Smoke versus Vapor

The Tobacco Industry vs the Electronic Cigarette


Nitrosamine Levels


After reading the FDA's "Smoke and Mirrors" report released on July 22nd 2009, I was under the impression that there was a severe problem related to the Nitrosamine levels contained in the Electronic Cigarette ... that was however, only until I ran across the chart below, which was supplied by Dr. Michael Siegel, a professor in the Social and Behavioral Sciences Department, Boston University School of Public Health with over 20 years of experience in tobacco control, primarily as a researcher. As stated in his blog titled "The Rest of the Story: Tobacco News Analysis and Commentary", these are the comparative levels of carcinogens found in the Electronic Cigarette, FDA approved NRTs and real cigarettes.

These tests, and I will refer to Table 1. page 4 of the FDA report, actually showed that nitrosamines were not detected in the majority of the samples tested and the results of Dr. Michael Siegels research show levels as follows ... Electronic Cigarette - 8.183 (this is a decimal point) versus Tobacco Product - 7,450 (this is not a decimal point) I figured I'd be kind and go with one of the less toxic brands. The information for the Canadian brands was found in the Canadian Cigarette Data 2004 report. 


These numbers based on scientific findings showed the following:

Maximum Tobacco-Specific Nitrosamine Levels in Various
Cigarettes and Nicotine-Delivery Products (ng/g, except for nicotine gum and patch which are ng/patch or ng/gum piece)

Product

NNN

NNK

NAT

NAB

Total

Electronic Cigarette

3.87

1.46

2.16

0.69

8.18

Nicotine Gum

2

ND

ND

ND

2

Nicotine Patch

ND

8

ND

ND

8

Swedish Snus





2400

Canadian Mild Ultra

445

540

552

NQ

1537

Du Maurier Regular

308

523

448

NQ

1277

Export A Ultra Light King

794

848

752

122

2516

Gitanes Kings

6369

1477

2965

354

11165

Benson & Hedges Ultra Mild

522

733

629

NQ

1884

Winston

2200

580

560

25

3365

Newport

1100

830

1900

55

3885

Camel

3100

1400

2800

150

7450

Skoal

4500

470

4100

220

9290

Marlboro

4300

1800

4900

190

11190

" One of the most important groups of carcinogens in tobacco and tobacco smoke is the tobacco-specific nitrosamines. These nitrosamine carcinogens are formed from nicotine and related compounds by a nitrosation reaction that occurs during the curing and processing of tobacco. They are called tobacco-specific nitrosamines because they are found only in tobacco products (and possibly in some other nicotine-containing products). Thus the tobacco-specific nitrosamines are present in both "smokeless" tobacco products such as oral snuff and in cigarette smoke. They are the most prevalent strong carcinogens in "smokeless" tobacco products, occurring at much higher levels than in any other marketed product designed for oral use. They are among the most important carcinogens in cigarette smoke, along with combustion products and other carcinogens.

Among the tobacco-specific nitrosamines, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) are the most carcinogenic. NNK and its metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) are potent systemic lung carcinogens in rats. Tumors of the nasal cavity, liver, and pancreas are also observed in NNK- or NNAL-treated rats. NNN is an effective esophageal carcinogen in the rat, and induces respiratory tract tumors in mice, hamsters, and mink. A mixture of NNK and NNN caused oral tumors when swabbed in the rat oral cavity. Thus, considerable evidence supports the role of tobacco-specific nitrosamines as important causative factors for cancers of the lung, pancreas, esophagus, and oral cavity in people who use tobacco products. 

Metabolism and chemical binding to DNA (adduct formation) are critical in cancer induction by NNK and NNN.

Human metabolism of NNK and NNN varies widely from individual to individual, and current research is attempting to identify those individuals who are particularly sensitive to the carcinogenic effects of these compounds. Such individuals would be at higher risk for cancer when they use tobacco products or are exposed to secondhand smoke. Identification of high-risk individuals could lead to improved methods of prevention of tobacco-related cancer, and improved risk valuation for insurers. " Wiki




I located the following chart in a 1994 study determining the TSNA levels in Nicorette Chewing Gum.

May 1994 Nicorette Study
Table 1 : Determination of TSNA in "Nicorette" Chewing Gum
The obtained results for fortified and real samples are listed below.
Values represent ng TSNA per piece of chewing gum. 
 


