ENDS Toxicity / Carcinogenic

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Studies, Surveys, Papers, and Case Studies

  • Sometimes it's necessary to view the PDF version to access the full study.
  • This page is for referencing the possible benefits of ENDS products vs. smoking cigarettes from a toxicological standpoint. (Electronic Nicotine Delivery Systems are also known as vapor technology, ecigarettes, ecigs, EVP, etc.)
  • If you'd prefer someone else to add a study to a topic, there is a subject section called "Suggested studies to add to this page". You may put the link in that section for one of the regular page editors to address.
  • Instructions for anyone who would like to add content to this page are at the bottom of the page.


ENDS vs Smoking Tobacco, Heated Tobacco Product/Heat not Burn, or Nicotine Replacement Therapy

2020 Association of electronic cigarette use with lead, cadmium, barium, and antimony body burden: NHANES 2015-2016

  • 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.
  • 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

2020 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

  • We first report that HTP (Heated Tobacco Product) delivers slightly less nicotine and emits much lower amounts of carbonyl and PAH compounds than tobacco cigarettes.
  • However, HTP emissions still contain carcinogenic compounds (e.g. formaldehyde, acetaldehyde and benzo[a]pyrene) and the amounts of carbonyls and PAHs in HTP aerosols are higher than in e-cig vapours.
  • In accordance with the levels of toxic compounds in each aerosol, HTP aerosol exhibits reduced cytotoxicity compared to cigarette smoke but higher than e-cig vapours (vapors).
  • HTP and e-cig have the potential to increase oxidative stress and inflammatory response, in a manner very similar to that of cigarette smoke, but only after a more intensive exposure. In addition, our data support that e-cig use at higher power settings emit higher carbonyl and PAH compounds and, consequently, generate more oxidative stress.
  • Finally, this study contributes to a better understanding of HTP and e-cig emission properties and their related toxicological impacts and provides important data needed for risk assessment purposes, by demonstrating that HTP might be less harmful than tobacco cigarettes but considerably more harmful than e-cig.
  • PDF Version
  • Citation: Dusautoir R, Zarcone G, Verriele M, Garc¸on G, Fronval I, Beauval N, Allorge D, Riffault V, Locoge N, Lo-Guidice J-Marc, Antherieu S, 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, Journal of Hazardous Materials (2020), doi: 10.1016/j.jhazmat.2020.123417
  • Acknowledgement: This work was supported by the French Institute of Cancer (INCa) and the French Institute for Public Health Research (IResP): Contracts n°INCa_11505 and n°INCa_13648.


2020 Five-Day Changes in Biomarkers of Exposure Among Adult Smokers After Completely Switching From Combustible Cigarettes to a Nicotine-Salt Pod System

  • The results of this study concorded with evidence that complete switching from combustible cigarettes to vapor products may reduce exposure to key carcinogens and other toxicants known to be associated with tobacco-related diseases.
  • PDF Version
  • Citation: Joanna Jay, BA, Erika L Pfaunmiller, PhD, Norman J Huang, PhD, Gal Cohen, PhD, Donald W Graff, PharmD, Five-Day Changes in Biomarkers of Exposure Among Adult Smokers After Completely Switching From Combustible Cigarettes to a Nicotine-Salt Pod System, Nicotine & Tobacco Research, Volume 22, Issue 8, August 2020, Pages 1285–1293, doi:10.1093/ntr/ntz206
  • Acknowledgements: JJ, NJH, GC, and DWG are employees of JUUL Labs, Inc. ELP is an employee of Frontage Labs. ELP and DWG were employed by Celerion Inc. at the time the study was conducted. Celerion is a contract research organization that performs studies on tobacco and nicotine-containing products, sponsored by the pharmaceutical and tobacco industries.
  • Keywords: nicotine, smoking, adult, biological markers, tobacco, urine, cigarettes, smokers


2018 The American Cancer Society Public Health Statement on Eliminating Combustible Tobacco Use in the United States

  • Many consumers are misinformed about the harms of electronic nicotine delivery systems (ENDS).
  • Many adults believe, erroneously, that ENDS are as harmful as combustible tobacco products, and the level of public understanding has deteriorated over time. In 2012, only11.5% of respondents to a national survey held this view. By 2015, 35.7% of respondents mistakenly believed that the harm associated with electronic cigarettes (e-cigarettes) was “about the same” as that of smoking conventional cigarettes.
  • Thus, public misunderstanding underscores the urgent need for consumer education about the absolute and relative risks posed by different tobacco products and to reinvigorate smokers’ understanding of the importance of quitting combustible tobacco.
  • Although the long-term effects of ENDS are not known, current-generation ENDS are markedly less harmful than combustible tobacco products
  • Some early evidence suggests that e-cigarettes may help some smokers reduce or quit combustible tobacco use.
  • PDF Version


2018 Carbonyl emissions from a novel heated tobacco product (IQOS): comparison with an e-cigarette and a tobacco cigarette

  • The IQOS heated tobacco product emits substantially lower levels of carbonyls than a commercial tobacco cigarette but higher levels than an e-cigarette.
  • PDF Version
  • Citation: Farsalinos KE, Yannovits N, Sarri T, Voudris V, Poulas K, Leischow SJ. Carbonyl emissions from a novel heated tobacco product (IQOS): comparison with an e-cigarette and a tobacco cigarette. Addiction. 2018 Nov;113(11):2099-2106. doi: 10.1111/add.14365. Epub 2018 Jul 10. PMID: 29920842.
  • Keywords: Carbonyls; electronic cigarettes; harm reduction; heated tobacco products; nicotine; smoking.


2018 Chemical Composition of myblu™ Pod-System E-Cigarette Aerosols: A Quantitative Comparison with Conventional Cigarette Smoke

  • Of the 51 toxicants tested, eight were detected in the e-cigarette aerosols but at substantially lower levels than reported in cigarette smoke.
  • 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

2018 Measurements of electronic cigarette-generated particles for the evaluation of lung cancer risk of active and passive users

  • In this study, we have demonstrated that no clinically relevant, product-related safety findings were observed for smokers of Combustible Cigarettes (CC) switching to an Electronic Vapor Product (EVP) for 12 weeks under real-life settings. Adverse Effects (AEs) reported by subjects switching to the EVP occurred primarily within the first week after switching, and only 1.3% of all AEs reported were considered to be almost definitely related to the product. Up to a third of all reported AEs in the EVP group were related to nicotine withdrawal symptoms, which were observed to decrease after the first two weeks from product switch. EVP use was associated with significant decreases in exposure to nicotine and other chemicals such as benzene and acrolein, typically found in CC smoke. Changes were also observed in the level of WBC, haemoglobin, RBC and LDL cholesterol, which although minor, were consistent with those observed after smoking cessation. The data presented in this study shows the potential that EVPs may offer to smokers looking for an alternative to CCs.
  • PDF Version
  • Citation: Mauro Scungio, Luca Stabile, Giorgio Buonanno, Measurements of electronic cigarette-generated particles for the evaluation of lung cancer risk of active and passive users, Journal of Aerosol Science, Volume 115, 2018, Pages 1-11, ISSN 0021-8502, doi:10.1016/j.jaerosci.2017.10.006.
  • Keywords: E-cigs: Electronic cigarettesUltrafine particlesELCRLung cancer risk


2018 Comparison of Nicotine and Toxicant Exposure in Users of Electronic Cigarettes and Combustible Cigarettes

  • In this population-based cohort study of 5105 participants, current exclusive e-cigarette users had greater concentrations of biomarkers of nicotine, tobacco-specific nitrosamines, volatile organic compounds, and metals compared with never tobacco users. However, these concentrations were lower than those observed in current exclusive cigarette smokers and dual users of both products.
  • PDF Version
  • Citation: Goniewicz ML, Smith DM, Edwards KC, Blount BC, Caldwell KL, Feng J, Wang L, Christensen C, Ambrose B, Borek N, van Bemmel D, Konkel K, Erives G, Stanton CA, Lambert E, Kimmel HL, Hatsukami D, Hecht SS, Niaura RS, Travers M, Lawrence C, Hyland AJ. Comparison of Nicotine and Toxicant Exposure in Users of Electronic Cigarettes and Combustible Cigarettes. JAMA Netw Open. 2018 Dec 7;1(8):e185937. doi: 10.1001/jamanetworkopen.2018.5937. PMID: 30646298; PMCID: PMC6324349.


2018 Public Health Consequences of E-Cigarettes

  • There is conclusive evidence that completely substituting e-cigarettes for combustible tobacco cigarettes reduces users’ exposure to numerous toxicants and carcinogens present in combustible tobacco cigarettes.
  • There is substantial evidence that except for nicotine, under typical conditions of use, exposure to potentially toxic substances from e-cigarettes is significantly lower compared with combustible tobacco cigarettes.
  • There is substantial evidence that completely switching from regular use of combustible tobacco cigarettes to e-cigarettes results in reduced short-term adverse health outcomes in several organ systems.
  • There is moderate evidence that risk and severity of dependence are lower for e-cigarettes than combustible tobacco cigarettes.
  • There is moderate evidence from randomized controlled trials that e-cigarettes with nicotine are more effective than e-cigarettes without nicotine for smoking cessation.
  • While the overall evidence from observational trials is mixed, there is moderate evidence from observational studies that more frequent use of e-cigarettes is associated with an increased likelihood of cessation.
  • There is moderate evidence that second-hand exposure to nicotine and particulates is lower from e-cigarettes compared with combustible tobacco cigarettes.
  • There is limited evidence for improvement in lung function and respiratory symptoms among adult smokers with asthma who switch to e-cigarettes completely or in part (dual use).
  • There is limited evidence for reduction of chronic obstructive pulmonary disease (COPD) exacerbations among adult smokers with COPD who switch to e-cigarettes completely or in part (dual use).
  • There is limited evidence suggesting that switching to e-cigarettes will improve periodontal disease in smokers.
  • Link above is to the PDF of 750 page report
  • Citation: National Academies of Sciences, Engineering, and Medicine. 2018. Public Health Consequences of E-Cigarettes. Washington, DC: The National Academies Press. doi:10.17226/24952.


2017 Benzene formation in electronic cigarettes

  • The risks from benzene will be lower from e-cigarettes than from conventional cigarettes.
  • 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.

2017 Comparative tumor promotion assessment of e‐cigarette and cigarettes using the in vitro Bhas 42 cell transformation assay

  • Results from this study suggest that e‐cigarettes may have reduced tumor promoter activity compared to conventional cigarettes and therefore may provide a safer alternative to cigarettes.
  • PDF Version
  • Citation: Breheny D, Oke O, Pant K, Gaça M. Comparative tumor promotion assessment of e-cigarette and cigarettes using the in vitro Bhas 42 cell transformation assay. Environ Mol Mutagen. 2017 May;58(4):190-198. doi: 10.1002/em.22091. PMID: 28444993; PMCID: PMC5435921.
  • Acknowledgements: The authors are employees of British American Tobacco or BioReliance Corporation. BioReliance conducted all experimental work and were funded by British American Tobacco. Nicoventures, UK, is a wholly‐owned subsidiary of British American Tobacco.


