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*Blood lead levels, and urinary cadmium, barium, and antimony levels were similar between participants who used e-cigarettes and participants who did not.
*In this study, blood lead levels, and urinary cadmium, barium, and antimony levels were similar between participants who ever-used e-cigarettes and participants who did not, and therefore, e-cigarette use was not a major source of heavy metals.
*However, participants with a smoking history were more likely to have higher blood lead and urinary cadmium than participants who neither used e-cigarettes nor cigarettes.
*However, participants with a smoking history were more likely to have higher blood lead and urinary cadmium than participants who neither used e-cigarettes nor cigarettes.
*[https://sci-hub.se/10.1016/j.jtemb.2020.126602 PDF Version]
*[https://sci-hub.se/10.1016/j.jtemb.2020.126602 PDF Version]
*Citation: R. Constance Wiener, Ruchi Bhandari, Association of electronic cigarette use with lead, cadmium, barium, and antimony body burden: NHANES 2015-2016, Journal of Trace Elements in Medicine and Biology, Volume 62, 2020, 126602, ISSN 0946-672X, doi: 10.1016/j.jtemb.2020.126602
*Citation: R. Constance Wiener, Ruchi Bhandari, Association of electronic cigarette use with lead, cadmium, barium, and antimony body burden: NHANES 2015-2016, Journal of Trace Elements in Medicine and Biology, Volume 62, 2020, 126602, ISSN 0946-672X, doi: 10.1016/j.jtemb.2020.126602
*Acknowledgement: Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number U54GM104942-4. The content is solely the responsibility of the author and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
*Keywords: e-Cigarettes; Metals; Lead; Cadmium; Barium; Antimony


===2020 [https://www.sciencedirect.com/science/article/pii/S0304389420314060?via%3Dihub 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]=== <!--T:5-->
===2020 [https://www.sciencedirect.com/science/article/pii/S0304389420314060?via%3Dihub 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]=== <!--T:5-->
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*Link above to the PDF form of the information presented at: 1st Scientific Summit, Tobacco Harm Reduction, Kallithea, Greece, June 2018
*Link above to the PDF form of the information presented at: 1st Scientific Summit, Tobacco Harm Reduction, Kallithea, Greece, June 2018
*Citation: Grant O’Connell1, Tanvir Walele1, Chris Prue1, Gene Gillman, Xavier Cahours, Olivia Hibbert & John D. Pritchard
*Citation: Grant O’Connell1, Tanvir Walele1, Chris Prue1, Gene Gillman, Xavier Cahours, Olivia Hibbert & John D. Pritchard
*Acknowledgement: This work was supported by Fontem Ventures B.V. Imperial Brands plc is the parent company of Fontem Ventures B.V., the manufacturer of the e-cigarette products used in this study.


===2018 [https://www.sciencedirect.com/science/article/abs/pii/S0021850217301155 Measurements of electronic cigarette-generated particles for the evaluation of lung cancer risk of active and passive users]=== <!--T:15-->
===2018 [https://www.sciencedirect.com/science/article/abs/pii/S0021850217301155 Measurements of electronic cigarette-generated particles for the evaluation of lung cancer risk of active and passive users]=== <!--T:15-->
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*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342216/pdf/pone.0173055.pdf PDF Version]
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342216/pdf/pone.0173055.pdf PDF Version]
*Citation: Pankow JF, Kim K, McWhirter KJ, Luo W, Escobedo JO, Strongin RM, Duell AK, Peyton DH. Benzene formation in electronic cigarettes. PLoS One. 2017 Mar 8;12(3):e0173055. doi: 10.1371/journal.pone.0173055. PMID: 28273096; PMCID: PMC5342216.
*Citation: Pankow JF, Kim K, McWhirter KJ, Luo W, Escobedo JO, Strongin RM, Duell AK, Peyton DH. Benzene formation in electronic cigarettes. PLoS One. 2017 Mar 8;12(3):e0173055. doi: 10.1371/journal.pone.0173055. PMID: 28273096; PMCID: PMC5342216.
*Acknowledgements: NIH and FDA supported this work via award R01ES025257. In particular, the work reported in this publication was supported by NIEHS and the FDA Center for Tobacco Products (CTP).


