{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:42:54Z","timestamp":1791290574146,"version":"4.3.0"},"reference-count":152,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T00:00:00Z","timestamp":1718236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Toxicol."],"abstract":"<jats:p><jats:italic>In vitro<\/jats:italic> toxicology research has accelerated with the use of <jats:italic>in silico<\/jats:italic>, computational approaches and human <jats:italic>in vitro<\/jats:italic> tissue systems, facilitating major improvements evaluating the safety and health risks of novel consumer products. Innovation in molecular and cellular biology has shifted testing paradigms, with less reliance on low-throughput animal data and greater use of medium- and high-throughput <jats:italic>in vitro<\/jats:italic> cellular screening approaches. These new approach methodologies (NAMs) are being implemented in other industry sectors for chemical testing, screening candidate drugs and prototype consumer products, driven by the need for reliable, human-relevant approaches. Routine toxicological methods are largely unchanged since development over 50 years ago, using high-doses and often employing <jats:italic>in vivo<\/jats:italic> testing. Several disadvantages are encountered conducting or extrapolating data from animal studies due to differences in metabolism or exposure. The last decade saw considerable advancement in the development of <jats:italic>in vitro<\/jats:italic> tools and capabilities, and the challenges of the next decade will be integrating these platforms into applied product testing and acceptance by regulatory bodies. Governmental and validation agencies have launched and applied frameworks and \u201croadmaps\u201d to support agile validation and acceptance of NAMs. Next-generation tobacco and nicotine products (NGPs) have the potential to offer reduced risks to smokers compared to cigarettes. These include heated tobacco products (HTPs) that heat but do not burn tobacco; vapor products also termed electronic nicotine delivery systems (ENDS), that heat an e-liquid to produce an inhalable aerosol; oral smokeless tobacco products (e.g., Swedish-style snus) and tobacco-free oral nicotine pouches. With the increased availability of NGPs and the requirement of scientific studies to support regulatory approval, NAMs approaches can supplement the assessment of NGPs. This review explores how NAMs can be applied to assess NGPs, highlighting key considerations, including the use of appropriate <jats:italic>in vitro<\/jats:italic> model systems, deploying screening approaches for hazard identification, and the importance of test article characterization. The importance and opportunity for fit-for-purpose testing and method standardization are discussed, highlighting the value of industry and cross-industry collaborations. Supporting the development of methods that are accepted by regulatory bodies could lead to the implementation of NAMs for tobacco and nicotine NGP testing.<\/jats:p>","DOI":"10.3389\/ftox.2024.1376118","type":"journal-article","created":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T04:52:04Z","timestamp":1718254324000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Applying new approach methodologies to assess next-generation tobacco and nicotine products"],"prefix":"10.3389","volume":"6","author":[{"given":"David","family":"Thorne","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damian","family":"McHugh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam","family":"Simms","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. Monica","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Fujimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Moses","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Gaca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,6,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"441","DOI":"10.14573\/altex.1406111","article-title":"State-of-the-art of 3D cultures (organs-on-a-chip) in safety testing and pathophysiology","volume":"31","author":"Alepee","year":"2014","journal-title":"ALTEX"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1080\/08958370802207318","article-title":"Association of Inhalation Toxicologists (AIT) working party recommendation for standard delivered dose calculation and expression in non-clinical aerosol inhalation toxicology studies with pharmaceuticals","volume":"20","author":"Alexander","year":"2008","journal-title":"Inhal. Toxicol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1093\/toxsci\/kfn255","article-title":"Toxicity testing in the 21st century: bringing the vision to life","volume":"107","author":"Andersen","year":"2009","journal-title":"Toxicol. Sci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1016\/j.drudis.2013.05.015","article-title":"The Tox21 robotic platform for the assessment of environmental chemicals--from vision to reality","volume":"18","author":"Attene-Ramos","year":"2013","journal-title":"Drug Discov. Today"},{"key":"B5","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/j.etp.2017.03.004","article-title":"Phenotypical changes in a differentiating immortalized bronchial epithelial cell line after exposure to mainstream cigarette smoke and e-cigarette vapor","volume":"69","author":"Aufderheide","year":"2017","journal-title":"Exp. Toxicol. Pathol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/j.etp.2017.01.015","article-title":"Metaplastic phenotype in human primary bronchiolar epithelial cells after repeated exposure to native mainstream smoke at the air-liquid interface","volume":"69","author":"Aufderheide","year":"2017","journal-title":"Exp. Toxicol. Pathol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1016\/j.etp.2015.04.006","article-title":"Ciliatoxicity in human primary bronchiolar epithelial cells after repeated exposure at the air-liquid interface with native mainstream smoke of K3R4F cigarettes with and without charcoal filter","volume":"67","author":"Aufderheide","year":"2015","journal-title":"Exp. Toxicol. Pathol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/s13065-023-00918-1","article-title":"Harmful and potentially harmful constituents (HPHCs) in two novel nicotine pouch products in comparison with regular smokeless tobacco products and pharmaceutical nicotine replacement therapy products (NRTs)","volume":"17","author":"Back","year":"2023","journal-title":"BMC Chem."