence":"additional","affiliation":[{"name":"Reemtsma Cigarettenfabriken GmbH, an Imperial Brands PLC Company  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Otte","sequence":"additional","affiliation":[{"name":"Reemtsma Cigarettenfabriken GmbH, an Imperial Brands PLC Company  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7975-9489","authenticated-orcid":false,"given":"Tiandan","family":"Wu","sequence":"additional","affiliation":[{"name":"Reemtsma Cigarettenfabriken GmbH, an Imperial Brands PLC Company  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0664-0693","authenticated-orcid":false,"given":"Liam","family":"Simms","sequence":"additional","affiliation":[{"name":"Group Science and Regulatory Affairs Imperial Brands PLC  Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1463-9406","authenticated-orcid":false,"given":"Matthew","family":"Stevenson","sequence":"additional","affiliation":[{"name":"Group Science and Regulatory Affairs Imperial Brands PLC  Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.18502\/ajmb.v16i2.14859"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfh061"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.2.6186.357"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btz220"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20103\u2010540\u201069248\u20105_2"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1515\/bmc\u20102012\u20100001"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.talanta.2018.02.048"},{"key":"e_1_2_10_9_1","volume-title":"How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking\u2010Attributable Disease: A Report of the Surgeon General","author":"Centers for Disease Control and Prevention (US)","year":"2010"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18112386"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/ftox.2024.1395670"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2022.105510"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.61223"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2016.10.016"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/mutage\/geaa033"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2019.03.018"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213\u2010016\u20104338\u20102"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00038.2022"},{"key":"e_1_2_10_19_1","unstructured":"FDA.2012.Harmful and Potentially Harmful Constituents in Tobacco Products and Tobacco Smoke; Established List. Federal Register."},{"key":"e_1_2_10_20_1","unstructured":"Food and Drug Administration.2012. \u201cHarmful and Potentially Harmful Constituents in Tobacco Products.\u201d Federal Register 77. View source."},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2017.10.006"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/2050\u20106511\u201015\u201041"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424\u2010023\u201002809\u20109"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2021.102150"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrestox.5b00321"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx400405s"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrep.2020.100865"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfr281"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440\u20101843.2012.02132.x"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/jfbc.12962"},{"key":"e_1_2_10_31_1","volume-title":"IARC Monographs on the Evaluation of Carcinogenic Risks to Humans","author":"International Agency for Research on Cancer","year":"2007"},{"key":"e_1_2_10_32_1","volume-title":"Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction","author":"Institute of Medicine (US) Committee to Assess the Science Base for Tobacco Harm Reduction","year":"2001"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204\u2010019\u201002565\u20109"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2017.09.016"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrgentox.2012.02.007"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1012723"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2009.080591"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxics10010008"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/cosmetics11020047"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.3791\/53987"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2021.743060"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrestox.6b00188"},{"key":"e_1_2_10_43_1","volume-title":"Evidence Review of E Cigarettes and Heated Tobacco Products 2018","author":"McNeill A.","year":"2018"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/dta.3344"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11081485"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep35478"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.3389\/ftox.2024.1373325"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11739\u2010021\u201002813\u2010w"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41021\u2010018\u20100098\u2010z"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.26762.2"},{"key":"e_1_2_10_51_1","volume-title":"Public Health Consequences of E Cigarettes","author":"National Academies of Sciences, Engineering, and Medicine","year":"2018"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1159\/000360220"},{"key":"e_1_2_10_53_1","unstructured":"Organisation for Economic Co operation and Development.2025.Principles of Quantitative In\u00a0Vitro to In\u00a0Vivo Extrapolation QIVIVE. OECD Series on Testing and Assessment no. 411.https:\/\/one.oecd.org\/document\/ENV\/CBC\/MONO(20259\/en\/pdf)."},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2023.105546"},{"key":"e_1_2_10_55_1","volume-title":"E Cigarettes and Harm Reduction an Evidence Review","author":"Royal College of Physicians","year":"2024"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1089\/aivt.2019.0015"},{"key":"e_1_2_10_57_1","first-page":"119","article-title":"Inter Laboratory Reproducibility of Reference Cigarettes","volume":"29","author":"Sakai Y.","year":"2020","journal-title":"Beitr\u00e4ge Zur Tabakforschung International"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2013.04.016"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2016.10.001"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.crtox.2021.08.003"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.crtox.2020.11.001"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.3389\/ftox.2022.747508"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.3390\/life14111361"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.4064"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2017.08.016"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.3389\/ftox.2024.1376118"},{"key":"e_1_2_10_67_1","volume-title":"The Health Consequences of Smoking 50 Years of Progress","author":"U.S. Department of Health and Human Services","year":"2014"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2020.104866"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00123.2020"},{"key":"e_1_2_10_70_1","volume-title":"WHO Report on the Global Tobacco Epidemic 2011","author":"World Health Organization","year":"2011"},{"key":"e_1_2_10_71_1","unstructured":"World Health Organization.2020.Tobacco Fact Sheet.View source."},{"key":"e_1_2_10_72_1","doi-asserted-by":"crossref","unstructured":"Yordas Ltd L.Carramusa W.Mune et\u00a0al.2024. \u201cNew Approach Methodologies NAMs to Support Regulatory Decisions for Chemical Safety.\u201dhttps:\/\/doi.org\/10.46756\/001c.122591.","DOI":"10.46756\/001c.122591"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2020.104799"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.21037\/jtd\u201024\u2010927"}],"container-title":["Journal of Applied Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.70448","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jat.70448","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.70448","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:07:06Z","timestamp":1791245226000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jat.70448"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,5]]},"references-count":73,"alternative-id":["10.1002\/jat.70448"],"URL":"https:\/\/doi.org\/10.1002\/jat.70448","archive":["Portico"],"relation":{},"ISSN":["0260-437X","1099-1263"],"issn-type":[{"value":"0260-437X","type":"print"},{"value":"1099-1263","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,5]]},"assertion":[{"value":"2026-07-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"jat.70448"}}