===2017 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5435921/ Comparative tumor promotion assessment of e‐cigarette and cigarettes using the in vitro Bhas 42 cell transformation assay]=== <!--T:23-->
===2017 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5435921/ Comparative tumor promotion assessment of e‐cigarette and cigarettes using the in vitro Bhas 42 cell transformation assay]=== <!--T:23-->
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*From this study, it is unlikely that the ECIG-generated aerosol contains enough of the other trace metals to induce significant pathology.
*From this study, it is unlikely that the ECIG-generated aerosol contains enough of the other trace metals to induce significant pathology.
*[https://sci-hub.se/10.3389/fphys.2016.00663 PDF Version]
*[https://sci-hub.se/10.3389/fphys.2016.00663 PDF Version]
*Citation: Palazzolo, D. L., Crow, A. P., Nelson, J. M., & Johnson, R. A. (2017). Trace Metals Derived from Electronic Cigarette (ECIG) Generated Aerosol: Potential Problem of ECIG Devices That Contain Nickel. Frontiers in Physiology, 7. doi:10.3389/fphys.2016.00663  
*Citation: Palazzolo, D. L., Crow, A. P., Nelson, J. M., & Johnson, R. A. (2017). Trace Metals Derived from Electronic Cigarette (ECIG) Generated Aerosol: Potential Problem of ECIG Devices That Contain Nickel. Frontiers in Physiology, 7. doi:10.3389/fphys.2016.00663
*Acknowledgements: This work was supported by an intramural grant from the DeBusk College of Osteopathic Medicine.
 
 


===2017 [https://www.acpjournals.org/doi/10.7326/M16-1107 Nicotine, Carcinogen, and Toxin Exposure in Long-Term E-Cigarette and Nicotine Replacement Therapy Users]=== <!--T:31-->
===2017 [https://www.acpjournals.org/doi/10.7326/M16-1107 Nicotine, Carcinogen, and Toxin Exposure in Long-Term E-Cigarette and Nicotine Replacement Therapy Users]=== <!--T:31-->
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*[https://www.rcplondon.ac.uk/file/3563/download PDF Version]
*[https://www.rcplondon.ac.uk/file/3563/download PDF Version]
*Citation: Royal College of Physicians. Nicotine without smoke: Tobacco harm reduction. London: RCP, 2016.
*Citation: Royal College of Physicians. Nicotine without smoke: Tobacco harm reduction. London: RCP, 2016.
*Acknowledgement: The Tobacco Advisory Group acknowledges the help of the UK Centre for Tobacco and Alcohol Studies (www.ukctas.net), which is funded by the UK Clinical Research Collaboration, in writing this report; and thanks Natalie Wilder, Claire Daley, Jane Sugarman and James Partridge in the Royal College of Physicians Publications Department for their work in producing the report.


===2016 [https://www.sciencedirect.com/science/article/pii/S0273230016302938?via%3Dihub A randomised, parallel group study to evaluate the safety profile of an electronic vapour (vapor) product over 12 weeks]=== <!--T:37-->
===2016 [https://www.sciencedirect.com/science/article/pii/S0273230016302938?via%3Dihub A randomised, parallel group study to evaluate the safety profile of an electronic vapour (vapor) product over 12 weeks]=== <!--T:37-->
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*[https://sci-hub.se/10.1016/j.yrtph.2016.10.003 PDF Version]
*[https://sci-hub.se/10.1016/j.yrtph.2016.10.003 PDF Version]
*Citation: Ana S. Cravo, Jim Bush, Girish Sharma, Rebecca Savioz, Claire Martin, Simon Craige, Tanvir Walele, A randomised, parallel group study to evaluate the safety profile of an electronic vapour product over 12 weeks, Regulatory Toxicology and Pharmacology, Volume 81, Supplement 1, 2016, Pages S1-S14, ISSN 0273-2300, doi: 10.1016/j.yrtph.2016.10.003.
*Citation: Ana S. Cravo, Jim Bush, Girish Sharma, Rebecca Savioz, Claire Martin, Simon Craige, Tanvir Walele, A randomised, parallel group study to evaluate the safety profile of an electronic vapour product over 12 weeks, Regulatory Toxicology and Pharmacology, Volume 81, Supplement 1, 2016, Pages S1-S14, ISSN 0273-2300, doi: 10.1016/j.yrtph.2016.10.003.
*Acknowledgement: This work was funded and supported by Fontem Ventures B.V. Imperial Brands plc is the parent company of Fontem Ventures B.V., the manufacturer of the EVP prototype used in this study.