},{"key":"B9","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/0360-1285(81)90008-3","article-title":"Product formation mechanisms inside a burning cigarette","volume":"7","author":"Baker","year":"1981","journal-title":"Prog. Energy Combust. Sci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.fct.2004.01.001","article-title":"An overview of the effects of tobacco ingredients on smoke chemistry and toxicity","volume":"42","author":"Baker","year":"2004","journal-title":"Food Chem. Toxicol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"14620","DOI":"10.1038\/s41598-017-14815-w","article-title":"Functional coupling of human pancreatic islets and liver spheroids on-a-chip: towards a novel human ex vivo type 2 diabetes model","volume":"7","author":"Bauer","year":"2017","journal-title":"Sci. Rep."},{"key":"B12","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1093\/toxsci\/kfs319","article-title":"In vitro exposure of precision-cut lung slices to 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole lysylamide dihydrochloride (NSC 710305, Phortress) increases inflammatory cytokine content and tissue damage","volume":"131","author":"Behrsing","year":"2013","journal-title":"Toxicol. Sci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.tiv.2017.11.016","article-title":"In vitro to in vivo extrapolation for high throughput prioritization and decision making","volume":"47","author":"Bell","year":"2018","journal-title":"Toxicol. Vitro"},{"key":"B14","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1038\/nmeth.3697","article-title":"Small airway-on-a-chip enables analysis of human lung inflammation and drug responses in vitro","volume":"13","author":"Benam","year":"2016","journal-title":"Nat. Methods"},{"key":"B15","first-page":"89","article-title":"In vitro models of inhalation toxicity and disease. The report of a FRAME workshop","volume":"37","author":"Berube","year":"2009","journal-title":"Altern. Lab. Anim."},{"key":"B16","doi-asserted-by":"publisher","first-page":"110","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","volume":"334","author":"Bishop","year":"2020","journal-title":"Toxicol. Lett."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.toxlet.2023.03.006","article-title":"A contextualised e-cigarette testing strategy shows flavourings do not impact lung toxicity in vitro","volume":"380","author":"Bishop","year":"2023","journal-title":"Toxicol. Lett."},{"key":"B18","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1177\/2472555219830087","article-title":"3D cell-based assays for drug screens: challenges in imaging, image analysis, and high-content analysis","volume":"24","author":"Booij","year":"2019","journal-title":"SLAS Discov."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1177\/2397847317726351","article-title":"Organs-on-a-chip: new in vitro tools multi-organ-on-a-chip challenges, limitations, and future prospects for fluidic devices","volume":"1","author":"Bovard","year":"2017","journal-title":"Toxicol. Res. Appl."},{"key":"B20","doi-asserted-by":"publisher","first-page":"3814","DOI":"10.1039\/c8lc01029c","article-title":"A lung\/liver-on-a-chip platform for acute and chronic toxicity studies","volume":"18","author":"Bovard","year":"2018","journal-title":"Lab. Chip"},{"key":"B21","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.toxlet.2020.10.005","article-title":"Optimization of aqueous aerosol extract (AqE) generation from e-cigarettes and tobacco heating products for in vitro cytotoxicity testing","volume":"335","author":"Bozhilova","year":"2020","journal-title":"Toxicol. Lett."},{"key":"B22","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1002\/em.21996","article-title":"Genotoxic mode of action predictions from a multiplexed flow cytometric assay and a machine learning approach","volume":"57","author":"Bryce","year":"2016","journal-title":"Environ. Mol. Mutagen."},{"key":"B23","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1002\/em.22083","article-title":"Interlaboratory evaluation of a multiplexed high information content in vitro genotoxicity assay","volume":"58","author":"Bryce","year":"2017","journal-title":"Environ. Mol. Mutagen."},{"key":"B24","doi-asserted-by":"publisher","first-page":"517","DOI":"10.4161\/19336918.2014.970001","article-title":"Flow shear stress regulates endothelial barrier function and expression of angiogenic factors in a 3D microfluidic tumor vascular model","volume":"8","author":"Buchanan","year":"2014","journal-title":"Cell. adh. Migr."},{"key":"B25","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1002\/jat.3165","article-title":"Adverse Outcome Pathways can drive non-animal approaches for safety assessment","volume":"35","author":"Burden","year":"2015","journal-title":"J. Appl. Toxicol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1007\/s11626-020-00517-7","article-title":"Invited review: human air-liquid-interface organotypic airway tissue models derived from primary tracheobronchial epithelial cells\u2014overview and perspectives","volume":"57","author":"Cao","year":"2021","journal-title":"Vitro Cell. Dev. Biol. Anim."