2017 E-cigarettes emit very high formaldehyde levels only in conditions that are aversive to users: A replication study under verified realistic use conditions

  • In realistic conditions, formaldehyde in e-cigarettes is lower than cigarette smoke
  • The high levels of formaldehyde emissions that were reported in a previous study were caused by unrealistic use conditions that create the unpleasant taste of dry puffs to e-cigarette users and are thus avoided.
  • The study shows the critical need to verify that realistic use conditions are tested in laboratory studies of e-cigarette emissions. This would ensure that abuse of devices in the laboratory setting is avoided and that findings have clinical relevance and represent realistic exposure of e-cigarette users.
  • PDF Version
  • Citation: Konstantinos E. Farsalinos, Vassilis Voudris, Alketa Spyrou, Konstantinos Poulas, E-cigarettes emit very high formaldehyde levels only in conditions that are aversive to users: A replication study under verified realistic use conditions, Food and Chemical Toxicology, Volume 109, Part 1, 2017, Pages 90-94, ISSN 0278-6915, doi: 10.1016/j.fct.2017.08.044.
  • Keywords: Smoking; Electronic cigarette; Formaldehyde; Dry puff; Aerosol


2017 Have combustible cigarettes met their match? The nicotine delivery profiles and harmful constituent exposures of second-generation and third-generation electronic cigarette users

  • While not harmless, electronic cigarettes (e-cigarettes) have demonstrated a much more favourable (favorable) toxicological profile than combustible cigarettes—the worldwide leading cause of preventable death. Average eCO levels (ppm) were significantly higher in smokers than in e-cigarette users. Compared with cigarettes, G2 and G3 e-cigarettes resulted in significantly lower levels of exposure to a potent lung carcinogen and cardiovascular toxicant.
  • PDF Version
  • Citation: Wagener TL, Floyd EL, Stepanov I, et alHave combustible cigarettes met their match? The nicotine delivery profiles and harmful constituent exposures of second-generation and third-generation electronic cigarette usersTobacco Control 2017;26:e23-e28.
  • Acknowledgements: Intramural funds to TLW were used to complete this study. Part of TLW’s, ELF’s, LMD’s, ELL’s, NM’s, APT’s, and LQ’s salary support is provided by the Oklahoma Tobacco Research Center, which is provided funding from the Oklahoma Tobacco Settlement Endowment Trust. The Oklahoma Shared Clinical and Translational Resources (U54 GM104938) provided phlebotomy support to this study.


2017 Trace Metals Derived from Electronic Cigarette (ECIG) Generated Aerosol: Potential Problem of ECIG Devices That Contain Nickel

  • In general, the findings of this study suggest that the concentrations of most trace metals extracted from cigarette smoke exceed the concentrations of trace metals extracted from ECIG-generated aerosol.
  • Only Ni in the ECIG-generated aerosol was higher than control (smoke). The most probable source of Ni in this aerosol is the core assembly.
  • From this study, it is unlikely that the ECIG-generated aerosol contains enough of the other trace metals to induce significant pathology.
  • 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

2017 Nicotine, Carcinogen, and Toxin Exposure in Long-Term E-Cigarette and Nicotine Replacement Therapy Users

  • Former smokers with long-term e-cigarette–only or NRT-only use may obtain roughly similar levels of nicotine compared with smokers of combustible cigarettes only, but results varied. Long-term NRT-only and e-cigarette–only use, but not dual use of NRTs or e-cigarettes with combustible cigarettes, is associated with substantially reduced levels of measured carcinogens and toxins relative to smoking only combustible cigarettes.
  • PDF Version
  • Citation: Shahab, L., Goniewicz, M. L., Blount, B. C., Brown, J., McNeill, A., Alwis, K. U., … West, R. (2017). Nicotine, Carcinogen, and Toxin Exposure in Long-Term E-Cigarette and Nicotine Replacement Therapy Users. Annals of Internal Medicine, 166(6), 390. doi:10.7326/m16-1107
  • Acknowledgement: This work was supported by Cancer Research UK (grant C27061/A16929, with additional funding from grants C1417/A14135 and C36048/A11654). Dr. Brown's post is funded by a fellowship from the Society for the Study of Addiction, and Cancer Research UK also provides support (grants C1417/A7972 and C44576/A19501). Drs. McNeill and West are part of the UK Centre for Tobacco and Alcohol Studies, which is a UK Clinical Research Collaboration Public Health Research Centre of Excellence. Funding from the Medical Research Council, British Heart Foundation, Cancer Research UK, Economic and Social Research Council, and the National Institute for Health Research under the auspices of the UK Clinical Research Collaboration is gratefully acknowledged (grant MR/K023195/1). Dr. Goniewicz was supported by the National Institute on Drug Abuse and the National Cancer Institute of the National Institutes of Health (awards R01DA037446 and P30 CA016056, respectively) and by an award from Roswell Park Alliance Foundation.


