Low Nitrosamine Levels in Altria and Reynolds Moist Snuff Products, say Minnesota Researchers

I discussed a year ago the tempest-in-a-teapot issue of tobacco specific nitrosamines (TSNAs) in smokeless tobacco products (here). TSNAs are contaminants found only in tobacco, and they are present in vanishingly small concentrations – mainly in the single-digit parts-per-million range. “Regardless of current TSNA levels,” I wrote, “anti-tobacco extremists will call for reductions.”

Last month, the University of Minnesota’s Stephen Hecht, Irina Stepanov and Dorothy Hatsukami (a member of the FDA Tobacco Products Scientific Advisory Committee) published a letter in Tobacco Control (here), demanding TSNA reductions. This, despite the fact that their data showed that TSNA levels in moist snuff products from Altria and Reynolds were at historically low levels in 2010. I have commented on this group’s anti-smokeless-tobacco articles before (here and here).

Hecht et al. list the levels of NNN and NNK in several Altria and Reynolds brands:

NNN + NNK Levels in Moist Snuff and Snus, in Parts Per Million (ppm), Dry Weight
Brand	NNN+NNK (ppm)
Altria
Copenhagen	5.6
Copenhagen Long Cut	5.8
Copenhagen LC Wintergreen	4.6
Skoal Long Cut Straight	4.9
Skoal Long Cut Wintergreen	5.2
Skoal Bandits Wintergreen	5.2
Marlboro Snus Rich	0.7
Marlboro Snus Spearmint	0.9
Marlboro Snus Peppermint	0.8
Marlboro Snus Mild	0.8
Reynolds
Grizzly	11.1
Kodiak Wintergreen	5.1
Camel Snus Frost	1.5
Camel Snus Mellow	1.7

These NNN and NNK levels are lower, across the board, than those of moist snuff products from the 1980s and 1990s, which I documented in a review article in 2004 (here). Epidemiologic studies from the 1980s and 1990s show that oral cancer risks among moist snuff users were minimally elevated, if at all, when those higher level products were being used.

While Hecht and colleagues assert that “smokeless tobacco is carcinogenic to humans, causing oral, pancreatic and esophageal cancer,” a comprehensive study of cancer risks among smokeless users (here) documented no significant risk for any of these cancers. There is virtually no evidence that current TSNA levels are associated with ANY significant cancer risks. Reducing current levels cannot lower an immeasurable cancer risk.

The article by Hecht et al. indicates that the authors are comfortable with TSNA levels in Marlboro and Camel snus, and that they view these products as acceptable cigarette substitutes. Perhaps Drs. Hecht, Stepanov and Hatsukami will now endorse them in this manner.

Polycyclic Aromatic Hydrocarbons in Smokeless Tobacco: Much Ado About Snuffing

In August, I wrote about a report by a prohibitionist University of Minnesota group claiming that one pinch of smokeless tobacco is five times more dangerous than smoking. They reported that smokeless tobacco products contain PAHs, a complex family of chemicals that are formed during the incomplete burning of almost any product, including coal, oil, gas, wood or other organic matter.

The researchers, led by Irina Stepanov and Stephen Hecht, pitched these claims to national media at a press conference sponsored by the American Chemical Society. But they refused to share their results with other scientists, pleading that “we are in process of publishing a full paper on this study.”

That paper has just been published, and it has been pitched again to national media. Again, the headlines scream “high levels of toxins,” and Stepanov et al. portray the results in almost apocalyptic terms: “Our findings render PAHs one of the most prevalent groups of carcinogens in smokeless tobacco. Urgent measures are required from the U.S. tobacco industry to modify manufacturing processes so that the levels of these toxicants and carcinogens in U.S. moist snuff are greatly reduced.”

Are the PAHs really toxins? Are the levels really “high”? Are emergency measures really indicated?

Unproven toxins

Stepanov analyzed smokeless tobacco samples from the U.S. market for 23 PAHs, and the manuscript implies that all of these are proven cancer-causing chemicals (carcinogens). Not even close.

I compared Stepanov’s list with a database maintained by the authoritative International Agency for Research on Cancer. IARC has reviewed several hundred chemicals for cancer-causation, and it has classified them on the strength of the scientific evidence as (Group 1) Carcinogenic to humans, (Group 2a) Probably carcinogenic, (Group 2b) Possibly carcinogenic, and (Group 3) Not classifiable. Groups 2a and 2b are largely based on animal or laboratory studies with no direct human evidence. IARC is a recognized authority, but it is inclined to label chemicals as human carcinogens if there is even a shred of evidence.

Readers will be amazed at how many IARC Group 1 carcinogens are on Stepanov’s list: Exactly ONE. Her list included one chemical IARC calls “probable”, while eight agents are in the still less threatening category of “possible”. More importantly, twelve (over half!) are NOT EVEN CLASSIFIED. (I couldn't find the remaining chemical in any IARC list.)

Low, Low Levels

Stepanov not only misrepresented the number of carcinogens. She implied that levels were dangerously high, stating that “moist snuff can be considered an important source of human exposure to PAHs.” Her data contains virtually no evidence for this statement.

In order to discuss Stepanov’s data, I’ll have to give a short primer or review of the metric system weights. Let’s start with a reference weight 1 kilogram, which is about 2.2 pounds.

1 kilogram = 1000 grams
1 gram = 1000 milligrams
1 milligram = 1000 micrograms
1 microgram = 1000 nanograms

Stepanov reported PAH concentrations in nanograms per gram of (dry) tobacco. A nanogram is one trillionth of a kilogram, or one billionth of a gram, so we are talking about vanishingly small amounts.