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1002\/dta.3275","article-title":"In vitro cytoxicity profile of e-cigarette liquid samples on primary human bronchial epithelial cells","volume":"15","author":"Caruso","year":"2023","journal-title":"Drug Test. Anal."},{"key":"B28","doi-asserted-by":"publisher","first-page":"105090","DOI":"10.1016\/j.tiv.2021.105090","article-title":"Exploring in vitro to in vivo extrapolation for exposure and health impacts of e-cigarette flavor mixtures","volume":"72","author":"Chang","year":"2021","journal-title":"Toxicol. Vitro"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1076752","DOI":"10.3389\/ftox.2023.1076752","article-title":"Twenty-eight day repeated exposure of human 3D bronchial epithelial model to heated tobacco aerosols indicates decreased toxicological responses compared to cigarette smoke","volume":"5","author":"Chapman","year":"2023","journal-title":"Front. Toxicol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/j.arbres.2023.01.016","article-title":"Deposition and clinical impact of inhaled particles in the lung","volume":"59","author":"Clara","year":"2023","journal-title":"Arch. Bronconeumol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"503502","DOI":"10.1016\/j.mrgentox.2022.503502","article-title":"A comparison of cigarette smoke test matrices and their responsiveness in the mouse lymphoma assay: a case study","author":"Crooks","year":"2022","journal-title":"Mutat. Res. Genet. Toxicol. Environ. Mutagen."},{"key":"B32","doi-asserted-by":"publisher","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":"B33","doi-asserted-by":"publisher","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. Vitro"},{"key":"B34","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.crtox.2021.02.004","article-title":"Multi-endpoint analysis of human 3D airway epithelium following repeated exposure to whole electronic vapor product aerosol or cigarette smoke","volume":"2","author":"Czekala","year":"2021","journal-title":"Curr. Res. Toxicol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/s00204-014-1421-5","article-title":"SEURAT: safety evaluation ultimately replacing animal testing--recommendations for future research in the field of predictive toxicology","volume":"89","author":"Daston","year":"2015","journal-title":"Arch. Toxicol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1038\/nprot.2016.172","article-title":"Preparation, characterization, and in vitro dosimetry of dispersed, engineered nanomaterials","volume":"12","author":"DeLoid","year":"2017","journal-title":"Nat. Protoc."},{"key":"B37","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1002\/em.22274","article-title":"Predictions of genotoxic potential, mode of action, molecular targets, and potency via a tiered multiflow\u00ae assay data analysis strategy","volume":"60","author":"Dertinger","year":"2019","journal-title":"Environ. Mol. Mutagen."},{"key":"B38","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/s0273-2300(03)00068-0","article-title":"Implications of the lack of accuracy of the lifetime rodent bioassay for predicting human carcinogenicity","volume":"38","author":"Ennever","year":"2003","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"455A","DOI":"10.1021\/es0406740","article-title":"Internal exposure: linking bioavailability to effects","volume":"38","author":"Escher","year":"2004","journal-title":"Environ. Sci. Technol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1186\/s12889-023-15535-9","article-title":"Burden of smoking on disease-specific mortality, DALYs, costs: the case of a high-income European country","volume":"23","author":"Farcher","year":"2023","journal-title":"BMC Public Health"},{"key":"B41","doi-asserted-by":"publisher","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."},{"key":"B42","doi-asserted-by":"publisher","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. Vitro"},{"key":"B43","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/1743-8977-10-25","article-title":"Growth of human bronchial epithelial cells at an air-liquid interface alters the response to particle exposure","volume":"10","author":"Ghio","year":"2013","journal-title":"Part. Fibre Toxicol."},{"key":"B44","doi-asserted-by":"publisher","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":"B45","doi-asserted-by":"publisher","first-page":"327","DOI":"10.14573\/altex.1510051","article-title":"Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology","volume":"32","author":"Gordon","year":"2015","journal-title":"ALTEX"},{"key":"B46","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1165\/ajrcmb.14.1.8534481","article-title":"Mucociliary differentiation of serially passaged normal human tracheobronchial epithelial cells","volume":"14","author":"Gray","year":"1996","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.toxrep.2023.02.005","article-title":"Chemical and in vitro toxicological comparison of emissions from a heated tobacco product and the 1R6F reference cigarette","volume":"10","author":"Hashizume","year":"2023","journal-title":"Toxicol. Rep."},{"key":"B48","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1016\/j.tiv.2009.12.019","article-title":"Cigarette smoke total particulate matter increases mucous secreting cell numbers in vitro: a potential model of goblet cell hyperplasia","volume":"24","author":"Haswell","year":"2010","journal-title":"Toxicol. Vitro"},{"key":"B49","unstructured":"Health Canada. Health Canada official methods for the testing of tobacco products (mainstream smoke)2024"},{"key":"B50","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1093\/toxsci\/kfv323","article-title":"The extended ToxTracker assay discriminates between induction of DNA damage, oxidative stress, and protein misfolding","volume":"150","author":"Hendriks","year":"2016","journal-title":"Toxicol. Sci."