Science of the Total Environment 642 (2018) 137–147

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Science of the Total Environment

journal homepage: www.elsevier.com/locate/scitotenv

Second-hand aerosol from tobacco and electronic cigarettes: Evaluation

of the smoker emission rates and doses and lung cancer risk of passive
smokers and vapers
Pasquale Avino a,b, Mauro Scungio c, Luca Stabile d, Gino Cortellessa d,
Giorgio Buonanno d,e,f, Maurizio Manigrasso g,⁎
a
Department of Agricultural, Environmental and Food Sciences (DiAAA), University of Molise, via F. De Sanctis, I-86100 Campobasso, Italy
b
Institute of Ecotoxicology & Environmental Sciences, Kolkata, India
c
Department of Economics, Engineering, Society and Business Organization, University of Tuscia, Viterbo, Italy
d
Department of Civil and Mechanical Engineering, University of Cassino and Southern Lazio, I-03043 Cassino, FR, Italy
e
Queensland University of Technology, Brisbane, Australia
f
Department of Engineering, University “Parthenope”, I-80100 Naples, Italy
g
DIT, INAIL Settore Ricerca, Certificazione e Verifica, via R. Ferruzzi 38/40, I-00143 Rome, Italy

H I G H L I G H T S G R A P H I C A L A B S T R A C T

• Smokers present a 4.5-fold higher parti-

cle number emission rate than vapers.
• The dose received by passive smokers is
up to15-fold higher than passive vaper
one.
• The maximum dose was received by
passive smokers and vapers at the 21st
generation.
• ELCR for passive smokers is 5 orders of
magnitude higher than the passive
vaper one.

a r t i c l e i n f o a b s t r a c t

Article history: Smoking activities still represent the main, and preventable, cause of lung cancer risk worldwide. For this reason,
Received 24 February 2018 a number of studies were carried out to deepen and better characterize the emission of cigarette-generated main-
Received in revised form 13 May 2018 stream aerosols in order to perform an a-priori evaluation of the particle doses and related lung cancer risks re-
Accepted 5 June 2018
ceived by active smokers. On the contrary, a gap of knowledge still exists in evaluating the dose and risk received
Available online 18 June 2018
by passive smokers in indoor private micro-environments (e.g. homes). For this purpose, in the present paper, an
Editor: Wei Huang experimental campaign was performed to evaluate the exposure to second-hand aerosol from conventional and
electronic cigarettes and to estimate the consequent dose received by passive smokers/vapers and the related
Keywords: lung cancer risk.
Second-hand smoke Measurements of exposure levels in terms of particle number, PM10 and black carbon concentrations, as well as
Ultrafine particles particle size distributions, were performed in a naturally ventilated indoor environment during smoking activi-
Cigarettes ties of tobacco and electronic cigarettes. The particle emission rates of smokers and vapers, for the different aero-
Electronic cigarettes sol metrics under investigation, were evaluated. Moreover, for a typical exposure scenario, the dose received by
Dose
the passive smokers/vapers in a naturally ventilated indoor micro-environment was estimated through a
Risk
Multiple-Path Particle Dosimetry (MPPD) model able to assess the particle dose received in the different tracts

⁎ Corresponding author.
E-mail address: m.manigrasso@inail.it (M. Manigrasso).

