{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:57:23Z","timestamp":1792036643893,"version":"4.4.0"},"reference-count":98,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T00:00:00Z","timestamp":1668470400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicology in Vitro"],"published-print":{"date-parts":[[2023,2]]},"DOI":"10.1016\/j.tiv.2022.105510","type":"journal-article","created":{"date-parts":[[2022,11,11]],"date-time":"2022-11-11T06:09:48Z","timestamp":1668146988000},"page":"105510","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":31,"special_numbering":"C","title":["Multiple endpoint in vitro toxicity assessment of a prototype heated tobacco product indicates substantially reduced effects compared to those of combustible cigarette"],"prefix":"10.1016","volume":"86","author":[{"given":"Fiona","family":"Chapman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar Trelles","family":"Sticken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Wieczorek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah Jean","family":"Pour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ole","family":"Dethloff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Budde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Rudd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Mason","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukasz","family":"Czekala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam","family":"Simms","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Nahde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant","family":"O'Connell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Stevenson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.tiv.2022.105510_bb0005","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.toxrep.2021.01.014","article-title":"Systematic review of biomarker findings from clinical studies of electronic cigarettes and heated tobacco products","volume":"8","author":"Akiyama","year":"2021","journal-title":"Toxicol. Rep."},{"issue":"3","key":"10.1016\/j.tiv.2022.105510_bb0010","doi-asserted-by":"crossref","first-page":"201","DOI":"10.7888\/juoeh.39.201","article-title":"Comparison of chemicals in mainstream smoke in heat-not-burn tobacco and combustion cigarettes","volume":"39","author":"Bekki","year":"2017","journal-title":"J. UOEH"},{"issue":"20","key":"10.1016\/j.tiv.2022.105510_bb0015","doi-asserted-by":"crossref","first-page":"4190","DOI":"10.1093\/bioinformatics\/btz187","article-title":"Gladiatox: global assessment of dose-indicator in toxicology","volume":"35","author":"Belcastro","year":"2019","journal-title":"Bioinformatics"},{"key":"10.1016\/j.tiv.2022.105510_bb0020","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/978-3-540-69248-5_2","article-title":"Nicotine chemistry, metabolism, kinetics and biomarkers","volume":"192","author":"Benowitz","year":"2009","journal-title":"Handb. Exp. Pharmacol."},{"issue":"11","key":"10.1016\/j.tiv.2022.105510_bb0025","doi-asserted-by":"crossref","first-page":"2675","DOI":"10.1007\/s00216-020-02502-1","article-title":"Comprehensive chemical characterization of the aerosol generated by a heated tobacco product by untargeted screening","volume":"412","author":"Bentley","year":"2020","journal-title":"Anal. Bioanal. Chem."},{"key":"10.1016\/j.tiv.2022.105510_bb0030","doi-asserted-by":"crossref","DOI":"10.1016\/j.toxlet.2020.07.011","article-title":"Evaluation of a high-throughput in vitro endothelial cell migration assay for the assessment of nicotine and tobacco delivery products","author":"Bishop","year":"2020","journal-title":"Toxicol. Lett."},{"issue":"Pt A","key":"10.1016\/j.tiv.2022.105510_bb0035","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.fct.2017.05.023","article-title":"A novel hybrid tobacco product that delivers a tobacco flavour note with vapour aerosol (part 2): in vitro biological assessment and comparison with different tobacco-heating products","volume":"106","author":"Breheny","year":"2017","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.tiv.2022.105510_bb0040","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.yrtph.2017.07.032","article-title":"Nicotine pharmacokinetic profiles of the tobacco heating system 2.2, cigarettes and nicotine gum in Japanese