2017 Comparing the cancer potencies of emissions from vapourised nicotine products including e-cigarettes with those of tobacco smoke

  • Most e-cigarette analyses indicate cancer potencies <1% that of tobacco smoke and <10% that of a heat-not-burn prototype, although a minority of analyses indicate higher potencies.
  • Optimal combinations of device settings, liquid formulation and vaping behaviour normally result in e-cigarette emissions with much less carcinogenic potency than tobacco smoke.
  • Article in Lung Disease News: E-Cigarettes Carry Much Less Risk of Lung Cancer Than Cigarette Smoke, Study Finds
  • PDF Version
  • Citation: Stephens WE Comparing the cancer potencies of emissions from vapourised (vaporised) nicotine products including e-cigarettes with those of tobacco smoke Tobacco Control 2018;27:10-17.


2016: Royal College of Physicians - Nicotine without Smoke

  • Provision of the nicotine that smokers are addicted to without the harmful components of tobacco smoke can prevent most of the harm from smoking.
  • E-cigarettes are marketed as consumer products and are proving much more popular than NRT as a substitute and competitor for tobacco cigarettes.
  • E-cigarettes appear to be effective when used by smokers as an aid to quitting smoking.
  • The hazard to health arising from long-term vapour (vapor) inhalation from the e-cigarettes available today is unlikely to exceed 5% of the harm from smoking tobacco.
  • In the interests of public health it is important to promote the use of e-cigarettes, NRT and other non-tobacco nicotine products as widely as possible as a substitute for smoking…
  • PDF Version
  • Citation: Royal College of Physicians. Nicotine without smoke: Tobacco harm reduction. London: RCP, 2016.

2016 A randomised, parallel group study to evaluate the safety profile of an electronic vapour (vapor) product over 12 weeks

  • In this study, we have demonstrated that no clinically relevant, product-related safety findings were observed for smokers of Combustible Cigarettes (CCs) switching to an Electronic Vapor Product (EVP) for 12 weeks under real-life settings. AEs reported by subjects switching to the EVP occurred primarily within the first week after switching, and only 1.3% of all AEs reported were considered to be almost definitely related to the product. Up to a third of all reported AEs in the EVP group were related to nicotine withdrawal symptoms, which were observed to decrease after the first two weeks from product switch. EVP use was associated with significant decreases in exposure to nicotine and other chemicals such as benzene and acrolein, typically found in CC smoke. Changes were also observed in the level of WBC, haemoglobin, RBC and LDL cholesterol, which although minor, were consistent with those observed after smoking cessation. The data presented in this study shows the potential that EVPs may offer to smokers looking for an alternative to CCs.
  • 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.

2016 Exposure to Nicotine and Selected Toxicants in Cigarette Smokers Who Switched to Electronic Cigarettes: A Longitudinal Within-Subjects Observational Study

  • After switching from tobacco to e-cigarettes, nicotine exposure remains unchanged, while exposure to selected carcinogens and toxicants is substantially reduced.
  • PDF Version
  • Citation: Maciej L. Goniewicz, PharmD, PhD, Michal Gawron, PharmD, Danielle M. Smith, MPH, Margaret Peng, BSc, Peyton Jacob, III, PhD, Neal L. Benowitz, MD, Exposure to Nicotine and Selected Toxicants in Cigarette Smokers Who Switched to Electronic Cigarettes: A Longitudinal Within-Subjects Observational Study, Nicotine & Tobacco Research, Volume 19, Issue 2, 1 February 2017, Pages 160–167, doi: 10.1093/ntr/ntw160
  • Acknowledgement: This work was supported by the Ministry of Science and Higher Education of Poland (grant number N N404 025638). Instrumentation and analytical chemistry at UCSF was supported by the National Institutes of Health, P30 DA012393 and S10 RR026437.


2016 Tobacco Consumption and Toxicant Exposure of Cigarette Smokers Using Electronic Cigarettes

  • Smokers using ECs over 4 weeks maintained cotinine levels and experienced significant reductions in carbon monoxide, NNAL, and two out of eight measured VOC metabolites. Those who switched exclusively to ECs for at least half of the study period significantly reduced two additional VOCs.
  • 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

2016 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 BoEs 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.
  • Blood nicotine biomarker levels were lower in the cessation (75 %–96 %) and e-cigarette use groups (11 %–83 %); dual users had no significant reductions.
  • All groups experienced significant decreases in exhaled CO (27 %–89 %). Exhaled NO increases (46 %–63 %) were observed in the cessation and e-cigarette use groups; dual users had minimal changes.
  • By Day 5, all groups had greater reductions in smoking urge compared to cessation. However, reductions were larger in the dual use group.
  • No serious adverse events were observed.
  • 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.

2016 The mutagenic assessment of an electronic-cigarette and reference cigarette smoke using the Ames assay in strains TA98 and TA100

  • In the presence and absence of metabolic activation, e-cigarette ACM and aerosol were deemed non-mutagenic in tester strains TA98 and TA100, under the test conditions described previously, despite clear positive control responses. Conversely, 3R4F cigarette smoke TPM and freshly generated whole smoke were clearly positive.
  • In the case of freshly generated cigarette smoke, a positive response in both strains was observed within 24 min, whereas e-cigarette aerosols remained negative up to 3 h.
  • PDF Version
  • Citation: Thorne, D., Crooks, I., Hollings, M., Seymour, A., Meredith, C., & Gaca, M. (2016). The mutagenic assessment of an electronic-cigarette and reference cigarette smoke using the Ames assay in strains TA98 and TA100. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 812, 29–38. doi:10.1016/j.mrgentox.2016.10.005
  • Acknowledgement: The authors are employees of British American Tobacco or Covance Laboratories Ltd. Covance Laboratories Ltd., Harrogate, UK, conducted all experimental work and were funded by BritishAmerican Tobacco. Nicoventures Ltd., UK, is a wholly-owned subsidiary of British American Tobacco.