===2016 [https://academic.oup.com/ntr/article-abstract/19/2/160/2631650?redirectedFrom=fulltext Exposure to Nicotine and Selected Toxicants in Cigarette Smokers Who Switched to Electronic Cigarettes: A Longitudinal Within-Subjects Observational Study]=== <!--T:39-->
===2016 [https://academic.oup.com/ntr/article-abstract/19/2/160/2631650?redirectedFrom=fulltext Exposure to Nicotine and Selected Toxicants in Cigarette Smokers Who Switched to Electronic Cigarettes: A Longitudinal Within-Subjects Observational Study]=== <!--T:39-->
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*Smokers using [[Special:MyLanguage/Abbreviations|EC]]s over 4 weeks maintained cotinine levels and experienced significant reductions in carbon monoxide, [[Special:MyLanguage/Abbreviations|NNAL]], and two out of eight measured [[Special:MyLanguage/Abbreviations|VOC]] metabolites. Those who switched exclusively to ECs for at least half of the study period significantly reduced two additional VOCs.
*Smokers using [[Special:MyLanguage/Abbreviations|EC]]s over 4 weeks maintained cotinine levels and experienced significant reductions in carbon monoxide, [[Special:MyLanguage/Abbreviations|NNAL]], and two out of eight measured [[Special:MyLanguage/Abbreviations|VOC]] metabolites. Those who switched exclusively to ECs for at least half of the study period significantly reduced two additional VOCs.
*[https://sci-hub.se/10.1093/ntr/ntw333 PDF Version]
*[https://sci-hub.se/10.1093/ntr/ntw333 PDF Version]
*Citation: Pulvers, K., Emami, A. S., Nollen, N. L., Romero, D. R., Strong, D. R., Benowitz, N. L., & Ahluwalia, J. S. (2016). Tobacco Consumption and Toxicant Exposure of Cigarette Smokers Using Electronic Cigarettes. Nicotine & Tobacco Research, ntw333. doi:10.1093/ntr/ntw333  
*Citation: Pulvers, K., Emami, A. S., Nollen, N. L., Romero, D. R., Strong, D. R., Benowitz, N. L., & Ahluwalia, J. S. (2016). Tobacco Consumption and Toxicant Exposure of Cigarette Smokers Using Electronic Cigarettes. Nicotine & Tobacco Research, ntw333. doi:10.1093/ntr/ntw333
*Acknowledgement: This study was funded by the University of Minnesota (JA), P30 DA012393 (NB), P50 CA180890 (NB), and California State University San Marcos (KP).
 
 
 
===2016 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4940751/ Reductions in biomarkers of exposure, impacts on smoking urge and assessment of product use and tolerability in adult smokers following partial or complete substitution of cigarettes with electronic cigarettes]=== <!--T:43-->