smokers","volume":"89","author":"Brossard","year":"2017","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"10.1016\/j.tiv.2022.105510_bb0045","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.talanta.2018.02.048","article-title":"Determination of eight carbonyl compounds in aerosols trapped in phosphate buffer saline solutions to support in vitro assessment studies","volume":"184","author":"Buratto","year":"2018","journal-title":"Talanta"},{"key":"10.1016\/j.tiv.2022.105510_bb0050","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1136\/tc.2007.024158","article-title":"Mandated lowering of toxicants in cigarette smoke: a description of the world health organization tobreg proposal","volume":"17","author":"Burns","year":"2008","journal-title":"Tob. Control."},{"key":"10.1016\/j.tiv.2022.105510_bb0055","doi-asserted-by":"crossref","DOI":"10.1016\/j.tiv.2020.104905","article-title":"Comparison of passive-dosed and solvent spiked exposures of procarcinogen, benzo[a]pyrene, to human lymphoblastoid cell line, MCL-5","volume":"67","author":"Chapman","year":"2020","journal-title":"Toxicol. in Vitro"},{"key":"10.1016\/j.tiv.2022.105510_bb0065","author":"CORESTA Heated Tobacco Products Task Force"},{"key":"10.1016\/j.tiv.2022.105510_bb0070","doi-asserted-by":"crossref","DOI":"10.1016\/j.tca.2019.178475","article-title":"An experimental investigation into the operation of an electrically heated tobacco system","volume":"684","author":"Cozzani","year":"2020","journal-title":"Thermochim. Acta"},{"key":"10.1016\/j.tiv.2022.105510_bb0075","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1016\/j.fct.2018.05.058","article-title":"Evaluation of flavourings potentially used in a heated tobacco product: chemical analysis, in vitro mutagenicity, genotoxicity, cytotoxicity and in vitro tumour promoting activity","volume":"118","author":"Crooks","year":"2018","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.tiv.2022.105510_bb0080","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.tiv.2019.03.018","article-title":"High content screening in NHBE cells shows significantly reduced biological activity of flavoured e-liquids, when compared to cigarette smoke condensate","volume":"58","author":"Czekala","year":"2019","journal-title":"Toxicol. in Vitro"},{"key":"10.1016\/j.tiv.2022.105510_bb0085","doi-asserted-by":"crossref","DOI":"10.1093\/mutage\/geaa033","article-title":"The in vitro toxtracker and aneugen clastogen evaluation extension assay as a tool in the assessment of relative genotoxic potential of e-liquids and their aerosols","author":"Czekala","year":"2021","journal-title":"Mutagenesis"},{"key":"10.1016\/j.tiv.2022.105510_bb0090","doi-asserted-by":"crossref","DOI":"10.1016\/j.tiv.2019.104652","article-title":"Comparison of cytotoxicity of IQOS aerosols to smoke from Marlboro red and 3R4F reference cigarettes","volume":"61","author":"Davis","year":"2019","journal-title":"Toxicol. in Vitro"},{"issue":"1","key":"10.1016\/j.tiv.2022.105510_bb0095","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1093\/mutage\/13.1.19","article-title":"The effectiveness of Salmonella strains TA100, TA102 and TA104 for detecting mutagenicity of some aldehydes and peroxides","volume":"13","author":"Dillon","year":"1998","journal-title":"Mutagenesis"},{"issue":"6","key":"10.1016\/j.tiv.2022.105510_bb0100","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1093\/carcin\/bgq073","article-title":"Benzo[a]pyrene diol epoxide stimulates an inflammatory response in normal human lung fibroblasts through a p53 and JNK mediated pathway","volume":"31","author":"Dreij","year":"2010","journal-title":"Carcinogenesis"},{"key":"10.1016\/j.tiv.2022.105510_bb0105","doi-asserted-by":"crossref","DOI":"10.1016\/j.jhazmat.2020.123417","article-title":"Comparison of the chemical composition of aerosols from heated tobacco products, electronic cigarettes and tobacco cigarettes and their toxic impacts on the human bronchial epithelial BEAS-2B cells","volume":"401","author":"Dusautoir","year":"2021","journal-title":"J. Hazard. Mater."},{"key":"10.1016\/j.tiv.2022.105510_bb0110","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.yrtph.2017.09.009","article-title":"Assessment of tobacco heating product THP1.0. Part 2: product design, operation and thermophysical characterisation","volume":"93","author":"Eaton","year":"2018","journal-title":"Regul. Toxicol. Pharmacol."