HomeMy WebLinkAboutCOM 1091.152 2012-2014Murashige, Laura
From: Tim Michel <tmichel67@gmail.com>
Sent: Tuesday, December 16, 2014 11:49 AM
To: Council Testimony
Subject: Strongly Oppose Bill 302
Attachments: Ecigarettes_and_Smokefree_policies.pdf; Effects of Ecig vapor on indoor air quality.pdf;
Peering throgh the mist.pdf; Second Hand Vapor.pdf
Aloha Councilmembers,
I STRONGLY OPPOSE Bill 302!!! There is no scientific basis for a bill like this. This bill is based purely on
fear. Allowing ourselves to legislate based on fear, is opening the door for political process that is unkind and
not why we create laws. There are many opinions on both sides of this issue. However the science only supports
one side. All recent reports state that the level of harm in secondhand vapor is negligible. Attached are the
studies I am getting this from. There is no public outcry for a law of this kind. On the contrary, the public outcry
is against it. This bill wrongly puts E -Cigarettes in the same category as combustible cigarettes. They are not
alike in any way except the nicotine. Without combustion, there is no smoke! This bill will frighten people
away from trying something that could possibly prolong, or in some cases, save somebodies life. Do the right
thing for your constituents and public health! Vote NO on Bill 302.
Mahalo for your time,
Tim Michel
Pahoa, HI
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E -cigarettes and Smoke-free Policies
What are E -cigarettes and what do they contain?
• E -cigarettes are battery operated devices that vaporize a liquid solution consisting of ingredients generally
regarded as safe for human consumption (89-90% propylene glycol, vegetable glycerin, water, flavoring) and a
small amount of nicotine. (Laugesen, 2008)
• Electronic cigarettes are a completely smokeless alternative to traditional cigarettes and are not marketed as a
nicotine addiction treatment. (Cahn and Siegel, 2011)
• Testing by the FDA found tobacco specific nitrosamines and tobacco specific impurities in the unvaporized liquid
"at very low levels," equivalent to the quantity found in FDA -approved nicotine products. (USFDA 2009).
• FDA testing detected a non-toxic amount of diethylene glycol (DEG) at 1% (approximately 0.01 g) in one of 18
cartridges tested. (USFDA 2009).
• The major hazard from DEG occurs following the ingestion of relatively large single doses. The estimated lethal
dose of DEG for humans is approximately 1 ml/kg. (Health Canada, 2010)
• Multiple companies have had their products tested for diethylene glycol and none of the samples have turned up
positive. (Siegel, 2011)
• A puff of e -cigarette mist delivers only 10% of the nicotine delivered by a similar puff of smoke from a
conventional cigarette. (Laugesen, 2009) (Bullen, 2010)
• E -cigarette use mimics smoking; but, there is no combustion and the user inhales vapor, not smoke. (Cahn and
Siegel, 2010)
Do E -cigarettes give off secondhand smoke?
• The e -cigarette generates no side -stream smoke from its artificially lit tip. (Laugesen, 2008)
• After the user inhales, the residual aerosol, or vapor, is exhaled into the surrounding air. (Trtchounian, Williams,
& Talbot, 2010)
• The exhaled vapor of the e -cigarette is composed of propylene glycol, and contains almost no nicotine; and no
carbon monoxide. (Laugesen, 2008)
Is secondhand vapor from e -cigarettes harmful?
• E -cigarette vapor was tested for over 50 cigarette smoke toxicants and none were found. (Laugesen 2009)
• "Lacking any active ingredient or any gaseous products of combustion, the PG mist or `smoke' is not harmful to
bystanders." (Laugesen, 2008)
• Electronic cigarettes tested did not expose users to "measurable levels of nicotine or carbon monoxide, although
both suppressed nicotine/tobacco abstinence symptom ratings." (Eissenberg, 2010)
Are there other facts or concerns about the use of e -cigarettes?
• They are proving acceptable as a complete replacement for smoking for up to 79% of consumers. (Heavner,
Dunworth, Bergen, Nissen, & Phillips, 2008)
• Over 90% of users report that their health has improved. (Heavner, Dunworth, Bergen, Nissen, & Phillips, 2008)
• Smokers with a documented history of recurring relapses were able to quit and to remain abstinent for at least six
months after taking up an e -cigarette. (Polosa, 2011)
• e -Cigarettes can substantially decrease cigarette consumption without causing significant side effects in smokers
not intending to quit. (Polosa, 2011)
• Sales of e -cigarettes to youth should be prohibited in the same manner as all tobacco and nicotine products.
• Surveys of e -cigarette users strongly indicate that the devices do not have a strong appeal for young adults and
youth. High start-up costs and maintenance requirements for e -cigarettes discourage youth from choosing e -
cigarettes over traditional cigarettes. (CASAA, 2010)
• The vast majority of e -cigarette users surveyed are current and former long-time smokers between the ages of 30
to 65. (CASAA, 2010)
• A great number of e -cigarette users report that traditional cigarettes to taste extremely foul after switching to e -
cigarettes, further reducing the urge to return to smoking. This effect would greatly minimize the risk of e -
cigarettes becoming a "gateway product" and initiating youth to smoking traditional cigarettes. (CASAA, 2010)
• E -cigarettes are easily distinguishable from traditional cigarettes. There is no lingering smoke, no unpleasant
odor, no ashes, no embers, no side stream smoke from the tip and no butts. Many e -cigarette brands are available
in colors and shapes which further distinguish them from traditional cigarettes. (CASAA, 2011)
How is the U.S. government responding to the so-called risks involved with e -cigarettes?
• The Hon. Judge Richard J. Leon of the U.S. District Court for the District of Columbia granted an injunction
against FDA seizures of e -cigarette imports. (Leon, 2010)
• Judge Leon stated that the FDA has failed to produce any evidence that the products have harmed anyone.
• The District Court and the U.S. District Court of Appeals stated that the FDA may regulate e -cigarettes under the
Family Smoking Prevention and Tobacco Control Act, but not as drugs or devices under the Food, Drug, and
Cosmetics Act. (Garland, Kavanaugh & Williams, 2010)
• The FDA announced its intention to regulate electronic cigarettes as "tobacco products." (FDA, 2011)
What are the recommendations regarding e -cigarettes and smoke-free policies?
• The Consumer Advocates for Smoke-free Alternatives Association strongly opposes including e -cigarettes in
smoking bans.
Allowing indoor use provides smokers with a powerful incentive to switch to a reduced harm alternative to
smoking. (CASAA, 2010)
Electronic cigarettes, as a tobacco harm reduction product, are supported by the American Association of Public
Health Physicians, the American Council on Science and Health, Smokefree Pennsylvania and tobacco control
researchers such as Dr. Carl Philips, Dr. Brad Rodu and Dr. Michael Siegel.
For more information, contact the Consumer Advocates for Smoke-free Alternatives Association, http://CASAA.or
E -cigarettes and Smoke-free Policies
Bullen, C., McRobbie, H., Thornley, S., Glover, M., Lin, R., & Laugesen, M. (2010). Effect of an electronic nicotine delivery device
(e cigarette) on desire to smoke and withdrawal, user preferences and nicotine delivery: randomised cross-over trial. Tobacco Control.
2010 Apr;19(2):98-103. http://www.ncbi.nlm.nih.gov/pubmed/20378585
Cahn, Z., & Siegel, M. (2010). Electronic cigarettes as a harm reduction strategy for tobacco control: A step forward or a repeat of
past mistakes? Journal of Public Health Policy 32: 16-31. http•//www hsph harvard edu/centers-institutes/population-
development/files/article.iphp.pdf
Consumer Advocates for Smoke-free Alternatives Association (2011) CASAA Position Statement on Electronic Cigarettes.
http://www.casaa.orv,/files/Casaa%20Position%2OStatemepLpdf
Garland, Kavanaugh, & Williams. United States Court of Appeals for the District of Columbia Circuit. Case: 10-5032 Document:
1281606 Filed: 12/07/2010. http://www casaa org/files/ct%20app%20opinion%20on%20iniunction.pdf
Health Canada. (2010). Diethylene glycol; classification with respect to acute toxicity. Date Modified: 2010-09-21.
http•//www he-sc gc ca/ewh-semt/occurtravail/whmis-simdut/ substance/diethylene-eng.php
Heavner, K., Dunworth, J., Bergen, P., Nissen ,C., & Phillips, CV. (20 10) Electronic cigarettes (e -cigarettes) as potential tobacco harm
reduction products: Results of an online survey of e -cigarette users. Tobacco
Harm Reduction 2010 Yearbook, Chapter 19. http://tobaccohamireduction.orv-/thr2O I Oyearbook.html
Laugesen, M. (2008). Safety Report on the Ruyan® e -cigarette Cartridge and Inhaled Aerosol. Health New Zealand.
http://www.healthnz.co.nz/RuyanCartridgeReport30-Oct-Q8.pdf
Laugesen, M. (2009). Ruyan® E -cigarette Bench -top tests. Poster 5-11 at Society for Research on Nicotine and Tobacco (SRNT)
Dublin, Updated 07 May, 2009. http://www.healthnz.co.nz/DublinEcigBenchtopHandout.Rdf
Leon, RJ. United States District Court for the District of Columbia. Order, Civil Case No. 09-771 (RJL). Filed 01/14/2010.
http://www.casaa.org/files/SE-vs-FDA-RuliDg.pdf
Siegel, M. Letter to Members of the Health Committee of the New York State Assembly regarding Assembly Bill A01468
(01/23/2011). htti)://www.casaa.org/files/MSietel-NYA01468%201etter.doc
Trtchounian A., Williams M., & Talbot, P. (July 19, 20 10) Conventional and electronic cigarettes (e-ciagrettes) have different
smoking characteristics. Nicotine & Tobacco Research Advance Access. Doi: 10.1093/ntr/ntg114
U.S. Food and Drug Administration. (5/4//09). Final Report: Evaluation of e -cigarettes.
htti)://www.fda.gov/downloads/Drujzs/ScienceResearch/UCM I73250.pdf
Polosa, R., Caponnetto,P., Russo, C., Leotta, C., Campagna, D., Successful smoking cessation with electronic cigarettes in smokers
with a documented history of recurring relapses: a case series Journal of Medical Case Reports 2011, 5:585 doi: 10. 1186/1752-1947-5-
585 http•//wwwnedicalcasereports coin/content/pdf/1752-1947-5-585.pdf
Andrea R. Vansickel, Caroline O. Cobb, Michael F. Weaver, and Thomas E. Eissenberg, A Clinical Laboratory Model for Evaluating
the Acute Effects of Electronic "Cigarettes": Nicotine Delivery Profile and Cardiovascular and Subjective Effects,
http://www casaa org/files/Virg=iania%20Commonwealth%20University%20Study.pdf
Riccardo Polosa, Pasquale Caponnetto, Jaymin B Morjaria, Gabriella Papale, Davide Campagna and Cristina Russo, Effect of an
electronic nicotine delivery device (e -Cigarette) on smoking reduction and cessation: a prospective 6 -month pilot study,
httD://www.biomedcentral.com/1471-2458/11/786
For more information, contact the Consumer Advocates for Smoke-free Alternatives Association, http://CASAA.M
Burstyn BMC Public Health 2014, 14:18
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Public Health
RESEARCH ARTICLE Open Access
Peering through the mist: systematic review of
what the chemistry of contaminants in electronic
cigarettes tells us about health risks
Igor Burstyn
Abstract
Background: Electronic cigarettes (e -cigarettes) are generally recognized as a safer alternative to combusted
tobacco products, but there are conflicting claims about the degree to which these products warrant concern for
the health of the vapers (e -cigarette users). This paper reviews available data on chemistry of aerosols and liquids of
electronic cigarettes and compares modeled exposure of vapers with occupational safety standards.
Methods: Both peer-reviewed and "grey" literature were accessed and more than 9,000 observations of highly
variable quality were extracted. Comparisons to the most universally recognized workplace exposure standards,
Threshold Limit Values (TL.Vs), were conducted under "worst case" assumptions about both chemical content of
aerosol and liquids as well as behavior of vapers.
