July 20, 2013

Stanton A. Glantz, PhD

9 chemicals identified so far in e-cig vapor that are on the California Prop 65 list of carcinogens and reproductive toxins

California's landmark Proposition 65, the Safe Drinking Water and Toxic Enforcement Act of 1986, was enacted as a ballot initiative in November 1986. The Proposition was intended by its authors to protect California citizens and the State's drinking water sources from chemicals known to cause cancer, birth defects or other reproductive harm, and to inform citizens about exposures to such chemicals. Proposition 65 requires the Governor to publish, at least annually, a list of chemicals known to the state to cause cancer or reproductive toxicity. Products containing chemicals on the Proposition 65 list are required to carry the following warning in California:  "WARNING: This product contains chemicals known to the State of California to cause cancer and birth defects or other reproductive harm."
 
The following compounds that are on the Proposition 65 list have already been identified in mainstream or secondhand (sidestream) e-cigarette vapor:
 
Acetaldehyde (MS) 
Cadmium (MS)
Formaldehyde (MS,SS)
Isoprene (SS)
Lead (MS)
Nickel (MS)
Nicotine (MS, SS)
N-Nitrosonornicotine (MS, SS)
Toluene (MS, SS)
 
As the two papers linked above note, there are other toxic chemicals in the vapor as well as ultrafine particles, that likely have cardiovascular effects. E-cigarettes do not deliver "pure nicotine" and "harmless water vapor."

Comments

Comment: 

I think it should be noted that all E Cig fluids are made in China currently and the tobacco fluid is from Chinese tobacco leaf  where human waste is used as as a fertilizer. Chinese air pollution is absorbed by humans and exits in the waste accounting for the extremely high levels of heavy metals in all Chinese cigarettes. 
 
Both RJR and PM stated in their press releases that they will only use American made fluids that they deemed of high quality. If one reads between the lines  they realize what is in the Chinese product and by eliminating or lowering the toxins  could argue their product is safer.
 
Caution is indicted in approaching the problem as a toxicity problem and playing into their hands. 
 
Of concern is the very high levels of propylene glycol which ranges from 50 up percent of the fluid.  As user will take 50 to 80 bouts of 80 ml of E Cigarette fluid per day and no one has computed the risk. PG is listed in a number of toxicity data bases as a lung irritant and thee are some animal studies but no human. 
 
Eclipse used glycerine and for some reason the Chinese PG. it could be cost.
 
A major importance is the constituents in the flavor fluid that comprise about 15 that have very potent effects on abuse liability and little data available on effects. 
 
Without the flavor ingredients e cigarettes appear to be rejected as was Eclipse, Accord and Premier for poor performance in  providing or surprising nicotine effects.
 
Greg Connolly

Comment: 

Results: We found that the e-cigarette vapours contained some toxic substances. The levels of the toxicants were 9–450 times lower than in cigarette smoke and were, in many cases, comparable with trace amounts found in the reference product.
Conclusions: Our findings are consistent with the idea that substituting tobacco cigarettes with e-cigarettes may substantially reduce exposure to selected tobacco-specific toxicants. E-cigarettes as a harm reduction strategy among smokers unwilling to quit, warrants further study.

Comment: 

The unsigned comment is quoting the abstract of the paper by http://tobaccocontrol.bmj.com/content/early/2013/03/05/tobaccocontrol-20... target="_blank";Goniewicz, et al that I used to get compounds to compare with the Proposition 65 list.  Their paper also compared the levels of these compounds with a nicotine inhaler (the "reference" product" they refer to in the abstract, but did not fully develop that comparison.
Here are the results computed from Table 3 in their paper:
                                   ecig   inhaler   ratio
Formaldehyde        28.2      2.0         14
Acetaldehyde            7.4       1.1          7
Acrolein                    11.5      ND          --
o-methylbenzyne      3.9       0.7         6
Toluene                      0.8       ND         --
p,m-xylene                 0.1       ND         --
NNN                            1.5       ND         --
NNK                             6.6      ND         --
Cadmium                  0.09    0.03        3
Nickel                         0.19    0.19        1
Lead                           0.09    0.04        2
ND=not detected
Looked at this way, an e-cig delivers 14 times as much formaldehyde, 7 times as much actaldehyde, 6 times as much o-methylbenzene, 3 times as much cadmium and twice as much lead as a nicotine inhaler, as well as acrolein, toulene, p,m-xylene, NNN and NNK, which were not detected in the "reference device". 
Based on these comparisons, one could use the data in this paper to conclude that nicotine inhalers would be a safer approach to delivering nicotine in a harm reduction strategy than e-cigarettes.
 