},{"key":"B51","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/1743-8977-7-36","article-title":"ISDD: a computational model of particle sedimentation, diffusion and target cell dosimetry for in vitro toxicity studies","volume":"7","author":"Hinderliter","year":"2010","journal-title":"Part. Fibre Toxicol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"864742","DOI":"10.3389\/fphar.2022.864742","article-title":"Application of an accessible interface for pharmacokinetic modeling and in vitro to in vivo extrapolation","volume":"13","author":"Hines","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1186\/1465-9921-14-97","article-title":"Prolonged cigarette smoke exposure alters mitochondrial structure and function in airway epithelial cells","volume":"14","author":"Hoffmann","year":"2013","journal-title":"Respir. Res."},{"key":"B54","doi-asserted-by":"publisher","first-page":"1662","DOI":"10.1126\/science.1188302","article-title":"Reconstituting organ-level lung functions on a chip","volume":"328","author":"Huh","year":"2010","journal-title":"Science"},{"key":"B55","unstructured":"Validation, qualification, and regulatory acceptance of new approach methodologies2023"},{"key":"B56","unstructured":"A strategic roadmap for establishing new approaches to evaluate the safety of chemicals and medical products in the United States2018"},{"key":"B57","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.tiv.2016.09.004","article-title":"Repeated whole cigarette smoke exposure alters cell differentiation and augments secretion of inflammatory mediators in air-liquid interface three-dimensional co-culture model of human bronchial tissue","volume":"38","author":"Ishikawa","year":"2017","journal-title":"Toxicol. Vitro"},{"key":"B58","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/j.tiv.2018.10.001","article-title":"Multi-omics analysis: repeated exposure of a 3D bronchial tissue culture to whole-cigarette smoke","volume":"54","author":"Ishikawa","year":"2019","journal-title":"Toxicol. Vitro"},{"key":"B59","doi-asserted-by":"publisher","first-page":"512086","DOI":"10.1155\/2013\/512086","article-title":"Systems approaches evaluating the perturbation of xenobiotic metabolism in response to cigarette smoke exposure in nasal and bronchial tissues","volume":"2013","author":"Iskandar","year":"2013","journal-title":"Biomed. Res. Int."},{"key":"B61","doi-asserted-by":"publisher","first-page":"3229","DOI":"10.1007\/s00204-019-02565-9","article-title":"Application of a multi-layer systems toxicology framework for in vitro assessment of the biological effects of Classic Tobacco e-liquid and its corresponding aerosol using an e-cigarette device with MESH technology","volume":"93","author":"Iskandar","year":"2019","journal-title":"Arch. Toxicol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1016\/j.toxrep.2018.08.015","article-title":"Effects of repeated cigarette smoke extract exposure over one month on human bronchial epithelial organotypic culture","volume":"5","author":"Ito","year":"2018","journal-title":"Toxicol. Rep."},{"key":"B63","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1002\/jat.3982","article-title":"In vitro long-term repeated exposure and exposure switching of a novel tobacco vapor product in a human organotypic culture of bronchial epithelial cells","volume":"40","author":"Ito","year":"2020","journal-title":"J. Appl. Toxicol."},{"key":"B64","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.toxlet.2019.08.004","article-title":"An inter-laboratory in vitro assessment of cigarettes and next generation nicotine delivery products","volume":"315","author":"Ito","year":"2019","journal-title":"Toxicol. Lett."},{"key":"B65","doi-asserted-by":"publisher","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."},{"key":"B66","doi-asserted-by":"publisher","first-page":"3263","DOI":"10.1158\/1055-9965.EPI-09-0965","article-title":"Evaluation of in vitro assays for assessing the toxicity of cigarette smoke and smokeless tobacco","volume":"18","author":"Johnson","year":"2009","journal-title":"Cancer Epidemiol. Biomarkers Prev."},{"key":"B67","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1242\/dmm.024547","article-title":"Using the mouse to model human disease: increasing validity and reproducibility","volume":"9","author":"Justice","year":"2016","journal-title":"Dis. Model Mech."},{"key":"B68","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/1743-8977-10-31","article-title":"An improved 3D tetraculture system mimicking the cellular organisation at the alveolar barrier to study the potential toxic effects of particles on the lung","volume":"10","author":"Klein","year":"2013","journal-title":"Part. Fibre Toxicol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1515\/cttr-2016-0015","article-title":"Cigarette mainstream smoke: the evolution of methods and devices for generation, exposure and collection","volume":"27","author":"Klus","year":"2016","journal-title":"Contrib. Tob. Nicotine Res."},{"key":"B70","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1007\/BF02191906","article-title":"Culture-dependent expression of Na+ conductances in airway epithelial cells","volume":"431","author":"Kunzelmann","year":"1996","journal-title":"Pflugers Arch."},{"key":"B71","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1089\/aivt.2017.0034","article-title":"Air\u2013liquid interface in vitro models for respiratory toxicology research: consensus workshop and recommendations","volume":"4","author":"Lacroix","year":"2018","journal-title":"Appl. Vitro Toxicol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1007\/s00216-024-05126-x","article-title":"Non-targeted analytical comparison of a heated tobacco product aerosol against mainstream cigarette smoke: does heating tobacco produce an inherently different set of aerosol constituents?","volume":"416","author":"Lang","year":"2023","journal-title":"Anal. Bioanal. Chem."