Results: 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. The vast majority of
predicted exposures are < <1% of -fLV. Predicted exposures to acrolein and formaldehyde are typically <5% TLV.
Considering exposure to the aerosol as a mixture of contaminants did not indicate that exceeding half of TLV for
mixtures was plausible. Only exposures to the declared major ingredients — propylene glycol and glycerin — warrant
attention because of precautionary nature of TLVs for exposures to hydrocarbons with no established toxicity.
Conclusions: 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.
Keywords: Vaping, e -cigarettes, Tobacco harm reduction, Risk assessment, Aerosol, Occupational exposure limit
Background
Electronic cigarettes (also known as e -cigarettes) are
generally recognized as a safer alternative to combusted
tobacco products (reviewed in [11), but there are con-
flicting claims about the degree to which these products
warrant concern for the health of the vapers (e -cigarette
users). A vaper inhales aerosol generated during heating
Correspondence: igor.burstyn@drexel.edu
Department of Environmental and Occupational Health, School of Public
Health, Drexel University, Nesbitt Hall, 3215 Market St. Floor 6, Office 614,
Philadelphia, PA 19104, USA
of liquid contained in the e -cigarette. The technology
and patterns of use are summarized by Etter [1], though
there is doubt about how current, complete and accurate
this information is. Rather conclusive evidence has been
amassed to date on comparison of the chemistry of aero-
sol generated by electronic cigarettes to cigarette smoke
[2-8]. However, it is meaningful to consider the question
of whether aerosol generated by electronic cigarettes
would warrant health concerns on its own, in part because
vapers will include persons who would not have been
smokers and for whom the question of harm reduction
,0 2014 Bu sNn; lice. s,e P (Wed C entral Ltd I his is an open access i cie dlstriouted under the term of he Cren ve
BiolVW Central t ornmons At button cense (h•ip //cre.ativecommons o d/licenses/by 2.0), which oermtn unrestrcted use, dist jbu-ion, and
,eproduct on n any n d um, prodded the o,ginal wo h is oroperi; o;ed-
Burstyn BMC Public Health 2014, 14:18
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from smoking is therefore not relevant, and perhaps more
importantly, simply because there is value in minimizing
the harm of those practicing harm reduction.
One way of approaching risk evaluation in this setting
is to rely on the practice, common in occupational hy-
giene, of relating the chemistry of industrial processes
and the emissions they generate to the potential worst
case of personal exposure and then drawing conclusions
about whether there would be interventions in an occu-
pational setting based on comparison to occupational
exposure limits, which are designed to ensure safety of
unintentionally exposed individuals. In that context, ex-
posed individuals are assumed to be adults, and this
assumption appears to be suitable for the intended con-
sumers of electronic cigarettes. "Worst case" refers to
the maximum personal exposure that can be achieved
given what is known about the process that generates
contaminated atmosphere (in the context of airborne
exposure considered here) and the pattern of interaction
with the contaminated atmosphere. It must be noted
that harm reduction notions are embedded in this ap-
proach since it recognizes that while elimination of the
exposure may be both impossible and undesirable, there
nonetheless exists a level of exposure that is associated
with negligible risks. To date, a comprehensive review
of the chemistry of electronic cigarettes and the aerosols
they generate has not been conducted, depriving the
public of the important element of a risk -assessment
process that is mandatory for environmental and occu-
pational health policy-making.
The present work considers both the contaminants
present in liquids and aerosols as well as the declared in-
gredients in the liquids. The distinction between exposure
to declared ingredients and contaminants of a consumer
product is important in the context of comparison to oc-
cupational or environmental exposure standards. Occupa-
tional exposure limits are developed for unintentional
exposures that a person does not elect to experience. For
example, being a bread baker is a choice that does not in-
volve election to be exposed to substances that cause
asthma that are part of the flour dust (most commonly,
wheat antigens and fungal enzymes). Therefore, suitable
occupational exposure limits are created to attempt to
protect individuals from such risk on the job, with no pre-
sumption of "assumed risk" inherent in the occupation.
Likewise, special regulations are in effect to protect per-
sons from unintentional exposure to nicotine in work-
places (http://www.cdc.gov/niosh/docs/81-123/pdfs/0446.
pdf, accessed July 12, 2013), because in environments
where such exposures are possible, it is reasonable to pro-
tect individuals who do not wish to experience its effects.
In other words, occupational exposure limits are based on
protecting people from involuntary and unwanted expo-
sures, and thus can be seen as more stringent than the
Page 2 of 14
standards that might be used for hazards that people
intentionally choose to accept.
By contrast, a person who elects to lawfully consume
a substance is subject to different risk tolerance, as is
demonstrated in the case of nicotine by the fact that
legally sold cigarettes deliver doses of nicotine that ex-
ceed occupational exposure limits [9]: daily intake of
20 mg of nicotine, assuming nearly 100% absorption in
the lungs and inhalation of 4 m3 of air, corresponds to
roughly 10 times the occupational exposure limit of
0.5 mg/m3 atmosphere over 8 hours [10]. Thus, whereas
there is a clear case for applicability of occupational ex-
posure limits to contaminants in a consumer product
(e.g. aerosol of electronic cigarettes), there is no corre-
sponding case for applying occupational exposure limits
to declared ingredients desired by the consumer in a
lawful product (e.g. nicotine in the aerosol of an elec-
tronic cigarette). Clearly, some limits must be set for
voluntary exposure to compounds that are known to be
a danger at plausible doses (e.g. limits on blood alcohol
level while driving), but the regulatory framework should
reflect whether the dosage is intentionally determined and
whether the risk is assumed by the consumer. In the case
of nicotine in electronic cigarettes, if the main reason the
products are consumed is as an alternative source of nico-
tine compared to smoking, then the only relevant question
is whether undesirable exposures that accompany nicotine
present health risks, and the analogy with occupational
exposures holds. In such cases it appears permissible to
allow at least as much exposure to nicotine as from
smoking before admitting to existence of new risk. It is
expected that nicotine dosage will not increase in
switching from smoking to electronic cigarettes because
there is good evidence that consumers adjust consump-
tion to obtain their desired or usual dose of nicotine
[11]. The situation is different for the vapers who want
to use electronic cigarettes without nicotine and who
would otherwise not have consumed nicotine. For these
individuals, it is defensible to consider total exposure,
including that from any nicotine contamination, in
comparison to occupational exposure limits. In consid-
eration of vapers who would never have smoked or
would have quit entirely, it must be remembered that
the exposure is still voluntary and intentional, and com-
parison to occupational exposure limits is legitimate
only for those compounds that the consumer does not
elect to inhale.
The specific aims of this review were to:
1. Synthesize evidence on the chemistry of liquids and
aerosols of electronic cigarettes, with particular
emphasis on the contaminants.
2. Evaluate the quality of research on the chemistry of
liquids and aerosols produced by electronic cigarettes.
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3. Estimate potential exposures from aerosols produced
by electronic cigarettes and compare those potential
exposures to occupational exposure standards.
Methods
Literature search
Articles published in peer-reviewed journals were re-
trieved from PubMed (http://www.ncbi.nlm.nih.gov/
pubmed/) available as of July 2013 using combinations
of the following keywords: "electronic cigarettes", "e -ciga-
rettes", "smoking alternatives", "chemicals", "risks", "elec-
tronic cigarette vapor", "aerosol", "ingredients", "e -cigarette
liquid", "e-cig composition", "e-cig chemicals", "e-cig chem-
ical composition", "e -juice electronic cigarette", "electronic
cigarette gas", "electronic cigars". In addition, references of
the retrieved articles were examined to identify further
relevant articles, with particular attention paid to non -peer
reviewed reports and conference presentations. Unpub-
lished results obtained through personal communications
were also reviewed. The Consumer Advocates for Smoke-
free Alternatives Association (CASAA) was asked to re-
view the retrieved bibliography to identify any reports or
articles that were missed. The papers and reports were
retained for analysis if they reported on the chemistry of e -
cigarette liquids or aerosols. No explicit quality control cri-
teria were applied in selection of literature for examination,
except that secondary reporting of analytical results was
not used. Where substantial methodological problems that
precluded interpretation of analytical results were noted,
these are described below. For each article that contained
relevant analytical results, the compounds quantified,
limits of detection, and analytical results were summarized
in a spreadsheet. Wherever possible, individual analyt-
ical results (rather than averages) were recorded (see
Additional file 1). Data contained in Additional file 1 is
not fully summarized in the current report but can be
used to investigate a variety of specific questions that
may interest the reader. Each entry in Additional file 1
is identified by a Reference Manage ID that is linked to
source materials in a list in Additional file 2 (linked via
ReflD); copies of all original materials can be requested.
Comparison of observed concentrations in aerosol to
occupational exposure limits
For articles that reported mass or concentration of specific
compounds in the aerosol (generated by smoking ma-
chines or from volunteer vapers), measurements of com-
pounds were converted to concentrations in the "personal
breathing zone",' which can be compared to occupational
exposure limits (OELs). The 2013 Threshold Limit Values
(TLVs) [10] were used as OELs because they are the most
up to date and are most widely recognized internationally
when local jurisdictions do not establish their own regula-
tions (see http://www.ilo.org/safework/info/publications/
Page 3 of 14
WCMS_113329/lang—en/index.htm; accessed July 3, 2013).
TLVs are more protective that of US Occupation Safety
and Health Administration's Permissible Exposure Limits
because TLVs are much more often updated with current
knowledge. However, all OELs generally agree with each
other because they are based on the same body of know-
ledge. TLVs (and all other OELs) aim to define environ-
mental conditions to which nearly all persons can be
exposed to all day over many years without experiencing
adverse health effects. Whenever there was an uncertainty
in how to perform the calculation, a "worst case" scenario
was used, as is the standard practice in occupational hy-
giene, where the initial aim is to recognize potential for
hazardous exposures and to err on the side of caution.
The following assumptions were made to enable the cal-
culations that approximate the worst-case personal expos-
ure of a vaper (Equation 1):
1. Air the vaper breathes consists of a small volume of
aerosol generated by e -cigarettes that contains a
specific chemical plus pristine air;
2. The volume of aerosols inhaled from e -cigarettes is
small compared to total volume of air inhaled;
3. The period of exposure to the aerosol considered was
8 hours for comparability to the standard working
shift for which TLVs were developed (this does not
mean only 8 hours worth of vaping was considered
but, rather, a day's worth of exposure was modeled as
being concentrated into just 8 hours);
4. Consumption of 150 puffs in 8 hours (an upper
estimate based on a rough estimate of 150 puffs by a
typical vaper in a day [1]) was assumed. (Note that if
vaping over 16 hours "day" was considered then air
into which contaminants from vaping are diluted
into would have to increase by a factor of 2, thereby
lowering estimated exposure; thus, the adopted
approach is entirely still in line with "worst case"
assessment);
5. Breathing rate is 8 liters per minute [12,13];
6. Each puff contains the same quantity of compounds
studied.
[mg/m3] = mg/puff x puffs/ (8 hr day)
X 1/ (m3 air inhaled in 8 hr)
(1)
The only exception to this methodology was when
assessing a study of aerosol emitted by 5 vapers in a 60 m`;
room over 5 hours that seemed to be a sufficient approxi-
mation of worst-case "bystander" exposure [6]. All calcu-
lated concentrations were expressed as the most stringent
(lowest) TI.V for a specific compound (i.e. assuming the
most toxic form if analytical report is ambiguous) and
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expressed as "percent of TLV. Considering that all the
above calculations are approximate and reflecting that
exposures in occupational and general environment can
easily vary by a factor of 10 around the mean, we added a
1.0 -fold safety factor to the "percent of TLV calculation.
This safety factor accounts for considerable uncertainty
about the actual number and volume of puffs since the
number of puffs is hard to estimate accurately with re-
ports as high as 700 puffs per day [14]. Details of all
calculations are provided in an Excel spreadsheet (see
Additional file 3).