 

Comment: 

E-cigarettes are definitely expected to deliver more chemicals to the user than clean air. And nicotine inhaler is delivering more toxic chemicals than clean air.
I wish everyone can quit smoking by using clean air. Next best thing, i wish the can quit smoking by using a nicotine inhaler. And now, let's discuss about the 85-95% of smokers who cannot do that. Unf-ortunately, smoking addiction is not only about nicotine, it is about pleasure, sensory (visual, gustatory, olfactory) and motor stimulation. That is why de-nicotinized cigarettes were effective in suppressing tobacco abstinence symptoms, as http://onlinelibrary.wiley.com/doi/10.1111/j.1360-0443.2005.01030.x/abst... et al have shown. 
Going back to the study by http://tobaccocontrol.bmj.com/content/early/2013/03/05/tobaccocontrol-20... et al, they also published another table, shown below:
 
                             Conventional cigarette     Electronic cigarette        Ratio
Formaldehyde               1.6–52                           0.20–5.61                     9
Acetaldehyde                52–140                          0.11–1.36                    450
Acrolein                         2.4–62                          0.07–4.19                       15
Toluene                         8.3–70                          0.02–0.63                      120
NNN                           0.005–0.19                  0.00008–0.00043            380
NNK                            0.012–0.11                 0.00011–0.00283              40
 
In other words, e-cigarette emits 9-450-fold less chemicals compared to tobacco.
The issue is not whether e-cigarettes are safer than nicotine inhaler. They are not (although i am not sure if the levels detected can have any measurable risk for health). The issue is what should we do for the vast majority of smokers who are unable to quit with currently approved medical methods. For these people, e-cigarette SHOULD be available as a less harmful alternative.
 
Konstantinos Farsalinos

Comment: 

No one I know -- including me -- claims that an individual e-cigarette delivers more toxins than an individual conventional cigarette.
The point is that assertions commonly made in e-cig promotions that the vapor only includes "pure nicotine" and that exhaled e-cig vapor is just "harmless water vapor" are not correct.
As far as whether e-cigs are an effective strategy for reducing harm, that will depend on whether there is high levels of dual use (which all studies to date have observed), which obviates most or all of the benefit of the fact that an individual e-cig is less toxic as well as whether or not e-cigs deter cessation.

Comment: 

Which vapour? Which manufacturer? Talk about fear mongering. Absolute nonsense.

Comment: 

You can access  them through the links in the post.

Comment: 

Professor Glantz, Professor Siegel has responded to your e-cig nicotine inhaler comparison in part as follows.  I'd be very much interested in hearing your response. Please see his blog for his full response.  Thanks.
------------------------
The analysis is essentially comparing the amount of these chemicals produced by one cartridge of an electronic cigarette versus one cartridge of a nicotine
inhaler.
Sound like a fair comparison? Comparing apples to apples?
Well, no.
While 150 puffs is the approximate dose of vapor that an electronic cigarette user inhales per day (about one cartridge - depending on the brand), a typical nicotine inhaler user will go through about 16 cartridges per day. Obviously, these figures vary depending on the individual, but it is not unreasonable to assume that a typical vaper would take 150 puffs per day, while a nicotine inhaler user might use 16 cartridges per day.
Since what we are interested in is the difference in toxicant exposure, we must take the number of cartridges used per day into our analysis.  What we want to estimate and compare is the total daily exposure to these various chemicals.
So here is Dr. Glantz's table reproduced correctly to represent a comparison of daily carcinogen intake rather than intake from one cartridge:
                              ecig      inhaler    ratio
Formaldehyde     28.2      32.0        0.9
Acetaldehyde         7.4      17.6        0.4
Acrolein                 11.5      ND
o-methylbenzyne   3.9      11.2        0.3
Toluene                   0.8      ND
p,m-xylene              0.1      ND
NNN                         1.5      ND
NNK                          6.6      ND
Cadmium              0.09        0.48     0.2
Nickel                     0.19        3.0       0.1
Lead                       0.09        0.64     0.1
ND=not detected
You can see that in contrast to what Dr. Glantz reported, the estimated daily exposure to six carcinogens is substantially higher for use of a nicotine inhaler compared to use of electronic cigarettes, based on the very same data that he believes is valid. As you can see, this changes the conclusion quite a bit.