},{"issue":"4","key":"10.1016\/j.tiv.2022.105510_bb0115","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1080\/01926230701320337","article-title":"Apoptosis: a review of programmed cell death","volume":"35","author":"Elmore","year":"2007","journal-title":"Toxicol. Pathol."},{"issue":"8","key":"10.1016\/j.tiv.2022.105510_bb0120","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1093\/ntr\/ntx138","article-title":"Nicotine delivery to the aerosol of a heat-not-burn tobacco product: comparison with a tobacco cigarette and E-cigarettes","volume":"20","author":"Farsalinos","year":"2017","journal-title":"Nicotine Tob. Res."},{"issue":"6","key":"10.1016\/j.tiv.2022.105510_bb0125","doi-asserted-by":"crossref","first-page":"A387","DOI":"10.1016\/j.chest.2019.04.089","article-title":"Patterns of use, past smoking status, and biochemically verified current smoking status of heated tobacco product (IQOS) shops customers: preliminary results","volume":"155","author":"Farsalinos","year":"2019","journal-title":"CHEST"},{"issue":"6","key":"10.1016\/j.tiv.2022.105510_bb0130","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1177\/1091581812461810","article-title":"Modification of smoke toxicant yields alters the effects of cigarette smoke extracts on endothelial migration: an in vitro study using a cardiovascular disease model","volume":"31","author":"Fearon","year":"2012","journal-title":"Int. J. Toxicol."},{"issue":"1","key":"10.1016\/j.tiv.2022.105510_bb0135","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.tiv.2012.08.018","article-title":"In vitro models for assessing the potential cardiovascular disease risk associated with cigarette smoking","volume":"27","author":"Fearon","year":"2013","journal-title":"Toxicol. in Vitro"},{"issue":"1","key":"10.1016\/j.tiv.2022.105510_bb0140","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/0027-5107(93)90049-L","article-title":"The cytokinesis-block micronucleus technique: a detailed description of the method and its application to genotoxicity studies in human populations","volume":"285","author":"Fenech","year":"1993","journal-title":"Mutat. Res."},{"key":"10.1016\/j.tiv.2022.105510_bb0145","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.yrtph.2017.10.006","article-title":"Assessment of novel tobacco heating product THP1.0. Part 3: comprehensive chemical characterisation of harmful and potentially harmful aerosol emissions","volume":"93","author":"Forster","year":"2018","journal-title":"Regul. Toxicol. Pharmacol."},{"issue":"1\u20132","key":"10.1016\/j.tiv.2022.105510_bb0150","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.mrgentox.2011.10.014","article-title":"Reduction of misleading (\u201cfalse\u201d) positive results in mammalian cell genotoxicity assays. I. Choice of cell type","volume":"742","author":"Fowler","year":"2012","journal-title":"Mutat. Res."},{"issue":"6","key":"10.1016\/j.tiv.2022.105510_bb0155","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1016\/j.tiv.2013.05.001","article-title":"Metabolic characterization of cell systems used in in vitro toxicology testing: lung cell system BEAS-2B as a working example","volume":"27","author":"Garcia-Canton","year":"2013","journal-title":"Toxicol. in Vitro"},{"key":"10.1016\/j.tiv.2022.105510_bb0160","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/2050-6511-15-41","article-title":"Characterisation of an aerosol exposure system to evaluate the genotoxicity of whole mainstream cigarette smoke using the in vitro \u03b3H2AX assay by high content screening","volume":"15","author":"Garcia-Canton","year":"2014","journal-title":"BMC Pharmacol. Toxicol."},{"issue":"9","key":"10.1016\/j.tiv.2022.105510_bib492","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1038\/sj.cdd.4401950","article-title":"Mechanisms of cytochrome c release from mitochondria","volume":"13","author":"Garrido","year":"2006","journal-title":"Cell Death Differ"},{"key":"10.1016\/j.tiv.2022.105510_bb0165","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.yrtph.2017.08.005","article-title":"Assessment of tobacco heating product THP1.0. Part 8: study to determine puffing topography, mouth level exposure and consumption among Japanese users","volume":"93","author":"Gee","year":"2018","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"10.1016\/j.tiv.2022.105510_bb0170","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1016\/j.toxrep.2019.10.007","article-title":"In vitro mutagenicity of gas-vapour phase extracts from flavoured and unflavoured heated tobacco products","volume":"6","author":"Godec","year":"2019","journal-title":"Toxicol. Rep."