No systematic attempt was made to convert the con-
tent of the studied liquids into potential exposures be-
cause sufficient information was available on the
chemistry of aerosols to use those studies rather than
making the necessary simplifying assumptions to do the
conversion. However, where such calculations were per-
formed in the original research, the following approach
was used: under the (probably false — see the literature
on formation of carbonyl compounds below) assumption
of no chemical reaction to generate novel ingredients,
composition of liquids can be used to estimate potential
for exposure if it can be established how much volume
of liquid is consumed in given 8 hours, following an al-
gorithm analogous to the one described above for the
aerosols (Equation 2):
[mg/m3] = mg/(mL liquid) x(ml, liquid)/puff
xpuffs/ (8 hr day)
x 1/ (m3 air inhaled in 8 hr)
(2)
Comparison to cigarette smoke was not performed
here because the fact that e -cigarette aerosol is at least
orders of magnitude less contaminated by toxic com-
pounds is uncontroversial [2-8].
The study adhered to the PRISMA guidelines for sys-
tematic reviews (http://www.prisina-statemeiit.org/).
Results and discussion
General comments on methods
In excess of 9,000 determinations of single chemicals
(and rarely, mixtures) were reported in reviewed articles
and reports, typically with multiple compounds per elec-
tronic cigarette tested [2-8,15-43]. Although the quality
of reports is highly variable, if one assumes that each re-
port contains some information, this asserts that quite a
bit is known about composition of e -cigarette liquids
and aerosols. The only report that was excluded from
consideration was work of McAuley et al. [24] because
of clear evidence of cross -contamination — admitted to
by the authors — with cigarette smoke and, possibly,
reagents. The results pertaining to non -detection of
tobacco -specific nitrosamines (TSNAs) are potentially
Page 4 of 14
trustworthy, but those related to polycyclic aromatic hy-
drocarbons (PAH) are not since it is incredible that
cigarette smoke would contain fewer PAHs, which arise
from incomplete combustion of organic matter, than
aerosol of e -cigarettes that do not burn organic matter
[24]. In fairness to the authors of that study, similar
problems may have occurred in other studies but were
simply not reported, but it is impossible to include a
paper in a review once it is known for certain that its
quantitative results are not trustworthy. When in doubt,
we erred on the side of trusting that proper quality con-
trols were in place, a practice that is likely to increase
appearance of atypical or erroneous results in this re-
view. From this perspective, assessment of concordance
among independent reports gains higher importance
than usual since it is unlikely that two experiments would
be flawed in the same exact manner (though of course this
cannot be assured).
It was judged that the simplest form of publication
bias — disappearance of an entire formal study from the
available literature — was unlikely given the exhaustive
search strategy and the contested nature of the research
question. It is clearly the case that only a portion of all
industry technical reports were available for public ac-
cess, so it is possible that those with more problematic
results were systematically suppressed, though there is
no evidence to support this speculation. No formal
attempt was made to ascertain publication bias in situ
though it is apparent that anomalous results do gain
prominence in typical reviews of the literature: diethyl-
ene glycol [44,45] detected at non -dangerous levels (see
details below) in one test of 18 of early -technology prod-
ucts by the US Food and Drugs Administration (FDA)
[23] and one outlier in measurement of formaldehyde
content of exhaled air [4] and aldehydes in aerosol gen-
erated from one e -cigarette in Japan [38]. It must be
emphasized that the alarmist report of aldehydes in ex-
periments presented in [38] is based on the concentra-
tion in generated aerosol rather than air inhaled by the
vaper over prolonged period of time (since vapers do
not inhale only aerosol). Thus, results reported in [38]
cannot be the basis of any claims about health risk, a
fallacy committed both by the authors themselves and
commentators on this work [45].
It was also unclear from [38] what the volume of aero-
sol sampled was — a critical item for extrapolating to
personal exposure and a common point of ambiguity in
the published reports. However, in a personal exchange
with the authors of [38] [July 11, 20131, it was clarified
that the sampling pump drew air at 500 mL/min through
e -cigarette for 10 min, allowing more appropriate calcula-
tions for estimation of health risk that are presented below.
Such misleading reporting is common in the field that con-
fuses concentration in the aerosol (typically measured
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directly) with concentration in the air inhaled by the vaper
(never determined directly and currently requiring add-
itional assumptions and modeling). This is important
because the volume of aerosol inhaled (maximum
—8 L/day) is small compared to the volume of air inhaled
daily (8 L/min); this point is illustrated in the Figure 1.
A similar but more extreme consideration applies to
the exposure of bystanders which is almost certainly
several orders of magnitude lower than the exposure of
vapers. In part this is due to the absorption, rather than
exhalation, of a portion of the aerosol by the vapers: there
is no equivalent to the "side -stream" component of expos-
ure to conventional cigarettes, so all of the exposure to a
bystander results from exhalation. Furthermore, any envir-
onmental contamination that results from exhalation of
aerosol by vaper will be diluted into the air prior to enter-
ing a bystander's personal breathing zone. Lastly, the
number of puffs that affect exposure to bystander is likely
to be much smaller than that of a vaper unless we are to
assume that vaper and bystander are inseparable.
It is unhelpful to report the results in cigarette -
equivalents in assessments that are not about cigarette
exposure, as in [43], because this does not enable one to
estimate exposures of vapers. To be useful for risk as-
sessment, the results on the chemistry of the aerosols
and liquids must be reported in a form that enables the
calculations in Equations 1 and 2. It must be also be
noted that typical investigations consisted of qualitative
and quantitative phases such that quantitative data is
available mostly on compounds that passed the qualita-
tive screen. In the qualitative phase, presence of the
Page 5 of 14
compounds above a certain limit of detection is deter-
mined. In the quantitative phase, the amount of only the
compounds that are detected in the qualitative phase is es-
timated. This biased all reports on concentration of com-
pounds towards both higher levels and chemicals which a
particular lab was most adept at analyzing.
Declared Ingredients: comparison to occupational
exposure limits
Propylene glycol and glycerin
Propylene glycol and glycerin have the default or pre-
cautionary 8 -hour TLV of 10 mg/m3 set for all organic
mists with no specific exposure limits or identified
toxicity (http://www.osha.gov/dts/chemicalsampling/data/
CH_243600.html; accessed July 5, 2013). These interim
TLVs tend to err on the side of being too high and are typ-
ically lowered if evidence of harm to health accumulates.
For example, in a study that related exposure of theatrical
fogs (containing propylene glycol) to respiratory symp-
toms [46], "mean personal inhalable aerosol concentra-
tions were 0.70 mg/m3 (range 0.02 to 4.1)" [47]. The only
available estimate of propylene concentration of propylene
glycol in the aerosol indicates personal exposure on the
order of 3-4 mg/m3 in the personal breathing zone over 8
hours (under the assumptions we made for all other com-
parisons to TI Vs) [2]. The latest (2006) review of risks of
occupational exposure to propylene glycol performed by
the Health Council of the Netherlands (known for OELs
that are the most protective that evidence supports and
based exclusively on scientific considerations rather
than also accounting for feasibility as is the case for the
A B
Figure 1 Illustrating the difference between concentrations in the aerosol generated by vaping and inhaled air in a day. Panel A shows
a black square that represents aerosol contaminated by some compound as it would be measured by a "smoking machine" and extrapolated to
dosage from vaping in one day. This black square is located inside the white square that represents total uncontaminated air that is inhaled in a
day by a vaper. The relative sizes of the two squares are exaggerated as the volume of aerosol generated in vaping relative to inhaled air is much
smaller than is illustrated in the figure. Panel 8 shows how exposure from contaminated air (black dots) is diluted over a day for appropriate
comparison to occupational exposure limits that are expressed in terms of "time -weighted average" or average contamination over tirne rather
than as instantaneous exposures. Exposure during vaping occurs in a dynamic process where the atmosphere inhaled by the vaper alternates
between the smaller black and larger white squares in Panel A. Thus, the concentration of contaminants that a vaper is exposed to over a day is
much smaller than that which is rneasured in the aerosol (and routinely improperly cited as reason for concern about "high" exposures).
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TLVs) recommended exposure limit of 50 mg/m3 over
8 hours; concern over short-term respiratory effects
was noted [http://www.gezondheidsraad.nl/sites/default/
ffles/200702OSH.pdf; accessed July 29, 2013]. Assuming
extreme consumption of the liquid per day via vaping (5
to 25 ml/day and 50-95% propylene glycol in the liquid),b
levels of propylene glycol in inhaled air can reach 1-6 mg/
in . It has been suggested that propylene glycol is very
rapidly absorbed during inhalation [4,6] making the calcu-
lation under worst case scenario of all propylene glycol be-
coming available for inhalation credible. It must also be
noted that when consuming low -nicotine or nicotine -free
liquids, the chance to consume larger volumes of liquid
increases (large volumes are needed to reach the target
dose or there is no nicotine feedback), leading to the
upper end of propylene glycol and glycerin exposure.
Thus, estimated levels of exposure to propylene glycol and
glycerin are close enough to TLV to warrant concern.
However, it is also important to consider that propylene
glycol is certainly not all absorbed because visible aerosol
is exhaled in typical vaping. Therefore, the current calcula-
tion is in the spirit of a worst case assumption that is
adopted throughout the paper.
Nicotine
Nicotine is present in most e -cigarette liquids and has TLV
of 0.5 mg/m3 for average exposure intensity over 8 hours.
If approximately 4 m3 of air is inhaled in 8 hours, the con-
sumption of 2 mg nicotine from e -cigarettes in 8 hours
would place the vapor at the occupational exposure limit.
For a liquid that contains 18 mg nicotine/ml, TLV would
be reached upon vaping —0.1-0.2 ml of liquid in a day, and
so is achieved for most anyone vaping nicotine -containing
e -cigarettes [1]. Results presented in [25] on 16 e -cigarettes
also argue in favor of exceedance of TLV from most any
nicotine -containing e -cigarette, as they predict >2 mg of
nicotine released to aerosol in 150 puffs (daily consump-
tion figure adopted in this report). But as noted above,
since delivery of nicotine is the purpose of nicotine -
containing e -cigarettes, the comparison to limits on unin-
tended, unwanted exposures does not suggest a problem
and serves merely to offer complete context. If nicotine is
present but the liquid is labeled as zero -nicotine [25,44], it
could be treated as a contaminant, with the vaper not
intending to consume nicotine and the TLV, which would
be most likely exceeded, is relevant. However, when nico-
tine content is disclosed, even if inaccurately, then com-
parison to TLV is not valid. Accuracy in nicotine content is
a concern with respect to truth in advertising rather than
unintentional exposure, due to presumed (though not yet
tested) self-regulation of consumption by persons who use
e -cigarettes as a source of nicotine.
Overall, the declared ingredients in the liquid would
warrant a concern by standards used in occupational
Page 6 of 14
hygiene, provided that comparison to occupational ex-
posure limits is valid, as discussed in the introduction.
However, this is not to say that the exposure is affirma-
tively believed to be harmful; as noted, the TLVs for pro-
pylene glycol and glycerin mists is based on uncertainty
rather than knowledge. These TLVs are not derived from
knowledge of toxicity of propylene glycol and glycerin
mists, but merely apply to any compound of no known
toxicity present in workplace atmosphere. This aspect of
the exposure from e -cigarettes simply has little prece-
dent (but see study of theatrical fogs below). Therefore,
the exposure will provide the first substantial collection
evidence about the effects, which calls for monitoring of
both exposure levels and outcomes, even though there
are currently no grounds to be concerned about the im-
mediate or chronic health effects of the exposure. The
argument about nicotine is presented here for the sake
of completeness and consistency of comparison to TLVs,
but in itself does not affect the conclusions of this analysis
because it should not be modeled as if it were a contamin-
ant when declared as an ingredient in the liquid.
Contaminants
Polycyclic aromatic hydrocarbons
Polycyclic aromatic hydrocarbons (PAH) were quantified
in several reports in aerosols [5,6,43] and liquids [7,19,42].
