Dr Konstantions Farsalinos
Researcher
Onassis Cardiac Surgery, Greece
Department of Pharmacology, University of Patras, Greece
SAFETY EVALUATION OF ELECTRONIC
CIGARETTES
CHEMISTRY-TOXICOLOGY-ENVIRONMENTAL EXPOSURE
Dr Konstantinos Farsalinos Researcher
Onassis Cardiac Surgery Center, Greece
University Hospital Gathuisberg, Belgium
University of Patras, Greece
COI
2 (unpublished yet) studies using unrestricted funds provided to the institution by e-
cigarette companies
In 2 studies, institutions unrelated to me were funded by e-cigarette companies
1 study funded by a non-profit association
1 study funded by crowdfunding campaign
18 publications with no funding or other support
No funding from tobacco industry
No funding from pharmaceutical industry
E-CIGARETTE COMPOSITION
• 5 basic ingredients
• Glycerol
• Propylene glycol
• Water
• Nicotine
• Flavourings
• Food-approved substances (except tobacco absolute)
• Limited knowledge for many in the context of heating and inhalation risk
• Flavorings
• Contaminants-additives
• Nitrosamines (from nicotine)
• Aldehydes
• Solvents
• Colorings
E-CIGARETTE COMPOSITION
• Glycerol/propylene glycol
• Expecting minimal toxicity per se
• Found safe in cells and animal toxicology studies (Robertson et al. 1947; Werley et al. 2011; Renne et
al. 1992)
• Thermal degradation leads to production of aldehydes (Antal et al. 1985; Stein et al. 1983)
THERMAL DEGRADATION
Goniewicz et al., Tob Control 2013
THERMAL DEGRADATION
Kosmider et al., Nicotine Tob Res 2014
VAPOR CYTOTOXICITY
0
20
40
60
80
100
6.25% 12.50% 25.00% 50.00% 100.00%
PG/VG (50/50) Tobacco cigarette
Farsalinos et al., Int J Environm Res Public Health 2013
NICOTINE
• Cytotoxicity not associated with nicotine levels in e-liquids
Farsalinos et al., Int J Environm Res Public Health 2013
FLAVOURINGS
• Cytotoxicity seems to be associated with specific flavours or with amount of flavouring added to the e-liquid
Romagna, Farsalinos et al, Inhal Toxicol 2013
Coffee
flavor
FLAVOURINGS
• Cytotoxicity seems to be associated with specific flavours or with amount of flavouring added to the e-liquid
More than 100 times difference between e-
liquids in cinnamaldehyde content
Behar et al, Toxicol in Vitro 2013
Toxicity depends on the amounts of
cinnamaldehyde in the liquid
FLAVOURINGS
• Evaluation of 159 e-liquid samples (sweet flavors) from 36 manufacturers.
• 74.2% contained diacetyl and/or acetyl propionyl – food-approved flavourings associated with respiratory
disease when inhaled.
• Substances readily delivered to the vapor.
• Daily exposure levels 100 and 10 times lower compared to smoking.
Farsalinos et al., Nicotine Tob Res 2014
FLAVOURINGS-TOBACCO
• Evaluation of 21 e-liquid samples, 10 made with conventional flavours and 11 made from Natural Extracts of
Tobacco (NET liquids-using tobacco leaves to extract flavour).
• Nicotine accuracy compared to label no difference between groups.
• Nitrosamines present in nanogram/mL range, no difference between groups.
• Nitrates found in almost all NET liquids (but only 2 conventional liquids).
• Acetaldehyde found in almost all conventional liquids, but only in a small minority of NET liquids.