2016 Electronic cigarette aerosol induces significantly less cytotoxicity than tobacco smoke

  • Under the conditions tested, Vype ePen e-cigarette aerosol was significantly less cytotoxic than reference 3R4F cigarette smoke.
  • 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

2015 Development of an in vitro cytotoxicity model for aerosol exposure using 3D reconstructed human airway tissue; application for assessment of e-cigarette aerosol

  • Despite being tested with a more intense puffing regime, e-cigarette aerosol showed no acute cytotoxicity in this study when compared with traditional 3R4F reference cigarette smoke.
  • Under the study conditions cigarette smoke demonstrated a dose-dependent response that resulted in near-complete cell death after a 6 h exposure period. In contrast, e-cigarette aerosol showed no decrease in tissue viability following a 6 h exposure, despite appropriate positive control responses. Furthermore, cytotoxicity appears to be unaffected by different e-cigarette formulations as tested in this study.
  • PDF Version
  • Citation: Neilson, L., Mankus, C., Thorne, D., Jackson, G., DeBay, J., & Meredith, C. (2015). Development of an in vitro cytotoxicity model for aerosol exposure using 3D reconstructed human airway tissue; application for assessment of e-cigarette aerosol. Toxicology in Vitro, 29(7), 1952–1962. doi:10.1016/j.tiv.2015.05.018
  • Acknowledgement: Louise Neilson, David Thorne and Clive Meredith are employees of British American Tobacco. Courtney Mankus, Jason DeBay and George Jackson are employees of MatTek Corporation, USA. All work conducted was funded by British American Tobacco.


2014 Comparison of select analytes in aerosol from e-cigarettes with smoke from conventional cigarettes and with ambient air

  • 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.
  • 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

2014 Safety evaluation and risk assessment of electronic cigarettes as tobacco cigarette substitutes: a systematic review

  • Existing evidence indicates that E-cigarette (EC) use is by far a less harmful alternative to smoking. There is no tobacco and no combustion involved in EC use; therefore, regular vapers may avoid several harmful toxic chemicals that are typically present in the smoke of tobacco cigarettes. Indeed, some toxic chemicals are released in the EC vapor as well, but their levels are substantially lower compared with tobacco smoke, and in some cases (such as nitrosamines) are comparable with the amounts found in pharmaceutical nicotine products. Surveys, clinical, chemistry and toxicology data have often been mispresented or misinterpreted by health authorities and tobacco regulators, in such a way that the potential for harmful consequences of EC use has been largely exaggerated. It is obvious that some residual risk associated with EC use may be present, but this is probably trivial compared with the devastating consequences of smoking. Moreover, ECs are recommended to smokers or former smokers only, as a substitute for conventional cigarettes or to prevent smoking relapse; thus, any risk should be estimated relative to the risk of continuing or relapsing back to smoking and the low efficacy of currently approved medications for smoking cessation should be taken into consideration….
  • 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.

2014 Levels of selected carcinogens and toxicants in vapor from electronic cigarettes

  • The levels of potentially toxic compounds in e-cigarette vapor is from 9 to 450-fold lower than those in the smoke from conventional cigarettes, and in many cases comparable to the trace amounts present in pharmaceutical preparation (Note: Reference product was a medicinal nicotine inhaler.). Our findings support the idea that substituting tobacco cigarettes with electronic cigarettes may substantially reduce exposure to tobacco-specific toxicants.
  • PDF Version
  • Citation: Goniewicz ML, Knysak J, Gawron M, Kosmider L, Sobczak A, Kurek J, Prokopowicz A, Jablonska-Czapla M, Rosik-Dulewska C, Havel C, Jacob P 3rd, Benowitz N. Levels of selected carcinogens and toxicants in vapour from electronic cigarettes. Tob Control. 2014 Mar;23(2):133-9. doi: 10.1136/tobaccocontrol-2012-050859. Epub 2013 Mar 6. PMID: 23467656; PMCID: PMC4154473.
  • Acknowledgement: This study was conducted while the first author was at Medical University of Silesia, Poland and was supported by the Ministry of Science and Higher Education of Poland under grant number N N404 025638. Analysis of nitrosamines at the University of California, San Francisco was supported by grants P30 DA012393 and S10 RR026437 from the National Institutes of Health.


2014 Evaluation of Toxicant and Carcinogen Metabolites in the Urine of E-Cigarette Users Versus Cigarette Smokers

  • With respect to the compounds analyzed here, e-cigarettes have a more favorable toxicity profile than tobacco cigarettes.
  • PDF Version
  • Citation: Hecht SS, Carmella SG, Kotandeniya D, Pillsbury ME, Chen M, Ransom BW, Vogel RI, Thompson E, Murphy SE, Hatsukami DK. Evaluation of toxicant and carcinogen metabolites in the urine of e-cigarette users versus cigarette smokers. Nicotine Tob Res. 2015 Jun;17(6):704-9. doi: 10.1093/ntr/ntu218. Epub 2014 Oct 21. PMID: 25335945; PMCID: PMC4481723.
  • Acknowledgement: This work was supported by the National Cancer Institute at the National Institutes of Health (R01 CA081301, U19 CA157345, and CA77598).