},{"issue":"1","key":"10.1016\/j.tiv.2022.105510_bb0175","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1021\/acs.chemrestox.5b00321","article-title":"In vitro systems toxicology assessment of a candidate modified risk tobacco product shows reduced toxicity compared to that of a conventional cigarette","volume":"29","author":"Gonzalez-Suarez","year":"2016","journal-title":"Chem. Res. Toxicol."},{"key":"10.1016\/j.tiv.2022.105510_bb0180","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.tox.2013.08.012","article-title":"Dose metric considerations in in vitro assays to improve quantitative in vitro-in vivo dose extrapolations","volume":"332","author":"Groothuis","year":"2015","journal-title":"Toxicology"},{"issue":"1","key":"10.1016\/j.tiv.2022.105510_bb0185","doi-asserted-by":"crossref","first-page":"14701","DOI":"10.1038\/s41598-022-19167-8","article-title":"An abuse liability assessment of the glo tobacco heating product in comparison to combustible cigarettes and nicotine replacement therapy","volume":"12","author":"Hardie","year":"2022","journal-title":"Sci. Rep."},{"key":"10.1016\/j.tiv.2022.105510_bb0190","article-title":"Cigarette smoke, but not novel tobacco vapor products, causes epigenetic disruption and cell apoptosis","volume":"24","author":"Hattori","year":"2020","journal-title":"Biochem. Biophys. Rep."},{"issue":"4","key":"10.1016\/j.tiv.2022.105510_bb0195","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1093\/ntr\/ntz013","article-title":"Reduction in exposure to selected harmful and potentially harmful constituents approaching those observed upon smoking abstinence in smokers switching to the menthol tobacco heating system 2.2 for 3 months (part 1)","volume":"22","author":"Haziza","year":"2020","journal-title":"Nicotine Tob. Res."},{"issue":"3","key":"10.1016\/j.tiv.2022.105510_bb0200","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.jphs.2021.07.005","article-title":"Comparison of cytotoxicity of cigarette smoke extract derived from heat-not-burn and combustion cigarettes in human vascular endothelial cells","volume":"147","author":"Horinouchi","year":"2021","journal-title":"J. Pharmacol. Sci."},{"issue":"3","key":"10.1016\/j.tiv.2022.105510_bb0205","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.mito.2011.01.010","article-title":"The multiple functions of cytochrome c and their regulation in life and death decisions of the mammalian cell: from respiration to apoptosis","volume":"11","author":"H\u00fcttemann","year":"2011","journal-title":"Mitochondrion"},{"key":"10.1016\/j.tiv.2022.105510_bb0210","author":"International Agency for Research on Cancer"},{"key":"10.1016\/j.tiv.2022.105510_bb0215","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.fct.2018.02.063","article-title":"Comparative biological impacts of an aerosol from carbon-heated tobacco and smoke from cigarettes on human respiratory epithelial cultures: a systems toxicology assessment","volume":"115","author":"Iskandar","year":"2018","journal-title":"Food Chem. Toxicol."},{"issue":"65","key":"10.1016\/j.tiv.2022.105510_bb0220","first-page":"160","article-title":"ISO 3402:1999: tobacco and tobacco products - atmosphere for conditioning and testing","volume":"65","author":"ISO","year":"1999","journal-title":"ICS"},{"issue":"65","key":"10.1016\/j.tiv.2022.105510_bb0225","first-page":"160","article-title":"Routine analytical cigarette-smoking machine \u2014 definitions and standard conditions","volume":"65","author":"ISO","year":"2012","journal-title":"ICS"},{"issue":"65","key":"10.1016\/j.tiv.2022.105510_bb0230","first-page":"160","article-title":"ISO 20768:2018 - vapour products - routine analytical vaping machine - definitions and standard conditions","volume":"65","author":"ISO","year":"2018","journal-title":"ICS"},{"issue":"65","key":"10.1016\/j.tiv.2022.105510_bb0235","first-page":"160","article-title":"ISO 20778:2018 - cigarettes - routine analytical cigarette smoking machine - definitions and standard conditions with an intense smoking regime","volume":"65","author":"ISO","year":"2018","journal-title":"ICS"},{"key":"10.1016\/j.tiv.2022.105510_bb0245","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.yrtph.2017.08.006","article-title":"Comparative assessment of HPHC yields in the tobacco heating system THS2.2 and commercial cigarettes","volume":"90","author":"Jaccard","year":"2017","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"10.1016\/j.tiv.2022.105510_bb0250","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.yrtph.2017.09.016","article-title":"Assessment of tobacco heating product THP1.0. Part 5: in vitro dosimetric and cytotoxic assessment","volume":"93","author":"Jaunky","year":"2018","journal-title":"Regul. Toxicol. Pharmacol."