},{"key":"B73","doi-asserted-by":"publisher","first-page":"2055","DOI":"10.1007\/s00204-018-2213-0","article-title":"Building predictive in vitro pulmonary toxicity assays using high-throughput imaging and artificial intelligence","volume":"92","author":"Lee","year":"2018","journal-title":"Arch. Toxicol."},{"key":"B74","doi-asserted-by":"publisher","first-page":"760","DOI":"10.3390\/toxics10120760","article-title":"Advancing new approach methodologies (NAMs) for tobacco harm reduction: synopsis from the 2021 CORESTA SSPT-NAMs symposium","volume":"10","author":"Lee","year":"2022","journal-title":"Toxics"},{"key":"B75","unstructured":"New approach methods (NAMs) symposium-II: applications in tobacco regulatory sciences, the 2023 CORESTA SSPT symposium\n            LeeK. M.\n            PourS. J.\n            ZhangJ.\n            KeyserB.\n            IskandarA.\n            ItoS.\n          2023"},{"key":"B76","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1016\/j.ejpb.2010.10.014","article-title":"An in vitro triple cell co-culture model with primary cells mimicking the human alveolar epithelial barrier","volume":"77","author":"Lehmann","year":"2011","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"B77","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.tiv.2016.07.019","article-title":"In vitro toxicity testing of cigarette smoke based on the air-liquid interface exposure: a review","volume":"36","author":"Li","year":"2016","journal-title":"Toxicol. Vitro"},{"key":"B78","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1089\/aivt.2016.0031","article-title":"Development of an adverse outcome pathway for the onset of hypertension by oxidative stress-mediated perturbation of endothelial nitric oxide bioavailability","volume":"3","author":"Lowe","year":"2017","journal-title":"Appl. Vitro Toxicol."},{"key":"B79","doi-asserted-by":"publisher","first-page":"8","DOI":"10.3390\/toxics10010008","article-title":"The emission of VOCs and CO from heated tobacco products, electronic cigarettes, and conventional cigarettes, and their health risk","volume":"10","author":"Lu","year":"2021","journal-title":"Toxics"},{"key":"B80","doi-asserted-by":"publisher","first-page":"750254","DOI":"10.3389\/ftox.2021.750254","article-title":"An adverse outcome pathway for decreased lung function focusing on mechanisms of impaired mucociliary clearance following inhalation exposure","volume":"3","author":"Luettich","year":"2021","journal-title":"Front. Toxicol."},{"key":"B81","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1089\/aivt.2016.0032","article-title":"The adverse outcome pathway for oxidative stress-mediated EGFR activation leading to decreased lung function","volume":"3","author":"Luettich","year":"2017","journal-title":"Appl. Vitro Toxicol."},{"key":"B82","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.fct.2018.02.013","article-title":"Assessment of mitochondrial function following short- and long-term exposure of human bronchial epithelial cells to total particulate matter from a candidate modified-risk tobacco product and reference cigarettes","volume":"115","author":"Malinska","year":"2018","journal-title":"Food Chem. Toxicol."},{"key":"B83","doi-asserted-by":"publisher","first-page":"121","DOI":"10.12688\/f1000research.74718.1","article-title":"The product science of electrically heated tobacco products: a narrative review of the scientific literature","volume":"11","author":"Malt","year":"2022","journal-title":"F1000Research"},{"key":"B84","doi-asserted-by":"publisher","first-page":"47013","DOI":"10.1289\/EHP8495","article-title":"CATMoS: collaborative acute toxicity modeling suite","volume":"129","author":"Mansouri","year":"2021","journal-title":"Environ. Health Perspect."},{"key":"B85","doi-asserted-by":"publisher","first-page":"388","DOI":"10.14573\/altex.1811221","article-title":"How complex should an in vitro model be? Evaluation of complex 3D alveolar model with transcriptomic data and computational biological network models","volume":"36","author":"Marescotti","year":"2019","journal-title":"ALTEX"},{"key":"B86","doi-asserted-by":"publisher","first-page":"1662","DOI":"10.1021\/acs.chemrestox.6b00188","article-title":"Chemical composition of aerosol from an E-cigarette: a quantitative comparison with cigarette smoke","volume":"29","author":"Margham","year":"2016","journal-title":"Chem. Res. Toxicol."},{"key":"B87","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.ejpb.2015.03.002","article-title":"Chip-based human liver-intestine and liver-skin co-cultures--A first step toward systemic repeated dose substance testing in vitro","volume":"95","author":"Maschmeyer","year":"","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"B88","doi-asserted-by":"publisher","first-page":"2688","DOI":"10.1039\/c5lc00392j","article-title":"A four-organ-chip for interconnected long-term co-culture of human intestine, liver, skin and kidney equivalents","volume":"15","author":"Maschmeyer","year":"","journal-title":"Lab. Chip"},{"key":"B89","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.jbiotec.2015.02.002","article-title":"A multi-organ chip co-culture of neurospheres and liver equivalents for long-term substance testing","volume":"205","author":"Materne","year":"2015","journal-title":"J. Biotechnol."},{"key":"B90","volume-title":"Nicotine vaping in England: an evidence update including health risks and perceptions, September 2022. A report commissioned by the Office for Health Improvement and Disparities","author":"McNeil","year":"2022"},{"key":"B91","volume-title":"Evidence review of e-cigarettes and heated tobacco products 2018. A report commissioned by Public Health England","author":"McNeill","year":"2018"},{"key":"B92","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1002\/dta.3344","article-title":"Key challenges for in vitro testing of tobacco products for regulatory applications: recommendations for dosimetry","volume":"15","author":"Miller-Holt","year":"2023","journal-title":"Drug Test. Anal."