Farsalinos et al., submitted for publication
Tobacco products All liquids Ratio NET liquids Ratio
NNN (ng/day) 32970.4 18.9 1744 27.1 1217
NNK (ng/day) 6204.0 20.4 304 21.5 289
Total nitrosamines (ng/day) 39174.4 39.4 994 48.6 806
Nitrate (μg/day) 40628.5 134.9 301 248.6 163
Acetaldehyde (μg/day) 178.2 5.8 31 1.1 162
Formaldehyde (μg/day) 57.1 12.1 5 16.0 4
Total phenols (μg/day) 2372.2 5.2 456 6.6 359
Table 3. Difference between smokeless tobacco products and electronic cigarette liquids in daily exposure to
selected tobacco-derived toxins. For electronic cigarettes, a daily consumption of 3 mL liquid was assumed.
HEAVY METALS
• Expected finding due to the metallic structure of atomizers, coils
• Heavy metals are common contaminants in water, food and in inhalational pharmaceutical products
• USP has defined the maximum acceptable daily intake from inhalational medications
• Studies failed to compare the levels of heavy metals found in e-cigarettes with pharmaceutical standards
(Williams et al., PLoS One 2013).
E-cigarette (1000 puffs/day) Inhalational medications maximum
acceptable daily intake
Lead (Pb) 1,7 5
Chromium (Cr) 0,7 25
Nickel (Ni) 0,5 1,5
Copper (Cu) 20,3 70
Comparison between daily exposure to heavy metals from electronic cigarette liquids (Williams et al., PLoS
One 2013) and maximum acceptable intake from inhalational medications
• Chemicals of concern are PAHs, TSNAs, aldehydes, VOC
• Nicotine is not a reason for concern (not even in smoking exposure)
• Passive e-cigarette exposure salivary cotinine levels 0.24ng/ml (600-1000 times
lower than smokers) no biological or physiological effect (intake of 0.025mg/day)
• PAHs absent
• TSNAs so low that even for the vaper it is questionable whether they can cause any harm
• Main exposure from e-cigarettes is expected to be propylene glycol and glycerol, some
flavouring compounds
ENVIRONMENTAL EXPOSURE
ENVIRONMENTAL EXPOSURE
Czogala et al., Nicotine Tob Res 2013
ENVIRONMENTAL EXPOSURE
Long, Int J Environm Res Public Health 2014
ENVIRONMENTAL EXPOSURE
Romagna, Farsalinos et al., SRNT Europe 2013
POPULATION EFFECT
• Many toxic chemicals present in cigarette smoke are absent from e-cigarette liquid and vapor.
• Others are present at levels lower by orders of magnitude
Tobacco / e-cigarette ratio
Total nitrosamines 1000 - 1800
Nitrate 160 - 300
Acetaldehyde 30 - 400
Formaldehyde 1 - 9
Polycyclic aromatic
hydrocarbons ∞
Phenols 350 - 450
Acrolein 15
Carbon monoxide ∞
Toluene 100
Benzene ∞
1,3 butadiene 50 - ∞
POPULATION EFFECT
• Reasonable expectation: risk reduction >95% (most probably 99%)
• US population: 40 million smokers, 480,000 smoking-attributable deaths, 0.8% average annual
quit rate from 2002 to 2012 (CDC data)
• Cessation leads to gradual reduction in risk (almost equal to never-smokers in 15-20 years)
• What would happen if a THR initiative such as e-cigarette use was endorsed (considering a 5%
residual risk from e-cigarette use)? How many deaths would be averted in 10 and 20 years?
132 607
132 607
132 607 342
1012
542
2188
965
3520
0
500
1000
1500
2000
2500
3000
3500
4000
4500
2% switchrate
10 years
2% switchrate
20 years
5% switchrate
10 years
5% switchrate
20 years
10% switchrate
10 years
10% switchrate
20 years
Nu
mb
er o
f d
eath
s av
erte
d
(th
ou
san
ds)
Annual quit rate (1%) Annual switch rate (from tobacco to e-cigarettes)
POPULATION EFFECT
Nitzkin, Farsalinos. 20-years projection of mortality attributed to smoking in the US by endorsing a
THR initiative (e-cigarette use).
Similar (if not stronger) effects
expected in the European Union
(700,000 deaths annually
attributed to smoking)