Spiked

Found

Real Samples [ng/piece]


[ng/piece]

[ng/piece]

1

2

3

NNN

92

107

31

n .d .

n .d .

NAT

96

85

26

13 (*)

15 (*)

NAB

107

63

14



NNK

139

129

19

18

18

(*) no separation from NAB ; NAB included in NAT              value n .d . not detected


References
[1] Determination of tobacco-specific nitrosamines (TSNA) in tobacco by thermal energy analyser (TEA) PM-Europe laboratory procedure, compiled by JBE ; March 1993
[2] Determination of TSNA in Masterpiece Chewing Gum Haut S .A ., PM-USA Inter-Office Memorandum to Kinser R .D . ; April 1987
[3] Determination of TSNA in Chewbacco Chewing Gum Haut S .A., PM-USA Inter-Office Memorandum to Ellis C .K . ; May 1988



Tobacco-specific nitrosamines Rationale.

Trace levels are found in all nicotine products extracted from tobacco; higher levels suggest the presence of tobacco. Very low levels suggest the e-cigarette cartridge liquid is tobacco free.

Method. Labstat method TWT-333. Determination of tobacco specific nitrosamines (TSNAs) in whole tobacco, modified for the e-cartridges supplied, using LC-MS/MS.
Laboratory. Labstat International ULC, Kingston, Ontario, Canada.

Results. TSNAs, found only in tobacco, were not found in the Ruyan e-cigarette cartridge liquid except at trace quantity, at a very low level uncharacteristic of tobacco.

Table 2.2 Tobacco specific nitrosamines (TSNAs) in the cartridge liquid of the Ruyan e-cigarette, November 2007

Nicotine
per Cartridge

Sample
ID

NNN
(ng/cartridge)
Observation

NAT
(ng/cartridge)
Observation

NAB
(ng/cartridge)
Observation

NNK
(ng/cartridge)
Observation

TSNAs
(ng/cartridge)
Total

0 mg

073277

BDL

BDL

NQ

0.260

0.260

6 mg

073278

1.42

1.02

BDL

0.628

3.068

11 mg

073279

1.83

1.36

NQ

1.01

4.200

16 mg

073280

3.87

2.16

0.693

1.46

8.183

Labstat
200713





Average TSNAs

3.928

BDL = Below the limit of detection. NQ = Not quantifiable.
TSNA = tobacco specific nitrosamines. NAB= nitrosoanabasine
NNN= nitrosonornicotine, NAT= nitrosoanatabine,
NNK= 4-nitrosomethylamino-1-(3-pyridyl)-1-butanone

Full Health New Zealand - Ruyan Cartridge Report

Comment.

1) Tobacco-specific nitrosamines (TSNAs) were found, equal to 8 ng, in the 1g of liquid of the 16 mg cartridge. This amount is extremely small, equal for example, to the amount reported to be present in a nicotine medicinal patch. (8 ng in 1g = eight parts per trillion).

2) These very small amounts traces are likely to be due to the fact that even medicinal grade nicotine is extracted from tobacco.

3) The level in the 16 mg nicotine cartridge, for example, is 31 times the level in the 0 mg cartridge. On a daily dose basis, TSNAs in the 16 mg nicotine e-cartridge are 1200 times less than in the tobacco of 20 manufactured cigarettes, and 3000 times less than the daily dose in a can of Swedish moist snuff.14

Conclusion. The Ruyan e-cigarette cartridge does not contain carcinogenic levels of TSNAs, in that no product containing these trace levels has been shown to cause cancer.

13 Rickert W. Determination of Tobacco specific Nitrosamines by LC-MS/MS. Project NZ9. Nov.30, 2007.
Labstat International ULC. Kingston Ontario, Canada.




These are some of the test results that the FDA based the boycott and ban of the electronic cigarette products on. The chart below shows the results of these tests, although there does not seem to be a control sample that was used to test them against.

