Skip to main content

Main menu

  • Home
  • Current issue
  • ERJ Early View
  • Past issues
  • ERS Guidelines
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • Open access
    • Peer reviewer login
  • Alerts
  • Subscriptions
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

User menu

  • Log in
  • Subscribe
  • Contact Us
  • My Cart

Search

  • Advanced search
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

Login

European Respiratory Society

Advanced Search

  • Home
  • Current issue
  • ERJ Early View
  • Past issues
  • ERS Guidelines
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • Open access
    • Peer reviewer login
  • Alerts
  • Subscriptions

High nicotine exposure in rodents is unlikely to inform about its toxicity in humans

Rosalia Emma, Riccardo Polosa, Massimo Caruso
European Respiratory Journal 2019 54: 1801073; DOI: 10.1183/13993003.01073-2018
Rosalia Emma
1Dept of Clinical and Experimental Medicine, University of Catania, Catania, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Rosalia Emma
Riccardo Polosa
1Dept of Clinical and Experimental Medicine, University of Catania, Catania, Italy
2Center of Excellence for the acceleration of HArm Reduction (CoEHAR), University of Catania, Catania, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Massimo Caruso
1Dept of Clinical and Experimental Medicine, University of Catania, Catania, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Massimo Caruso
  • For correspondence: mascaru@unict.it
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

More realistic exposures protocols are required to provide reliable toxicological information about electronic cigarette use in the context of smoking harm reduction http://bit.ly/2YkZHWG

To the Editor:

We read with interest the research letter by Reinikovaite et al. [1], in which the authors reported same level of damage in the lungs of Sprague Dawley rats subjected to whole body chronic exposure of e-cigarette vapour emissions and cigarette smoke, as well as to subcutaneous injection of nicotine. Their conclusion is that e-cigarette use and long-time consumption of nicotine are just as toxic as tobacco cigarettes. We appreciate the authors' intention to address concerns related to the potential long-term health effects of e-cigarette use and nicotine exposure, but there are a number of methodological considerations that lessen the impact of their findings.

First, in spite of the authors' effort to establish a meaningful puff/puff comparison between e-cigarette vapour and cigarette smoke, rats weighting about 200 g were being exposed to 600 puffs of vapour or smoke in just over 4 h in small gas chambers of <1 m3 volume. Humans weigh, on average, 400 times more than Sprague Dawley rats and yet they usually inhale the same 600 puffs in just over 3 days. Under these specific experimental conditions, animals' overexposure to aerosol mass and its contents is highly likely. This is not uncommon, as there is proliferation of toxicological studies that are often performed with high-dose exposure protocols that are not applicable to normal human consumption [2]. When calculating the dose to be used, particularly if this is based upon human data, allometric scaling should be used, to take into account the large differences in metabolic rate between animals of different body mass [3, 4]. Moreover, in the work of Reinikovaite et al. [1], rats were exposed daily for 4 h for a total of 5 weeks; such exposure protocol is designed to maximise harm for the induction of pathological status (e.g. emphysema or chronic obstructive pulmonary disease (COPD)), which is used to study the characteristics of the disease in animal models (inflammation, basic mechanisms, response to therapies, etc.) [5]. Also, we noted that the authors did not mention animal health during the study, and standard toxic endpoints detailed in Organisation for Economic Cooperation and Development test number 413 (organ weights, gross pathology, etc.) were not assessed [6].

Second, in trying to equate similar level of plasma nicotine of adult smokers in the much smaller animal model (weighing approximately 400 times less than humans), the authors end up injecting a highly toxic dose. In histopathological studies of rats, it has been found that subcutaneous administration of nicotine doses similar to those used by Reinikovaite et al. [1] can cause extensive tissue damage, not only in the lung, but also in other organs including the liver, kidneys and brain [7, 8]. Thus, the dose used in the study is toxic and far from being informative of the nicotine effects in humans under the normal condition of consumption. It would have been ideal to include a rat group exposed to e-cigarette without nicotine to reach more revealing conclusions. Moreover, given that it is well established that the protease/anti-protease ratio is the central component of our understanding of emphysema, it is incongruous to advance the alternative hypothesis that it is nicotine causing lung destruction in smokers. This hypothesis is also at variance with the epidemiological evidence; for example, biomass fuel combustion is a well-known causative factor for COPD not dependent on nicotine [9, 10].

Third, in stark contrast with the concerns raised by Reinikovaite et al. [1] that e-cigarettes are as toxic as tobacco cigarettes and can cause lung damage, there is emerging evidence from real-life surveys [11] and the prospective evaluation of lung function and high-resolution computed tomography of regular vapers who have never smoked in their life [12], indicating that long term e-cigarette use is unlikely to raise significant lung health concerns. Moreover, despite their being millions of regular e-cigarette users worldwide, there has been no evidence of emerging respiratory disease outbreaks in recent years.

Shareable PDF

Supplementary Material

This one-page PDF can be shared freely online.

Shareable PDF ERJ-01073-2018.Shareable

Footnotes

  • Conflict of interest: R. Emma has no conflicts of interest to disclose.

  • Conflict of interest: R. Polosa has served as a consultant for Pfizer, Global Health Alliance for treatment of tobacco dependence, ECITA (Electronic Cigarette Industry Trade Association, in the UK), Arbi Group Srl, and Health Diplomats (a consulting company that delivers solutions to global health problems with special emphasis on harm minimisation); has received lecture fees from a number of European electronic cigarette industry and trade associations (including FIVAPE in France and FIESEL in Italy) which were directly donated to vapers advocacy non-profit organisations; and is also currently involved in the following pro bono activities: scientific advisor for LIAF, Lega Italiana Anti Fumo (Italian acronym for Italian Anti-Smoking League), the Consumer Advocates for Smoke-free Alternatives (CASAA) and the International Network of Nicotine Consumers Organizations (INNCO); chair of the European Technical Committee for standardisation on “Requirements and test methods for emissions of electronic cigarettes” (CEN/TC 437; WG4).

  • Conflict of interest: M. Caruso has no conflicts of interest to disclose.

  • Received June 8, 2018.
  • Accepted June 16, 2019.
  • Copyright ©ERS 2019
https://www.ersjournals.com/user-licence

References

  1. ↵
    1. Reinikovaite V,
    2. Rodriguez IE,
    3. Karoor V, et al.
    The effects of electronic cigarette vapour on the lung: direct comparison to tobacco smoke. Eur Respir J 2018; 51: 1701661.
    OpenUrlAbstract/FREE Full Text
  2. ↵
    1. Volti G L,
    2. Polosa R,
    3. Caruso M
    . Assessment of E-cigarette impact on smokers: the importance of experimental conditions relevant to human consumption. Proc Natl Acad Sci 2018; 115: E3073–E3074.
    OpenUrlFREE Full Text
  3. ↵
    1. Nair AB,
    2. Jacob S
    . A simple practice guide for dose conversion between animals and human. J Basic Clin Pharm 2016; 7: 27–31.
    OpenUrlCrossRefPubMed
  4. ↵
    1. Huang Q,
    2. Riviere JE
    . The application of allometric scaling principles to predict pharmacokinetic parameters across species. Expert Opin Drug Metab Toxicol 2014; 10: 1241–1253.
    OpenUrlCrossRefPubMed
  5. ↵
    1. Ghorani V,
    2. Boskabady MH,
    3. Khazdair MR, et al.
    Experimental animal models for COPD: a methodological review. Tob Induc Dis BioMed Central 2017; 15: 25.
    OpenUrl
  6. ↵
    Organisation for Economic Cooperation and Development. OECD Guidelines for the Testing of Chemicals, Section 4. Test No. 413: Subchronic Inhalation Toxicity: 90-day Study. https://doi.org/10.1787/9789264070806-en Date last accessed: February 11, 2019.
  7. ↵
    1. Adluri RS,
    2. Nagarajan D,
    3. Periyaswamy V, et al.
    Dose-response effect of ferulic acid against nicotine-induced tissue damage and altered lipid levels in experimental rats: a pathohistological evaluation. Fundam Clin Pharmacol 2008; 22: 557–567.
    OpenUrlPubMed
  8. ↵
    1. Balakrishnan A,
    2. Menon VP
    . Effect of hesperidin on nicotine toxicity and histopathological studies. Toxicol Mech Methods 2007; 17: 233–239.
    OpenUrlPubMed
  9. ↵
    1. Kurmi OP,
    2. Semple S,
    3. Simkhada P, et al.
    COPD and chronic bronchitis risk of indoor air pollution from solid fuel: a systematic review and meta-analysis. Thorax 2010; 65: 221–228.
    OpenUrlAbstract/FREE Full Text
  10. ↵
    1. Salvi SS,
    2. Barnes PJ
    . Chronic obstructive pulmonary disease in non-smokers. Lancet 2009; 374: 733–743.
    OpenUrlCrossRefPubMedWeb of Science
  11. ↵
    1. Farsalinos KE,
    2. Romagna G,
    3. Tsiapras D, et al.
    Characteristics, perceived side effects and benefits of electronic cigarette use: a worldwide survey of more than 19,000 consumers. Int J Environ Res Public Health 2014; 11: 4356–4373.
    OpenUrlCrossRefPubMed
  12. ↵
    1. Polosa R,
    2. Cibella F,
    3. Caponnetto P, et al.
    Health impact of E-cigarettes: a prospective 3.5-year study of regular daily users who have never smoked. Sci Rep 2017; 7: 13825.
    OpenUrl
PreviousNext
Back to top
View this article with LENS
Vol 54 Issue 2 Table of Contents
European Respiratory Journal: 54 (2)
  • Table of Contents
  • Index by author
Email