},{"key":"B93","doi-asserted-by":"publisher","first-page":"11325","DOI":"10.3390\/ijerph111111325","article-title":"Comparative in vitro toxicity profile of electronic and tobacco cigarettes, smokeless tobacco and nicotine replacement therapy products: E-liquids, extracts and collected aerosols","volume":"11","author":"Misra","year":"2014","journal-title":"Int. J. Environ. Res. Public Health."},{"key":"B94","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1177\/02611929221146536","article-title":"Key challenges and recommendations for in vitro testing of tobacco products for regulatory applications: consideration of test materials and exposure parameters","volume":"51","author":"Moore","year":"2023","journal-title":"Altern. Lab. Anim."},{"key":"B95","doi-asserted-by":"publisher","first-page":"105391","DOI":"10.1016\/j.tiv.2022.105391","article-title":"Donor-to-donor variability of a human three-dimensional bronchial epithelial model: a case study of cigarette smoke exposure","volume":"82","author":"Mori","year":"2022","journal-title":"Toxicol. Vitro"},{"key":"B96","volume-title":"Toxicity testing in the 21st century: a vision and a strategy","year":"2007"},{"key":"B97","doi-asserted-by":"publisher","first-page":"S7","DOI":"10.1186\/scrt368","article-title":"Novel in vitro respiratory models to study lung development, physiology, pathology and toxicology","volume":"4","author":"Nichols","year":"2013","journal-title":"Stem Cell Res. Ther."},{"key":"B98","doi-asserted-by":"publisher","first-page":"105582","DOI":"10.1016\/j.tiv.2023.105582","article-title":"Human vasculature-on-a-chip with macrophage-mediated endothelial activation: the biological effect of aerosol from heated tobacco products on monocyte adhesion","volume":"89","author":"Ohashi","year":"2023","journal-title":"Toxicol. Vitro"},{"key":"B99","unstructured":"Welcome to the collaborative adverse outcome pathway wiki (AOP-Wiki)2023"},{"key":"B100","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1080\/10937400050045264","article-title":"The practice of exposure assessment: a state-of-the-art review","volume":"3","author":"Paustenbach","year":"2000","journal-title":"J. Toxicol. Environ. Health B Crit. Rev."},{"key":"B101","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1093\/emph\/eow014","article-title":"Mouse models of human disease: an evolutionary perspective","volume":"2016","author":"Perlman","year":"2016","journal-title":"Evol. Med. Public Health"},{"key":"B102","doi-asserted-by":"publisher","first-page":"122208","DOI":"10.1016\/j.lfs.2023.122208","article-title":"Development of lung tissue models and their applications","volume":"334","author":"Petpiroon","year":"2023","journal-title":"Life Sci."},{"key":"B103","doi-asserted-by":"publisher","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":"B104","doi-asserted-by":"publisher","first-page":"105133","DOI":"10.1016\/j.tiv.2021.105133","article-title":"Effective exposure of chemicals in in vitro cell systems: a review of chemical distribution models","volume":"73","author":"Proen\u00e7a","year":"2021","journal-title":"Toxicol. Vitro"},{"key":"B105","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1002\/mabi.201100181","article-title":"Tissue-Specific stem cell differentiation in an in vitro airway model","volume":"11","author":"Prytherch","year":"2011","journal-title":"Macromol. Biosci."},{"key":"B106","doi-asserted-by":"publisher","first-page":"FSO180","DOI":"10.4155\/fsoa-2016-0092","article-title":"Integration concepts for multi-organ chips: how to maintain flexibility?","volume":"3","author":"Rogal","year":"2017","journal-title":"Future Sci. OA"},{"key":"B107","doi-asserted-by":"publisher","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":"Appl. Vitro Toxicol."},{"key":"B108","volume-title":"The principles of humane experimental technique","author":"Russell","year":"1959"},{"key":"B109","doi-asserted-by":"publisher","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":"B110","doi-asserted-by":"publisher","first-page":"8163","DOI":"10.1038\/srep08163","article-title":"Cigarette smoke alters primary human bronchial epithelial cell differentiation at the air-liquid interface","volume":"5","author":"Schamberger","year":"2015","journal-title":"Sci. Rep."},{"key":"B111","first-page":"214","article-title":"Predicting the future: opportunities and challenges for the chemical industry to apply 21st-century toxicity testing","volume":"54","author":"Settivari","year":"2015","journal-title":"J. Am. Assoc. Lab. Anim. Sci."},{"key":"B112","doi-asserted-by":"publisher","first-page":"84","DOI":"10.3109\/00498254.2012.731543","article-title":"Assessment of immunotoxicity using precision-cut tissue slices","volume":"43","author":"Sewald","year":"2013","journal-title":"Xenobiotica"},{"key":"B113","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1093\/toxsci\/kfad074","article-title":"Human cell-based in vitro systems to assess respiratory toxicity: a case study using silanes","volume":"195","author":"Sharma","year":"2023","journal-title":"Toxicol. Sci."