An overview of the issues relating to electronic nicotine delivery systems, aka e-cigarettes

1. Electronic Nicotine Delivery Systems
(“ENDS”) in the USA
Implications for Research and Policy
NATHAN K. COBB, MD 1,2
PETER SHIELDS, MD, PHD 2
JUSTIN BYRON, MA 3
DAVID ABRAMS, PHD 1,3
1 SCHROEDER INSTITUTE FOR TOBACCO RESEARCH AND POLICY STUDIES
2 LOMBARDI CANCER CENTER, GEORGETOWN UNIVERSITY MEDICAL CENTER
3 JOHNS HOPKINS BLOOMBERG SCHOOL OF PUBLIC HEALTH

2. Overview
• Definitions and Characteristics
• Available Data
• Research Implications
• Policy Implications

3. Electronic Nicotine Delivery Systems
• Definitions & Characteristics
– Common characteristics
– Vaporization process
– Use
– Refilling

4. Definition
• WHO
– “designed to deliver nicotine to the lungs”
– “draw a mixture of air and vapours into the respiratory
system”
– “contain electronic vaporization systems, a rechargeable
battery … electronic controls and replaceable cartridges
that may contain nicotine and other chemicals”
• FDA
– “battery powered device that provides inhaled dose of
nicotine by delivering a vaporized propylene glycol/nicotine
mixture.” • WHO Study Group on Tobacco Regulation. Report on the
Scientific Basis of Tobacco Product Regulation: Third Report of a
WHO Study Group. 955. 2009. Geneva, Switzerland.
• Westenberger BJ. Evaluation of e-cigarettes. Published FDA
correspondence, 5/4/2009. Available at http://www.fda.gov/
NewsEvents/PublicHealthFocus/ucm172906.htm .

5. Cigarette
• “A slender roll of cut tobacco enclosed in
paper and meant to be smoked …”
• Etymology: French cigarette, diminutive of
cigare cigar, from Spanish cigarro …
possibly from the Mayan sik'ar, from sik,
tobacco.
New Oxford American Dictionary 2nd edition.
Oxford University Press, Inc. 2005.

6. Sample Devices

7. Common Components
• Battery
• Heating element
• Absorbent with solution
– Nicotine
– Propylene glycol
– Flavorings

8. Vaporization
• As propylene glycol (or other alcohol) is
heated to 40-65C and forcibly drawn
through the device, it vaporizes.
– The combination of the negative pressure and
heating causes the vaporization – the exact
same process is used to create theatre fog.
– Theoretically, nicotine is carried along in this
process.

9. Use
“Electronic cigare-e uses advanced
microelectronic technology and
• The user inhales, creating negative pressure in the
device supercri6cal physical atomiza6on
• A mechanical switch enables a heating element.
technology to atomize the high‐purity
• Negative pressures draws propylene glycol over
and exci6ng nico6ne dilu6on
the heating element, causing to it vaporize.
extracted from tobacco into smoke
– Polyethylene glycol
for smoker’s sucking and accordingly
holds water from
meet the needs of those smokers.”
breath vapor, forming
the “smoke”, similar to ‐ Smoking Anywhere Manual
theatrical fog.

10. Refilling
• Multiple suppliers of
“juice” independent of
device manufacturers
• Marketed for 1-1.3ml refill
per cartridge
– Current high is 36mg/refill
– Single bottle may contains
as much as 1 gram of
nicotine in the volume of a
shot glass.

11. Refill Process

12. Distribution & Sourcing
• No comprehensive data available
• Most devices appear to be made in China
and then exported/rebranded
• In US, primary distribution appears to be
online and in mall kiosks
• Origin of refill solution and and nicotine
concentrate is unclear – pesticide vrs
pharma?

13. Available Data
• Device Content and Delivery
– Industry sponsored - Laugesen
– FDA & Georgetown/Schroeder
• Physiologic Effect
– Eissenberg 2010
• Behavioral
– None to date

14. Laugesen Report - 2008
• Ruyan e-cigarette
• Private company – Health New Zealand
– Activities funded by Ruyan Ltd
– Assays done by commercial laboratories
• Methods
– Variety of methods to detect multiple chemical
constituents
– Puffing methods poorly described

15. Laugesen Report - 2008
• Also found trace levels of TSNAs in the cartridge
• Other compounds detected
– Acetaldehyde
– Acetone
– Formaldehyde
– PAHs
• Lower levels than cigarettes, but higher than FDA-
approved NRT
• Limitations of FDA testing apply here

16. Content Testing
• FDA testing in house (Westenberger)
• GU/SI performed by Arista Labs
• Both groups tested same 2 devices (NJoy High
& Smoking Everywhere High.)
• Tested cartridge content and vapor content for:
– nicotine content
– impurities (TSNA, TSI)
– contaminants
Westenberger BJ. Evaluation of e-cigarettes. Published
FDA correspondence, 5/4/2009. Available at http://
www.fda.gov/NewsEvents/PublicHealthFocus/
ucm172906.htm .