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===2016 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4940751/ Reductions in biomarkers of exposure, impacts on smoking urge and assessment of product use and tolerability in adult smokers following partial or complete substitution of cigarettes with electronic cigarettes]===
*Subjects switching to e-cigarettes had significantly lower levels (29 %–95 %) of urinary [[Special:MyLanguage/Abbreviations|BoE]]s after 5 days. Nicotine equivalents declined by 25 %–40 %.  
*Subjects switching to e-cigarettes had significantly lower levels (29 %–95 %) of urinary [[Special:MyLanguage/Abbreviations|BoE]]s after 5 days. Nicotine equivalents declined by 25 %–40 %.  
*Dual users who substituted half of their self-reported daily cigarette consumption with e-cigarettes experienced 7 %–38 % reductions, but had increases (1 %–20 %) in nicotine equivalents.  
*Dual users who substituted half of their self-reported daily cigarette consumption with e-cigarettes experienced 7 %–38 % reductions, but had increases (1 %–20 %) in nicotine equivalents.  
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*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4940751/pdf/12889_2016_Article_3236.pdf PDF Version]
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4940751/pdf/12889_2016_Article_3236.pdf PDF Version]
*Citation: D'Ruiz CD, Graff DW, Robinson E. Reductions in biomarkers of exposure, impacts on smoking urge and assessment of product use and tolerability in adult smokers following partial or complete substitution of cigarettes with electronic cigarettes. BMC Public Health. 2016 Jul 11;16:543. doi: 10.1186/s12889-016-3236-1. PMID: 27401980; PMCID: PMC4940751.
*Citation: D'Ruiz CD, Graff DW, Robinson E. Reductions in biomarkers of exposure, impacts on smoking urge and assessment of product use and tolerability in adult smokers following partial or complete substitution of cigarettes with electronic cigarettes. BMC Public Health. 2016 Jul 11;16:543. doi: 10.1186/s12889-016-3236-1. PMID: 27401980; PMCID: PMC4940751.
*Acknowledgement: This study was funded by Fontem Ventures B.V., a fully owned subsidiary of Imperial Brands plc, and the manufacturer of the e-cigarette products used in this study.


===2016 [https://www.sciencedirect.com/science/article/pii/S1383571816301711?via%3Dihub The mutagenic assessment of an electronic-cigarette and reference cigarette smoke using the Ames assay in strains TA98 and TA100]=== <!--T:45-->
===2016 [https://www.sciencedirect.com/science/article/pii/S1383571816301711?via%3Dihub The mutagenic assessment of an electronic-cigarette and reference cigarette smoke using the Ames assay in strains TA98 and TA100]=== <!--T:45-->
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*Under the conditions tested, Vype ePen e-cigarette aerosol was significantly less cytotoxic than reference 3R4F cigarette smoke.
*Under the conditions tested, Vype ePen e-cigarette aerosol was significantly less cytotoxic than reference 3R4F cigarette smoke.
*[https://sci-hub.se/10.1080/15376516.2016.1217112 PDF Version]
*[https://sci-hub.se/10.1080/15376516.2016.1217112 PDF Version]
*Citation: Azzopardi, D., Patel, K., Jaunky, T., Santopietro, S., Camacho, O. M., McAughey, J., & Gaça, M. (2016). Electronic cigarette aerosol induces significantly less cytotoxicity than tobacco smoke. Toxicology Mechanisms and Methods, 26(6), 477–491. doi:10.1080/15376516.2016.1217112  
*Citation: Azzopardi, D., Patel, K., Jaunky, T., Santopietro, S., Camacho, O. M., McAughey, J., & Gaça, M. (2016). Electronic cigarette aerosol induces significantly less cytotoxicity than tobacco smoke. Toxicology Mechanisms and Methods, 26(6), 477–491. doi:10.1080/15376516.2016.1217112
*Acknowledgement: This study was funded by BAT. The authors are employees of British American Tobacco (BAT). Nicoventures Ltd., UK, is a wholly-owned subsidiary of British American Tobacco.
 