},{"key":"B114","doi-asserted-by":"publisher","first-page":"90","DOI":"10.3390\/cosmetics9050090","article-title":"A state-of-the-art review on the alternatives to animal testing for the safety assessment of cosmetics","volume":"9","author":"Silva","year":"2022","journal-title":"Cosmetics"},{"key":"B115","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.yrtph.2019.02.011","article-title":"Assessment of priority tobacco additives per the requirements of the EU Tobacco Products Directive (2014\/40\/EU): Part 1: background, approach, and summary of findings","volume":"104","author":"Simms","year":"2019","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"B116","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/j.crtox.2021.08.003","article-title":"Use of a rapid human primary cell-based disease screening model, to compare next generation products to combustible cigarettes","volume":"2","author":"Simms","year":"2021","journal-title":"Curr. Res. Toxicol."},{"key":"B117","doi-asserted-by":"publisher","first-page":"503129","DOI":"10.1016\/j.mrgentox.2019.503129","article-title":"Development of an integrated assay in human TK6 cells to permit comprehensive genotoxicity analysis in vitro","volume":"849","author":"Smart","year":"2020","journal-title":"Mutat. Res. Genet. Toxicol. Environ. Mutagen."},{"key":"B118","doi-asserted-by":"publisher","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":"B119","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.tiv.2018.07.020","article-title":"Long term effects of cigarette smoke extract or nicotine on nerve growth factor and its receptors in a bronchial epithelial cell line","volume":"53","author":"Stabile","year":"2018","journal-title":"Toxicol. Vitro"},{"key":"B120","doi-asserted-by":"publisher","first-page":"943982","DOI":"10.1155\/2012\/943982","article-title":"Evaluation of differentiated human bronchial epithelial cell culture systems for asthma research","volume":"2012","author":"Stewart","year":"2012","journal-title":"J. Allergy (Cairo)"},{"key":"B121","doi-asserted-by":"publisher","first-page":"1302","DOI":"10.1039\/c4lc01252f","article-title":"A lung-on-a-chip array with an integrated bio-inspired respiration mechanism","volume":"15","author":"Stucki","year":"2015","journal-title":"Lab. Chip"},{"key":"B122","doi-asserted-by":"publisher","first-page":"14359","DOI":"10.1038\/s41598-018-32523-x","article-title":"Medium throughput breathing human primary cell alveolus-on-chip model","volume":"8","author":"Stucki","year":"2018","journal-title":"Sci. Rep."},{"key":"B123","doi-asserted-by":"publisher","first-page":"2793","DOI":"10.1007\/s00204-015-1638-y","article-title":"High-throughput imaging-based nephrotoxicity prediction for xenobiotics with diverse chemical structures","volume":"90","author":"Su","year":"2016","journal-title":"Arch. Toxicol."},{"key":"B124","doi-asserted-by":"publisher","first-page":"3049","DOI":"10.1016\/j.apsb.2022.02.002","article-title":"Why 90% of clinical drug development fails and how to improve it?","volume":"12","author":"Sun","year":"2022","journal-title":"Acta. Pharm. Sin. B"},{"key":"B125","doi-asserted-by":"publisher","first-page":"947","DOI":"10.3390\/toxics11120947","article-title":"Aerosol emissions from heated tobacco products: a review focusing on carbonyls, analytical methods, and experimental quality","volume":"11","author":"Sussman","year":"2023","journal-title":"Toxics"},{"key":"B126","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.yrtph.2017.11.009","article-title":"Chemical analysis and in vitro toxicological evaluation of aerosol from a novel tobacco vapor product: a comparison with cigarette smoke","volume":"92","author":"Takahashi","year":"2018","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"B127","doi-asserted-by":"publisher","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":"B128","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1186\/s13104-020-05337-2","article-title":"In vitro biological assessment of the stability of cigarette smoke aqueous aerosol extracts","volume":"13","author":"Taylor","year":"2020","journal-title":"BMC Res. Notes"},{"key":"B129","doi-asserted-by":"publisher","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":"B130","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/s12989-018-0243-7","article-title":"ISD3: a particokinetic model for predicting the combined effects of particle sedimentation, diffusion and dissolution on cellular dosimetry for in vitro systems","volume":"15","author":"Thomas","year":"2018","journal-title":"Part Fibre Toxicol."},{"key":"B131","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1093\/toxsci\/kfz058","article-title":"The next generation blueprint of computational toxicology at the US Environmental Protection Agency","volume":"169","author":"Thomas","year":"2019","journal-title":"Toxicol. Sci."},{"key":"B132","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1016\/j.etp.2013.06.001","article-title":"A review of in vitro cigarette smoke exposure systems","volume":"65","author":"Thorne","year":"2013","journal-title":"Exp. Toxicol. Pathol."},{"key":"B133","doi-asserted-by":"publisher","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":"B134","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.mrgentox.2016.10.005","article-title":"The mutagenic assessment of an electronic-cigarette and reference cigarette smoke using the Ames assay in strains TA98 and TA100","volume":"812","author":"Thorne","year":"2016","journal-title":"Mutat. Res. Genet. Toxicol. Environ. Mutagen."},{"key":"B135","doi-asserted-by":"publisher","first-page":"503230","DOI":"10.1016\/j.mrgentox.2020.503230","article-title":"An experimental aerosol air\u2013agar interface mouse lymphoma assay methodology","author":"Thorne","year":"2020","journal-title":"Mutat. Res. Genet. Toxicol. Environ. Mutagen."},{"key":"B136","doi-asserted-by":"publisher","first-page":"110584","DOI":"10.1016\/j.fct.2019.110584","article-title":"Genotoxicity evaluation of tobacco and nicotine delivery products: Part One. Mouse lymphoma assay","volume":"132","author":"Thorne","year":"","journal-title":"Food Chem. Toxicol."