https://doi.org/10.1016/j.scitotenv.2018.06.059
0048-9697/© 2018 Elsevier B.V. All rights reserved.
138 P. Avino et al. / Science of the Total Environment 642 (2018) 137–147
of the respiratory systems. Furthermore, on the basis of scientific literature data about mass fraction of carcino-
genic compounds contained in cigarette-emitted particles (i.e. Heavy Metals, Benzo-a-pyrene and nitrosamines)
and the estimated doses, the excess life cancer risk (ELCR) for passive smokers/vapers was evaluated. Cumulative
respiratory doses for passive smokers were up to 15-fold higher than for passive vapers. The ELCR for second-
hand smokers was five orders of magnitude larger than for second-hand vapers.
1. Introduction
1.1. Conventional and electronic cigarette emissions
Tobacco-cigarette smoke has been recognized to increase lung can-
cer risk by a 5- to 10-fold factor in a dose dependent manner
(Schwartz and Cote, 2016). In fact, the International Agency for
Research on Cancer (2004) has identified N70 compounds in tobacco
smoke with sufficient evidence for carcinogenicity in either laboratory
animals or humans and sixteen of them have been classified as group
1 carcinogenic to humans. Some of these group 1 compounds, such as
Polycyclic Aromatic Hydrocarbons (PAHs) are emitted by cigarette com-
bustion, others, namely tobacco-specific N-nitrosamines, are mainly
produced during the curing process of tobacco (International Agency
for Research on Cancer, 2004).
Electronic cigarettes (e-cigs) have been commercialized with the
aim of eliminating the intake of such carcinogenic compounds. E-cigs
are battery-operated devices, where the liquid contained in a vial is va-
porized over an electric heater and the resulting aerosol is inhaled
through a mouthpiece. Therefore, e-cigs neither involve combustion
nor use cured tobacco leaves. However, several recently published stud-
ies have pointed out their health effects and the presence of harmful
compounds in their aerosol, even if at lower levels than for tobacco cig-
arettes (Farsalinos et al., 2014; Goniewicz et al., 2014). Kosmider et al.
(2014) found that e-cig vapors contain toxic and carcinogenic carbonyl
compounds at levels increasing with battery output voltage. Goniewicz
et al. (2014) reported the presence in e-cig aerosol of carbonyl com-
pounds, among which formaldehyde, tobacco-specific N-nitrosamines
NNN and NNK and metals, such as Pb, Cd and Ni, at levels 9–450 times
lower than in cigarette smoke,
Dosimetry studies on mainstream cigarette (Fuoco et al., 2017;
Stabile et al., 2017a) and e-cig aerosols have been carried out also
reporting size segregated data per airway generation (Manigrasso
et al., 2015a) and as function of the age of the user (hereinafter referred
as “vaper”; (Manigrasso et al., 2017a)). On average, 6.25 × 1010 particles
are deposited in the human respiratory tree after a single puff of an e-
cigarette. This dose represents about 30% of the daily doses of a non-
smoking individual (Buonanno et al., 2011a). Moreover, aerosol doses
are asymmetrically deposited in the lungs: in the right-upper lung
lobe, they are about twice than in left-upper lobe and 20% greater in
right-lower lobe than in the left-lower lobe (Manigrasso et al., 2015b).
Azzopardi et al. (2016) studied the cytotoxic effect of tobacco ciga-
rette and e-cig aerosol on human bronchial epithelial cells, reporting
the half-maximum effective concentration (EC50) for 60 min exposure.
When expressed for deposited mass, e-cig aerosol was significantly
(94%) less cytotoxic than conventional cigarette aerosol (60 min depos-
ited mass EC50 52.1 vs. 3.1 μg/cm2). However, it should be considered
that these cell viability data derive from in vitro acute exposure assess-
ments. To date no data from chronic exposure studies are available. The
urgent need of such data has been pointed out by Ganapathy et al.
(2017). They showed that e-cig aerosol extracts can cause significant
levels of DNA damage, even if at levels lower than observed for main-
stream smoke extracts. The authors observed increased cellular Reactive
Oxygen Species (ROS), and decreased total antioxidant capacity. More-
over, they observed decreased expression of proteins essential for DNA
damage repair and pointed out that this could increase cancer risk.
© 2018 Elsevier B.V. All rights reserved.
1.2. Second-hand smokers and “vapers”
A further concern related to the e-cigarette consumption is repre-
sented by their influence on the indoor air quality and the consequent
effects on passively exposed populations (hereinafter referred as
second-hand “vapers”). Great part of the studies addressing this issue
concludes that harmful compounds are present in the aerosol emitted
by e-cigs at lower concentrations than for tobacco cigarettes, but
above background concentrations, so that a health risk may be envis-
aged for the exposed population (Hess et al., 2016). Saffari et al.
(2014) performed ambient air sampling in a test room in order to com-
pare second hand exposure to e-cig aerosol and tobacco cigarette
smoke. They observed very lower particle-phase emissions from e-cigs
than from tobacco cigarette. Black carbon and PAHs abundantly present
in tobacco smoke were not detected in e-cig aerosols. Emission rates of
organic compounds and of inorganic elements were respectively N100
times and 10 times lower for e-cigs than for tobacco cigarettes, with
the exception of Ni and Ag, whose emission rates were higher for e-
cigs than for tobacco cigarettes. Similar studies and results were carried
out by other authors (McAuley et al., 2012; Schober et al., 2014; Schripp
et al., 2013). Moreover, Ballbè et al. (2014) reported nicotine concentra-
tions higher in homes with e-cigarettes users than in nonsmoking con-
trol homes and nicotine concentration 5.7 times higher in homes with
tobacco cigarette smokers than in homes with e-cigarettes users. Uri-
nary and salivary cotinine concentrations were higher than for control
homes. However, no statistically significant differences were observed
between e-cig and tobacco cigarette exposed individuals, suggesting
similar nicotine uptake. In agreement with these findings, Flouris et al.
(2013) reported similar serum cotinine increments for passive exposure
to tobacco cigarette smoke and to e-cig aerosol. Moreover, Flouris et al.
(2012) showed that second hand exposure to e-cig aerosol does not af-
fect complete blood count markers (blood sample collected 1 h after
passive smoking sessions). On the contrary, the authors observed in-
creased white blood cell count, lymphocyte count and granulocyte
count in individual exposed to passive tobacco smoke.
1.3. Aims of the work
Dosimetry studies on second-hand exposure to e-cigs aerosols are
very sparse. Sosnowski and Kramek-Romanowska (2016) estimated
the regional deposition efficiency of secondary e-cig aerosols during
passive vaping, based on the expected growth of the exhaled particles.
Protano et al. (2016) and Protano et al. (2017) measured the temporal
evolution in a test room of the number size distributions of aerosol
emitted by tobacco cigarettes, e-cigs and by the newly released IQOS®
(an electronic heat-not-burn device) estimating the relevant aerosol
deposition doses. Anyway, to date, no study has been performed neither
on the distribution per airway generation nor on the size distribution of
the aerosol doses deposited in the respiratory tree, due to second hand
vaping of e-cigs. Within this context, the purpose of this study is to:
i) measure the emission rate of smokers/vapers during smoking/vaping
activities, ii) estimate the size segregated and regional resolved aerosol
doses deposited in the respiratory systems of individuals exposed to
second-hand aerosols emitted by e-cigs and tobacco cigarettes, iii) esti-
mate the related lung cancer risk of individuals exposed to second-hand
aerosols on the basis of carcinogenic compounds in cigarette- and e-
 P. Avino et al. / Science of the Total Environment 642 (2018) 137–147
cigarette-generated aerosols detected by previous papers (Farsalinos
et al., 2015a; Gillman et al., 2016; Goniewicz et al., 2014; Mikheev
et al., 2016; Schober et al., 2014; Talih et al., 2015; Zhao et al., 2016).
2. Materials and methods
2.1. Site description
The experimental analysis was performed on April–July 2017 at the
European Accredited (EA) Laboratory of Industrial Measurements
(LAMI), University of Cassino and Southern Lazio, Italy in a naturally
ventilated 40 m3 room. The ventilation conditions of the room were
held constant during the tests, indeed the doors and windows were
kept close. The median air exchange rate (AER) of the test room was
evaluated on the basis of the CO2 decay curve (He et al., 2004) using a
non-dispersive infrared analyzer (Testo - Ambient CO2 probe). Such
CO2 decay test was performed under the same ventilation conditions
adopted in the smoking/vaping tests, i.e. doors and windows closed.
The median AER measured was equal to 0.21 h−1 which is typical of nat-
urally ventilated buildings (d'Ambrosio Alfano et al., 2016; d'Ambrosio
Alfano et al., 2012; Stabile et al., 2017b; Stabile et al., 2016).
2.2. Experimental apparatus
In order to measure particle size distributions and total concentra-
tions of the different airborne particle metrics in the room where
smoking and vaping sessions were performed, the following instru-
ments were used:
- a butanol-based Condensation Particle Counter (CPC 3775, TSI Inc.)
to measure the particle number concentration of particles N4 nm in
diameter up to 1 × 107 part·cm−3 with 1-s sampling time;
- a light-scattering laser photometer (DustTrak Aerosol Monitor 8534,
TSI Inc.) to measure particle mass concentrations in terms of PM1,
PM2.5, PM10 with 1-s sampling time;
- a Scanning Mobility Particle Sizer spectrometer (SMPS 3936, TSI
Inc.) to measure the particle number distribution in the sub-
micrometric particle range. In particular, the SMPS is made up of
an Electrostatic Classifier (EC 3080, TSI Inc.), which classifies parti-
cles according to their electrical mobility diameter, (Avino and
Manigrasso, 2017; Manigrasso and Avino, 2012) and a further CPC
3775 to count the classified particles, thus providing particle number
size distribution. In the experimental analysis a scan time of 135 s, an
aerosol flow rate of 0.3 L min−1 and a sheath flow rate of 3 L min−1
were selected, then providing particle number size distributions in
the 14–700 nm mobility diameter range;
- an Aethalometer (AE51, Magee Scientific), operating through light's
absorption (attenuation) of optically-absorbing particles technique,
to measure black carbon (BC) concentration with a time resolution
of 1 min;
- a thermo-dilution system made up of a Rotating Disk Thermodiluter
(RDTD model 379020, Matter Engineering AG) and a Thermal Condi-
tioner Air Supply (model 379030, Matter Engineering AG).
2.3. Methodology
2.3.1. Second-hand smoke exposure and evaluation of the emission rates
Second-hand smoke aerosol measurements, useful to calculate the
emission rates/factors of smokers and vapers, were performed in the
abovementioned 40-m3 room using the instrumentation described in
the Section 2.2. 10 volunteers were involved in the survey: they were
asked to perform three separated smoking/vaping sessions: smoking a
conventional cigarette with a nicotine concentration equal to 0.8 mg
and vaping an e-cigarette. In particular, a new (unused) rechargeable
e-cig (made up of a tank system) filled with a mint-flavored liquid
with a nicotine concentration of 12 mg mL−1 was used. The volunteers
139
smoked conventional cigarettes as they usually do and were asked to
vape the electronic cigarettes with a similar vaping behavior, i.e.
adopting the same vaping time and number of puffs of the smoking ses-
sion as well as trying to reproduce the same puff length and interpuff
time. The volunteers smoked/vaped sitting on a chair at a distance of
about 2 m from the instrumentations in order to allow the dispersion
of the emitted particles in the room then avoiding a direct exposure of
the experimental apparatus that would have led to an overestimate of
the emission rate/factor. The smoking/vaping tests were performed
considering 5-min measurements of background concentrations and
distributions followed by 60-min measurement including the
smoking/vaping session (roughly 5 min), and then further particle con-
centration and distribution decay useful for emission characterization.
The sampling times of CPC and DustTrak were chosen equal to 1-s, but
they were post-processed considering 1-min averaging time; for SMPS
a sampling length of 135 s was adopted.
The authors highlight that two different vaping tests were per-
formed per each volunteer in order to evaluate the exposure to both vol-
atile and non-volatile fractions of the e-cigarette-generated particles.
Indeed, since e-cigarettes emit aerosol mainly in the form of droplets,
due to the presence of solvents in e-liquids (i.e. propylene glycol and
glycerine), a significant volatile fraction is expected in comparison
with conventional cigarettes (Fuoco et al., 2014; Scungio et al., 2018).
Therefore, particle size number distributions were measured both
with and without thermo-dilution. In particular, the tests with the
thermo-dilution system were performed by connecting the SMPS and
the CPC to the thermo-dilution system and thermo-conditioning (i.e.
heating) the aerosol at 300 °C (with a dilution ratio of 1:40) to measure
only the non-volatile amount of the particles. More details on the parti-
cle volatility characterization were reported in (Fuoco et al., 2014;
Scungio et al., 2018).
In order to check whether particle concentrations measured during
vaping session with and without thermo-dilution were statistically sim-
ilar or not, a statistical comparison of the particle concentration data
during the two vaping sessions was performed. In particular, a prelimi-
nary normality test (Shapiro-Wilk test) was carried out to evaluate the
statistical distribution of the data. Since the assumption of Gaussian dis-
tribution was not met, a non-parametric test (Kruskal-Wallis test;
(Kruskal and Wallis, 1952)) was adopted considering a significance
level of 99% (a p-value lower than 0.01).
On the basis of particle and BC concentrations, the emission rates
(ERs) and emission factors (EFs) in terms of particle number, PM10,
and BC content were calculated for each smoking and vaping session.
Since the measurements were performed in a closed environment, the
overall second-hand smoke, combination of exhaled mainstream
smoke and sidestream smoke (only for conventional cigarettes), was in-
volved in the emission rates and factors: therefore, the tests performed
allowed to obtain the overall emission of smokers and vapers. In partic-
ular, the ER was evaluated on the basis of the particle concentration
trends applying the equation derived by He et al. (2004) and previously
applied for several indoor sources (Buonanno et al., 2011b; Buonanno
et al., 2009b, 2011c; Fuoco et al., 2014; Stabile et al., 2014):
 
C in −C in;0

ER ¼ V þ AER þ k ∙C in −AER∙C in;0 ð1Þ
Δt
where Cin and Cin,0 represent the peak and initial indoor particle concen-
trations, respectively, AER is the air exchange rate (as obtained through
the CO2 decay test), AER þ k is the average total removal rate due to both
particle exfiltration (related to the AER) and particle deposition (evalu-
ated by means of the particle deposition rate, k), Δt is time difference be-
tween initial and peak concentration, C in is the average indoor particle
concentration in the room, and V is the volume of the room. In the emis-
sion rate model particle condensation, evaporation and coagulation
were considered negligible: in the Results and discussions section, it
will be shown that such approximation can be considered acceptable
140 P. Avino et al. / Science of the Total Environment 642 (2018) 137–147
for the tests performed. Emission rate data for each test reported in the
Results and discussions section represent the median values of all the
measurements. Emission factors (EFs) of each cigarette/e-cigarette
were then evaluated multiplying the smoker/vaper emission rates by
the corresponding smoking/vaping time. For e-cigarettes, emission
rate data obtained without thermo-dilution system were discussed in
the results since no statistical differences with those obtained by
thermo-diluting the aerosol were recognized.
2.3.2. Dose evaluation
Particle size distribution trends were used to estimate the dose re-
ceived by second-hand smokers and vapers in a 40-m3 room supplied
by a natural ventilation system: the authors highlight that the measured
averaged air exchange rate (0.21 h−1) is typical of public and private
buildings not supplied by mechanical ventilation systems (d'Ambrosio
Alfano et al., 2012; Stabile et al., 2016; Stabile et al., 2015).
The overall doses (i.e. including volatile and non-volatile contribu-
tions) of aerosol deposited in the human respiratory tree were esti-
mated by means of the multiple-path particle dosimetry model
(MPPD v2.1, ARA 2009). The MPPD model was extensively described
in previous papers (Anjilvel and Asgharian, 1995; Asgharian et al.,
2001; Avino et al., 2013; Avino et al., 2015; Avino et al., 2016;
Ingebrethsen et al., 2011; Manigrasso et al., 2015c; Manigrasso et al.,
2017b; Manigrasso et al., 2017c; Sahu et al., 2013). It calculates the de-
position and the clearance of aerosols, from nanoparticles to coarse par-
ticles, in the respiratory system of humans and rats. It takes into account
the deposition mechanisms of diffusion, sedimentation, impaction, and
interception within the airway or airway bifurcation. The structure of
the human airway system is described as a sequence of dichotomous
branching that starts from the trachea. The progressively bifurcating air-
ways are classified by their generation number: the trachea is identified
as the first generation (Yeh and Schum, 1980). Particle number doses
are calculated as function of particle diameter and airway generation
number. The 60th percentile stochastic lung morphometry was
adopted, together with the following settings: (i) a uniformly-
expanding flow; (ii) an upright body orientation; and (iii) nasal breath-
ing with a 0.5 inspiratory fraction and no pause fraction. A Caucasian
adult male in the sitting-awake condition was considered with the fol-
lowing parameter based on the ICRP report (International Commission
on Radiological Protection, 1994): (i) a functional residual capacity
(FRC) of 3300 mL; (ii) an upper respiratory tract (URT) volume equal
to 50 mL; (iii) a 12-min−1 breathing frequency; and (iv) an air volume
inhaled during a single breath (tidal volume, VT) of 0.75 L.
Particle doses deposited into the human respiratory system
were estimated as incremental doses over the relevant background
values (i.e. the “extra dose”) calculated using incremental aerosol
concentrations over the background concentrations measured be-
fore the smoking/vaping sessions. The following extra dose values,
here reported in terms of particle number metrics (N), were
calculated:
- total particle number extra doses deposited after a single respiratory
act, as functions of airway generation number (G) and time (t)
X
107
ΔDdev
Tot−N ðt; GÞ ¼ V T ∙ ΔC N ðdi ; t Þ∙F ðdi ; GÞ
1¼1
where ΔCN(di,t) is the incremental aerosol number concentration as
function of particle diameter (di) and time, F(di,G) is the particle deposi-
tion fraction as function of particle diameter and airway generation
number (G), it was obtained by running the MPPD model separately
for each SMPS size channel (from 14 to 700 nm) considered to be com-
posed of a monodisperse aerosol. The super script “dev” refers to the cig-
arette smoked, either electronic cigarette (e-cig) or tobacco cigarette
(cig), 107 is the number of SMPS size channels.
- total cumulative particle number extra doses as functions of airway
generation number after a given exposure time t
X
t
ΔDdev
c−N ðt; GÞ ¼ ΔDdev
Tot−N ðt; GÞ ð3Þ
t¼t0
- ratio of conventional cigarette total cumulative particle number
extra dose to e-cig one, as function of time and airway generation
number
Rcig=e−cig ðt; GÞ ¼ ΔDcig e−cig
c−N ðt; GÞ=ΔDc−N ðt; GÞ ð4Þ
- particle number extra dose per each particle diameter and airway
generation number calculated at the particle concentration peak in
the room (tmax)
ΔD max −Ndev ðd; GÞ ¼ V T ∙ΔC N ðd; t max Þ∙F ðd; GÞ ð5Þ
Particle surface area extra doses were evaluated on the basis of the
particle size number distributions (measured for vaping sessions with-
out aerosol thermo-dilution) assuming that the particles were spherical.
In particular, particle surface area extra doses deposited in the alveolar
(referred to as δAlv) and tracheobronchial (referred to as δTB) regions
of the lung were calculated as cumulative surface area extra doses de-
posited in the tracheobronchial (airway generations 1–16) and alveolar
(airway generations 17–28) regions, respectively:
X
t
δAlv ¼ ΔDdev
c−SAlv ðt; G17−28 Þ ¼ ΔDdev
Tot−SAlv ðt; G17−28 Þ ð6Þ
t¼t0
X
t
δTB ¼ ΔDdev ΔDdev
c−STB ðt; G1−16 Þ ¼ Tot−STB ðt; G1−16 Þ ð7Þ
t¼t0
The doses calculated through the Eqs. (2)–(7) were reported as me-
dian values in the Results and discussions section. Such doses represent
the overall surface area doses (i.e. including volatile and non-volatile
contributions as obtained from the measurements without aerosol
thermo-conditioning) of particles received by the exposed population.
Moreover, in order to properly evaluate the surface area contribu-
tion to the lung cancer risk, the e-liquid solvent (i.e. the volatile fraction)
presents in the aerosol emitted by vapers should not be considered. To
this purpose, the non-volatile surface area doses, referred to as δAlv_n-v
and δTB_n-v, were calculated multiplying the overall surface are doses
(δAlv and δTB) by the ratio between non-volatile surface area concentra-
tion (measured with thermo-dilution at 300 °C) and that measured
without aerosol thermo-conditioning.
2.3.3. Lung cancer risk evaluation
ð2Þ
On the basis of the extra-dose values and the amount of carcinogenic
compounds carried by airborne particles, the excess lung cancer risk
(ELCR) due to the exposure to second-hand smoke in a 40-m3
naturally-ventilated room was evaluated. In particular the extra-ELCR,
i.e. the risk related to the extra-dose received by people exposed to
second-hand smoke with respect to those not exposed, was calculated.
The ELCR was evaluated through an ad-hoc model proposed by Sze-To
et al. (2012) able to take into account the contribution of the different
aerosol metrics: sub-micron particles, expressed as particle surface
area, and super-micron particles, expressed as PM10. Such model was
 P. Avino et al. / Science of the Total Environment 642 (2018) 137–147 141

