Wednesday, July 22, 2009

Tobacco-Specific Carcinogens Found in Nicotine Replacement Products; Will Anti-Smoking Groups Call for Removal of these Products from the Market?

Despite Laboratory Finding of Carcinogens in Nicotine Replacement Medications, FDA Fails to Hold Press Conference to Express Concern About Potential Dangers of Nicotine Replacement Products

The FDA today expressed concern about the safety of electronic cigarettes, due mainly to the detection of tobacco-specific nitrosamines (a carcinogen) in these products.

The FDA wrote: "The FDA’s 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’s analyses detected diethylene glycol, a chemical used in antifreeze that is toxic to humans, and in several other samples, the FDA analyses 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."

Based on the laboratory finding reported today by the FDA that electronic cigarette cartridges have detectable levels of tobacco-specific nitrosamines, the American Lung Association (ALA) has called for the removal of electronic cigarettes from the market.

In a press release entitled "American Lung Association Supports Food and Drug Administration Finding that E-Cigarettes are Harmful and Contain Carcinogens; Lung Association Urges FDA to Immediately Halt the Sale of Unapproved Products," the ALA wrote that: "FDA’s preliminary findings show e-cigarettes contain carcinogens and toxic chemicals, including ingredients found in antifreeze. ... For too long, e-cigarette manufacturers have sold these nicotine delivery devices – absent FDA review and approval. ... In light of these initial findings, the American Lung Association urges the FDA to act immediately to halt the sale and distribution of all e-cigarettes unless the products have been reviewed and approved for sale by the FDA."

At a press conference earlier today, the FDA released the results of laboratory testing of 18 types of electronic cigarette cartridges and reported that tobacco-specific nitrosamines (a carcinogen) were detected in five of the cartridges. Diethylene glycol was detected in one of 18 cartridges tested.

The FDA expressed concern over the safety of electronic cigarettes and announced that it may take enforcement action against the product. However, the FDA stopped short of declaring that it will pull electronic cigarettes off the market.

The Rest of the Story

What the FDA did not tell the media or the public, and what the American Lung Association failed to express alarm over, is the fact that nicotine replacement products themselves have been found to have detectable levels of tobacco-specific nitrosamines, including 4-(methylnirosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN). Both of these chemicals are consistently carcinogenic in laboratory animals and are widely recognized as carcinogens present in tobacco products.

The carcinogen NNK [4-(methylnirosamino)-1-(3-pyridyl)-1-butanone] was found to be present at a concentration of 0.008 micrograms per patch in NicoDerm CQ and NNN [N'-nitrosonornicotine] was found to be present at a concentration of 0.002 micrograms per piece in Nicorette.

Given the finding that nicotine replacement products and electronic cigarettes both contain carcinogens, why is it that the American Lung Association is only calling for the recall of electronic cigarettes, not other nicotine replacement products? Shouldn't the ALA also express concern about nicotine replacement medications due to the fact that they create documented exposure to carcinogens and that there is therefore no safe level of exposure to nicotine replacement products?

Also, shouldn't the FDA hold a similar press conference tomorrow to express concern over the safety of nicotine replacement medications, since these products expose consumers to known tobacco-specific carcinogens?

The FDA and several anti-smoking speakers also expressed concern over the potential use of electronic cigarettes by youths, due to the marketing of flavored versions of these products.

But the same FDA just gave approval to a pharmaceutical company to market cinnamon and cherry flavored nicotine lozenges. Don't these products also present a concern about the potential for youths to try them and be poisoned by the nicotine? Why are the anti-smoking groups silent about the marketing of cinnamon and cherry-flavored lozenges? Can you get any closer than that to a candy product?

Another concern of the FDA and the anti-smoking groups was that we don't have evidence that electronic cigarettes are effective for smoking cessation. Well, one can make the same argument about nicotine replacement products. And one can also argue that we know that Chantix is not safe. It has purportedly resulted in hundreds if not thousands of severe adverse effects including suicides.

My point is that the actions of the anti-smoking groups are hypocritical. How can they argue that electronic cigarettes - which have been found to have detectable level of carcinogens - should be removed from the market, while nicotine replacement products - which also have detectable levels of carcinogens - should be allowed to remain? Furthermore, why should Chantix, which is thought to have resulted in a number of actual deaths, be allowed to remain on the market? And, most important of all, why would the same anti-smoking groups that want e-cigs pulled off the market because we are not absolutely sure if they are safe support the FDA approval of all conventional cigarettes, despite their documented high levels of carcinogens?

I find it to be a joke that the FDA is making a huge deal out of the finding that there may be some small risk associated with electronic cigarettes at the same time it is poised to start approving a product that we know is going to kill more than 400,000 people over the next year. There wasn't any FDA press conference today about the health risks of cigarettes, smokeless tobacco products, or any of the tobacco products over which the FDA now has jurisdiction. How does that make any sense? And why is the FDA allowing Chantix to remain on the market when we know that it has already killed perhaps hundreds of people?

Remember, the valid question is not whether or not electronic cigarettes are safe. The question is whether or not electronic cigarettes are much safer than conventional ones. If they are, and if they help keep people off of the known highly toxic cigarette variety, then they could be a huge benefit to the public's health. We surely wouldn't want to pull them from the market, forcing vapers to return to the highly toxic conventional cigarettes, when these products may actually be saving their lives.

