NOT PEER REVIEWED In this interesting study by Cheah et al,1 the authors have raised
several safety issues concerning electronic cigarettes. The majority of
them were based either on the finding that nicotine content was
inconsistent or that chemical constitution (for example glycols) may be
hazardous to health.
There is some inconsistency in characterizing polypropylene glycol as
"a known irritant when inhaled or ingested" in introduction section and as
"a non-toxic chemical" in discussion section. This substance has been
"generally recognized as safe" (GRAS) by FDA for ingestion, however, only
few studies have evaluated the long term inhalation risk. A study by
Robertson et al2 found that in experimental animals inhaling large
quantities of propylene glycol for 12-18 months no lung, kidney, liver,
spleen or bone marrow irritation or disease was observed, while others
have used it on a daily basis as a vehicle for drug administration without
finding any significant irritant effects on the respiratory tract. There
are also no reports from electronic cigarette users that propylene glycol
has caused any significant irreversible damage besides some throat
irritation and cough, that has been resolved by using liquids not
containing propylene glycol.
Concerning the production of carbonyls, it should be mentioned that
electronically heated cigarettes that are mentioned in the study are in no
way similar to electronic cigarettes. The temperature in electrically
heated cigarettes is 600oC.3 Glycerol has a boiling point of 290oC, and
diluting it with 10% water (usually, for electronic cigarette liquids
glycerol is diluted with 15-20% water) the boiling point is 138oC,4
significantly lower than the 250oC needed to produce acrolein. These
theoretical concepts have been backed up by data provided by Schripp et
al,5 who found traces of formaldehyde not attributed to electronic
cigarette use, and Romagna et al,6 who found no acrolein or formaldehyde
in the air after electronic cigarette use for several hours.
An important finding of the study was the absence of nitrosamines.
This has been somewhat underestimated by the authors. Nicotine in
electronic cigarette liquids (and in other products, including
pharmaceutical products) is derived from tobacco. Therefore, there is a
possibility that nitrosamines may be present; in fact, they have been
detected in approved nicotine gum and patch products.7 We think that the
absence of nitrosamines is an important finding of this study and should
have been further discussed, since they are major causes of lung disease
including cancer.
Quality control during the production process is a major issue in
electronic cigarette industry. Unfortunately, the fact that no regulation
has been implemented by public health authorities allows low-quality
products to be available to the market. This may raise safety issues like
the presence of nitrosamines mentioned above. In addition, this is also
the reason for the inadequate labeling of these products. We think that
regulation standards should include proper labeling not only about the
contents but also about the risks of accidental exposure to the liquids,
similarly to other consumer products used daily in every home. However, we
believe that the nicotine content discrepancies that the authors have
found do not represent a major health risk, since it is well known that
smoking is a dynamic process and changes in response to the yield
characteristics of the cigarette.8 Most probably, the users would have
adjusted their smoking pattern to the nicotine levels obtained by the use
of these liquids. In fact, this has been a problem of tobacco cigarettes,
with FTC protocol levels of nicotine significantly underestimating
nicotine doses to smokers.8 This is accompanied by an underestimation of
doses of carcinogens obtained by smokers, like nitrosamines, which were
not found in electronic cigarettes tested in this study. Thus, it is not
the nicotine that poses a health risk but other chemicals that are
released during the smoking process.
References
1. Cheah NP, Chong NWL, Tan J, Morsed FA, Yee SK. Electronic nicotine
delivery systems: regulatory and safety challenges: Singapore perspective.
Tob Control, 2012. Dec 1 [Epub ahead of print]
2. Robertson OH, Loosli CG, Puck TT, Wise H, Lemon WM, Lester W Jr.
Tests for the chronic toxicity of propylene glycol and triethylene glycol
on monkeys and rats by vapor inhalation and oral administration. J
Pharmacol Exper Ther 1947;91:52-76.
3. Patskan G, Reininghaus W. Toxicological evaluation of an
electrically heated cigarette. Part 1: overview of technical concepts and
summary of findings. J Appl Toxicol 2003;23:323-8
4. Flick EW. Industrial solvents handbook, 5th edition, 1998. ISBN 0-
8155-1413-1 Noyes Data Co, 1998
5. Schripp T, Markewitz D, Uhde E, Salthammer T. Does e-cigarette
consumption cause passive vaping? Indoor Air 2012. Jun 2 [Epub ahead of
print]
6. Romagna G, Allifranchini E, Bocchieto E, Todeshi S, Esposito M,
Farsalinos K. Cytotoxicity of electronic cigarette vapor extract on
cultured mammalian fibroblasts (ClearStream-Life project): comparison with
tobacco smoke extract [abstract].
[http://www.srnteurope.org/assets/Abstract-Book-Final.pdf] Poster RRP17.
14th Annual Meeting of the Society for Research on Nicotine and Tobacco
Europe, Helsinki, 2012. (accessed December 2012).
7. Cahn Z, Siegel M. Electronic cigarettes as a harm reduction
strategy for tobacco control: a step forward of a repeat of past mistakes?
J Public Health Policy 2011;32:16-31.
8. Djordjevic MV, Stellman SD, Zang E. Doses of nicotine and lung
carcinogens delivered to cigarette smokers. J Natl Cancer Inst 2000;92:106
-11.