applied in our previous papers to evaluate the overall lung cancer risk of different compounds and no age-dependent effect: therefore, the life-
Italian population (Buonanno et al., 2015; Buonanno et al., 2017), as time risk is just linearly proportional to the amount of particles depos-
well as to estimate the risk at a receptor site of a waste-to-energy ited and their toxicity. Further limitations and assumptions of the risk
plant (Scungio et al., 2016) and that characteristics of active smokers model are hereinafter reported.
and vapers (Scungio et al., 2018; Stabile et al., 2017a). The extra-ELCR The mass fraction of carcinogenic compounds carried by the parti-
lifetime (assumed as 70 years) risk due to the exposure to a single cles emitted by smokers and vapers was evaluated on the basis of scien-
smoking/vaping activity per day was evaluated as: tific literature data reported in an our previous papers (and summarized
in Table 1) where the ELCRs due to direct inhalation of mainstream cig-
SFm   arette and e-cigarette aerosols were calculated (Scungio et al., 2018;
ELCRextra smoking ¼ ∙ c ∙ðδ þ δTB Þ þ δPM10 ð8Þ
BW f Alv Stabile et al., 2017a): i.e. the relative amount of carcinogenic com-
pounds (mi/PM10) carried by particles of second-hand smoke was con-
SFm  
ELCRextra vaping ¼ ∙ c ∙ðδ þ δTB n−v Þ þ δPM10 ð9Þ sidered equal to that typical of the mainstream aerosol, therefore the
BW f Alv n−v
SFm values characteristics of mainstream aerosols were adopted.
where BW is the average body weight of the population (70 kg), δAlv and In Table 1 SFm of cigarette- and e-cigarette-generated particles and
δTB are the alveolar and tracheobronchial particle surface area dose re- the relative contribution of each compound to such SFm, are also re-
ceived by the exposed people for a single smoking session, δAlv_n-v and ported as obtained by our previous studies evaluating cigarette- and
δTB_n-v are the non-volatile amount of alveolar and tracheobronchial e-cigarette generated lung cancer risk (Scungio et al., 2018; Stabile
particle surface area dose received by the exposed people for a single et al., 2017a). Such data represents the most probable SFm (and relative
vaping session, δPM10 is the PM10 extra doses received by the exposed contribution) values as obtained considering the typical mass fraction of
people for a single smoking/vaping session, SFm is the inhalation slope chemical compounds obtained from scientific literature data for the cig-
factor of the mixture composed by n carcinogenic pollutants on PM10 arette and e-cigarette (with nicotine) investigated. SFm value of conven-
P tional cigarettes (1.31 × 10−3 kg d mg−1, representing the median value
evaluated as ni SFi ∙ PM
mi
10
, SFi is the inhalation slope factor used to describe
of the data obtained for different brands reported in Stabile et al. (2017a))
the lifetime cancer potency of the i-th pollutant (i.e. the percent increase
resulted much higher than e-cigarette one (1.85 × 10−6 kg d mg−1) and
in the risk of getting cancer associated with exposure to a unit concentra-
larger than those typical of cooking-generated particulate matters (Sze-
tion of a chemical every day for a lifetime, here assumed equal to
To et al., 2012). Particle toxicity data reported in Table 1 clearly highlight
70 years), mi is the mass concentration of the i-th pollutant present on
that the median SFm for conventional cigarettes is mainly due to the
the PM10 mass, cf is the conversion coefficient (6.6 × 10−13 mg nm−2),
tobacco-specific nitrosamines (NNK and NNN), whereas a lower contri-
obtained by Sze-To et al. (2012), representing the equivalent toxicity of
bution is due to BaP and heavy metals (As, Cd, Ni). SFm for e-cigarette-
the particle surface area metric expressed as particle mass. The SFs of
generated particles is mainly due to Cd, As, and NNK. The authors point
the carcinogenic chemicals investigated in the present paper were ob-
out that (i) detailed discussions on the toxicity of particles, (ii) data anal-
tained from the Office of Environmental Health Hazard Assessment
ysis, (iii) type of cigarettes/e-cigarettes investigated, (iv) scientific refer-
(2009): in particular, SF values for PAHs (expressed as benzo-a-pyrene,
ences for chemical characterization of the emitter aerosols are reported
BaP), As, Cd, Ni, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
in abovementioned previous papers (Scungio et al., 2018; Stabile et al.,
(hereinafter reported as NNK), and N′-nitrosonornicotine (hereinafter
2017a).
reported as NNN) are equal to 3.9, 15.1, 6.3, 0.91, 22.1, and
1.40 kg day mg−1, respectively.
3. Results and discussions
Once the lifetime ELCRextra was estimated, the extra-ELCR corre-
sponding to a specific exposure scenario (in terms of number of ciga-
3.1. Emission factor of smokers and vapers
rettes and years of exposure) was evaluated as:

Y In Fig. 1, an illustrative example of typical trends measured in the

ELCRextra scenario ¼ ELCRextra ∙N cig ∙
70
where Ncig is the number of cigarettes/e-cigarettes which people is pas-
sively exposed to in indoor on daily-basis, and Y is the number of year of
exposure. The authors point out that the contribution of the PM10 dose
(δPM10) in Eqs. (8)–(9) was ignored since previous papers showed that
such contribution is negligible (Buonanno et al., 2015; Buonanno et al.,
2017; Scungio et al., 2016; Stabile et al., 2017a; Sze-To et al., 2012).
Moreover, the authors also highlight that the Eqs. (8)–(10) were ob-
tained by Sze-To et al. (2012) considering no synergic effects of the
ð10Þ test room during cigarette and e-cigarette smoking experiments is re-
ported. In particular, total particle number (measured without
thermo-dilution), PM10 and Black Carbon concentration trends are re-
ported for one of the volunteers under examination. During cigarette-
smoking test, all of the three aerosol metrics clearly increased in con-
centration over the relevant background concentration levels. During
e-cigarette-smoking test, no increase in PM10 and BC concentrations
with respect to the background was measured, whereas a detectable in-
crease, even if much lower than typical of the conventional cigarettes,
was observed for particle number concentrations.

Table 1
Typical carcinogenic compound concentrations in mainstream aerosol emitted by conventional and electronic cigarettes and corresponding slope factors of the mixture (SFm) as obtained
by Stabile et al. (2017a) and Scungio et al. (2018).

