ENDS Toxicity / Carcinogenic

Studies, Surveys, Papers, and Case Studies

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

Flavoring in ENDS Products

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

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.

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.

More Information

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