2013 Cytotoxicity evaluation of electronic cigarette (EC) vapor extract on cultured mammalian fibroblasts (ClearStream-LIFE): comparison with tobacco cigarette smoke (CS) extract

  • This study indicates that EC vapor is significantly less cytotoxic compared to tobacco CS.
  • 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

ENDS (without comparison to other products)

2023: 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.

2018 Metal emissions from e-cigarettes: a risk assessment analysis of a recently-published study

  • EC emissions contain trace levels of metals. For almost all metals, unrealistically high levels of liquid need to be consumed in order for total daily exposure to exceed established limits.
  • PDF Version
  • Citation: : Konstantinos E. Farsalinos & Brad Rodu (2018): Metal emissions from ecigarettes: a risk assessment analysis of a recently-published study, Inhalation Toxicology, DOI: 10.1080/08958378.2018.1523262
  • Acknowledgements: In the past 36 months, two studies by KF were performed using unrestricted funds from the nonprofit association AEMSA and one study by the nonprofit association Tennessee Smoke-Free Association. BR is supported by unrestricted grants from tobacco manufacturers to the University of Louisville and by the Kentucky Research Challenge Trust Fund.
  • KEYWORDS: E-cigarettes; aerosol; metals; risk assessment


2016 Characterization of potential impurities and degradation products in electronic cigarette formulations and aerosols

  • Most potential impurities or degradation products were not detectable.
  • Impurities or degradation products found were below occupational exposure limits
  • Citation: Jason W. Flora, Naren Meruva, Chorng B. Huang, Celeste T. Wilkinson, Regina Ballentine, Donna C. Smith, Michael S. Werley, Willie J. McKinney, Characterization of potential impurities and degradation products in electronic cigarette formulations and aerosols, Regulatory Toxicology and Pharmacology, Volume 74, 2016, Pages 1-11, ISSN 0273-2300, doi: 10.1016/j.yrtph.2015.11.009.
  • Keywords, E-cigarettes, E-vapor, Harmful and potentially harmful constituents (HPHC), Formulation, Aerosol


2014 Peering through the mist: systematic review of what the chemistry of contaminants in electronic cigarettes tells us about health risks

  • Threshold Limit Values (TLVs), were conducted under “worst case” assumptions about both chemical content of aerosol and liquids as well as behavior of vapers.
  • There was no evidence of potential for exposures of e-cigarette users to contaminants that are associated with risk to health at a level that would warrant attention if it were an involuntary workplace exposures.
  • Current state of knowledge about chemistry of liquids and aerosols associated with electronic cigarettes indicates that there is no evidence that vaping produces inhalable exposures to contaminants of the aerosol that would warrant health concerns by the standards that are used to ensure safety of workplaces. However, the aerosol generated during vaping as a whole (contaminants plus declared ingredients) creates personal exposures that would justify surveillance of health among exposed persons in conjunction with investigation of means to keep any adverse health effects as low as reasonably achievable.
  • Exposures of bystanders are likely to be orders of magnitude less, and thus pose no apparent concern.
  • PDF Version
  • Burstyn, I. Peering through the mist: systematic review of what the chemistry of contaminants in electronic cigarettes tells us about health risks. BMC Public Health 14, 18 (2014). doi: 10.1186/1471-2458-14-18
  • Acknowledgements: Funding for this work was provided by The Consumer Advocates for Smoke-free Alternatives Association (CASAA) Research Fund. CASAA is an all-volunteer, donation-funded, non-profit organization devoted to defending consumer access to and promoting tobacco harm reduction; it is a consumer (not industry) advocacy NGO. For more information, see http://casaa.org/. CASAA exercised no editorial control over the author’s writing or analysis: the author, not the funder, had full control of the content.
  • Keywords: Vaping, e-cigarettes, Tobacco harm reduction, Risk assessment, Aerosol, Occupational exposure limit


2013 Electronic Cigarettes: A Short Review

  • From our review of the literature and bearing in mind the long experience with theatrical mists, the short-term toxicity can be considered to be very low
  • Many smokers see the e-cigarette as a good way to quit smoking
  • PDF Version
  • Citation: J.F. Bertholon, M.H. Becquemin, Annesi-Maesano, B. Dautzenberg, Respiration 2013;86:433–438, Electronic Cigarettes: A Short Review, DOI: 10.1159/000353253
  • Key Words: Electronic cigarettes, Propylene glycol, Nicotine


Flavoring in ENDS Products (Flavour)

2019 High Content Screening in NHBE cells shows significantly reduced biological activity of flavoured e-liquids, when compared to cigarette smoke condensate

  • Our results clearly show a lower toxicity of e-liquids, including flavoured e-liquids, when compared to CSC (cigarette smoke condensate). Typically, more than 100 times higher concentrations of CFs (Base liquids, with or without nicotine, and commercial, flavoured, nicotine-containing e-liquids) are required to elicit the same response as those observed for 3R4F CSC in specific endpoints.
  • Flavours play a critical role in attracting, and retaining smokers to e-cigarettes.
  • PDF Version
  • Citation: Lukasz Czekala, Liam Simms, Matthew Stevenson, Edgar Trelles-Sticken, Paul Walker, Tanvir Walele, High Content Screening in NHBE cells shows significantly reduced biological activity of flavoured e-liquids, when compared to cigarette smoke condensate, Toxicology in Vitro, Volume 58, 2019, Pages 86-96, ISSN 0887-2333, doi:10.1016/j.tiv.2019.03.018.
  • Acknowledgements: This work was funded and supported by Fontem Ventures B.V., part of Imperial Brands Group PLC.
  • Keywords: Flavours, In vitro, Normal Human Bronchial Epithelial cells, High Content Screening, E-liquids, Cigarette, flavor, flavoring, flavored


