Toxicity / Carcinogenic


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

Giorgio Romagna, Elena Allifranchini, Elena Bocchietto, Stefano Todeschi, Mara Esposito, Konstantinos E. Farsalinos
Published online: 06 Jun 2013

Conclusions: This study indicates that EC vapor is significantly less cytotoxic compared tobacco CS. These results should be validated by clinical studies.


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

RanaTayyarah, Gerald A.Long
Published online: Dec 2014

Conclusions: The purpose of this study was to determine content and delivery of e-cigarette ingredients and to compare e-cigarette aerosol to conventional cigarettes with respect to select HPHCs for which conventional cigarette smoke is routinely tested. Routine analytical methods were adapted and verified for e-cigarette testing. Aerosol collection was conducted using conventional smoking machines and an intense puffing regime. As machine puffing cannot, and is not intended to, mimic human puffing, results of this study are limited to the scope of the comparisons made between the e-cigarette and conventional cigarette products tested.

Testing of the e-cigarette aerosol indicates little or no detectable levels of the HPHC constituents tested.

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

Konstantinos E. Farsalinos, Riccardo Polosa
Published online: 13 Feb 2014

Conclusions: “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…..”

Levels of selected carcinogens and toxicants in vapor from electronic cigarettes

Goniewicz Maciej Lukasz, Knysak Jakub, Gawron Michal, Kosmider Leon, Sobczak Andrzej, Kurek Jolanta, Prokopowicz Adam, Jablonska-Czapla Magdalena, Rosik-Dulewska Czeslawa, Havel Christopher, Jacob Peyton, Benowitz Neal
Published online: Mar 2014

Results: 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.

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

Stephen S. Hecht, Steven G. Carmella, Delshanee Kotandeniya, Makenzie E. Pillsbury, Menglan Chen, Benjamin W. S. Ransom, Rachel Isaksson Vogel, Elizabeth Thompson, Sharon E. Murphy, Dorothy K. Hatsukami
Published online: Oct 2014

Conclusion: “With respect to the compounds analyzed here, e-cigarettes have a more favorable toxicity profile than tobacco cigarettes.”


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

Louise Neilsona, Courtney Mankusb, David Thornea, George Jackson, Jason DeBay, Clive Mereditha
Published online: Oct 2015

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.


Royal College of Physicians - Nicotine without Smoke

Amanda Amos, Deborah Arnott, Richard Ashcroft, Paul Aveyard, Linda Bauld, Ilze Bogdanovica, John Britton, Meghan Chenoweth, Jeff Collin, Martin Dockrell, Peter Hajek, Nick Hopkinson, Tessa Langley, Sarah Lewis, Ann McNeill, Hayden McRobbie, Marcus Munafò, Magdalena Opazo Breton, Rachel F Tyndale, Jennifer Ware, Robert West
Published online: Apr 2016

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 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…

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

Ana S.Cravo, Jim Bush, Girish Sharma, Rebecca Savioz, Claire Martin, Simon Craige, Tanvir Walele
Published online: Nov 2016

Conclusion: “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.”

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

Maciej L. Goniewicz, Michal Gawron, Danielle M. Smith, Margaret Peng, Peyton Jacob III, Neal L. Benowitz
Published online: 17 Aug 2016

Conclusion: “After switching from tobacco to e-cigarettes, nicotine exposure remains unchanged, while exposure to selected carcinogens and toxicants is substantially reduced”

Tobacco Consumption and Toxicant Exposure of Cigarette Smokers Using Electronic Cigarettes

Kim Pulvers, Ashley S Emami, Nicole L Nollen, Devan R Romero, David R Strong, Neal L Benowitz, Jasjit S Ahluwalia
Published online: 21 Dec 2016

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.

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

Carl D. D’Ruiz, Donald W. Graff, Edward Robinson
Published online: 16 Jul 2016

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.

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

D.Thorne, I.Crooks, M.Hollings, A.Seymour, C.Meredith, M.Gaca
Published online: Dec 2016

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.

Electronic cigarette aerosol induces significantly less cytotoxicity than tobacco smoke

David Azzopardi, Kharishma Patel, Tomasz Jaunky, Simone Santopietro,Oscar M. Camacho, John McAughey & Marianna Gaça
Published online: Sep 2016

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


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

William E Stephens
Published online: 4 Aug 2017

“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

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

Lion Shahab, Maciej L. Goniewicz, Benjamin C. Blount, Jamie Brown, Ann McNeill, K. Udeni Alwis, June Feng, Lanqing Wang, Robert West
Published online: 21 Mar 2017

Conclusion: “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.” 

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

Dominic L. Palazzolo, Andrew P. Crow, John M. Nelson, Robert A. Johnson
Published online: 10 Jan 2017

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.

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

Theodore L Wagener, Evan L Floyd, Irina Stepanov, Leslie M Driskill, Summer G Frank, Ellen Meier, Eleanor L Leavens, Alayna P Tackett, Neil Molina, Lurdes Queimado
Published online: 21 Mar 2017

While not harmless, electronic cigarettes (e-cigarettes) have demonstrated a much more favourable 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.

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

Konstantinos E. Farsalinos, Vassilis Voudris, Alketa Spyrou, Konstantinos Poulas
Published online: Nov 2017

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. 

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

Damien Breheny, Oluwatobiloba Oke, Kamala Pant, Marianna Gaça
Published online: 26 Apr 2017

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.

Benzene formation in electronic cigarettes

James F. Pankow, Kilsun Kim, Kevin J. McWhirter, Wentai Luo, Jorge O. Escobedo, Robert M. Strongin, Anna K. Duell, David H. Peyton
Published online: 8 Mar 2017

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


Public Health Consequences of E-Cigarettes

Kathleen Stratton, Leslie Y. Kwan, and David L. Eaton

Comparisons of using e-cigarettes vs smoking:

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.

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

Maciej L. Goniewicz, PharmD, Danielle M. Smith, Kathryn C. Edwards, Benjamin C. Blount, Kathleen L. Caldwell, Jun Feng, Lanqing Wang, Carol Christensen, Bridget Ambrose, Nicolette Borek, Dana van Bemmel, Karen Konkel, Gladys Erives, Cassandra A. Stanton, Elizabeth Lambert, Heather L. Kimmel, Dorothy Hatsukami, Stephen S. Hecht, Raymond S. Niaura, Mark Travers, Charles Lawrence, Andrew J. Hyland
Published online: 14 Dec 2018

Findings: “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.” 

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

Mauro Scungio, Luca Stabile, Giorgio Buonanno
Published online: Jan 2018

Conclusion: “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.” 

The American Cancer Society Public Health Statementon Eliminating Combustible Tobacco Use in theUnited States

Clifford E. Douglas, Rosie Henson, Jeffrey Drope, Richard C. Wender
Published online: 11 Jun 2018

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.


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

R. Constance Wiener, Ruchi Bhandari
Published online: Dec 2020

Blood lead levels, and urinary cadmium, barium, and antimony levels were similar between participants who used e-cigarettes and participants who did not.

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.

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

Romain Dusautoir, Gianni Zarcone, Marie Verriele, Guillaume Garçon, Isabelle Fronval, Nicolas Beauval, Delphine Allorge, Véronique Riffault, Nadine Locoge, Jean-MarcLo-Guidice, Sébastien Anthérieu
Published online: 5 Jan 2021

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. 

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. 

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

Joanna Jay, Erika L Pfaunmiller, Norman J Huang, Gal Cohen, Donald W Graff
Published online: 8 Aug 2020

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