Comment: 

It's one thing if e-cigarettes were only marketed to smokers unable to quit, but the tobacco industry is interested in marketing these devices to a much wider consumer base, namely, young people who have not taken up smoking but due to various social and peer influences, would be attracted to the e-cigs and might then try actual tobacco products.  The ultimate goal is proliferation, not reduction, of tobacco usage. 

Comment: 

Given http://tobaccoanalysis.blogspot.com/2013/07/anti-smoking-researcher-misl... target="_blank";Mike Siegel's criticism of my interpretation of the results in the http://tobaccocontrol.bmj.com/content/early/2013/03/05/tobaccocontrol-20... target="_blank";Goniewicz paper, I checked with the authors about why and how they used the nicotine inhaler to compare it with the levels of toxins inhaled from ecigarettes.  Here is what Maciej Goniewicz said:
"The inhalator was used as a comparator. Nicotine inhalator was puffed exactly the same way as ecig. There were 15 series of 10 puffs. All test were repeated 3 times with new cartridge.
"We also had blank sample - just indoor air puffed the same way (included in the table as 'Blank sample')."
<strong;<em;So this is a fair comparison.</em;</strong;
Siegel also ignores the fact that five of the carcinogens and reproductive toxins found in ecig vapor were not detected at all in the nicotine inhaler:&nbsp; acrolein, toluene, p,m,-xylene, NNN, and NNK.
His statement that nicotine inhaler users consume 16 cartridges a day -- the central point in his calculation -- is inconsistent with data on actual use.&nbsp; The http://www.nicotrol.com/inhaler.aspx " target="_blank";Nicotrol website reports that in one of their clinical trials participants used a minimum of 4 to a maximum of 20 cartridges per day.&nbsp;&nbsp; Thus, while some users may consume 16 cartridges a day, it is certainly not the typical number.
The /sites/g/files/tkssra4661/f/u9/NicoretteMonoINHALER.pdf" target="_blank";product monograph for the inhaler used in the Goniewicz study, Nicorette says to individualize the dose but general advice is to use 6-12 cartridges per day for 3 months. On http://www.rxlist.com/nicotrol-drug/indications-dosage.htm " target="_blank";another site summarizing the nicotrol product use it says people use an average of 6 cartridges per day and a maximum of 16.
A broader point is that the inhaler is FDA regulated and has standard low levels of these toxins while the e-cigarette samples are all over the board and the products differ so much especially in terms of cartridge and battery size that you don't know how much toxic chemicals a user is exposed to.
&nbsp;

Comment: 

"Caution is indicted in approaching the problem as a toxicity problem and playing into their hands"
A very good point.
If we all agree that cigs are far more toxic, then anything that undermines quitting smoking is highly toxic, and the evidence so far suggests that e-cigs undermine at least as much cessation as they aid. A narrow focus on e-cigarettes as product misses that.
Jon Krueger

Comment: 

If I pay for access. Why not post them in the clear?

Comment: 

This is not true.
I am simply going to list my critical thinking thought proccess while reading this comment.
1.) Not "all" fluid is made in China. You are also assuming that the only flavor available is tobacco. This is an over-generalization.
2.) 80ml of ecig juice PER DAY is a lot. Even spread over a week, that is a lot. I have never met anyone, nor would it be possible to use that much juice per day; even constantly vaping on a high power device.
3.) PG is food approved. Claiming that there has been no human testing only makes this point invalid. Lab rats dont use ecigs.

Comment: 

The fact that PG is approved as a food additive does not mean anything about its safety when inhaled as a heated aerosol.

Comment: 

This article is useless <strong;without MENTIONING THE PRODUCTS TESTED!!!</strong; &nbsp;C'mon people!! &nbsp;<strong;WHICH products or brands did you test that had these chemicals in them!!???</strong;

Comment: 

... that the blog post links to.

Comment: 

Pg is used to suspend medications in solution for use with nebulizers in both hospital and home settings. That fact speaks volumes for its safety as a breathable aerosol.

Comment: 

They are used to deliver drugs to treat disease, not as recreational devices.&nbsp;

Comment: 

Its a fake comment. Greg Conolly is a lobbyist for ecigs and is very knowledgable. This post was not oosted by him nor is it a quote or paraphrase of anything that was ever said by him.

Comment: 

Greg Conley is a lawyer and lobbyist for e-cigarettes.&nbsp; Greg Connolly is a dentist and public health researcher, who has been a public health official in Massachusetts and member of the Harvard School of Public Health faculty.
&nbsp;
They are often confused, probably to the consternation of both.

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