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Aziemah Zulkifli, Emilia Zainal Abidin*, Najihah Zainol Abidin, Amer SiddiqAmerNordin,
Sarva Mangala Praveena, Sharifah Norkhadijah Syed Ismail, Irniza Rasdi,
KarmegamKaruppiah and Anita Abd Rahman
Abstract
Objective: This paper primarily aimed to review articles
which specifically quantified the risk of electronic cigarettes (e-cigarette) usage via the health risk assessment
(HRA) approach.
Methods: Systematic literature searches were conducted
using PubMed search engine databases. Search terms such
as electronic cigarette, e-cigarette, electronic nicotine
delivery systems, electronic cigarette liquid, electronic
cigarette vapors, and health risk assessment were
used to identify the relevant articles to be included in this
review. To enable comparison, hazard quotient (HQ) and
lifetime cancer risk (LCR) for the chemicals measured in
the selected articles were calculated for three of the articles
using the formula: [1] HQ=average daily dose (ADD)/reference dose (RfD) or exposure air concentration (EC)/reference concentration (RfC); [2] LCR=lifetime average daily
dose (LADD) cancer slope factor (CSF) or exposure air
concentration (EC) inhalation unit risk (IUR).
Results: Four articles pertaining to HRA of e-cigarettes
were critically reviewed, three of the papers focused on
specific chemicals namely nicotine, propylene glycol (PG),
glycerol and 1,2-propanediol, while one article evaluated
Background
Evidence from international studies reveal that the popularity of electronic cigarettes (e-cigarettes) is increasing
rapidly among the world population despite the controversies surrounding the e-cigarettes impact on health (1
3). This phenomenon should be considered as an issue of
concern by health organizations, such as the World Health
Organization (WHO), as the safety of e-cigarettes has yet
to be decisively established (4).
The users of e-cigarettes have increased in numbers in
many countries (1, 5, 6). Data provided by Regan etal. (5)
and King etal. (6) demonstrate increments in the percentage of e-cigarette users in the United States of America
(USA) from 0.6% in 2009 to 8.5% in 2013. Similarly, the
population-based Global Adult Tobacco Survey (GATS)
conducted from 2011 to 2013 reported high prevalence of
current e-cigarette users in four countries namely Greece
(2.2%), Qatar (1.8%), Malaysia (3.9%) and Indonesia
(2.5%) with Malaysia being the country with the highest
Methods
A systematic literature search was conducted to identify published
scientific studies related to e-cigarette usage and HRA. A set of relevant search terms were used separately or in combination in PubMed search engine. The following were the search terms included in
this study: electronic cigarette, e-cigarette, electronic nicotine
delivery systems, electronic cigarette liquid, electronic cigarette
vapors, and health risk assessment. The search date range was
restricted between the years 2000 and August 2015.
The inclusion criteria of the articles to be considered in the
review were the following: [1] written in English, [2] open access
journal [3] dealt mainly or partly with e-cigarette and/or health risk
assessment. The search yielded a total of 24 articles that met the
harmful
health
effects of
inhaling
nicotine-free
shisha-pen
vapor: a
chemical
risk
assessment
of the main
components
propylene
glycol and
glycerol
NJOY
A risk was characterized using the following
e-cigarette
equation:
health risk
Hazard quotient (HQ):
assessment (Expected dose, mg/kg-day)/(dose criterion,
mg/kg-day)
*HQ <1 indicates that the expected exposure
does not exceed the dose criterion
(maximum level of exposure to a toxicant at
which no adverse effects are expected)
Exponent (27)
Concentration of;
i) propylene glycol: 54%
ii) glycerol: 46%
Vapor in shisha-pen comprised of:
i) 0.7 mg/puff of propylene glycol
ii) 0.6 mg/puff glycerol
Hazard assessment:
i) Propylene glycol: no evidence that PG is carcinogenic to human
Risk assessment:
i) Step 1:
a) propylene glycol:
Estimated maximum alveolar conc. in after one puff: 430603 mg/m3 (exceed peak acceptable
concentration) demonstrate that a risk of irritating effects on the respiratory tract epithelium due to
propylene glycol exist
b) glycerol: maximum alveolar concentration (1Calv; max)= 348495 mg/m3 (no MOE is calculated; due
to lack of relevant human inhalation studies)
ii) Step 2:
a) propylene glycol:
NOAEL (mg/m3):LOAEL: M
in 176
Max 851
Mean 309
b) glycerol:
NOAEL: 165 mg/m3
LOAEL: 662 mg/m3
iii) Step 3: risk on local effects;
a) propylene glycol:
MOE for respiratory tract irritation=0.32 (LOAEL)
b) no MOE is calculated. However, inhaled concentration of glycerol in one puff: 348495 mg/m3 compared
to NOAEL (165 mg/mg3) and LOAEL (662 mg/m3) for local irritant effect to the respiratory tract in rats
Risk assessment
Methodology
Title
Title
Methodology
Risk assessment
Electronic
cigarettes:
overview of
chemical
composition
and
exposure
estimation
Determination of concentration of
Farsalinos etal. (25) Are metals i) Two studies from literature in measuring I)Average daily exposure from 13 e-cigarette: 2.6387 times lower than the safety cut-off point of PDEs,
emitted from metals emitted to the aerosol from 13
325 times lower than MRL, 66577,514 times lower than safety cut-off point of RELs
electronic
e-cigarette products were chosen.