A can of moist snuff contains about 30 grams of tobacco, but about 50% of this weight is water, so the effective tobacco content is 15 grams.

The most important PAH on Stepanov’s list is benzo(a)pyrene (BaP), the only IARC Group 1 carcinogen. In Stepanov’s ideal world, no one would consume BaP; but we live in the real world, in which a fundamental tenet of toxicology is: the dose determines the poison. Despite Stepanov’s rhetoric, the level of BaP is very low in her tests, at an average of 56 nanograms per gram. That means that a one-can per day user is potentially exposed to 840 nanograms of BaP per day.

What does this level mean? Fortunately, the federal Environmental Protection Agency (EPA) has information that provides perspective. It says that “BaP is commonly found … in cigarette smoke, in grilled and broiled foods, and … in some water sources.” According to a study published in the Journal of Agricultural and Food Chemistry, a person eating a char-broiled quarter-pound hamburger consumes about 400 nanograms of BaP. The EPA says that water can have 780 nanograms of BaP per gallon and still be acceptable. This means that someone who eats a quarter-pound burger and drinks a half-gallon of water may consume about as much BaP as a can-per-day moist snuff user.

The EPA gives guidance for consumption of 5 other PAHs on Stepanov’s list, which are available in this document from the CDC. In fact, it gives specific consumption levels of these chemicals which are “not likely to cause any harmful health effects.” Using this information, I have estimated the number of cans of moist snuff that can be safely consumed daily by a 110-pound man with respect to these 5 PAHs:

PAH	Stepanov’s Concentration (nanograms per gram)	Number of Cans Per Day That Can Be Safely Consumed
Anthracene	844	1185
Acenaphthene	105	1905
Fluoranthene	1400	95
Fluorene	827	161
Pyrene	1290	78

I have been very conservative in developing these estimates. First, Stepanov used special solvents to get maximal extraction of PAHs from the samples; I have assumed that smokeless users consume those amounts, which is probably a serious overestimate. It is well known that PAHs are not very soluble in water, so it is likely that actual PAH consumption by smokeless users is much lower than the level reported by Stepanov.

One final comment: the EPA has estimated that on average, a person in the U.S. is exposed to about 3 milligrams of all PAHs every day. That’s 3 million nanograms. A person consuming a can of moist snuff per day is exposed to 174,000 nanograms, which is less than 6% of normal daily exposure.

No tobacco product is perfectly safe, but there is very little epidemiologic evidence that using smokeless tobacco, including American moist snuff, is associated with any cancer. Despite this, Stepanov and colleagues chemically characterize these products as major causes of cancer. Their rhetoric is not sustained by their data.

Minnesota Researchers to Smokeless Users: You’re Better Off Smoking!

In mid August the American Chemical Society, “the world’s largest scientific society,” held its national meeting in Washington, DC. The ACS has an impressive media machine, and on August 16 it was mobilized to promote a presentation entitled “Analysis of 21 polycyclic aromatic hydrocarbons in smokeless tobacco by gas chromatography-mass spectrometry,” by Irina Stepanov, a research associate at the University of Minnesota Masonic Cancer Center. The ACS media blitz included a press conference with Stepanov, which you can watch here.

Stepanov made some utterly incredible claims during her presentation, which were reported in an article published on the website of U.S. News & World Report under the headline “Chewing Tobacco No Safer Than Smoking”:

(1) “Tobacco users who think it's safer to dip snuff or chew tobacco than smoke are dead wrong, researchers say.”

(2) “A study has found that taking one pinch of smokeless tobacco delivers the same amount of polycyclic aromatic hydrocarbons (PAHs) as smoking five cigarettes.”

Let’s be perfectly clear: Irina Stepanov was asserting not only that smokeless tobacco is not safer than smoking, but that it is five times more dangerous than smoking!

Readers of this blog are familiar with the epidemiologic evidence linking smokeless tobacco use and cancer: almost a big fat zero. Numerous research studies have established that the cancer risks from using smokeless tobacco are so low that they are barely measurable.

Irina Stepanov made her claims about smokeless tobacco at a very public national meeting, and the American Chemical Society was an enthusiastic partner in promoting her research to the media. Surprisingly, after launching this unsubstantiated attack on smokeless tobacco, both Stepanov and the Chemical Society have refused to share her presentation with this researcher.

On August 19, I emailed Stepanov requesting a copy of her presentation. Her response on August 22 was bizarre: “We are in process of publishing a full paper on this study. So, the abstract is the only material that is available for sharing.”

That excuse for withholding her data is unprofessional. Researchers routinely provide copies of their public conference presentations to others in academia, regardless of the pendency of publication of fuller texts.

Refusal to share a conference presentation may violate the spirit, if not the letter, of the National Institutes of Health grants policy on data sharing. NIH funds Stepanov’s research group, the University of Minnesota and the Masonic Cancer Center, which also promoted Stepanov’s Chemical Society presentation. The NIH position is crystal clear: “It is NIH policy that the results and accomplishments of the activities that it funds should be made available to the public. PIs and grantee organizations are expected to make the results and accomplishments of their activities available to the research community and to the public at large.”

This episode is simply the latest in a series of attacks on smokeless tobacco by Minnesota anti-tobacco extremists. Almost the same approach and rhetoric were used in these 2007 articles in the New York Times and Fox News.

The main objective of this blog is to “examine and comment on the scientific foundation for tobacco policies and fallacies.” But that examination and commentary is contingent upon the scientific information being made available. In this case, Irina Stepanov, assisted by the American Chemical Society, has made a mockery of the long-standing tradition of open communication of scientific information.