17. Testing Results - Contaminants
• FDA
– Tobacco specific nitrosamines (TNSAs) in Njoy, not
Smoking Everywhere in heated cartridge contents
– Diethylene glycol in 1 sample.
• Georgetown/SI
– butyl acetate, diethyl carbonate, benzoic acid ,
quinoline, dioctyl phthalate 2,6-dimethyl phenol
• Both
– TSI (cotinine, anabasine, myosmine, B-nicotyrine) in
all samples

18. Vapor Testing
• FDA 2009
– 100cc puffs via sparging apparatus; each puff
pulled with 100cc syringe through a gas
trapping bottle. Contents analyzed using gas
chromatography.
• GU/SI 2009
– 35cc puffs into XAD-4 pads, under ISO
conditions. Pad contents analyzed using gas
chromatography.

19. Testing Results - Nicotine

20. Nicotine Variability
• All cartridges yielded less nicotine than
labeled.
• FDA found different contents in identically
labeled cartridges (26.8-43.2 mcg).
• GU/SI found that first 10 puffs yielded
approximately 4x nicotine of later puffs
• Different testing methods yielded markedly
different amounts of nicotine per puff.

21. Eeissenberg
• Tested serum and craving levels after
using 2 brands of ENDS (Njoy and Crown
7; 16mg) against “usual brand”
• “instructed to puff normally and then
puffed ad libitum 10 times (30-s interpuff
interval)”
• Assessment at 5,15,30,45 min, then cycle
repeated.
Eissenberg T. Electronic nicotine delivery devices:
Ineffective nicotine delivery and craving suppression after
acute administration. Tob Control 2010, Feb;19(1):87-8
19.

22. Testing Results – Serum & Craving
Eissenberg T. Electronic nicotine delivery devices:
Ineffective nicotine delivery and craving suppression after
acute administration. Tob Control 2010, Feb;19(1):87-8
19.

23. Testing Results – Serum & Craving
Eissenberg T. Electronic nicotine delivery devices:
Ineffective nicotine delivery and craving suppression after
acute administration. Tob Control 2010, Feb;19(1):87-8
19.

24. Wheat from Chaff
• TSI indicate tobacco origin of the nicotine;
they are found in NRTs.
• Diethylene glycol is the most feared
contaminant in PG products, and the
cause of several mass poisonings.
• Nicotine content is highly varied across
brands, batches and puffs

25. Research Implications
• Safety
– Pharmacodynamics
• Dose delivered, rapidity, serum concentrations?
• Maximum dose feasible?
– Exposure to harmful chemicals leading to
health effects such as lung and other cancers
through laboratory and human studies

26. Research Implications
• Machine Testing
• Consumer behavior
• Device limits (temperature etc)
• Behavior
– Cessation aid
– Delaying or subverting smoking cessation
– Enticing former smokers to resume smoking
– Serving as a gateway for new smokers

27. Policy Implications
• When is an ENDS not an ENDS?
• Change the carrier?
• Change the dosing?
• Change the absorption?
• Change the electronics?
• What defines a “tobacco product”?
• What other drugs could be legally
concentrated and delivered this way?

28. Policy Implications
• Most manufacturers have stuck to a harm
reduction argument, although a few have
made cessation claims.
• Proponents have argued that by removing
the primary carcinogens the “e-cigarette”
becomes a less harmful cigarette.
• Currently, FDA regulation has been
blocked in the courts:

29. Sottera v FDA
“More importantly, it is apparent from Congress's broad
definition of "tobacco product" that it intended the
Tobacco Act's regulatory scheme to cover far more than
the fixed array of traditional tobacco products at issue in
Brown & Williamson Tobacco. Both the FLCAA and the
CSTHEA only apply to "cigarettes," "little cigars," and
"smokeless tobacco," which Congress defined with
considerable specificity, yet the Tobacco Act applies to
"tobacco products," which Congress defined expansively
as "any product made or derived from tobacco that is
intended for human consumption.”
Sottera v US FDA, US District Court DC, 1/14/2010

30. Conclusions
• Product and manufacturing variability
appear to be significant
• Safety concerns are different and
independent from cigarette concerns
• Definitions and classifications are a
challenge for regulation, but should not
exempt the products from such.

31. References
• Eissenberg T. Electronic nicotine delivery devices: Ineffective nicotine delivery and
craving suppression after acute administration. Tob Control 2010, Feb;19(1):87-8 19.
• Flouris AD, Oikonomou DN. Electronic cigarettes: Miracle or menace? BMJ
2010;340:c311 340.
• Pauly J, Li Q, Barry MB. Tobacco-Free electronic cigarettes and cigars deliver
nicotine and generate concern. Tob Control 2007, Oct;16(5):357 PMCID:
PMC259855416.
• Simpson D. World: E-Cigarettes are here. Tob Control 2009, Apr;18(2):80-1 18
• Wollscheid KA, Kremzner ME. Electronic cigarettes: safety concerns and regulatory
issues. Am J Health Syst Pharm 2009; 66(19):1740-1742.
• WHO Study Group on Tobacco Regulation. Report on the Scientific Basis of Tobacco
Product Regulation: Third Report of a WHO Study Group. 955. 2009. Geneva,
Switzerland, World Health Organization. WHO technical report series.
• Westenberger BJ. Evaluation of e-cigarettes. Published FDA correspondence,
5/4/2009. Available at http://www.fda.gov/NewsEvents/PublicHealthFocus/
ucm172906.htm .