These compounds include well-known carcinogens, the
levels of which are not subject to TLV but are instead to
be kept "as low as reasonably achievable" [10]. For PAH,
only non -carcinogenic pyrene that is abundant in the
general environment was detected at 36 ng/cartridge in 5
samples of liquid [7]; PAHs were not detected in most of
the analyses of aerosols, except for chrysene in the analysis
of the aerosol of one e -cigarette [43].
Tobacco -specific nitrosamines
The same risk assessment considerations that exist for
PAH also hold for carcinogenic tobacco -specific nitrosa-
mines (TSNAs) [48] for which no occupational exposure
limits exist because (a) these exposures do not appear to
occur in occupational settings often enough to warrant
development of TLVs, and (b) it is currently accepted in
establishing TLVs that carcinogens do not have minimal
thresholds of toxicity. As expected, because the TSNAs
are contaminants of nicotine from tobacco leaf, there is
also evidence of association between nicotine content of
the liquid and TSNA concentrations, with reported con-
centrations <5 ng/cartridge tested [7]. Smaller studies of
TSNA content in liquids are variable, with some not
reporting any detectable levels [18,33,35] and others
clearly identifying these compounds in the liquids when
controlling for background contamination (n = 9) [23].
Analyses of aerosols indicate that TSNAs are present in
amounts that can results in doses of < ng/day [5,33] to
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µg/day [8] (assuming 150 puffs/day) (see also [43]). The
most comprehensive survey of TSNA content of 105 sam-
ples of liquids from 11 manufactures indicates that almost
all tested liquids (>90%) contained TSNAs in pg/L quan-
tities [36]. This is roughly equivalent to 1/1.000 of the
concentration of TSNAs in modern smokeless tobacco
products (like snus), which are in the ppm range [48]. For
example, 10 pg/L (0.01 ppm) of total TSNA in liquid [36]
can translate to a daily dose of 0.025-0.05 pg from vap-
ing (worst case assumption of 5 ml liquid/day); if 15 g of
snus is consumed a day [49] with 1 ppm of TSNAs [48]
and half of it were absorbed, then the daily dose is esti-
mated to be 7.5 µg, which is 150-300 times that due to
the worst case of exposure from vaping. Various assump-
tions about absorption of TSNAs alter the result of this
calculation by a factor that is dwarfed in magnitude com-
pared to that arising from differences considered above.
This is reassuring because smokeless tobacco products,
such as snus, pose negligible cancer risk [50], certainly
orders of magnitude smaller than smoking (if one con-
siders the chemistry of the products alone). In general, it
appears that the cautious approach in face of variability
and paucity of data is to seek better understanding of the
predictors of presence of TSNA in liquids and aerosols
so that measures for minimizing exposure to TSNAs
from aerosols can be devised. This can include consider-
ing better control by manufactures who extract the nico-
tine frorn tobacco leaf.
Volatile organic compounds
Total volatile organic compounds (VOC) were deter-
mined in aerosol to be non-detectable [3] except in one
sample that appeared to barely exceed the background
concentration of 1 mg/M3 by 0.73 mg/m3 [6]. These re-
sults are corroborated by analyses of liquids [19] and
most likely testify to insensitivity of employed analytic
methods for total VOC for characterizing aerosol gener-
ated by e -cigarettes, because there is ample evidence that
specific VOC are present in the liquids and aerosols.`
Information on specific commonly detected VOC in the
aerosol is given in Table 1. It must be observed that
these reported concentrations are for analyses that first
observed qualitative evidence of the presence of a given
VOC and thus represent worst case scenarios of expos-
ure when VOC is present (i.e. zero -level exposures are
missing from the overall summary of worst case expo-
sures presented here). For most VOC and aldehydes,
one can predict the concentration in air inhaled by a
vaper to be < <1% of TLV. The only exceptions to this
generalization are:
(a) acrolein: —1% of TLV (average of 12 measurements)
[40] and measurements at a mean of 2% of TLV
(average of 150 measurements) [41] and
Page 7 of 14
(b) formaldehyde: between 0 and 3% of TLV based on
18 tests (average of 12 measurements at 2% of
TLV, the most reliable test) [40] and an average of
150 results at 4% of TLV [41].
Levels of acrolein in exhaled aerosol reported in [6]
were below 0.0016 mg/m`i and correspond to predicted
exposure of <1% of TLV (Table 2). It must re-emphasized
that all calculations based on one electronic cigarette ana-
lyzed in [38] are best treated as qualitative in nature (i.e.
indicating presence of a compound without any particular
meaning attached to the reported level with respect to
typical levels) due to great uncertainty about whether the
manner in which the e -cigarette was operated could have
resulted in overheating that led to generation of acrolein
in the aerosol. In fact, a presentation made by the author
of [38] clearly stated that the "atomizer, generating high
concentration carbonyls, had been burned black" [40,41].
In unpublished work, [40] there are individual values of
formaldehyde, acrolein and glyoxal that approach TLV,
but it is uncertain how typical these are because there is
reason to believe the liquid was overheated; considerable
variability among brands of electronic cigarettes was also
noted. Formaldehyde and other aldehydes, but not acro-
lein, were detected in the analysis one e -cigarette [43].
'.I'he overwhelming majority of the exposure to specific
VOC that are predicted to result from inhalation of the
aerosols lie far below action level of 50% of TLV at which
exposure has to be mitigated according to current code of
best practice in occupational hygiene [51].
Finding of an unusually high level of formaldehyde by
Schripp et al. [4] — 0.5 ppm predicted vs. 15 -minute TLV
of 0.3 ppm (not given in Table 2) — is clearly attributable
to endogenous production of formaldehyde by the volun-
teer smoker who was consuming e -cigarettes in the ex-
perimental chamber, since there was evidence of build-up
of formaldehyde prior to vaping and liquids used in the
experiments did not generate aerosol with detectable for-
maldehyde. This places generalizability of other findings
from [4] in doubt, especially given that the only other
study of exhaled air by vapers who were not current
smokers reports much lower concentrations for the same
compounds [6] (Table 2). It should be noted that the re-
port by Romagna et al. [6] employed more robust meth-
odology, using 5 volunteer vapers (no smokers) over an
extended period of time. Except for benzene, acetic acid
and isoprene, all calculated concentrations for detected
VOC were much below 1% of TLV in exhaled air [6]. In
summary, these results do not indicate that VOC gener-
ated by vaping are of concern by standards used in occu-
pational hygiene.
Diethylene glycol and ethylene glycol became a con-
cern following the report of their detection by FDA [44],
but these compounds are not detected in the majority of
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Page 8 of 14
Table 1 Exposure predictions based on analysis of aerosols generated by smoking machines: volatile organic
compounds
Compound N# Estimated concentration in personal Ratio of most stringent TLV (%) Reference
breathing zone
PPM mg/m3 Calculated directly Safety factor 10
Acetaldehyde
1
0.005
0.02
0.2
[51
3
0.003
0.01
0.1
[41
12
0.001
0.004
0.04
181
1
0.00004
0.0001
0.001
[31
1
0.0002
0.001
0.008
[31
150
0.001
0.004
0.04
[40,411
1
0.008
0.03
3
[ 381
Acetone
1
0.002
0.0003
0.003
[381
150
0.0004
0.0001
0.001
[40,411
Acrolein
12
0.001
1
13
181
150
0.002
2
20
[40,411
1
0.006
6
60
[381
Butanal
150
0.0002
0.001
0.01
[40,411
Crotonaldehyde
150
0.0004
0.01
0.1
[40,411
Formaldehyde
1
0.002
0.6
6
151
3
0.008
3
30
[41
12
0.006
2
20
181
1
<0.0003
<0.1
<1
[31
1
0.0003
0.1
1
[31
150
0.01
4
40
[40,411
1
0.009
3
30
[381
Glyoxal
1
0.002
2
20
[381
150
0.006
6
60
[40,411
o-Methylbenzaldehyde
12
0.001
0.05
0.5
181
p,m-Xylene
12
0.00003
0.001
0.01
[81
Propanal
3
0.002
0.01
0.1
141
150
0.0006
0.002
0.02
[40,411
1
0.005
0.02
0.2
[381
Toluene
12
0.0001
0.003
0.03
181
Valeraldehyde
150
0.0001
0.0001
0.001
[40,411
"Average is presented when N> 1
tests performed to date [3,1.5,17,19,23]. Ten batches of
the liquid tested by their manufacture did not report any
diethylene glycol above 0.05% of the liquid [42]. Methods
used to detect diethylene glycol appear to be adequate to
be informative and capable of detecting the compound in
quantities < <1% of TLV [15,17,23]. Comparison to TLV is
based on a worst case calculation analogous to the one
performed for propylene glycol. For diethylene glycol,
TLV of 10 mg/m3 is applicable (as in the case of all
aerosols with no know toxicity by inhalation), and there
is a recent review of regulations of this compound con-
ducted for the Dutch government by the Health Council
of the Netherlands (jurisdiction with some of the most
strict occupational exposure limits) that recommended
OEL of 70 mg/m3 and noted lack of evidence for tox-
icity following inhalation [littp://www.gezondheidsraad.
nt/sites/default/files/200703OSH.pdf; accessed July 29;
2013]. In conclusion, even the quantities detected in the
single FDA result were of little concern, amounting to
less than 1% of TLV.
Inorganic compounds
Special attention has to be paid to the chemical form of
compounds when there is detection of metals and other
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Table 2 Exposure predictions for volatile organic compounds based on analysis of aerosols generated by volunteer
vapers _
Compound N" Estimated concentration in _ Ratio of most stringent TLV (%) Reference
personal breathing zone (ppm) Calculated directly safety factor 10
2-butanone (MEK)
3
0.04
0.0007
1
0.002
2-furaldehyde
3
0.01
Acetaldehyde
3
0.07
Acetic acid
3
0.3
Acetone
3
0.4
Acrolein
1
<0.001
Benzene
3
0.02
Butyl hydroxyl toluene
1
4E-05
Isoprene
3
0.1
Limonene
3
0.009
0.000001
1
2E-05
m,p-Xyelen
3
0.01
Phenol
3
0.01
Propanal
3
0.004
Toluene
3
...
0.01
"Average is presented when
N > 1.
elements by inductively coupled plasma mass spectrom-
etry (ICP -MS) [8,26]. Because the parent molecule that
occurs in the aerosol is destroyed in such analysis, the
results can be misleading and not interpretable for risk as-
sessment. For example, the presence of sodium (4.18 µg/
10 puffs) [26] does not mean that highly reactive and toxic
sodium metal is in the aerosol, which would be impossible
given its reactivity, but most likely means the presence of
the ubiquitous compound that contains sodium, dissolved
table salt (NaCl). If so, the corresponding daily dose of
NaCl that arises from these concentrations from 150 puffs
is about 10,000 times lower than allowable daily intake ac-
cording to CDC (http://www.cdc.gov/features/dssodium/;
accessed July 4, 2013). Likewise, a result for presence of
silica is meaningless for health assessment unless the crys-
talline form of SiO-, is known to be present. When such
ambiguity exists, a TLV equivalence calculation was not
performed. We compared concentrations to TLVs when it
was even remotely plausible that parent molecules were
present in the aqueous solution. However, even these are
to be given credence only in an extremely pessimistic ana-
lyst, and further investigation by more appropriate analyt-
ical methods could clarify exactly what compounds are
present, but is not a priority for risk assessment.
It should also be noted that one study that attempted
to quantify metals in the liquid found none above 0.1-
0.2 ppm levels [7] or above unspecified threshold [19].