Concentrations of chemical compounds in the mainstream aerosol PM10

BaP As Cd Ni NNK NNN

Conventional cigarettes (ng cig−1) 10–14 3–9 40–123 0–0.54 93–136 139–240 4.77–8.51 × 103 mg m−3a
Electronic-cigarettes (ng puff−1) NLOD 0.13 0.64 0.40–1.23 0.06–0.18 0.01–0.22 3.03–8.06 × 106 ng puff−1

Relative contribution of chemical compounds to the SFm SFm (kg d mg−1)

BaP As Cd Ni NNK NNN

Conventional cigarettes 2% 3% 13% 0% 74% 8% 1.31 × 10−3

Electronic-cigarettes 0% 20% 42% 8% 28% 2% 1.85 × 10−6
a
PM10 concentration data were converted in mg cig−1 on the basis of the puff volume data and number of puff per cigarette reported in Stabile et al. (2017a).
142 P. Avino et al. / Science of the Total Environment 642 (2018) 137–147

Fig. 1. Example of total particle number, PM10 and Black Carbon (BC) concentrations measured in the test room during cigarette and e-cigarette smoking/vaping experiments.

In Fig. 2 particle size distribution temporal evolutions corresponding
to the trends reported in Fig. 1 are shown. During cigarette test the in-
crease of particle number concentration is due to the emission of the
smoking activity of particles with a mode of roughly 100 nm. On the
contrary, electronic cigarette vapers emit particles (measured without
thermo-dilution) sized with a mode of about 30 nm. For all the tests,
no noticeable coagulation processes were recognized during the
decay, since no particle size increase was measured, then showing
that the dilution process is faster than the coagulation one. The particle
number distribution mode of the second-hand aerosol here reported
are coherent with the particle number distribution mode of the main-
stream aerosol (roughly 30 nm) measured by Scungio et al. (2018)
when using the same electronic cigarette liquid and model. The authors
point out that different electronic cigarette types and/or liquids may re-
sult in different modes of the mainstream aerosols: they were found to
range from 24 to 36 nm (Schober et al., 2014), to N100 nm (Fuoco et al.,
2014; Ingebrethsen et al., 2012).
In Table 2 the ranges of peak concentrations measured during ciga-
rette and e-cigarette (without thermo-dilution) smoking tests were re-
ported for all the aerosol metrics under investigation. Such data clearly
confirm the abovementioned information described in the illustrative
trends of Fig. 1: indeed, higher peaks in terms of number concentrations
were measured during cigarette smoking tests (even higher than 1
× 105 part cm−3) in comparison with electronic cigarette vaping tests
(about 3 × 104 part cm−3). Peak concentrations of PM10 and BC were
not recognized during electronic cigarette vaping tests, whereas high
peaks during cigarette smoking tests were recognized: as an example,
peaks of PM10 and BC concentrations up to 1 mg m−3 and 20 μg m−3, re-
spectively, were measured. Tests performed using the thermo-dilution
systems at 300 °C during e-cigarette vaping sessions, showed a not sig-
nificant reduction of particle number concentrations, whereas the mode
of about 30 nm measured without thermo-dilution shifted down to
24 nm (Scungio et al., 2018), due to the elimination of the volatile ma-
terial. As a consequence, a reduction of total surface area concentration
of about 10% was observed. Therefore, the surface area dose of non-
volatile particles received by second-hand vapers (δAlv_n-v + δTB_n-v) is
equal to 0.9-fold the overall surface dose including both volatile and
non-volatile materials (δAlv + δTB).
In Table 2 the median emission rates and emission factors, calcu-
lated on the basis of the concentration trends and smoking/vaping be-
haviors, are also reported: median particle number emission rates
equal to 4.31 × 1011 and 9.62 × 1010 part·min−1 were measured for
smokers and vapers, respectively. Median smoker emission rate is
higher than or comparable to other typical indoor sources as laser
printers (Scungio et al., 2017), 3-D printers (Stabile et al., 2017c), but
lower than the other main indoor combustion sources, i.e. cooking ac-
tivities (Stabile et al., 2014) and incense and candle burning processes
(Stabile et al., 2012). On the contrary, median PM10 and BC emission
rates (roughly 5 mg min−1 and 66 μg min−1) are even higher than
such other indoor combustion sources (Buonanno et al., 2009b;

Fig. 2. Example of particle number distributions measured in the room during the cigarette (a) and e-cigarette without thermo-conditioning (b) smoking experiments whose total
concentration trends are reported in Fig. 1.
 P. Avino et al. / Science of the Total Environment 642 (2018) 137–147 143

Table 2 (including smoking sessions) received by second-hand smokers was

Ranges of peak concentrations, median emission rates and median emission factors in about 10-fold higher than for e-cig: 1.0 × 1010 particles (3.2 × 109 par-
terms of number, PM10 and black carbon measured for smokers and vapers. For vapers
data without thermos-dilution were considered. Emission factors of the e-cigarettes/
ticles and 7.9 × 109 particles deposited in the tracheobronchial and al-
vapers are referred to the typical smoking behavior of a conventional cigarette. veolar regions, respectively). The corresponding median particle
surface area doses deposited in the alveolar and tracheobronchial re-
Cigarettes/smokers e-Cigarettes/vapers
gions resulted equal to 485 and 3.6 mm2 (non-volatile contribution
4
Peak N_peak 7.29 × 10 –1.26 × 2.36 × 104–3.11 × only) for second-hand smokers and vapers, respectively.
concentrations (part·cm−3) 105 104
In Fig. 5 the ratio of extra doses received by smokers and vapers as
PM10_peak (mg 0.271–0.983 bLOD
m−3) function of the airway generation (Rcig/e−cig(t, G)) is reported. The figure
BC_peak (μg m−3) 3.53–21.1 bLOD clearly highlights that the highest Rcig/e−cig(t, G) values (about 15) were
Emission rates ER_N 4.31 × 1011 9.62 × 1010 found at the 2nd and 27th airway generations.
(part·min−1) In Fig. 6 the particle number extra dose for each particle diameter and
ER_PM10 (mg 4.92 Negligible
min−1)
airway generation number calculated at the particle concentration peak
ER_BC (μg min−1) 66.2 Negligible in the test room, (ΔDcig e−cig
max−N(d, G), and ΔDmax−N(d, G)) are shown for
Emission factors EF_N (part·cig−1) 2.80 × 1012 5.51 × 1011 smokers and vapers. The maximum doses were estimated at the 22nd
EF_PM10 (mg 32.0 Negligible airway generation for 82 nm particles (ΔDcig 4
max−N(82,22)=6.6 × 10 par-
cig−1)
ticles) for passive smokers and at the 21st airway generation for 29 nm
EF_BC (μg cig−1) 430 Negligible e−cig
particles (ΔDmax−N (29, 21) = 1.2 × 104 particles) for passive vapers.