},{"key":"B137","doi-asserted-by":"publisher","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":"","journal-title":"Food Chem. Toxicol."},{"key":"B138","doi-asserted-by":"publisher","first-page":"239784732110222","DOI":"10.1177\/23978473211022267","article-title":"A survey of aerosol exposure systems relative to the analysis of cytotoxicity: a Cooperation Centre for Scientific Research Relative to Tobacco (CORESTA) perspective","volume":"5","author":"Thorne","year":"2021","journal-title":"Toxicol. Res. Appl."},{"key":"B139","unstructured":"Alternative test methods and strategies to reduce vertebrate animal testing2023"},{"key":"B140","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.tiv.2018.02.019","article-title":"The biological effects of long-term exposure of human bronchial epithelial cells to total particulate matter from a candidate modified-risk tobacco product","volume":"50","author":"Van Der Toorn","year":"2018","journal-title":"Toxicol. Vitro"},{"key":"B141","doi-asserted-by":"publisher","first-page":"2865","DOI":"10.1007\/s00204-022-03365-4","article-title":"A framework for establishing scientific confidence in new approach methodologies","volume":"96","author":"Van Der Zalm","year":"2022","journal-title":"Arch. Toxicol."},{"key":"B142","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.ejphar.2015.02.055","article-title":"The safety, efficacy and regulatory triangle in drug development: impact for animal models and the use of animals","volume":"759","author":"Van Meer","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"B143","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1111\/j.1432-0436.2006.00069.x","article-title":"A three-dimensional model of differentiation of immortalized human bronchial epithelial cells","volume":"74","author":"Vaughan","year":"2006","journal-title":"Differentiation"},{"key":"B144","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1016\/j.tiv.2010.11.011","article-title":"Chronic exposure to cigarette smoke condensate in vitro induces epithelial to mesenchymal transition-like changes in human bronchial epithelial cells, BEAS-2B","volume":"25","author":"Veljkovic","year":"2011","journal-title":"Toxicol. Vitro"},{"key":"B145","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1093\/toxsci\/kfu199","article-title":"Adverse outcome pathway (AOP) development I: strategies and principles","volume":"142","author":"Villeneuve","year":"2014","journal-title":"Toxicol. Sci."},{"key":"B146","doi-asserted-by":"publisher","first-page":"775","DOI":"10.17179\/excli2020-1463","article-title":"3Rs toxicity testing and disease modeling projects in the European Horizon 2020 research and innovation program","volume":"19","author":"Vinken","year":"2020","journal-title":"EXCLI J."},{"key":"B147","doi-asserted-by":"publisher","first-page":"3172","DOI":"10.1002\/smll.201600314","article-title":"Buoyant nanoparticles: implications for nano-biointeractions in cellular studies","volume":"12","author":"Watson","year":"2016","journal-title":"Small"},{"key":"B148","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1002\/em.22360","article-title":"Benchmark dose analysis of DNA damage biomarker responses provides compound potency and adverse outcome pathway information for the topoisomerase II inhibitor class of compounds","volume":"61","author":"Wheeldon","year":"2020","journal-title":"Environ. Mol. Mutagen."},{"key":"B149","doi-asserted-by":"publisher","first-page":"1050","DOI":"10.1002\/jat.4442","article-title":"Characterisation of a smoke\/aerosol exposure in vitro system (SAEIVS) for delivery of complex mixtures directly to cells at the air-liquid interface","volume":"43","author":"Wieczorek","year":"2023","journal-title":"J. Appl. Toxicol."},{"key":"B150","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1038\/nprot.2015.021","article-title":"Efficient generation of functional CFTR-expressing airway epithelial cells from human pluripotent stem cells","volume":"10","author":"Wong","year":"2015","journal-title":"Nat. Protoc."},{"key":"B151","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1152\/physrev.00048.2006","article-title":"Pathobiology of cigarette smoke-induced chronic obstructive pulmonary disease","volume":"87","author":"Yoshida","year":"2007","journal-title":"Physiol. Rev."},{"key":"B152","doi-asserted-by":"publisher","first-page":"787756","DOI":"10.3389\/ftox.2021.787756","article-title":"Evaluation of inhalation exposures and potential health impacts of ingredient mixtures using in vitro to in vivo extrapolation","volume":"3","author":"Zhang","year":"2021","journal-title":"Front. Toxicol."},{"key":"B153","doi-asserted-by":"publisher","first-page":"1472","DOI":"10.3390\/ijms23031472","article-title":"Transport turnover rates for human OCT2 and MATE1 expressed in Chinese hamster ovary cells","volume":"23","author":"Zhang","year":"2022","journal-title":"Int. J. Mol. Sci."}],"updated-by":[{"DOI":"10.3389\/ftox.2024.1460271","type":"corrigendum","label":"Corrigendum","source":"publisher","updated":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T00:00:00Z","timestamp":1721347200000}}],"container-title":["Frontiers in Toxicology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/ftox.2024.1376118\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T13:28:04Z","timestamp":1721309284000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/ftox.2024.1376118\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,13]]},"references-count":152,"alternative-id":["10.3389\/ftox.2024.1376118"],"URL":"https:\/\/doi.org\/10.3389\/ftox.2024.1376118","relation":{"corrigendum":[{"id-type":"doi","id":"10.3389\/ftox.2024.1460271","asserted-by":"object"}]},"ISSN":["2673-3080"],"issn-type":[{"value":"2673-3080","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,13]]},"article-number":"1376118"}}