Thank you for your interest in spreading the word on European Respiratory Society .

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
High nicotine exposure in rodents is unlikely to inform about its toxicity in humans
(Your Name) has sent you a message from European Respiratory Society
(Your Name) thought you would like to see the European Respiratory Society web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Print
Citation Tools
High nicotine exposure in rodents is unlikely to inform about its toxicity in humans
Rosalia Emma, Riccardo Polosa, Massimo Caruso
European Respiratory Journal Aug 2019, 54 (2) 1801073; DOI: 10.1183/13993003.01073-2018

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
High nicotine exposure in rodents is unlikely to inform about its toxicity in humans
Rosalia Emma, Riccardo Polosa, Massimo Caruso
European Respiratory Journal Aug 2019, 54 (2) 1801073; DOI: 10.1183/13993003.01073-2018
del.icio.us logo Digg logo Reddit logo Technorati logo Twitter logo CiteULike logo Connotea logo Facebook logo Google logo Mendeley logo
Full Text (PDF)

Jump To

  • Article
    • Abstract
    • Shareable PDF
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF
  • Tweet Widget
  • Facebook Like
  • Google Plus One

More in this TOC Section

Agora

  • Wider access to rifapentine-based regimens is needed for TB care globally
  • Airway immune responses to COVID-19 vaccination in COPD patients
  • Screening for PVOD in heterozygous EIF2AK4 variant carriers
Show more Agora

Correspondence

  • Treatable traits in ILD: why not consider acute exacerbations?
  • Inclusion of lung health outcomes in TB treatment trials
  • Understanding confounding in Mendelian randomisation studies
Show more Correspondence

Related Articles

Navigate

  • Home
  • Current issue
  • Archive

About the ERJ

  • Journal information
  • Editorial board
  • Press
  • Permissions and reprints
  • Advertising

The European Respiratory Society

  • Society home
  • myERS
  • Privacy policy
  • Accessibility

ERS publications

  • European Respiratory Journal
  • ERJ Open Research
  • European Respiratory Review
  • Breathe
  • ERS books online
  • ERS Bookshop

Help

  • Feedback

For authors

  • Instructions for authors
  • Publication ethics and malpractice
  • Submit a manuscript

For readers

  • Alerts
  • Subjects
  • Podcasts
  • RSS

Subscriptions

  • Accessing the ERS publications

Contact us

European Respiratory Society
442 Glossop Road
Sheffield S10 2PX
United Kingdom
Tel: +44 114 2672860
Email: journals@ersnet.org

ISSN

Print ISSN:  0903-1936
Online ISSN: 1399-3003

Copyright © 2023 by the European Respiratory Society