Table 3 indicates that most metals that were detected
were present at <1% of TLV even if we assume that the
0.02
0.2
L41
0.0007
0.007
[61
0.7
7
[41
0.3
3
[41
3
30
[41
0.2
2
[4]
<0.7
<7
[61
3
33
[41
0.0002
0.002
[61
7
70
[ 41
0.03
0.3
141
0.000001
0.00001
[61
0.01
0.1
[41
0.3
3
[41
0.01
0.1
[41
0.07
0.7
N
analytical results imply the presence of the most hazard-
ous molecules containing these elements that can occur
in aqueous solution. For example, when elemental chro-
mium was measured, it is compared to TLV for insoluble
chromium IV that has the lowest TLV of all chromium
compounds. Analyses of metals given in [43] are not sum-
marized here because of difficulty with translating re-
ported units into meaningful terms for comparison with
the TLV, but only mercury (again with no information on
parent organic compound) was detected in trace quan-
tities, while arsenic, beryllium, chromium, cadmium, lead
and nickel were not. Taken as the whole, it can be inferred
that there is no evidence of contamination of the aerosol
with metals that warrants a health concern.
Consideration of exposure to a mixture of contaminants
All calculations conducted so far assumed only one con-
taminant present in clean air at a time. What are the im-
plications of small quantities of various compounds with
different toxicities entering the personal breathing zone
at the same time? For evaluation of compliance with ex-
posure limits for mixtures, Equation 3 is used:
OELmixture = E1 1(Ci1TLVi), (3)
where Ci is the concentration of the ith compound (i =
1,...,n, where n > 1 is the number of ingredients present
in a mixture) in the contaminated air and TLVi is the
TLV for the ith compound in the contaminated air; if
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Table 3 Exposure predictions based on analysis of aerosols generated by smoking machines: inorganic compounds"
Element
Assumed compound containing the
N"" Estimated concentration
Ratio of most stringent
TLV (%)
Reference
quantified
element for comparison with TLV
in personal breathing
Calculated directly
Safety factor 10
zone (mg/m3)
Aluminum
Respirable Al metal & insoluble compounds
1 0.002
02
1.5
[261
Barium
Ba & insoluble compounds
1 0.00005
0.01
0.1
[201
Boron
Boron oxide
1 0.02
0.1
1.5
[261
Cadmium
Respirable Cd & compounds
12 0.00002
1
10
[81
Chromium
Insoluble Cr (IV) compounds
1 3E-05
0.3
3
[261
Copper
Cu fume
1 0.0008
0.4
4.0
[261
Iron
Soluble iron salts, as Fe
1 0.002
0.02
0.2
[261
Lead
Inorganic compounds as Pb
1 7E-05
0.1
1
[261
12 0.000025
0.05
0.5
181
Magnesium
Inhalable magnesium oxide
1 0.00026
0.003
0.03
[261
Manganese
Inorganic compounds, as Mn
1 8E-06
0.04
0.4
[261
Nickel
Inhalable soluble inorganic compounds,
1 2E-05
0.02
0.2
[261
as Ni
12 0.00005
0.05
0.5
[81
Potassium
KOH
1 0.001
0.1
1
[261
Tin
Organic compounds, as Sn
1 0.0001
0.1
1
[261
Zinc
Zinc chloride fume
1 0.0004
0.04
0.4
[261
Zirconium
Zr and compounds
1 3E-05
0.001
0.01
[261
Siilfitr
SO,
1 0.002
0.3
3
[261
"The actual molecular form in the aerosol unknown and so worst case assumption was made if it was physically possible (e.g. it is not possioie Tor eiemeinui
lithium & sodium to be present in the aerosol); there is no evidence from the research that suggests the metals were in the particular highest risk form, and in
most cases a general knowledge of chemistry strongly suggests that this is unlikely. Thus, the TLV ratios reported here probably do not represent the (much
lower) levels that would result if we knew the molecular forms.
"Average is presented when N > 1.
OELmixture > 1, then there is evidence of the mixture ex-
ceeding TLV.
The examined reports detected no more than 5-10
compounds in the aerosol, and the above calculation
does not place any of them out of compliance with TLV
for mixture. Let us imagine that 50 compounds with
TLVs were detected. Given that the aerosol tends to con-
tain various compounds at levels, on average, of no more
than 0.5% of TLV (Tables 1 and 3), such a mixture with
50 ingredients would be at 25% of TLV, a level that is
below that which warrants a concern, since the "action
level" for implementation of controls is traditionally set
at 50% of TLV to ensure that the majority of persons ex-
posed have personal exposure below mandated limit
[51]. Pellerino et al. [2] reached conclusions similar to
this review based on their single experiment: contami-
nants in the liquids that warrant health concerns were
present in concentrations that were less than 0.1% of
that allowed by law in the European Union. Of course, if
the levels of the declared ingredients (propylene glycol,
glycerin, and nicotine) are considered, the action level
would be met, since those ingredients are present in the
concentrations that are near the action level. There are
no known synergistic actions of the examined mixtures,
so Equation 3 is therefore applicable. Moreover, there is
currently no reason to suspect that the trace amounts of
the contaminants will react to create compounds that
would be of concern.
Conclusions
By the standards of occupational hygiene, current data
do not indicate that exposures to vapers from contami-
nants in electronic cigarettes warrant a concern. There
are no known toxicological synergies among compounds
in the aerosol, and mixture of the contaminants does
not pose a risk to health. However, exposure of vapers to
propylene glycol and glycerin reaches the levels at which,
if one were considering the exposure in connection with
a workplace setting, it would be prudent to scrutinize
the health of exposed individuals and examine how ex-
posures could be reduced. This is the basis for the rec-
ommendation to monitor levels and effects of prolonged
exposure to propylene glycol and glycerin that comprise
the bulk of emissions from electronic cigarettes other
than nicotine and water vapor. From this perspective, and
taking the analogy of work on theatrical fogs [46,47], it can
be speculated that respiratory functions and symptoms
(but not cancer of respiratory tract or non-malignant re-
spiratory disease) of the vaper is of primary interest. Moni-
toring upper airway irritation of vapers and experiences of
Burstyn BMC Public Health 2014, 14:18
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unpleasant smell would also provide early warning of
exposure to compounds like acrolein because of known
immediate effects of elevated exposures (http://www.atsdr.
cdc.gov/toxprofiles/tpl24-c3.pdf, accessed July 11, 2013).
However, it is questionable how much concern should be
associated with observed concentrations of acrolein and
formaldehyde in the aerosol. Given highly variable assess-
ments, closer scrutiny is probably warranted to understand
sources of this variability, although there is no need at
present to be alarmed about exceeding even the occupa-
tional exposure limits, since occurrence of occasional high
values is accounted for in established TLVs. An important
clue towards a productive direction for such work is the
results reported in [40,41] that convincingly demonstrate
how heating the liquid to high temperatures generates
compounds like acrolein and formaldehyde in the aerosol.
A better understanding about the sources of TSNA in the
aerosol may be of some interest as well, but all results to
date consistently indicate quantities that are of no more
concern than TSNA in smokeless tobacco or nicotine re-
placement therapy (NRT) products. Exposures to nicotine
from electronic cigarettes is not expected to exceed that
from smoking due to self -titration [11]; it is only a con-
cern when a vapor does not intend to consume nicotine,
a situation that can arise from incorrect labeling of
liquids [25,44].
The cautions about propylene glycol and glycerin apply
only to the exposure experienced by the vapers them-
selves. Exposure of bystanders to the listed ingredients, let
alone the contaminants, does not warrant a concern as
the exposure is likely to be orders of magnitude lower
than exposure experienced by vapers. Further research
employing realistic conditions could help quantify the
quantity of exhaled aerosol and its behavior in the envir-
onment under realistic worst-case scenarios (i.e., not small
sealed chambers), but this is not a priority since the ex-
posure experienced by bystanders is clearly very low com-
pared to the exposure of vapers, and thus there is no
reason to expect it would have any health effects.
The key to malting the best possible effort to ensure
that hazardous exposures from contaminants do not
occur is ongoing monitoring of actual exposures and esti-
mation of potential ones. Direct measurement of personal
exposures is not possible in vaping due to the fact the
aerosol is inhaled directly, unless, of course, suitable bio -
markers of exposure can be developed. The current review
did not identify any suitable biomarkers, though cotinine
is a useful proxy for exposure to nicotine -containing liq-
uids. Monitoring of potential composition of exposures is
perhaps best achieved though analysis of aerosol gener-
ated in a manner that approximates vaping, for which
better insights are needed on how to modify "smoking
machines" to mimic vaping given that there are docu-
mented differences in inhalation patterns [52] that depend
Page 11 of 14
on features of e -cigarettes [14]. These smoking machines
would have to be operated under a realistic mode of op-
eration of the atomizer to ensure that the process for
generation of contaminants is studied under realistic
temperatures. To estimate dosage (or exposure in per-
sonal breathing zone), information on the chemistry of
the aerosol has to be combined with models of the inhal-
ation pattern of vapers, mode of operation of e -cigarettes
and quantities of liquid consumed. Assessment of exhaled
aerosol appears to be of little use in evaluating risk to
vapers due to evidence of qualitative differences in the
chemistry of exhaled and inhaled aerosol.
Monitoring of liquid chemistry is easier and cheaper
than assessment of aerosols. This can be done systematic-
ally as a routine quality control measure by the manufac-
turers to ensure uniform quality of all production batches.
However, we do not know how this relates to aerosol
chemistry because previous researchers did not appropri-
ately pair analyses of chemistry of liquids and aerosols. It
is standard practice in occupational hygiene to analyze the
chemistry of materials generating an exposure, and it is
advisable that future studies of the aerosols explicitly pair
these analyses with examination of composition of the liq-
uids used to generate the aerosols. Such an approach can
lead to the development of predictive models that relate
the composition of the aerosol to the chemistry of liquids,
the e -cigarette hardware, and the behavior of the vaper, as
these, if accurate, can anticipate hazardous exposures be-
fore they occur. The current attempt to use available data
to develop such relationships was not successful due to
studies failing to collect appropriate data. Systematic mon-
itoring of quality of the liquids would also help reassure
consumers and is best done by independent laboratories
rather than manufactures to remove concerns about im-
partiality (real or perceived).
Future work in this area would greatly benefit from
standardizing laboratory protocols (e.g. methods of ex-
traction of compounds from aerosols and liquids, estab-
lishment of "core" compounds that have to be quantified
in each analysis (as is done for PAH and metals), devel-
opment of minimally informative detection limits that
are needed for risk assessment, standardization of oper-
ation of "vaping machine", etc.), quality control experi-
ments (e.g. suitable positive and negative controls without
comparison to conventional cigarettes, internal standards,
estimation of % recovery, etc.), and reporting practices (e.g.
in units that can be used to estimate personal exposure,
use of uniform definitions of limits of detection and quan-
tification, etc.), all of which would improve on the cur-
rently disjointed literature. Detailed recommendations on
standardization of such protocols lie outside of scope of
this report.
All calculations conducted in this analysis are based
on information about patterns of vaping and the content
Burstyn BMC Public Health 2014, 14:18
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of aerosols and liquids that are highly uncertain in their
applicability to "typical' vaping as it is currently prac-
ticed and says even less about future exposures due to
vaping (e.g. due to development of new technology).
However, this is similar to assessments that are routinely
performed in occupational hygiene for novel technology
as it relied on "worst case" calculations and safety mar-
gins that attempt to account for exposure variability.
The approach adopted here and informed by some data
is certainly superior to some currently accepted practices
in the regulatory framework in occupational health that
rely purely on description of emission processes to make
claims about potential for exposure (e.g. [53]). Clearly,
routine monitoring of potential and actual exposure is
required if we were to apply the principles of occupa-
tional hygiene to vaping. Detailed suggestions on how to
design such exposure surveillance are available in [54].
While vaping is obvious not an occupational exposure,
occupational exposure standards are the best available
option to use. If there were a standard for voluntary con-
sumer exposure to aerosols, it would be a better fit, but
no such standard exists. The only candidate standard is
the occupational standard, which is conservative (more
protective) when considered in the context of voluntary
exposures, as argued above, and any suggestion that an-
other standard be used needs to be concrete and justified.