Sample

Tobacco specific nitrosamines (TSNA)A

mg nicotine/cartridge by HPLC-UV

10% ACN and 1% PA in water extraction

methanol extraction

Smoking Everywhere

e-cigarettes

NAB


NAT


NNK


NNN


fiber absorbent


plug & wrapper


fiber absorbent


555 High





4.9

1.8

5.98

Cherry High





4.88

0.86

5.5

Tobacco Original MED

ND

ND

D

D

4.44

1.03

5.15

Menthol HIGH





4.02

0.71

4.23

Tobacco Original LOW

ND

ND

D

D

2.93

0.51

2.65

Menthol MED





2.26

0.31

2.71

Apple LOW

ND

ND

ND

ND

1.63

0.61

1.78

Menthol LOW





1.42

0.3

1.57

Vanilla LOW

ND

ND

ND

ND

1.18

0.34

0.96

Tobacco Original NO

ND

ND

ND

ND

0.04

O

0.03

Vanilla NO





0.04

0.01

0.05

Cherry NO





0.01

0

0.07

Chocolate NO

ND

ND

ND

ND

0.01

0

0.03

Apple NO

ND

ND

ND

ND

0

0

0


Njoy e-cigarettes

NAB

NAT

NNK

NNN

fiber absorbent

plug & wrapper

fiber absorbent

Menthol HIGH

D

D

D

D

6.66

1.97

6.76

Regular MED

D

D

D

D

4.09

1.58

4.31

Menthol MED

D

D

D

D

3.98

1.46

4.77

Regular LOW





3.35

1.56

5.16

Control Sample “Nicotrol 10 mg" cartridge                 Mfgr. specification

?

?

?

?

?

?

?

D= detected, , ND= not detected NAB = N-nitrosoanabasine (LOQ = 21 ppb); NAT = N-nitrosoanatabine (LOQ = 21 ppb); NNK = 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (LOQ = 75 ppb); NNN = N-nitrosonornicotine (LOQ = 24 ppb)

A analyte was detected but at a level less than the limit-of-quantitation. Open boxes indicate the sample was not available for testing. DEG = diethylene glycol ? indicates no testing or information not provided

B Limit of detection Cotinine 20 ppb. Anabasine 10 ppb; myosmine 69 ppb; β-nicotyrine 170 ppb – present but at less than the level of the Nicotrol specification


The FDA released a press release stating that they were concerned about the safety of these products. The FDA Division of Pharmaceutical Analysis analyzed the ingredients in a small sample of cartridges from two leading brands of electronic cigarettes. In one sample, the FDA analysis detected diethylene glycol, a chemical used in antifreeze that is toxic to humans, and in several other samples, the FDA analysis detected carcinogens, including nitrosamines. These tests indicate that these products contained detectable levels of known carcinogens and toxic chemicals to which users could potentially be exposed. They sent a warning to the consumer to boycott these devices and in doing so convinced many large corporations, activist groups, health officials and others in a position of power and influence to ban and control the sale of the electronic cigarettes.


Sample

Sparging Apparatus followed by LC-UV analysis

Head Space GC-MS @ 60 deg C*

mcg nicotine/100mL puff

mcg cotinine/100 ml puff (LOD ~0.03)

β-nicotyrine

nicotine

Smoking Everywhere e-cigarettes





555 High

31.5

0.4



Cherry High



ND

D

Tobacco Original MED

15.7

trace

ND

D

Menthol HIGH





Tobacco Original LOW





Menthol MED



ND

D

Apple LOW



ND

D

Menthol LOW

9.9

ND

ND

D

Vanilla LOW



ND

D

Tobacco Original NO



ND

ND

Vanilla NO



ND

ND

Cherry NO



ND

ND

Chocolate NO



ND

ND

Apple NO

0.35

ND

ND

ND


Njoy e-cigarettes





Menthol HIGH

43.2, 34.9, 26.8

trace

D

D

Regular MED



D

D

Menthol MED

10.6

ND

D

D

Regular LOW






Control (specs)

Nicotrol 10 mg cartridge

15.2

?

?

?

D= detected, , ND= not detected * Presence of tobacco specific impurities cotinine, nicotine-N-oxide, nornicotine, anabasine and myosmine was negative at 60 deg C. Open box indicate sample not tested.

A analyte was detected but at a level less than the limit-of-quantitation. Open boxes indicate the sample was not available for testing. DEG = diethylene glycol ? indicates no test or information not provided

B Limit of detection Cotinine 20 ppb. Anabasine 10 ppb; myosmine 69 ppb; β-nicotyrine 170 ppb � present but at less than the level of the Nicotrol specification

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