Stabile et al., 2012). In Table 2 emission factors are also summarized, for
each cigarette the smokers emit (as median value) 2.80 × 1012 particles,
32.0 mg of PM10, 430 μg of BC, whereas for each e-cigarette, the vapers
emit 5.51 × 1011 particles and negligible PM10 and BC amounts. The au-
thors, once again, point out that the emission factors of the e-cigarettes
are referred to the typical smoking behavior of a conventional cigarette
(i.e. roughly 5 min).
3.2. Aerosol deposition extra-doses in the respiratory system
In Fig. 3 the total particle number extra doses ΔDe−cig
Tot−N(t, G) and
ΔDcig
Tot−N(t, G) for e-cigarettes (corresponding to the measurements
without thermo-dilution) and tobacco-cigarettes, respectively, are
reported. Maximum median extra doses for e-cigarettes were
reached at the 21st airway generation (3.4 × 105 particles) and
about 52 min were necessary for ΔDe−cigTot−N(t, G) to decay to the back-
ground value. Maximum median total extra doses (ΔDcig Tot−N ) were
reached at the 21st airway also for the tobacco-cigarette (2.3 × 106
particles), even if, after about 52 min, the extra dose ΔDcig Tot_N was
still larger than 50% of the maximum value.
Fig. 4 shows the total median cumulative extra dose ΔDcig c−N(t, G)
and ΔD e−cig
c−N (t, G) for e-cigarettes and tobacco-cigarettes, respec-
tively. The total median extra dose due to 1-h exposure (including
vaping sessions) was about 1.1 × 109 particles with 3.3 × 108 parti-
cles and 8.1 × 108 particles deposited in the tracheobronchial (air-
way generations 1–16) and alveolar (airway generations 17–28)
regions, respectively. The median extra dose due to 1-h exposure
3.3. Extra-ELCR
Based on the median particle extra-dose values received for each
smoking/vaping activity and the corresponding particle toxicity (SFm
values, see Section 2.3.3), the median extra-risk for passive smokers/
vapers in a naturally ventilated 40-m3 room was evaluated. The risk
due to the exposure to a single daily smoking/vaping session for an entire
year (365 days per year) resulted equal to 8.56 × 10−5 and 8.97 × 10−10
for exposure to smoking and vaping activities, respectively. The extra-
risk due to the exposure to electronic cigarette second hand smoke is sig-
nificantly lower than the cigarette one (five order of magnitude), this is
due to both the lower toxicity of the particles emitted (median SFm
values three order of magnitude lower than cigarette ones) and the
lower indoor concentrations during vaping activities resulting in surface
area doses two order of magnitude lower than the cigarette-related ones.
In particular, the exposure to a single daily smoking session for an entire
year is greater than the maximum tolerable risk defined by the US EPA
(10−5, U.S. Environmental Protection Agency, 1991). In order to compare
the extra-risk due to the second-hand smoke with different exposure
patterns, in terms of years of exposure and number of cigarettes/e-
cigarettes, in Fig. 7 the ELCR received by people exposed to cigarette
and e-cigarette aerosols in naturally ventilated buildings as function of
exposure scenario (i.e. years of exposure and number of cigarettes/e-
cigarettes, ELCRextra-scenario) is reported. Indeed, quantifying the actual
exposure to second-hand smoke is not a trivial aspect since, differently
from active smokers, no statistics are available. To this purpose in Fig. 7
a parametric evaluation of the extra-risk was provided. For example, an

a) b)