},{"issue":"1","key":"10.1016\/j.tiv.2022.105510_bb0255","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1038\/s41598-019-55410-5","article-title":"A cross-category puffing topography, mouth level exposure and consumption study among Italian users of tobacco and nicotine products","volume":"10","author":"Jones","year":"2020","journal-title":"Sci. Rep."},{"issue":"8","key":"10.1016\/j.tiv.2022.105510_bb0260","doi-asserted-by":"crossref","first-page":"2102","DOI":"10.1016\/j.tiv.2015.08.004","article-title":"Biological impact of cigarette smoke compared to an aerosol produced from a prototypic modified risk tobacco product on normal human bronchial epithelial cells","volume":"29","author":"Kogel","year":"2015","journal-title":"Toxicol. in Vitro"},{"issue":"Suppl. 1","key":"10.1016\/j.tiv.2022.105510_bb0265","article-title":"Cytotoxic effects of heated tobacco products (HTP) on human bronchial epithelial cells","volume":"27","author":"Leigh","year":"2018","journal-title":"Tob. Control."},{"issue":"5","key":"10.1016\/j.tiv.2022.105510_bb0270","doi-asserted-by":"crossref","DOI":"10.4209\/aaqr.200241","article-title":"Modeled respiratory tract deposition of smoke aerosol from conventional cigarettes, electronic cigarettes and heat-not-burn products","volume":"21","author":"Li","year":"2021","journal-title":"Aerosol Air Qual. Res."},{"key":"10.1016\/j.tiv.2022.105510_bib491","first-page":"17023","article-title":"NF-\u03baB signaling in inflammation. Signal Transduct Target","volume":"2","author":"Liu","year":"2017","journal-title":"Ther"},{"issue":"2","key":"10.1016\/j.tiv.2022.105510_bb0275","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1093\/ntr\/ntw164","article-title":"Reduced exposure to harmful and potentially harmful smoke constituents with the tobacco heating system 2.1","volume":"19","author":"L\u00fcdicke","year":"2017","journal-title":"Nicotine Tob. Res."},{"issue":"6","key":"10.1016\/j.tiv.2022.105510_bb0280","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1007\/s00204-018-2215-y","article-title":"Levels of selected analytes in the emissions of \u201cheat not burn\u201d tobacco products that are relevant to assess human health risks","volume":"92","author":"Mallock","year":"2018","journal-title":"Arch. Toxicol."},{"key":"10.1016\/j.tiv.2022.105510_bb0285","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1177\/0269881112458731","article-title":"Reducing harm from tobacco use","volume":"27","author":"McNeill","year":"2013","journal-title":"J. Psychopharmacol."},{"key":"10.1016\/j.tiv.2022.105510_bb0290","series-title":"Evidence Review of E-Cigarettes and Heated Tobacco Products 2018. A Report Commissioned by Public Health England","author":"McNeill","year":"2018"},{"issue":"5","key":"10.1016\/j.tiv.2022.105510_bb0295","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1016\/j.tiv.2015.03.008","article-title":"Examination of the use of human sera as an exposure agent for in vitro studies investigating the effects of cigarette smoking on cellular cardiovascular disease models","volume":"29","author":"McQuillan","year":"2015","journal-title":"Toxicol. in Vitro"},{"issue":"1","key":"10.1016\/j.tiv.2022.105510_bb0300","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s41021-018-0098-z","article-title":"Advantages of evaluating \u03b3H2AX induction in non-clinical drug development","volume":"40","author":"Motoyama","year":"2018","journal-title":"Genes Environ."},{"key":"10.1016\/j.tiv.2022.105510_bb0305","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.yrtph.2017.10.001","article-title":"Assessment of tobacco heating product THP1.0. Part 9: the placement of a range of next-generation products on an emissions continuum relative to cigarettes via pre-clinical assessment studies","volume":"93","author":"Murphy","year":"2018","journal-title":"Regul. Toxicol. Pharmacol."