2019 Toxicity classification of e-cigarette flavouring compounds based on European Union regulation: analysis of findings from a recent study

  • The vast majority of flavouring (flavoring) compounds in e-cigarette liquids as reported in a recent study were present at levels far lower than needed to classify them as toxic.
  • PDF Version
  • Farsalinos, K., Lagoumintzis, G. Toxicity classification of e-cigarette flavouring compounds based on European Union regulation: analysis of findings from a recent study. Harm Reduct J 16, 48 (2019). doi: 10.1186/s12954-019-0318-2
  • Acknowledgements: The authors report no conflict of interest for the past 36 months. For the past 60 months, KF has published 2 studies funded by the non-profit association AEMSA and 1 study funded by the non-profit association Tennessee Smoke-Free Association.


2018 Do flavouring compounds contribute to aldehyde emissions in e-cigarettes?

  • Aldehyde emissions from all flavoured liquids were 79–99.8% lower than smoking and lower than commonly measured indoor levels and occupational and indoor safety limits.
  • PDF Version
  • Citation: Konstantinos E. Farsalinos, Vassilis Voudris, Do flavouring compounds contribute to aldehyde emissions in e-cigarettes?, Food and Chemical Toxicology, volume 115, 2018, Pages 212-217, ISSN 0278-6915, doi:10.1016/j.fct.2018.02.059.
  • Acknowledgements: The study was funded by Public Health England.


2015 An approach to ingredient screening and toxicological risk assessment of flavours in e-liquids

  • In vitro and Animal
  • Individual flavours or groups of flavours were added to the tobacco rod and the resultant smoke was analysed for priority smoke constituents and tested in several in vitro tests as well as 90-day rat inhalation studies. In general, addition of the flavours had no effect on, or reduced the levels of most of the measured smoke constituents.”
  • PDF Version
  • Citation: S. Costigan, C. Meredith, An approach to ingredient screening and toxicological risk assessment of flavours in e-liquids, Regulatory Toxicology and Pharmacology, Volume 72, Issue 2, 2015, Pages 361-369, ISSN 0273-2300, doi: 10.1016/j.yrtph.2015.05.018.
  • Acknowledgements: This work was joint funded by Nicoventures and British American Tobacco (BAT), and the authors are full time employees of Nicoventures and British American Tobacco (BAT).


Other ENDS Liquids Ingredients (PG/VG/Nicotine)

2020 Tobacco-Specific Nitrosamines (NNAL, NNN, NAT, and NAB) Exposures in the US Population Assessment of Tobacco and Health (PATH) Study Wave 1 (2013–2014)

  • Among established, every day, exclusive tobacco product users, the geometric mean urinary NNAL concentration was
  1. highest for smokeless tobacco users (993.3 ng/g creatinine),
  2. followed by all types of combustible tobacco product users (285.4 ng/g creatinine),
  3. poly tobacco users (278.6 ng/g creatinine),
  4. and e-cigarette (ENDS) product users (6.3 ng/g creatinine).
  • PDF Version
  • Citation: Baoyun Xia, PhD, Benjamin C Blount, PhD, Tonya Guillot, MPH, Christina Brosius, MPH, Yao Li, BS, Dana M Van Bemmel, PhD MPH, Heather L Kimmel, PhD, Cindy M Chang, PhD MPH, Nicolette Borek, PhD, Kathryn C Edwards, PhD, Charlie Lawrence, PhD, Andrew Hyland, PhD, Maciej L Goniewicz, PhD PharmD, Brittany N Pine, BS, Yang Xia, PhD, John T Bernert, B Rey De Castro, ScD, John Lee, BS, Justin L Brown, MPH, Stephen Arnstein, MS, Diane Choi, BS, Erin L Wade, BS, Dorothy Hatsukami, PhD, Gladys Ervies, PhD, Angel Cobos, BS, Keegan Nicodemus, BS, Dana Freeman, BS, Stephen S Hecht, PhD, Kevin Conway, PhD, Lanqing Wang, PhD, Tobacco-Specific Nitrosamines (NNAL, NNN, NAT, and NAB) Exposures in the US Population Assessment of Tobacco and Health (PATH) Study Wave 1 (2013–2014), Nicotine & Tobacco Research, , ntaa110:10.1093/ntr/ntaa110
  • Acknowledgements: This manuscript is supported with Federal funds from the National Institute on Drug Abuse, National Institutes of Health, and the Center for Tobacco Products, Food and Drug Administration, Department of Health and Human Services, under contract to Westat (contract nos. HHSN271201100027C and HHSN271201600001C) and through an interagency agreement between the FDA Center for Tobacco Products and the Centers for Disease Control and Prevention.
  • Keywords: creatinine, exposure, biological markers, nitrosamines, tobacco, urinary tract, electronic cigarettes, ENDS


2017 Toxicity of the main electronic cigarette components, propylene glycol, glycerin, and nicotine, in Sprague-Dawley rats in a 90-day OECD inhalation study complemented by molecular endpoints