 


===2015 [https://www.sciencedirect.com/science/article/pii/S0887233315001228?via%3Dihub Development of an in vitro cytotoxicity model for aerosol exposure using 3D reconstructed human airway tissue; application for assessment of e-cigarette aerosol]=== <!--T:49-->
===2015 [https://www.sciencedirect.com/science/article/pii/S0887233315001228?via%3Dihub Development of an in vitro cytotoxicity model for aerosol exposure using 3D reconstructed human airway tissue; application for assessment of e-cigarette aerosol]=== <!--T:49-->
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*Mainstream cigarette smoke HPHCs (∼3000 μg/puff) were 1500 times higher than e-cigarette HPHCs.
*No significant contribution of tested HPHC classes was found for the e-cigarettes.
*No significant contribution of tested HPHC classes was found for the e-cigarettes.
*[https://sci-hub.se/10.1016/j.yrtph.2014.10.010 PDF Version]
*[https://sci-hub.se/10.1016/j.yrtph.2014.10.010 PDF Version]
*Citation: Tayyarah, R., & Long, G. A. (2014). Comparison of select analytes in aerosol from e-cigarettes with smoke from conventional cigarettes and with ambient air. Regulatory Toxicology and Pharmacology, 70(3), 704–710. doi:10.1016/j.yrtph.2014.10.010  
*Citation: Tayyarah, R., & Long, G. A. (2014). Comparison of select analytes in aerosol from e-cigarettes with smoke from conventional cigarettes and with ambient air. Regulatory Toxicology and Pharmacology, 70(3), 704–710. doi:10.1016/j.yrtph.2014.10.010
*Acknowledgements: The company for which the study authors work and the companies that manufacture the e-cigarettes tested for this study are owned by the same parent company (Lorillard Tobacco Company)
 
 


===2014 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110871/ Safety evaluation and risk assessment of electronic cigarettes as tobacco cigarette substitutes: a systematic review]=== <!--T:53-->
===2014 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110871/ Safety evaluation and risk assessment of electronic cigarettes as tobacco cigarette substitutes: a systematic review]=== <!--T:53-->
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*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110871/pdf/10.1177_2042098614524430.pdf PDF Version]
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110871/pdf/10.1177_2042098614524430.pdf PDF Version]
*Citation: Farsalinos KE, Polosa R. Safety evaluation and risk assessment of electronic cigarettes as tobacco cigarette substitutes: a systematic review. Ther Adv Drug Saf. 2014 Apr;5(2):67-86. doi: 10.1177/2042098614524430. PMID: 25083263; PMCID: PMC4110871.
*Citation: Farsalinos KE, Polosa R. Safety evaluation and risk assessment of electronic cigarettes as tobacco cigarette substitutes: a systematic review. Ther Adv Drug Saf. 2014 Apr;5(2):67-86. doi: 10.1177/2042098614524430. PMID: 25083263; PMCID: PMC4110871.
*Acknowledegement: Riccardo Polosa is a Professor of Medicine and is supported by the University of Catania, Italy. He has received lecture fees and research funding from GlaxoSmithKline and Pfizer, manufacturers of stop smoking medications. He has also served as a consultant for Pfizer and Arbi Group Srl (Milano, Italy), the distributor of Categoria™ e-Cigarettes. His research on electronic cigarettes is currently supported by LIAF (Lega Italiana AntiFumo).
*Acknowledgement: Konstantinos Farsalinos is a researcher at Onassis Cardiac Surgery Center. He has never been funded by the pharmaceutical or the tobacco industry. For some of his studies, the institution has received financial compensation from electronic cigarette companies for the studies’ cost. His salary is currently being paid by a scholarship grant from the Hellenic Society of Cardiology.