In summary, analysis of the current state of knowledge
about the chemistry of contaminants in liquids and aero-
sols associated with electronic cigarettes indicates that
there is no evidence that vaping produces inhalable expo-
sures to these contaminants at a level that would prompt
measures to reduce exposure by the standards that are
used to ensure safety of workplaces. Indeed, there is suffi-
cient evidence to be reassured that there are no such risks
from the broad range of the studied products, though the
lack of quality control standards means that this cannot
be assured for all products on the market. However,
aerosol generated during vaping on the whole, when con-
sidering the declared ingredients themselves, if it were
treated in the same manner as an emission from industrial
process, creates personal exposures that would justify sur-
veillance of exposures and health among exposed persons.
Due to the uncertainty about the effects of these quantities
of propylene glycol and glycerin, this conclusion holds
after setting aside concerns about health effects of nico-
tine. This conclusion holds notwithstanding the benefits
of tobacco harm reduction, since there is value in under-
standing and possibly mitigating risks even when they are
known to be far lower than smoking. It must be noted that
the proposal for such scrutiny of "total aerosol" is not
based on specific health concerns suggested by com-
pounds that resulted in exceedance of occupational expos-
ure limits, but is instead a conservative posture in the face
of unknown consequences of inhalation of appreciable
Page 12 of 14
quantities of organic compounds that may or may not be
harmful at doses that occur during vaping.
Key conclusions:
Even when compared to workplace standards for
involuntary exposures, and using several
conservative (erring on the side of caution)
assumptions, the exposures from using e -cigarettes
fall well below the threshold for concern for
compounds with known toxicity. That is, even
ignoring the benefits of e -cigarette use and the fact
that the exposure is actively chosen, and even
comparing to the levels that are considered unacceptable
to people who are not benefiting from the exposure
and do not want it, the exposures would not generate
concern or call for remedial action.
Expressed concerns about nicotine only apply to
vapers who do not wish to consume it; a voluntary
(indeed, intentional) exposure is very different from
a contaminant.
There is no serious concern about the contaminants
such as volatile organic compounds (formaldehyde,
acrolein, etc.) in the liquid or produced by heating.
While these contaminants are present, they have
been detected at problematic levels only in a few
studies that apparently were based on unrealistic
levels of heating.
• The frequently stated concern about contamination
of the liquid by a nontrivial quantity of ethylene
glycol or diethylene glycol remains based on a single
sample of an early -technology product (and even
this did not rise to the level of health concern) and
has not been replicated.
• Tobacco -specific nitrosamines (TSNA) are present
in trace quantities and pose no more (likely much
less) threat to health than TSNAs from modern
smokeless tobacco products, which cause no
measurable risk for cancer.
Contamination by metals is shown to be at similarly
trivial levels that pose no health risk, and the
alarmist claims about such contamination are based
on unrealistic assumptions about the molecular
form of these elements.
• The existing literature tends to overestimate the
exposures and exaggerate their implications. This is
partially due to rhetoric, but also results from
technical features. The most important is confusion of
the concentration in aerosol, which on its own tells us
little about risk to heath, with the relevant and much
smaller total exposure to compounds in the aerosol
averaged across all air inhaled in the course of a day.
There is also clear bias in previous reports in favor of
isolated instances of highest level of chemical detected
Burstyn BMC Public Health 2014, 14:18
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across multiple studies, such that average exposure
that can be calculated are higher than true value
because they are "missing" all true zeros.
Routine monitoring of liquid chemistry is easier and
cheaper than assessment of aerosols. Combined with
an understanding of how the chemistry of the liquid
affects the chemistry of the aerosol and insights into
behavior of vapers, this can serve as a useful tool to
ensure the safety of e -cigarettes.
The only unintentional exposures (i.e., not the nicotine)
that seem to rise to the level that they are worth
further research are the carrier chemicals themselves,
propylene glycol and glycerin. This exposure is not
known to cause health problems, but the magnitude of
the exposure is novel and thus is at the levels for
concern based on the lack of reassuring data.
Endnotes
"Atmosphere that contains air inhaled by a person.
"This estimate of consumption was derived from infor-
mal reports from vaping community; 5 ml/day was iden-
tified as a high but not rare quantity of consumption
and 25 ml/day was the high end of claimed use, though
some skepticism was expressed about whether the latter
quantity was truly possible. High-quality formal studies
to verify these figures do not yet exist but they are con-
sistent with report of Etter (2012).
`The term "VOC" loosely groups together all organic
compounds present in aerosol and because the declared
ingredients of aerosol are organic compounds, it follows
that "VOC are present".
Additional files
Additional file 1: Summary of chemical analyses of a -cigarettes
extracted from the literature.
Additional file 2: Key to identifying articles listed in Additional file 1.
Additional file 3: Calculations conducted to compare reported
results to threshold limit values. Spreadsheet that iMplernented
calculations summarized in the article.
Competing interests
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.
Authors' information
IB is trained In both occupational hygiene and epiderniology and thus is an
expert in bring information that these two fields contribute to risk
assessment and policy making. IB does not and never has used any tobacco
products. Current research was completed by hire as independent research
contract during otherwise unpaid summer months. IB is an Associate
Professor at Drexel University and felt obliged to disclose his primary
academic appointment but this work was completed outside of the
structures of Drexel University.
Page 13 of 14
Acknowledgements
The author is thankful to Dr. Carl V Phillips, the CASAA Scientific Director, for
frank discussion of relevant scientific matters- The contribution of Charity
Curtis, Masters of Public Health student at Drexel University to the initial
literature search was greatly appreciated. Lastly, the author is deeply
indebted to pre -publication peer review that occurred upon release of the
content of this article as technical report - Burstyn I: Peering through the mist:
Whor does the chemistry of contaminants in electronic cigarettes tell us about
health risks? .July - August 2013, Drexel University School of Public Health,
Philadelphia, PA (http://publichealth.drexel.edu/-/media/files/publichealth/
ms08.pdf) - all the feedback Is greatly appreciated and the remaining flaws
in the report are author's sole responsibility.
Received: 26 August 2013 Accepted: 2 January 2014
Published: 9 January 2014
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doi:10.1186/1471-2458-14-18
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about health risks. BMC Public Health 2014 14:18.
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Nicotine & Tobacco'Research Advance Access published December 11, 2013
ORIGINAL INVESTIGATION
Secondhand Exposure to Vapors From Electronic
Cigarettes
Jan Czogala PhD', Maciej L. Goniewicz PharmD, PhD 1,2, Bartlomiej Fidelus PharmD', Wioleta Zielinska-
Danch PhD', Mark J. Travers PhD2, Andrzej Sobczak PhD' 3
'Department of General and Analytical Chemistry, School of Pharmacy and Laboratory Medicine, Medical University of
Silesia, Sosnowiec, Poland; 2Department of Health Behavior, Division of Cancer Prevention and Population Sciences, Roswell
Park Cancer Institute, Buffalo, Ny,• 3Department of Chemical Hazards, Institute of Occupational and Environmental Health,
Sosnowiec, Poland
Corresponding Author: Maciej L. Goniewicz, PhD, Department of Health Behavior, Division of Cancer Prevention and
Population Science, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA. Telephone: 716-845-
8541; Fax: 716-845-1265; E-mail: maciej.goniewicz@roswellpark.org
Received July 5, 2013; accepted November 10, 2013
ABSTRACT
Introduction: Electronic cigarettes (commonly referred as e -cigarettes) are designed to generate inhalable nicotine aerosol
(vapor). When an e -cigarette user takes a puff, the nicotine solution is heated and the vapor taken into lungs. Although no side -
stream vapor is generated between puffs, some of the mainstream vapor is exhaled by e -cigarette user. The aim of the study was
to evaluate the secondhand exposure to nicotine and other tobacco -related toxicants from e -cigarettes.
Materials and Methods: We measured selected airborne markers of secondhand exposure: nicotine, aerosol particles (PM2.5),
carbon monoxide, and volatile organic compounds (VOCs) in an exposure chamber. We generated e -cigarette vapor from 3 vari-
ous brands of e -cigarette using a smoking machine and controlled exposure conditions. We also compared secondhand exposure
with e -cigarette vapor and tobacco smoke generated by 5 dual users.
Results: The study showed that e -cigarettes area source of secondhand exposure to nicotine but not to combustion toxicants.
The air concentrations of nicotine emitted by various brands of e -cigarettes ranged from 0.82 to 6.23 pg/m3. The average con-
centration of nicotine resulting from smoking tobacco cigarettes was 10 times higher than from e -cigarettes (31.60±6.91 vs.
3.32±2.49 pg/m3, respectively; p :0081).
Conclusions: Using an e -cigarette in indoor environments may involuntarily expose nonusers to nicotine but not to toxic
tobacco -specific combustion products. More research is needed to evaluate health consequences of secondhand exposure to nico-
tine, especially among vulnerable populations, including children, pregnant women, and people with cardiovascular conditions.
INTRODUCTION
Passive smoking, also referred to as exposure to secondhand
smoke (SHS), happens when a person inhales a mixture of
toxic compounds released from burning cigarettes (California
Environmental Protection Agency, 2005; Nelson, 2001;
Wallace -Bell, 2003). Despite the comprehensive smoke-free
regulations introduced in many countries, passive smoking
remains a global health problem. It has been estimated that pas-
sive smoking causes more than six hundred thousand deaths
every year around the world (Oberg, Jaakkola, Woodward,
Peruga, & Priiss-Ustitn, 2011). Current laws and regulations
do not adequately protect vulnerable populations, including
children, pregnant women, and those with preexisting health
conditions, from exposure to SHS. Based on data from 192
countries, Oberg et al. (2011) estimated that 40% of children
had been exposed globally to SHS. SHS (also referred to as
environmental tobacco smoke, ETS) is comprised primarily of
sidestream smoke released from burning cigarettes during puff
breaks and smoke exhaled by smokers after each puff. While
SHS may contain the same toxic substances as mainstream
smoke, it contains higher concentrations of many toxic and
carcinogenic compounds than mainstream smoke. Although
toxicants released from burning cigarettes are diluted in the
indoor air, passive smokers are often exposed to secondhand
smoke for prolonged periods of time.
Electronic nicotine delivery systems (commonly referred as
electronic cigarettes or e -cigarettes) are new consumer prod-
ucts designed to generate nicotine aerosol (vapor) without
combustion of tobacco. A typical e -cigarette is composed of
three essential parts: the battery, the heating element or atom-
izer, and a cartridge or tank that holds a nicotine solution. The
product contains nicotine dissolved in propylene glycol, glyc-
erin, or the mixture of the two. When an e -cigarette user takes
doi:10.1093/ntr/ntt203
The Author 2013. Published by Oxford University Press on behalf of the Societyfor Research on Nicotine and Tobacco.
All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Page 1 of 8
Secondhand exposure to vapors from e -cigarettes
a puff, the nicotine solution is heated and the vapor can be
inhaled into lungs. E -cigarettes are designed to deliver nicotine
without toxic constituents of tobacco or tobacco combustion
toxicants and carcinogens. Studies have shown that vapor gen-
erated from e -cigarettes contains nicotine and that the devices
might be effective in delivering nicotine to the body. There
is also some evidence that the vapor may contain some toxic
compounds like carbonyls, traces of nitrosamines, or particles
of heavy metals (Bullen et al., 2010; Dawkins & Corcoran,
2013; Etter & Bullen, 2011; Goniewicz, Knysak, et al., 2013;
Goniewicz, Kuma, Gawron, Knysak, & Kosmider, 2013; Trehy
et al., 2011; Vansickel & Eissenberg. 2013; Vansickel, Cobb,
Weaver, & Eissenberg, 2010; Williams, Villarreal, Bozhilov,
Lin, & Talbot, 2013).
Analysis of global c -cigarette marketing indicates that
the products are promoted to circumvent smoke-free poli-
cies and to reduce exposure to secondhand smoke (Grana &
Ling, 2013). Although no sidestream vapor is generated from
e -cigarettes between puffs, some of the vapor is exhaled by the
user. A study by Schripp, Markewitz, Uhde, and Salthammer
(2013) showed that ultrafine particles, volatile organic com-
pounds (VOCs), and nicotine are released with exhaled vapor.