},{"issue":"24","key":"10.1016\/j.tiv.2022.105510_bb0310","doi-asserted-by":"crossref","first-page":"24911","DOI":"10.1074\/jbc.C400051200","article-title":"Nuclear translocation of cytochrome c during apoptosis","volume":"279","author":"Nur-E-Kamal","year":"2004","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.tiv.2022.105510_bb0315","series-title":"Test No. 487: In Vitro Mammalian Cell Micronucleus Test, OECD Guidelines for the Testing of Chemicals, Section 4","author":"OECD","year":"2016"},{"key":"10.1016\/j.tiv.2022.105510_bb0320","series-title":"Test No. 471: Bacterial Reverse Mutation Test, OECD Guidelines for the Testing of Chemicals, Section 4","author":"OECD","year":"2020"},{"issue":"6\u20137","key":"10.1016\/j.tiv.2022.105510_bb0325","doi-asserted-by":"crossref","first-page":"391","DOI":"10.3109\/1354750X.2015.1094134","article-title":"Switching from usual brand cigarettes to a tobacco-heating cigarette or snus: part 2. Biomarkers of exposure","volume":"20","author":"Ogden","year":"2015","journal-title":"Biomarkers"},{"issue":"3","key":"10.1016\/j.tiv.2022.105510_bb0330","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1108\/DAT-02-2020-0007","article-title":"Tobacco harm reduction in the 21st century","volume":"20","author":"O'Leary","year":"2020","journal-title":"Drugs Alcohol Today"},{"key":"10.1016\/j.tiv.2022.105510_bb0335","doi-asserted-by":"crossref","DOI":"10.1007\/s12668-021-00898-3","article-title":"Investigation of volatile organic compounds and benzo[a]pyrene contents in the aerosols of cigarettes and IQOS tobacco heating system using high-performance gas chromatography\/mass spectrometry","author":"Perezhogina","year":"2021","journal-title":"BioNanoScience"},{"issue":"11","key":"10.1016\/j.tiv.2022.105510_bb0340","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1093\/ntr\/ntab094","article-title":"Nicotine delivery and user ratings of IQOS heated tobacco system compared with cigarettes, juul, and refillable E-cigarettes","volume":"23","author":"Phillips-Waller","year":"2021","journal-title":"Nicotine Tob. Res."},{"issue":"5","key":"10.1016\/j.tiv.2022.105510_bb0345","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1093\/ntr\/ntv220","article-title":"Comparison of the pharmacokinetics of nicotine following single and ad libitum use of a tobacco heating system or combustible cigarettes","volume":"18","author":"Picavet","year":"2016","journal-title":"Nicotine Tob. Res."},{"key":"10.1016\/j.tiv.2022.105510_bb0350","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.tox.2015.11.007","article-title":"Systems toxicology-based assessment of the candidate modified risk tobacco product THS2.2 for the adhesion of monocytic cells to human coronary arterial endothelial cells","volume":"339","author":"Poussin","year":"2016","journal-title":"Toxicology"},{"key":"10.1016\/j.tiv.2022.105510_bb0355","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.fct.2018.07.025","article-title":"In vitro systems toxicology-based assessment of the potential modified risk tobacco product CHTP 1.2 for vascular inflammation- and cytotoxicity-associated mechanisms promoting adhesion of monocytic cells to human coronary arterial endothelial cells","volume":"120","author":"Poussin","year":"2018","journal-title":"Food Chem. Toxicol."},{"issue":"3","key":"10.1016\/j.tiv.2022.105510_bb0360","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1093\/bioinformatics\/bts686","article-title":"ToxPi GUI: an interactive visualization tool for transparent integration of data from diverse sources of evidence","volume":"29","author":"Reif","year":"2013","journal-title":"Bioinformatics"},{"issue":"13","key":"10.1016\/j.tiv.2022.105510_bb0365","first-page":"86","article-title":"Pre-market studies from five countries in Asia and Europe to measure the adoption of the tobacco heating system (THS) in smokers","volume":"50","author":"Roulet","year":"2017","journal-title":"Tob. Sci. Technol."},{"key":"10.1016\/j.tiv.2022.105510_bb0370","doi-asserted-by":"crossref","first-page":"214","DOI":"10.12688\/f1000research.17606.1","article-title":"Potential predictors of adoption of the tobacco heating system by U.S. adult smokers: an actual use study","volume":"8","author":"Roulet","year":"2019","journal-title":"F1000Res"},{"key":"10.1016\/j.tiv.2022.105510_bb0375","author":"Royal College of Physicians"},{"issue":"1","key":"10.1016\/j.tiv.2022.105510_bb0380","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1089\/aivt.2019.0015","article-title":"Chemical composition and in vitro toxicity profile of a pod-based E-cigarette aerosol compared to cigarette smoke","volume":"6","author":"Rudd","year":"2020","journal-title":"App. Vitro Toxicol."