===2014 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4154473/ Levels of selected carcinogens and toxicants in vapor from electronic cigarettes]=== <!--T:55-->
===2014 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4154473/ Levels of selected carcinogens and toxicants in vapor from electronic cigarettes]=== <!--T:55-->
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*This study indicates that EC vapor is significantly less cytotoxic compared to tobacco CS.
*This study indicates that EC vapor is significantly less cytotoxic compared to tobacco CS.
*[https://sci-hub.se/10.3109/08958378.2013.793439 PDF Version]
*[https://sci-hub.se/10.3109/08958378.2013.793439 PDF Version]
*Citation: Romagna, G., Allifranchini, E., Bocchietto, E., Todeschi, S., Esposito, M., & Farsalinos, K. E. (2013). Cytotoxicity evaluation of electronic cigarette vapor extract on cultured mammalian fibroblasts (ClearStream-LIFE): comparison with tobacco cigarette smoke extract. Inhalation Toxicology, 25(6), 354–361. doi:10.3109/08958378.2013.793439  
*Citation: Romagna, G., Allifranchini, E., Bocchietto, E., Todeschi, S., Esposito, M., & Farsalinos, K. E. (2013). Cytotoxicity evaluation of electronic cigarette vapor extract on cultured mammalian fibroblasts (ClearStream-LIFE): comparison with tobacco cigarette smoke extract. Inhalation Toxicology, 25(6), 354–361. doi:10.3109/08958378.2013.793439
*Acknowledgement: The study was funded by FlavourArt s.r.l. No author has received any financial compensation for this study. The study was investigator-initiated and investigator-driven. The sponsor had no involvement in the study design, data collection, analysis and interpretation, writing or approving the manuscript and decision to submit the manuscript for publication.
*Keywords: Cytotoxicity, electronic cigarette, fibroblasts, in vitro, nicotine, smoking, tobacco harm reduction
 
 


=ENDS (without comparison to other products)= <!--T:61-->
=ENDS (without comparison to other products)= <!--T:61-->


=== 2023: [https://pubmed.ncbi.nlm.nih.gov/37386281/ Assessing the impact of protonating acid combinations in e-cigarette liquids: a randomised, crossover study on nicotine pharmacokinetics] ===


* Frosina J, McEwan M, Ebajemito J, Thissen J, Taluskie K, Baxter-Wright S, Hardie G. Sci Rep. 2023 Jun 29;13(1):10563. doi: 10.1038/s41598-023-37539-6. PMID: 37386281
* Study in Humans
* Funding from industry
* BAT asks: does the protonating acid matter?
** ''little is known about the impact of different combinations of protonating acid on nicotine pharmacokinetics.''
* So this is an experiment with "different ratios of three common protonating acids-lactic, benzoic and levulinic".
** For most comparisons, Cmax and AUC0-60 following both fixed and ad libitum puffing were significantly higher for e-liquids containing 5% nicotine compared with 3.5% nicotine. However, Cmax and AUC0-60 were not statistically different for 5% nicotine e-liquids containing varying ratios of lactic, levulinic and benzoic acid when compared to an e-liquid containing lactic acid only. Mean scores for product liking were similar for all e-liquid formulations assessed, regardless of nicotine concentration, acid content, and whether the product was used in a fixed or ad libitum puffing regimen.
** While e-liquid nicotine concentration significantly affected users' nicotine uptake, the different combinations of benzoic, levulinic and lactic acid in the e-liquids assessed had limited impact on nicotine pharmacokinetics and product liking scores.<br />


===2018 [https://www.tandfonline.com/doi/abs/10.1080/08958378.2018.1523262?fbclid=IwAR0x50Ru0cjsq_ojjcc2Qgdd7LUCqdmBnMqklhOLZ4sVFtoRNN-uOLSYiPM&journalCode=iiht20 Metal emissions from e-cigarettes: a risk assessment analysis of a recently-published study]=== <!--T:62-->
===2018 [https://www.tandfonline.com/doi/abs/10.1080/08958378.2018.1523262?fbclid=IwAR0x50Ru0cjsq_ojjcc2Qgdd7LUCqdmBnMqklhOLZ4sVFtoRNN-uOLSYiPM&journalCode=iiht20 Metal emissions from e-cigarettes: a risk assessment analysis of a recently-published study]=== <!--T:62-->
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=Suggested studies to add to this page= <!--T:93-->
=Suggested studies to add to this page= <!--T:93-->


===2023: [https://www.sciencedirect.com/science/article/abs/pii/S0378427423001091?via%3Dihub A contextualised e-cigarette testing strategy shows flavourings do not impact lung toxicity in vitro]===
===2022: REPLICA Project: [https://www.biorxiv.org/content/10.1101/2022.10.28.514205v1 In Vitro Toxicity Profile of myblu™ electronic cigarette Aerosol Compared to Cigarette Smoke: the REPLICA project]===




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