  • Animal Study
  • Standard toxicological endpoints were complemented with systems toxicological analyses using transcriptomics, proteomics, and lipidomics of lung tissue, liver tissue, and serum. Both standard and systems toxicology endpoints demonstrated very limited biological effects of PG/VG aerosol with no signs of toxicity Systems toxicology analyses detected biological effects of nicotine exposure, which included up-regulation of the xenobiotic-metabolizing enzymes Cyp1a1 and Fmo3 in the lung and metabolic effects, likely interlinked with a generalized stress response to nicotine present in the exposure aerosols
  • PDF Version
  • Citation: Blaine Phillips, Bjoern Titz, Ulrike Kogel, Danilal Sharma, Patrice Leroy, Yang Xiang, Grégory Vuillaume, Stefan Lebrun, Davide Sciuscio, Jenny Ho, Catherine Nury, Emmanuel Guedj, Ashraf Elamin, Marco Esposito, Subash Krishnan, Walter K. Schlage, Emilija Veljkovic, Nikolai V. Ivanov, Florian Martin, Manuel C. Peitsch, Julia Hoeng, Patrick Vanscheeuwijck, Toxicity of the main electronic cigarette components, propylene glycol, glycerin, and nicotine, in Sprague-Dawley rats in a 90-day OECD inhalation study complemented by molecular endpoints, Food and Chemical Toxicology, Volume 109, Part 1, 2017, Pages 315-332, ISSN 0278-6915, doi:10.1016/j.fct.2017.09.001.
  • Acknowledgements: The work reported in this publication was funded solely by Philip Morris International (PMI). All authors are (or were) employees of PMI R&D or worked for PMI R&D under contractual agreements.


2017 A Review on the Safety of Inhalation of Propylene Glycol in E-cigarettes

  • Tests performed by the FDA have shown that e-cigarettes have similar nicotine levels and trace contaminants as NRT products.
  • Propylene glycol (PG) is generally recognized as safe by oral, dermal or inhalation routes and has been a common ingredient in all American made tobacco cigarettes for seven decades.”
  • PDF Version
  • Citation: A Review on the Safety of Inhalation of Propylene Glycol in E-cigarettes, Karyn I. Cotta}, 2017


2014 Peering through the mist: systematic review of what the chemistry of contaminants in electronic cigarettes tells us about health risks

  • Current state of knowledge about chemistry of liquids and aerosols associated with electronic cigarettes indicates that there is no evidence that vaping produces inhalable exposures to contaminants of the aerosol that would warrant health concerns by the standards that are used to ensure safety of workplaces
  • PDF Version
  • Burstyn, I. Peering through the mist: systematic review of what the chemistry of contaminants in electronic cigarettes tells us about health risks. BMC Public Health 14, 18 (2014). doi: 10.1186/1471-2458-14-18
  • Acknowledgements: Funding for this work was provided by The Consumer Advocates for Smoke-free Alternatives Association (CASAA) Research Fund. CASAA is an all-volunteer, donation-funded, non-profit organization devoted to defending consumer access to and promoting tobacco harm reduction; it is a consumer (not industry) advocacy NGO. For more information, see http://casaa.org/. CASAA exercised no editorial control over the author’s writing or analysis: the author, not the funder, had full control of the content.
  • Keywords: Vaping, e-cigarettes, Tobacco harm reduction, Risk assessment, Aerosol, Occupational exposure limit


2013 Analysis of refill liquids for electronic cigarettes

  • The nicotine content of electronic cigarette refill bottles is close to what is stated on the label. Impurities are detectable in some brands above the level set for nicotine products in the European Pharmacopoeia, but below the level where they would be likely to cause harm.
  • PDF Version
  • Citation: Etter, J.‐F., Zäther, E. and Svensson, S. (2013), E‐liquids. Addiction, 108: 1671-1679. doi: 10.1111/add.12235


2006 Reregistration Eligibility Decision (RED) for propylene glycol and dipropylene glycol (PDF Version)

  • Upon reviewing the available toxicity information, the Agency has concluded that there are no endpoints of concern for oral, dermal, or inhalation exposure to propylene glycol. This conclusion is based on the results of toxicity testing of propylene glycol in which dose levels near or above testing limits (as established in the OPPTS 870 series harmonized test guidelines) were employed in experimental animal studies and no significant toxicity observed.
  • A review of the available data has shown propylene glycol to be negative for carcinogenicity in studies conducted up to the testing limit doses established by the Agency; therefore, no further carcinogenic analysis is required.


PAGE EDITORS - Please add Studies, Surveys, Papers in this format to keep page organized

  • Topic
  • Year (list new to old) Name of Study (In link format to the study)
  • Note here if animal study (leave blank if not)
  • Brief Summary
  • Link to PDF Version
  • Citation
  • Acknowledgements (funded by, helped by)
  • Keywords
  • Other


Suggested studies to add to this page

2023: A contextualised e-cigarette testing strategy shows flavourings do not impact lung toxicity in vitro

2022: REPLICA Project: In Vitro Toxicity Profile of myblu™ electronic cigarette Aerosol Compared to Cigarette Smoke: the REPLICA project

2021: Comparison of biological and transcriptomic effects of conventional cigarette and electronic cigarette smoke exposure at toxicological dose in BEAS-2B cells

2021 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

An Assessment of Indoor Air Quality before, during and after Unrestricted Use of E-Cigarettes in a Small Room

Systematic review of biomarker findings from clinical studies of electronic cigarettes and heated tobacco products

More Information

  • Click on the category link below for more studies by topic on ENDS and Nicotine.