},{"issue":"3","key":"10.1016\/j.tiv.2022.105510_bb0385","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.yrtph.2014.04.016","article-title":"Exposure evaluation of adult male Japanese smokers switched to a heated cigarette in a controlled clinical setting","volume":"69","author":"Sakaguchi","year":"2014","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"10.1016\/j.tiv.2022.105510_bb0390","doi-asserted-by":"crossref","first-page":"S27","DOI":"10.1016\/j.yrtph.2016.10.001","article-title":"Evaluation of the tobacco heating system 2.2. Part 2: chemical composition, genotoxicity, cytotoxicity, and physical properties of the aerosol","volume":"81","author":"Schaller","year":"2016","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"10.1016\/j.tiv.2022.105510_bb0395","doi-asserted-by":"crossref","DOI":"10.1016\/j.envpol.2020.115863","article-title":"Immunotoxic mechanisms of cigarette smoke and heat-not-burn tobacco vapor on Jurkat T cell functions","volume":"268","author":"Scharf","year":"2021","journal-title":"Environ. Pollut."},{"key":"10.1016\/j.tiv.2022.105510_bb0400","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.crtox.2020.11.001","article-title":"The use of human induced pluripotent stem cells to screen for developmental toxicity potential indicates reduced potential for non-combusted products, when compared to cigarettes","volume":"1","author":"Simms","year":"2020","journal-title":"Curr. Res. Toxicol."},{"issue":"1","key":"10.1016\/j.tiv.2022.105510_bb0405","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1002\/jat.4064","article-title":"Collecting e-cigarette aerosols for in vitro applications: a survey of the biomedical literature and opportunities to increase the value of submerged cell culture-based assessments","volume":"41","author":"Smart","year":"2021","journal-title":"J. Appl. Toxicol."},{"key":"10.1016\/j.tiv.2022.105510_bb0410","doi-asserted-by":"crossref","first-page":"S17","DOI":"10.1016\/j.yrtph.2016.07.006","article-title":"Evaluation of the tobacco heating system 2.2. Part 1: description of the system and the scientific assessment program","volume":"81","author":"Smith","year":"2016","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"10.1016\/j.tiv.2022.105510_bb0415","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.4161\/cc.8.12.8865","article-title":"The apoptotic ring: a novel entity with phosphorylated histones H2AX and H2B and activated DNA damage response kinases","volume":"8","author":"Solier","year":"2009","journal-title":"Cell Cycle"},{"key":"10.1016\/j.tiv.2022.105510_bb0420","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.toxlet.2017.06.001","article-title":"A comparative assessment of e-cigarette aerosols and cigarette smoke on in vitro endothelial cell migration","volume":"277","author":"Taylor","year":"2017","journal-title":"Toxicol. Lett."},{"key":"10.1016\/j.tiv.2022.105510_bb0425","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.yrtph.2017.08.016","article-title":"Assessment of novel tobacco heating product THP1.0. Part 6: a comparative in vitro study using contemporary screening approaches","volume":"93","author":"Taylor","year":"2018","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"10.1016\/j.tiv.2022.105510_bb0430","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.yrtph.2017.08.017","article-title":"Assessment of novel tobacco heating product THP1.0. Part 7: comparative in vitro toxicological evaluation","volume":"93","author":"Thorne","year":"2018","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"10.1016\/j.tiv.2022.105510_bb0435","doi-asserted-by":"crossref","first-page":"110546","DOI":"10.1016\/j.fct.2019.05.054","article-title":"Genotoxicity evaluation of tobacco and nicotine delivery products: part two. In vitro micronucleus assay","volume":"132","author":"Thorne","year":"2019","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.tiv.2022.105510_bb0440","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1016\/j.toxrep.2020.08.013","article-title":"The genotoxicological assessment of a tobacco heating product relative to cigarette smoke using the in vitro micronucleus assay","volume":"7","author":"Thorne","year":"2020","journal-title":"Toxicol. Rep."