McAuley, Hopke, Zhao, and Babaian (2012) investigated emis-
sions and indoor air concentrations of common tobacco smoke
by-products from four different vaporized nicotine solutions
and found that they emitted traces of carbonyls, polyaromatic
hydrocarbons, tobacco -specific nitrosamines, and glycols.
There is limited evidence whether passive "vaping" exposes
nonusers to nicotine. One study showed that 1 -hr exposure
to secondhand cigarette smoke and to exhaled "secondhand"
e -cigarette vapors generated similar effects on serum cotinine
levels (Flouris et al., 2013).
As the popularity of e -cigarettes increases, it is becoming
important to further investigate patterns and levels of passive
exposure to nicotine and other toxicants from e -cigarettes. The
present study explores various factors that might contribute to
emission of chemicals from e -cigarettes. It also aims to com-
pare the passive exposure to nicotine, particulates, carbon mon-
oxide (CO), and VOCs from electronic and tobacco cigarettes.
MATERIALS AND METHODS
Study Protocols
We conducted two studies to assess emissions from e -ciga-
rettes. The first study (Study 1) was designed to evaluate major
factors that might affect exposure patterns. We generated vapor
from three different models of e -cigarettes and released the
vapor into an experimental exposure chamber. The aim of the
second study (Study 2) was to compare emissions Brom e -cig-
arettes and cigarette smoke generated by experienced users of
both products. Both studies are described in details below.
Study With Machine -Generated Vapors (Study 1)
Study 1 consisted of 12 experiments (Table 1; Experiments
1-12) conducted in an exposure chamber, each one lasting 2hr.
During the first hour, background levels of all analyzed mark-
ers were taken. During the second hour, vapor from e -cigarettes
was generated using a smoking machine and released into the
exposure chamber. We measured 1 -hr average concentrations
Page 2 of 8
of nicotine, aerosol particles (PM, 5), CO, and selected VOCs.
We also monitored changes in PM, 5 and CO levels over 2 hr.
Electronic Cigarettes
We studied three different models of e -cigarettes selected from
the popular brands in Poland: (a) Colinss Age with Camel High
atomized cartridge (cartomizer) (Colins Poland; EC1); (b)
Dekang 510 Pen with SGC Regular cartridge (Ecigars Polska;
EC2); and (c) Mild M201 Pen with Marlboro cartridge (Mild
Poland; EC3). Although all cartridges were labeled as contain-
ing 18 mg of nicotine, our previous study showed that they dif-
fered in nicotine levels: Colinss Camel contained I I mg, SGC
Regular contained 18 trig, and Mild Marlboro contained 19 mg
of the drug (Goniewicz, Kuma, et al., 2013). All products were
purchased from online stores or shopping mall kiosks, and e -cig-
arettes batteries were charged for 24 hr before the experiments.
Exposure Chamber
A 39-m3 laboratory room (3.4x4.1 x2.8 m) was equipped as
an exposure chamber. The chamber had plain acrylic painted
walls and tiled floor, with no windows, carpets, linings, or cur-
tains inside. It was equipped with a regulated exhaust, ventila-
tion system, and two fans for mixing the indoor air. Inside the
chamber, there was a sampling station equipped with pumps
and monitors, a smoking machine for generating e -cigarette
vapors (see Generation of Vapors From E -Cigarettes section),
and two chairs. The sampling station was located 1 m from
a smoking machine and 10cm above the level of e -cigarettes.
The air exchange rates were determined before each experi-
ment using a ventilation marker (methane) released into the
exposure chamber according to the method described pre-
viously (Czogala & Goniewicz, 2005). The ventilation rate
during the study varied from 1.37 (low) to 12.6 (high) air
changes per hour (see also Supplementary Materials). Before
each experiment, all surfaces inside the chamber were decon-
taminated by wiping with 10% aqueous solution of ethanol
and intensive ventilation. Only one person, who operated the
smoking machine and sampling station, was allowed inside the
exposure chamber during Study 1.
Generation of vapors From E -Cigarettes
In order to generate vapors from the e -cigarettes, a smoking
machine was placed in the exposure chamber. We used an
automatic single -channel piston -operated smoking machine
Palaczbot (Technical University of Lodz) designed to gener-
ate vapor from e -cigarettes (Goniewicz, Knysak, et al., 2013:
Goniewicz, Kuma, et al., 2013). In all experiments, the vapors
from e -cigarettes were generated using the following puff-
ing conditions: puff volume of 70ml, puff duration of 1.8 s,
and intervals between puffs of 10 s. Two doses of vapor (see
Generation of Vapors From E -Cigarettes section) were released
into the exposure chamber with 30 -min interval.
Vapors were generated from each of the three e -cigarettes
under two variants of ventilation (intensive vs. restricted) and
two variants of emission pattern (high vs. low) (3 brands x 2
variants of ventilation x 2 variants of emission). Ventilation of
the exposure chamber was controlled during each experiment
and adjusted by operating the exhaust. During the experiments
with intensive ventilation, exhaust from the exposure chamber
was fully opened, while it was partly closed during the experi-
ments with restricted ventilation.
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Secondhand exposure to vapors from e -cigarettes
In order to modify exposure patterns, vapors from e -ciga-
rettes were generated using 7 or 15 puffs, for low and high
exposure, respectively. The rationale for using two levels of
exposure (low vs. high) was to examine various doses of nico-
tine released with secondhand vapor. Although studies have
shown that e -cigarette vapors contain significant amounts of
nicotine, there are some controversy as to whether this nicotine
is effectively absorbed in the lungs (Zhang, Sumner. & Chen,
2013). If there is little absorption, vapor exhaled by e -cigarette
users might contain high levels of the drug. We assumed that if
an e -cigarette user takes 15 puffs, and no nicotine is absorbed,
then the entire amount of nicotine would be exhaled. If e -cig-
arettes effectively deliver nicotine to the bloodstream, exhaled
vapors will contain only some of nicotine inhaled by the user.
By releasing 7 puffs, we simulated the scenario in which
approximately half of the nicotine from 15 puffs is absorbed
and the balance is exhaled.
Analytical Procedures
Nicotine was measured using gas chromatography with nitrogen -
phosphorus detector following active sampling on XAD-4 sorp-
tion tubes (SKC Inc.) according to the National Institute of
Occupational Safety and Health reference method 2551 (National
Institute of Occupational Safety and Health, 2003) with a detec-
tion limit of 0.22 Itg/m3. Aerosol particles (PM, 5) were measured
continuously with a SidePak AMS 10 Personal Aerosol Monitor.
CO was also measured continuously with a Q -Trak Indoor Air
Quality 8550 monitor (both instruments from TSI Inc.). The
Sidepak was used with a calibration factor setting of 0.32, suit-
able for secondhand smoke (Jiang et al., 2011; Klepeis, Ott, &
Switzer, 2007). VOCs were analyzed using gas chromatography
with mass spectrometry following active sampling on Anasorb
CSC sorption tubes (SKC Inc.) according to the Occupational
Safety and Hazards Agency reference method (Occupational
Safety and Hazards Agency, 2000). The method allowed us
to measure 1I compounds: benzene, toluene, chlorobenzene,
ethylbenzene, m,p-xylene, o -xylene, styrene, naphthalene,
1,2 -dichlorobenzene, 1,3 -dichlorobenzene, and 1,4 -dichloroben-
zene. Each monitor was calibrated according to manufacturer's
recommendations, and all analytical procedures were validated
and described in details in the Supplementary Materials.
Study With Human -Generated Vapors and Smoke
(Study 2)
Subjects
We recruited five volunteers (all male; average age 37.6± 16.0;
body mass index 23.4±2.1; nicotine dependence by Fagerstrom
Test for Nicotine Dependence 5.8±2.9), who were dual users
of e -cigarettes and conventional tobacco cigarettes. The sub-
jects reported using e -cigarettes on average 14±7 times a
day for at least 8 months (12.0±4.2) and additionally smok-
ing on average 11 ±6 cigarettes per day for at least 5 years
(18.2±14.1). Two subjects reported using M201 pen -style
e -cigarette (18 mg/ml; Mild brand), two others used eGo model
(16mg/ml ; Janty brand), and one used M401 model (18 mg/ml:
Nicore brand, Atina Poland). Three volunteers smoked L&M
Blue Label brand of cigarettes (ISO yields/cigarette: nicotine
0.6 mg; tar 8 mg; CO 9 mg), and two smoked Marlboro Gold
brand (nicotine 0.5 mg; tar 7 mg; CO 7 mg). All volunteers who
participated in experiments were not given any money, gifts,
or other economic incentives. Study 2 protocol was reviewed
Page 4 of 8
and approved by the Institutional Review Board at the Medical
University of Silesia, Poland.
Emission of C -Cigarettes Vapors and Tobacco Smoke
Study 2 comprised five experiments (Table I; Experiments
13-17), each lasting for 3 hr. After background measures were
taken for l hr, a volunteer entered the room. Each volunteer used
ad libitum their own e -cigarette twice for 5 min with a 30 -min
interval. Then, the room was decontaminated as described
above and ventilated for 5 min. In the last hour, each subject
smoked ad libitum entire tobacco cigarettes of their own brand.
As with e -cigarettes, volunteers smoked two cigarettes lighting
the second cigarette 30 min after the first. One-hour average
concentrations of nicotine, aerosol particles (PMS 5). CO, and
VOCs were determined as described above (baseline, e -ciga-
rette, and tobacco cigarette). PM, 5 and CO levels were also
monitored continuously over 3 hr of each experiment. Only two
persons were allowed in the exposure chamber during Study 2:
volunteer and operator of the sampling station.
Statistical Analysis
We compared average concentrations of each airborne marker
using a nonparametric Mann-Whitney test. For both studies,
we assessed the differences between baseline measures and
each test condition (e -cigarette and tobacco cigarette). For
Study 2, we also assessed differences in average indoor con-
centrations of each marker between electronic and tobacco
cigarettes. For all tests, Statistica 10.0 software (StatSoft Inc.)
was used. The significance level was established as p < .05.
RESULTS
Secondhand Exposure to Nicotine From E -Cigarettes
Study 1
Nicotine was detected in the air during all experiments where
e -cigarette vapor was generated with the smoking machine
and released into the exposure chamber. Mean 1 -hr concentra-
tion of nicotine was 2.51 ± 1.68 pg/m3 and ranged from 0.82 to
6.23 pg/m3. Comparison of average indoor air nicotine concen-
trations in the exposure chamber from three e -cigarette brands
are presented in Figure 1. Changes between baseline values and
an average nicotine concentration after emission of machine -
generated vapors from e -cigarettes are presented in Table 1.
StudY 2
Figure 2 shows baseline concentrations of nicotine and 1 -hr
medium concentrations after using e -cigarettes or after srnok-
ing tobacco cigarettes by volunteers. The average concentra-
tion of nicotine resulting from smoking tobacco cigarettes
was 10 times higher than from e -cigarettes (31.60±6.91 vs.
3.32±2.49 pg/m3, respectively; p = .0081).
Secondhand Exposure to PM2,5 From E -Cigarettes
Study, l
Aerosol particles were detected in the air during all experiments
with vapor generated with the smoking machine and released
into the exposure chamber. Mean concentration of PMZ 5
was 33.1 ±26.9 pg/m3 and ranged from 6.6 to 85.0 µg/m3.
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Figure 1. Effect of e -cigarette brand on nicotine (left) and aerosol particle (right) concentration in the air inside exposure
chamber.
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background values and tobacco cigarette smoking. Note: 'Vapor generated with smoking machine (Study 1); eVapor exhaled by
users (Stud): 2).
Comparison of average indoor air PM1.5 levels in expo-
sure chamber from three c -cigarette brands are presented on
Figure 1. Changes between baseline values and mean PM2.5
levels after emission of machine -generated vapors from e -cig-
arettes are presented in Table 1.