II) One of 13 products: exposure 10% higher than PDE for cadmium at the extreme daily use of 1200 puffs
cigarettes
i) Estimated exposure (600 puffs/day)
a reason
were compared with chronic permissible
for health
daily exposure (PDE) (cadmium,
concern?
chromium, copper, lead and nickel),
A riskminimal risk level (MRL) (manganese),
assessment
and recommended exposure limit (REL)
analysis of
(aluminum, barium, iron, tin, titanium,
currently
zinc and zirconium)
available
literature
Table 1(continued)
1-methoxy-2-propanol (PGME)
1-hydroxy-2-propanone
Acetic acid
menthol
Carvone
Benzoic acid
5E-01
2.8E-01
1.7
1E-02
0.0001
8.5E-03
5E-05
9E-03
3.3
5c
0.0001b
0.1c
5E-4a
5E-03a
5E-05a
6.3E+00
2E-05a
2.2E-06
4.8E-04
8.4E-02
1.8E-03
IUR
(mg/m3)
7.2E-04d
1.6E-04d
0.14d
2.1d
14.5d
9.0d
0.38d
603d
495d
0.2893
0.0000069
0.000535
0.0300
0.0258d
0.00032e
0.00070e
0.00006e
0.00057e
0.0023d
0.00084e
0.00054e
0.00024e
0.062
0.0044e
0.0042d
0.0145d
0.2571d
0.3582
d
Exponent
(27)
0.00011e
0.047e
0.00002e
0.00187
e
0.00032
e
0.00070
e
0.00006
e
0.00057e
1.83E-05d
Exponent
(27)
Average daily dose (ADD) (mg/kg/day)d or Lifetime Average daily dose (LADD) (mg/kg/day)d
Exposure air concentration (mg/m3)e
or Exposure air concentration (mg/m3)e
RfD, Reference dose; RfC, reference concentration; MRL, minimal risk level; CSF, Cancer slope factor; IUR, Inhalation Unit Risk; a RfD value by IRIS EPA, b MRL value of by ATSDR, ccould not be estimated due to the absence of threshold toxicity value of the chemical, , not measured; , non-carcinogenic, , unavailability of the value.
3E-01
6E-01
7E-01
2E-01
Zirconium
Barium
Aluminum
1.4E-01
Zinc
Manganese
Ethyl vanilin
10
0.11
Titanium
Thujone
1,3-Propanediol
4E-01
Ethylene glycol
25
Iron
1,2-Propanediol @ PG
100
0.0008
5E-02
0.0035
3.0E-03
1.8E-03
Tin
Glycerol
4E-02
Acetaldehyde
Nickel
Lead
Copper
Chromium
Nicotine
Cadmium
CSF
(mg/kg/day)
Chemical constituents
ine-cigarette
Table 2:Additional analysis of estimated Average Daily Dose (ADD), Lifetime Average Daily Dose (LADD) and chemical-specific threshold toxicity value.
Hahn
Kienhuis
Farsalinos
etal. (26)
etal. (24)
etal. (25)
HQ
LCR
NJOY E-cig
E-liquid Shisha pen E-cig aerosol NJOY E-cig
Exponent
Hahn
Kienhuis
Farsalinos Exponent
(27) etal. (26)
etal. (24)
etal. (25)
(27)
Cadmium
28.5
1.03E-06
Chromium
0.6
5.04E-06
Lead
3.57E-08
1.54E-07
Nickel
1.6
Acetaldehyde
0.3582
Nicotine
475
0.2571
Glycerol
0.09
1,2-Propanediol @ PG
0.58
Ethylene glycol
5.25
1,3-Propanediol
0.014
4.95
24.1
0.0145
0.0042
Thujone
1.45E-03
Ethyl vanilin
1.44E-04
Copper
5.67E-04
Manganese
0.4
Aluminum
9.4
Barium
0.22
Iron
Tin
0.044
Titanium
2.4
Zinc
Zirconium
1.68E-04
1-methoxy-2-propanol (PGME)
0.0258
1-hydroxy-2-propanone
0.0023
Acetic acid
0.0300
menthol
0.2893
Carvone
0.0000069
Benzoic acid
0.000535
1.83E-07
HQ, Hazard quotient; LCR, lifetime cancer risk; acould not be estimated due to the absence of threshold toxicity value of the chemical; bold,
HQ value more than 1 (unacceptable risk for non-carcinogenic health effects), , non-carcinogenic; , not measured.
CpIR Ed EF
BW ATNC
CpIR EdEF
BW ATC
HQ=Hazard quotient
ADD=Average daily dose (mg/kg-day)
RfC=Reference dose (mg/kg-day)
For inhalation:
EC (mg/m3 )
HQ =
RfC (mg/m3 )
For inhalation:
LCR=EC (mg/m3)URF (mg/m3)-1
HQ=Hazard quotient
EC=Exposure air concentration (mg/m3)
RfC=Reference concentration (mg/m3)
Interpretation:
<1
Acceptable
>1
Unacceptable
Interpretation:
<106
Clearly acceptable
106 to 104
Acceptable
>104
Clearly unacceptable
Conclusion
From the further analysis of estimating the health risks of
all measured chemicals, there were six types of e-cigarette
constituents namely nicotine, PG, glycerol, cadmium, ethylene glycol, nickel, aluminum and titanium, which were
found to have the potential to contribute to the non-carcinogenic health risks to its users. There are limited HRA
studies and the ones available provide inconsistent scientific evidence on the health risk characterization arising
from the usage of e-cigarette. As such, there is a need to
perform more studies on HRA of e-cigarettes by using uniformed and comprehensive steps and similar reference
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