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2 (unpublished yet) studies using unrestricted funds provided to the institution by e-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

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f d

eath

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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)