Study 2
Figure 2 shows baseline concentrations of PM, 5 and 1 -hr mean
concentrations after using e -cigarettes or after smoking tobacco
cigarettes by volunteers. The mean concentration of PM2.5
resulting from smoking tobacco cigarettes was 7 times higher
than from c -cigarettes (819.3±228.6 vs. 151.7±86.8 pg/m3,
respectively; p = .0081). Figure 3 shows changes in PM2.5 con-
centration in the exposure chamber during one of the experi-
ments in Study 2 (Experiment 15; see Table 1).
Secondhand Exposure to CO From E -Cigarette
Studies l and 2
There were no changes in CO concentration after using c -cig-
arettes in both studies (l) > .05). However smoking of two
tobacco cigarettes in Study 2 increased CO concentration in the
Page 5 of 8
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Figure 2. Comparison of indoor air nicotine (left) and aerosol particle (right) concentrations released from e -cigarette with
background values and tobacco cigarette smoking. Note: 'Vapor generated with smoking machine (Study 1); eVapor exhaled by
users (Stud): 2).
Comparison of average indoor air PM1.5 levels in expo-
sure chamber from three c -cigarette brands are presented on
Figure 1. Changes between baseline values and mean PM2.5
levels after emission of machine -generated vapors from e -cig-
arettes are presented in Table 1.
Study 2
Figure 2 shows baseline concentrations of PM, 5 and 1 -hr mean
concentrations after using e -cigarettes or after smoking tobacco
cigarettes by volunteers. The mean concentration of PM2.5
resulting from smoking tobacco cigarettes was 7 times higher
than from c -cigarettes (819.3±228.6 vs. 151.7±86.8 pg/m3,
respectively; p = .0081). Figure 3 shows changes in PM2.5 con-
centration in the exposure chamber during one of the experi-
ments in Study 2 (Experiment 15; see Table 1).
Secondhand Exposure to CO From E -Cigarette
Studies l and 2
There were no changes in CO concentration after using c -cig-
arettes in both studies (l) > .05). However smoking of two
tobacco cigarettes in Study 2 increased CO concentration in the
Page 5 of 8
Secondhand exposure to vapors from e -cigarettes
2800
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Figure 3. Changes of aerosol particle PMz 5 concentrations during experiment of e -cigarette use and tobacco cigarette smoking
in exposure chamber.
exposure chamber on average by 2 to 3 ppm (vol/vol) (Table 1;
p < .05).
Secondhand Exposure to VOCs From E -Cigarettes
Study 1
During the study with machine -generated e -cigarette vapor,
only toluene was detected in the exposure chamber. No sta-
tistical difference was found between average toluene concen-
tration after release of e -cigarette vapor and baseline values
(6.63±0.21 vs. 4.15±2.69 lig/m3, respectively; p = .1582).
Study 2
As with Study 1, toluene was the only VOC detected in the
exposure chamber, and the use of e -cigarette did not change
the concentration of toluene (3.79±2.16 vs. 4.09±2.12 pg/
M3, respectively; p = .8513). Smoking two tobacco cigarettes
increased the concentration of four compounds: toluene, eth-
ylbenzene, m,p-xylene, and o -xylene (p < .05). For toluene,
the average concentration after smoking tobacco cigarettes
was 3.5 -fold higher than after using e -cigarettes (14.75±6.02
vs. 4.15±2.69 pg/m3, respectively; p < .05). The average con-
centrations of ethylbenzene, m,p-xylene, and o -xylene after
smoking tobacco cigarettes were 1.17± 1.44, 1.94±1.14, and
0.48±0.95 pg/n13, respectively; p < .05).
DISCUSSION
Principal Findings
The key finding of this study is that e -cigarettes emit significant
amounts of nicotine but do not emit significant amounts of CO
and VOCs. We also found that the level of secondhand expo-
sure to nicotine depends on the e -cigarette brand. However,
the emissions of nicotine from e -cigarettes were significantly
lower than those of tobacco cigarettes.
Strengths and Limitations of the Study
To our knowledge, this is one of the first studies to measure
the concentrations of nicotine, PM2.5, CO, and VOCs emitted
Page 6 of 8
by e -cigarettes and to compare the emissions of electronic and
conventional tobacco cigarettes in a conventionally ventilated,
full-sized room. By comparing e -cigarette vapors generated
with a smoking machine to those generated by experienced
e -cigarette users in a controlled setting allowed us to control
for potential factors that may affect exposure patterns.
Results from experiments with human subjects who used
both electronic and tobacco cigarettes allowed us to compare
the emissions and the potential exposures by the two products.
One of the most important aspects of our study is that the e -cig-
arette vapors and tobacco smoke were generated by long-term
dual users of the products, and we did not modified the way
volunteers were typically using the products.
Our findings are supported by results from study by
McAuley et al. (2012) who examined the chemical composi-
tion of freshly generated vapor collected in a small emission
chamber and found that the total air emission concentrations
for many pollutants from e -cigarettes were very low. Our study
examined the potential effect of various e -cigarette brands on
patterns of exposure, whereas McAuley et al. (2012) studied
vapors generated from the same model of e -cigarette with vary-
ing nicotine solutions and found that the chemical composi-
tion of the vapors from different solutions differed in levels of
nicotine and other chemicals. Our study showed that the level
of exposure also differs between e -cigarette brands. These find-
ings are also consisted with our previously reported data show-
ing high variability in composition of freshly generated vapors
among the products (Goniewicz, Kuma, et al., 2013). These
findings should be taken into careful consideration when expo-
sure to e -cigarette vapors is considered.
The study has several limitations. An important limitation
of our study is that we measured a limited number of chemi-
cals that might be contained within e -cigarette vapors. We
reported previously that e -cigarette vapors contain significant
levels of carbonyls, including toxic and carcinogenic formal-
dehyde, acetaldehyde, and acrolein (Goniewicz, Knysak,
et al., 2013). These compounds were not measured in this study.
Studies by Schripp, Markewitz, Uhde, and Salthammer (2013)
and McAuley et al. (2012) found that there is a risk of exposure
to carbonyls from e -cigarettes, although the levels of the com-
pounds were lower than those in SHS. We did not investigate
other significant factors affecting exposure to e -cigarette
vapors, for example, room volume and number of e -cigarettes
used simultaneously in a single room. The exposure chamber
input air was not filtered during the experiments, and ventila-
tion air exchange rates of exposure chamber were higher than
residential rates (Yamamoto, Shendell, Winer, & Zhang, 2010).
Finally, the study assessed concentrations of several markers in
the air but not serum concentrations in people exposed to sec-
ondhand vapors. These airborne concentrations do not necessar-
ily reflect the serum concentration and the impact on health of
people exposed to these vapors.
Unanswered Questions and Future Research
This study did not test potential health effects associated
with secondhand exposure to vapors from e -cigarettes. To
date, there are few studies that have tested the acute effects
of brief exposure to secondhand e -cigarette vapors. One study
by Flouris et al. (2012) found that acute passive "vaping" of
c -cigarettes did not influence complete blood count in human
subjects. Another study by the same authors found that con-
trolled 1 -hr exposure to e -cigarette vapors did not significantly
affect lung function in human subjects (Flouris et al., 2013).
We found no publications on the cardiovascular effects of pas-
sive exposure to e -cigarette vapors or on the health effects of
secondhand exposure to e -cigarette vapors among vulnerable
population, including children, pregnant women, and people
with cardiovascular conditions.
There is some discrepancy between our findings and results
reported recently by Flouris et al. (2013) on secondhand exposure
to nicotine. Our data suggest that secondhand exposure to nicotine
from e -cigarettes is on average 10 times less than from tobacco
smoke. Ilowever, Flouris et al. (2013) found that c -cigarettes and
tobacco cigarette generated similar- effects on serum cotinine
levels after 1 -hr passive exposure (2.4±09 vs. 2.6±0.6ng/ml,
respectively; p < .001). Future research should look for correla-
tion between indoor air levels of nicotine from e -cigarettes and its
uptake by passive smokers to explain this discrepancy.
Future research should also study exposure patterns over
extended periods of time and the potential health effects of
long-term exposure to secondhand e -cigarette vapors. Data
are also needed from the field studies conducted in homes
and public places where e -cigarettes are in use. Moreover, this
study only focused on nicotine and a limited number of chemi-
cals released from e -cigarettes. Further research is needed to
explore emission and exposure to other toxicants and carcino-
gens identified in e -cigarettes, for example, carbonyl com-
pounds (Goniewicz, Knysak, et al., 2013).
It remains unclear whether concentration of PM, 5 will
be a suitable and reliable airborne marker to evaluate emis-
sion and exposure to secondhand vapors from c -cigarettes.
Although some studies suggest that e -cigarette vapor and SHS
have comparable aerosol particle size distribution and deposi-
tion patterns, we found that concentration of e -cigarette aero-
sol particles tends to decrease rapidly when diluted in the air.
Figure 3 shows that there is a significant particle mass signal
from e -cigarette vapor but that it dissipates much more rapidly
than cigarette smoke. This may be due to the evaporation of the
aerosol in addition to deposition on the surfaces and removal
by ventilation. There is a need for developing an accurate
methodology to assess e -cigarette vapor indoor concentrations.
Finally, the vapor from e -cigarettes might be easily deposited
Nicotine & Tobacco Research
on surfaces to form "thirdhand" e -cigarette vapor, and studies
are needed to assess the deposition rate, potential formation of
toxic derivatives, and human exposure.
Implications for Policy Makers
The study showed that e -cigarettes might involuntarily expose
nonsmokers and people who do not use e -cigarettes to nicotine.
In the past, secondhand exposure to nicotine has been primarily
associated with exposure to ETS. E -cigarettes have created the
new scenario under which bystanders might be exposed to low
levels of nicotine but not to the other toxins found in tobacco
smoke. It remains unclear whether exposure to low levels of nic-
otine indoors causes any harm to bystanders, including children,
pregnant women, and person with cardiovascular conditions.
Besides nicotine, e -cigarette vapor contains significant
amounts of propylene glycol and vegetable glycerin. Although
both compounds are considered to be safe, there is lack of data on
health risk associated with prolonged exposure to their vapors.
Propylene glycol has been shown to cause upper airway irrita-
tion (Vardavas et al., 2011). Some volatile carbonyl compounds
have been also identified in the vapor of e -cigarettes (Goniewicz,
Knysak, et al., 2013). More research is needed about the health
risk associated with exposure to toxic constituents of the vapors.
The physicochemical changes may also occur after vapors are
released into ambient air. It has been shown that such changes
increase toxicity of tobacco smoke two- to four -fold (Schick
& Glantz, 2006). These data are needed to inform regulators
whether e -cigarettes should be included under smoke-free poli-
cies to protect nonusers from inhaling the toxicants.
E -cigarettes are promoted to circumvent smoke-free policies
(Grana & Ling, 2013). Exempting e -cigarettes from smoke-free
regulations, besides creating secondhand exposure to nicotine,
might have additional implications for public health. It remains
unclear whether observation of smokers using e -cigarettes,
especially by young people, might reverse the denonnalization
of smoking behavior as a social norm. Cigarette smokers might
use e -cigarettes as additional sources of nicotine in places with
smoking bans. Data are needed to determine whether dual use
of the products (e -cigarettes in addition to tobacco cigarettes)
results in reinforcement of nicotine addiction.
SUPPLEMENTARY MATERIAL
Supplementary Material can be found online at http://www.ntr.
oxfordjournals.org
FUNDING
This work was supported by the Ministry of Science and Higher
Education of Poland (N N404 016939). The study sponsor had
no involvement in the study design, collection, analysis, and
interpretation of data, the writing of the manuscript, or the
decision to submit the manuscript for publication.
DECLARATION OF INTERESTS
MLG received research funding from Pfizer, manufacturer of
stop smoking medication, and ivas.funded by the UK Centre
for Tobacco Control Studies (UKCTCS) during the study. AS
Page 7 of 8
Secondhand exposure to vapors from e -cigarettes
received research funds and travel expenses from Chic Group
Ltd., manufacturer of electronic cigarettes in Poland. Other
authors declare no conflict of interest.
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