Fig. 3. Temporal trend of total particle number extra doses (ΔDdev

Tot−N(t,G), dev = cig, e-cig) deposited into the respiratory tree, estimated for each single respiratory act, as functions of
cig
airway generation number (G) and time (t), over 1 h time exposure, including 5 min smoking/vaping sessions and post-smoking/vaping exposures: a) ΔDTot−N (t, G) for tobacco
cigarette, b) ΔDe−cig
Tot−N(t,G)) for e-cig.
144 P. Avino et al. / Science of the Total Environment 642 (2018) 137–147
Fig. 4. Total cumulative particle number extra doses deposited into the respiratory tree (ΔDdev
c−N(t,G) dev = cig, e-cig), estimated for each single respiratory act, as functions of airway
generation number (G), after a given exposure time (t), over 1 h time exposure, including 5 min smoking/vaping sessions and post-smoking/vaping exposures. a) ΔDcig
e−cig
tobacco cigarette, b) ΔDc−N (t,G) for e-cig.
exposure of 20 years to about 10 cigarettes/e-cigarettes per day (roughly
the smoking period and number of cigarettes considered for the typical
Italian smoking population in our previous studies, (Scungio et al.,
2018; Stabile et al., 2017a)) resulted in an overall risk of roughly 2
× 10−2 and 2 × 10−7 for exposure to smoking and vaping activity, re-
spectively. The corresponding risk values for smokers and vapers were
evaluated equal to 2–5 × 10−1 and 5–6 × 10−4 (Scungio et al., 2018;
Stabile et al., 2017a). The authors point out that such different risk be-
tween active and passive smokers/vapers is due to the different doses
they receive since the same toxicity of the particles was assumed. Due
to the smaller dose received by passive vapers, as reported in Fig. 7,
whatever the exposure scenario the ELCR is lower than the 10−5.
The authors point out that the evaluation of the dose and of the lung
cancer risk of second-hand smokers and vapers was here proposed for a
certain exposure scenario (naturally ventilated rooms of 40 m3) which
could be considered roughly similar to the actual exposure scenario in
Italy. Nonetheless, different exposure scenarios could be easily tested
on the basis of the emission rate/factor data here presented and
Fig. 5. Ratio of conventional cigarette total cumulative particle number extra dose to the e-
cig one (Rcig/e−cig(t,G)), as function of time (t) and airway generation number (G), over 1 h
time exposure, including 5 min smoking/vaping sessions and post-smoking/vaping
exposures (the surface represents the ratio of the two surfaces of Fig. 4a and b). Ratio of
extra doses received by smokers and vapers (Rcig/e−cig(t, G)), as function of time (t) and
airway generation number (G).
c−N(t, G) for
consolidated particle mass balance equations as applied by Scungio
et al. (2017).
3.4. Limitations of the study
The authors highlight that in the present study different tasks re-
lated to the cigarette and e-cigarette particle emission were analyzed:
a) characterization of the particle and black carbon emission of vapers
and smokers (emission factors/rates), b) estimate of the dose and lung
cancer risk received by passive smokers/vapers for a certain exposure
scenario. Both the tasks were performed on the basis of the measure-
ment of different aerosol metrics in a 40-m3 naturally ventilated room
where smoking and vaping activities were performed.
Emission factors/rates were commonly obtained adopting a particle
mass balance equation: thus, the uncertainty of the emission rate/factor
data is due to both the uncertainty of the instruments (assessed in our
previous studies (Buonanno et al., 2009a, 2010)) and the uncertainty
of the model itself. Indeed, the mass balance equation here applied
(Section 2.3.1) is based on simplified hypotheses, such as negligible par-
ticle condensation, evaporation and coagulation, and on average values
of particle concentration decay (dilution and deposition) whose contri-
bution to the uncertainty budget is not easily quantifiable and should be
addressed in future researchers.
The estimate of the dose received by passive smokers and vapers is
based on the dosimetry model MPPD (described in the Section 2.3.2)
which is intended to describe the deposition in each generation of the
respiratory system. The authors highlight that the estimated dose
value strongly depends on the smoking/vaping behaviors: in the pres-
ent paper similar smoking and vaping behaviors were adopted. This is
a source of uncertainty in the dose evaluation since the use of electronic
cigarettes should contribute to new vaping behaviors. Nonetheless, it
represents the only approach currently suitable to compare cigarette
and e-cigarette effect. Moreover, the uncertainty of the dose values is
also strongly influenced by the MPPD model assumptions (Asgharian
et al., 2014) and an exhaustive uncertainty budget is currently missing
in the scientific literature.
Consequently, the lung cancer risk assessment is also influenced by
the dose estimate, indeed the ELCR depends on the dose received by
the exposed population and the toxicity of the inhaled particles. The
toxicity contribution to the uncertainty budget is mainly related to the
carcinogenic compound concentrations: this is a key aspect since the lit-
erature is characterized by inconsistent and contradictory data and a
 P. Avino et al. / Science of the Total Environment 642 (2018) 137–147
Fig. 6. Particle number extra dose per each particle diameter and airway generation number calculated on the particle concentration peak in the test room, a) ΔDcig
cigarette, b) ΔDe−cig
max−N(d,G) for e-cig.
harmonized measurement methodology is still missing (Allen et al.,
2016; Jensen et al., 2015). Moreover, most of the data are related to
mainstream aerosols, therefore a proper evaluation of the mass fraction
of carcinogenic compounds on particle mass concentration for second-
hand aerosols can be hardly provided. To this end, in the present
study, the carcinogenic compound concentrations of the aerosol emit-
ted by the smokers/vapers were considered similar to that of the main-
stream aerosol: this assumption represents a main limitation of the
study which should be deepened in future studies. A further limitation
in the ELCR estimate is due to representativeness of the heavy metal
concentrations considered in the study: indeed, the metal emissions
are highly dependent on the type of atomizer used (Farsalinos et al.,
2015b), therefore a larger number of data should be considered to
take into account the different atomizer materials typically used.
Finally, besides the abovementioned uncertainty source due to the
data used in the calculation, the limits/uncertainties of the model itself
should be considered. As an example, the model is not able to take
into account non-linear effects of the age, previous smoking/vaping his-
tory of the exposed persons, possible synergic effects due to exposures
to other chemicals, effect of preexisting pathologies, or the particle as-
sumption rate. Nonetheless, despite such limitations, the ELCR model
here used is the most suitable model currently available as it is easily ac-
cessible also by engineers and air quality experts who can provide, on
Fig. 7. ELCR received by people exposed to cigarette and e-cigarette aerosols in naturally ventilated buildings as function of exposure scenario, i.e. years of exposure and number of
cigarettes/e-cigarettes.
145
max−N(d,G) for tobacco
the basis of their measurements, the order of magnitude of the risk.
Moreover, even if the unknown uncertainty could undermine the esti-
mated absolute ELCR value, the model allows to compare different ex-
posure scenarios providing good estimates of the relative differences
among them.
4. Conclusion
This study analyzed the aerosol emissions of smoker and vaper
volunteers in a naturally-ventilated 40-m3 test room. Based on it,
the particle dose deposited in the respiratory tree of passively ex-
posed individuals was calculated by MPPD model and utilized to es-
timate the lung cancer risks of second-hand smokers. Particle
number concentrations and size distributions, PM10 and Black Car-
bon were measured and the relevant emission rates were calculated.
The median emission rates of smokers and vapers in terms of particle
number were 4.3 × 1011 part·min−1 (2.80 × 1012 part·cig−1) and
9.62 × 1010 part·min−1 (5.51 × 1011 part·cig−1), respectively. Signifi-
cant PM10 (4.92 mg min−1; 32.0 mg cig−1) and BC (66.2 μg min−1;
430 μg cig−1) emissions were estimated for tobacco cigarette smokers,
whereas the relevant vaper emissions were negligible. After 1 h expo-
sure time, the extra doses received by second-hand smokers and vapers
in terms of particle number/surface area in the lung (sum of alveolar
146 P. Avino et al. / Science of the Total Environment 642 (2018) 137–147
and tracheobronchial regions) for the exposure scenario considered re-
sulted equal to 1 × 1010 particles/485 mm2 and 1 × 109 particles/
3.6 mm2. Depending on the airway generation, up to 15-fold higher cu-
mulative doses were estimated for passively exposed smokers than for
passively exposed vapers. Relying on such estimates and considering
the concentrations of carcinogenic compounds in the aerosol emitted
by smokers and vapers, the relevant lung cancer risk of second-hand ex-
posed individuals was estimated through a risk model. The lung cancer
risk for second-hand smokers was five orders of magnitude larger than
for second-hand vapers.
Acknowledgments
The authors wish to thank ARA for providing MPPD model. This
study was supported by National Institute for Insurance against Acci-
dents at Work (INAIL) Grant 2016-18.
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