Dr Konstantinos Farsalinos presentation from E-Cigarette Summit 2014

1. Dr Konstantions Farsalinos
Researcher
Onassis Cardiac Surgery, Greece
Department of Pharmacology, University of Patras, Greece

2. 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

3. 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2 (unpublished yet) studies using unrestricted funds provided to the institution by e- cigarette companies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

4. 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

5. 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)

6. THERMAL DEGRADATION
Goniewicz et al., Tob Control 2013

7. THERMAL DEGRADATION
Kosmider et al., Nicotine Tob Res 2014

8. 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

9. NICOTINE
•Cytotoxicity not associated with nicotine levels in e-liquids
Farsalinos et al., Int J Environm Res Public Health 2013

10. 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

11. 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

12. 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

13. 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.

14. 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

15. •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

16. ENVIRONMENTAL EXPOSURE
Czogala et al., Nicotine Tob Res 2013

17. ENVIRONMENTAL EXPOSURE
Long, Int J Environm Res Public Health 2014

18. ENVIRONMENTAL EXPOSURE
Romagna, Farsalinos et al., SRNT Europe 2013

19. 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 - ∞

20. 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?

21. 132
607
132
607
132
607
342
1012
542
2188
965
3520
0
500
1000
1500
2000
2500
3000
3500
4000
4500
2% switch
rate
10 years
2% switch
rate
20 years
5% switch
rate
10 years
5% switch
rate
20 years
10% switch
rate
10 years
10% switch
rate
20 years
Number of deaths averted (thousands)
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)