},{"key":"10.1016\/j.tiv.2022.105510_bb0445","series-title":"Assay Guidance Manual [Internet]. Bethesda (MD): Eli Lilly & Company and the National Center for Advancing Translational Sciences; 2004","article-title":"Nuclear factor Kappa B (NF-\u03baB) translocation assay development and validation for high content screening","author":"Trask","year":"2012"},{"issue":"6","key":"10.1016\/j.tiv.2022.105510_bb0450","doi-asserted-by":"crossref","first-page":"2474","DOI":"10.1128\/AAC.49.6.2474-2478.2005","article-title":"Mechanisms of antibacterial action of three monoterpenes","volume":"49","author":"Trombetta","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.tiv.2022.105510_bb0455","author":"United States Surgeon General"},{"key":"10.1016\/j.tiv.2022.105510_bb0460","series-title":"US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health","article-title":"The health consequences of smoking\u201350 years of progress: a report of the surgeon general. Atlanta, GA","author":"US Department of Health and Human Services","year":"2014"},{"key":"10.1016\/j.tiv.2022.105510_bb0465","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.fct.2015.09.016","article-title":"Aerosol from a candidate modified risk tobacco product has reduced effects on chemotaxis and transendothelial migration compared to combustion of conventional cigarettes","volume":"86","author":"van der Toorn","year":"2015","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.tiv.2022.105510_bb0470","doi-asserted-by":"crossref","DOI":"10.1016\/j.tiv.2021.105173","article-title":"In vitro toxicological evaluation of a tobacco heating product THP COO and 3R4F research reference cigarette on human lung cancer cells","volume":"74","author":"Wang","year":"2021","journal-title":"Toxicol. in Vitro"},{"key":"10.1016\/j.tiv.2022.105510_bb0475","doi-asserted-by":"crossref","DOI":"10.1016\/j.tiv.2020.104866","article-title":"A comparative in vitro toxicity assessment of electronic vaping product e-liquids and aerosols with tobacco cigarette smoke","volume":"66","author":"Wieczorek","year":"2020","journal-title":"Toxicol. in Vitro"},{"issue":"2","key":"10.1016\/j.tiv.2022.105510_bb0480","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1007\/s00204-017-2102-y","article-title":"A novel, integrated in vitro carcinogenicity test to identify genotoxic and non-genotoxic carcinogens using human lymphoblastoid cells","volume":"92","author":"Wilde","year":"2018","journal-title":"Arch. Toxicol."},{"key":"10.1016\/j.tiv.2022.105510_bb0485","doi-asserted-by":"crossref","DOI":"10.1016\/j.mrgentox.2019.503081","article-title":"Are all bacterial strains required by OECD mutagenicity test guideline TG471 needed?","volume":"848","author":"Williams","year":"2019","journal-title":"Mutat. Res. Genet. Toxicol. Environ. Mutagen."},{"issue":"3","key":"10.1016\/j.tiv.2022.105510_bb0490","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1093\/ntr\/nty200","article-title":"The future of nicotine regulation: key questions and challenges","volume":"21","author":"Zeller","year":"2019","journal-title":"Nicotine Tob. Res."}],"container-title":["Toxicology in Vitro"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0887233322002089?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0887233322002089?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:43:52Z","timestamp":1760136232000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0887233322002089"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2]]},"references-count":98,"alternative-id":["S0887233322002089"],"URL":"https:\/\/doi.org\/10.1016\/j.tiv.2022.105510","relation":{},"ISSN":["0887-2333"],"issn-type":[{"value":"0887-2333","type":"print"}],"subject":[],"published":{"date-parts":[[2023,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Multiple endpoint in vitro toxicity assessment of a prototype heated tobacco product indicates substantially reduced effects compared to those of combustible cigarette","name":"articletitle","label":"Article Title"},{"value":"Toxicology in Vitro","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.tiv.2022.105510","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 The Authors. Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"105510"}}