Conflict of Interest:
None declared
NOT PEER REVIEWED In this interesting study by Cheah et al,1 the authors have raised several safety issues concerning electronic cigarettes. The majority of them were based either on the finding that nicotine content was inconsistent or that chemical constitution (for example glycols) may be hazardous to health.
There is some inconsistency in characterizing polypropylene glycol as "a known irritant when inhaled or ingested" in introduction section and as "a non-toxic chemical" in discussion section. This substance has been "generally recognized as safe" (GRAS) by FDA for ingestion, however, only few studies have evaluated the long term inhalation risk. A study by Robertson et al2 found that in experimental animals inhaling large quantities of propylene glycol for 12-18 months no lung, kidney, liver, spleen or bone marrow irritation or disease was observed, while others have used it on a daily basis as a vehicle for drug administration without finding any significant irritant effects on the respiratory tract. There are also no reports from electronic cigarette users that propylene glycol has caused any significant irreversible damage besides some throat irritation and cough, that has been resolved by using liquids not containing propylene glycol.
Concerning the production of carbonyls, it should be mentioned that electronically heated cigarettes that are mentioned in the study are in no way similar to electronic cigarettes. The temperature in electrically heated cigarettes is 600oC.3 Glycerol has a boiling point of 290oC, and diluting it with 10% water (usually, for electronic cigarette liquids glycerol is diluted with 15-20% water) the boiling point is 138oC,4 significantly lower than the 250oC needed to produce acrolein. These theoretical concepts have been backed up by data provided by Schripp et al,5 who found traces of formaldehyde not attributed to electronic cigarette use, and Romagna et al,6 who found no acrolein or formaldehyde in the air after electronic cigarette use for several hours.
An important finding of the study was the absence of nitrosamines. This has been somewhat underestimated by the authors. Nicotine in electronic cigarette liquids (and in other products, including pharmaceutical products) is derived from tobacco. Therefore, there is a possibility that nitrosamines may be present; in fact, they have been detected in approved nicotine gum and patch products.7 We think that the absence of nitrosamines is an important finding of this study and should have been further discussed, since they are major causes of lung disease including cancer.
Quality control during the production process is a major issue in electronic cigarette industry. Unfortunately, the fact that no regulation has been implemented by public health authorities allows low-quality products to be available to the market. This may raise safety issues like the presence of nitrosamines mentioned above. In addition, this is also the reason for the inadequate labeling of these products. We think that regulation standards should include proper labeling not only about the contents but also about the risks of accidental exposure to the liquids, similarly to other consumer products used daily in every home. However, we believe that the nicotine content discrepancies that the authors have found do not represent a major health risk, since it is well known that smoking is a dynamic process and changes in response to the yield characteristics of the cigarette.8 Most probably, the users would have adjusted their smoking pattern to the nicotine levels obtained by the use of these liquids. In fact, this has been a problem of tobacco cigarettes, with FTC protocol levels of nicotine significantly underestimating nicotine doses to smokers.8 This is accompanied by an underestimation of doses of carcinogens obtained by smokers, like nitrosamines, which were not found in electronic cigarettes tested in this study. Thus, it is not the nicotine that poses a health risk but other chemicals that are released during the smoking process.
References 1. Cheah NP, Chong NWL, Tan J, Morsed FA, Yee SK. Electronic nicotine delivery systems: regulatory and safety challenges: Singapore perspective. Tob Control, 2012. Dec 1 [Epub ahead of print]
2. Robertson OH, Loosli CG, Puck TT, Wise H, Lemon WM, Lester W Jr. Tests for the chronic toxicity of propylene glycol and triethylene glycol on monkeys and rats by vapor inhalation and oral administration. J Pharmacol Exper Ther 1947;91:52-76.
3. Patskan G, Reininghaus W. Toxicological evaluation of an electrically heated cigarette. Part 1: overview of technical concepts and summary of findings. J Appl Toxicol 2003;23:323-8
4. Flick EW. Industrial solvents handbook, 5th edition, 1998. ISBN 0- 8155-1413-1 Noyes Data Co, 1998
5. Schripp T, Markewitz D, Uhde E, Salthammer T. Does e-cigarette consumption cause passive vaping? Indoor Air 2012. Jun 2 [Epub ahead of print]
6. Romagna G, Allifranchini E, Bocchieto E, Todeshi S, Esposito M, Farsalinos K. Cytotoxicity of electronic cigarette vapor extract on cultured mammalian fibroblasts (ClearStream-Life project): comparison with tobacco smoke extract [abstract]. [http://www.srnteurope.org/assets/Abstract-Book-Final.pdf] Poster RRP17. 14th Annual Meeting of the Society for Research on Nicotine and Tobacco Europe, Helsinki, 2012. (accessed December 2012).
7. Cahn Z, Siegel M. Electronic cigarettes as a harm reduction strategy for tobacco control: a step forward of a repeat of past mistakes? J Public Health Policy 2011;32:16-31.
8. Djordjevic MV, Stellman SD, Zang E. Doses of nicotine and lung carcinogens delivered to cigarette smokers. J Natl Cancer Inst 2000;92:106 -11.
Conflict of Interest:
None declared