If you look at the laboratory data provided by the FDA, you'll see that what is conspicuously missing is the results of the same exact testing of nicotine replacement products. While a nicotine inhaler was used as a control specimen for the nicotine testing, it was not subjected to testing for carcinogens?

Why not? Why would the FDA lab use the nicotine inhaler as a control specimen, but refuse to test it for carcinogens, just as electronic cigarettes were tested for carcinogens?

That, my friends, is inexcusable. It is deliberately trying to hide something from the public.

The report states that: "Nicotrol inhaler was used as a control for some test methods." Why only some test methods? If we are about to ban electronic cigarettes but keep NRT products, based on the finding that e-cigs have detectable levels of carcinogens, wouldn't we first want to demonstrate that e-cigs, unlike NRT products, have detectable levels of carcinogens?

For everyone's information, the finding that electronic cigarettes contain detectable levels of carcinogens is not new. We've known that for a long time. It's absolutely expected. Because the nicotine is derived from tobacco, it's close to impossible to isolate nicotine without retaining at least traces of the other tobacco constituents. That's the reason why pharmaceutical nicotine products also contain detectable levels of carcinogens.

The other thing that the FDA lab did not report is the level of the carcinogens in the electronic cigarette cartridges. One reason why the carcinogen levels in NRT products is not of tremendous concern is that the levels are orders of magnitude lower than in cigarettes (about two orders of magnitude at minimum, as I showed above). Before drawing any conclusions from the FDA lab results, we need to know the absolute level of the carcinogens, not just whether they were detectable. If the FDA has reviewed the literature (which it obviously has), it would know that nicotine replacement products themselves contain detectable levels of carcinogens. So the finding of detectable levels of carcinogens in e-cigs is not significant. What matters is the level of those carcinogens, and that is not something that the FDA has (yet) reported.

The detection of diethylene glycol (DEG) in one of the 18 cartridges is concerning and it may be that better techniques are necessary for preparing the propylene glycol solution. The level of DEG in that sample was significant. What is not clear is the dose of DEG that would be delivered through inhalation of the vaporized mixture. Most cases of antifreeze poisoning I am aware of have occured through ingestion, not inhalation of vapors. This is clearly an area of legitimate concern, but in and of itself, it doesn't mean that it would be prudent to recall the product from the market.

The decision about how to handle electronic cigarettes requires a careful consideration of the overall public health implications of the use of the product. One needs to weigh the clear benefits that this product appears to be having - the potential for a massive saving of lives from what could possibly be a breakthrough in smoking cessation technology - with the possible risks as well as the costs of forcing vapers to go back to conventional cigarette smoking (something which may have substantial public health costs).

The American Lung Association's simplistic view of this issue - there are carcinogens detected in e-cigs so they must be pulled from the market - is inappropriate, and could do far more harm than good.

To be sure, this is a challenging and complicated public health issue. But what it requires is not simplistic, ideological-based thinking. It requires taking a broad view and making a broad assessment of overall public health implications. It also requires objective and meaningful science, not just whether or not carcinogens are detectable in the product (something which we knew long before the FDA studied the product and something which is hardly relevant, since NRT products themselves contain detectable levels of carcinogens). It also requires consistency and rationality, and not blind adherence to any particular legal or policy ideology.

Most imporantly, it requires balanced, meaningful, and honest communication with the media and with the public. How meaningful is it to tell the media that e-cigarettes contain carcinogens and not to tell those same reporters that nicotine replacement products also contain carcinogens. A reporter walking away from that press conference is going to get the wrong impression. Perhaps that's by design, but I think it's unfortunate.

Just to make it clear, if one wanted to present a scare about NRT, one could easily do it by performing a lab analysis and holding a press conference to announce that there are detectable levels of several known human carcinogens in these products. This is the type of presentation that could easily be used to advocate for the removal of NRT from the market.

To be sure, there's plenty of reason for concern about electronic cigarettes. There's plenty of reason to take actions to ensure the product remains out of the hands of kids, to be sure that the labeling and advertising claims are accurate and supported, and to study the product for both safety and efficacy in smoking cessation. But the knee-jerk response of banning the product is not necessarily in the best interests of protecting the public's health. Most importantly, the evidence used to take such an action must be solid - the simple finding of detectable levels of carcinogens in the product or potential risk of harm from the product is not sufficient. By those grounds, the FDA should also be pulling nicotine replacement products from the market, and it should have pulled Chantix from the market months ago.

I think this is a perfect demonstration of why there's a need for the "rest of the story."


1. For the study which documents detectable levels of carcinogens in pharmaceutical nicotine replacement products, see: Stepanov I, Jensen J, Hatsukami D, Hecht SS. Tobacco-specific nitrosamines in new tobacco products. Nicotine and Tobacco Research 2006; 8:309-313.

2. For the previous laboratory report which had already documented trace levels of carcinogens in electronic cigarettes, see: Laugesen M. Safety report on the Ruyan e-cigarette cartridge and inhaled aerosol. Christchurch, New Zealand: Health New Zealand Ltd, 2008.

No comments: