The carcinogenic potency of the tobacco-specific nitrosamines NNN and NNK is well established, and the existing evidence indicates that these carcinogens can be nearly eliminated from tobacco products.13,14
A meaningful effort from the tobacco industry to make the necessary changes in their manufacturing approaches and dramatically reduce TSNA levels in cigarette filler, thus reducing smoke deliveries of these carcinogens, 15
was anticipated to take place about a decade ago. We here analyzed a sample of U.S. cigarettes purchased in the spring of 2010 to examine whether there are any reductions in TSNA levels in the filler and smoke of currently sold brands, including some varieties introduced to the U.S. market over the past decade.
The analytical method used in this study was first described in 1979, when NNN and NNK were quantified in the tobacco of an unidentified commercial filtered U.S. cigarette at 1.4 μg/g tobacco and 0.7 μg/g tobacco, respectively.5
If the values reported then are taken as a starting point and compared to those reported for the tobacco of U.S. commercial filtered cigarettes at two 15-year intervals – in 199522
and 2010 (this report) – the conclusion is that despite the available technology to produce cigarettes low in TSNA, the levels of these carcinogens in the tobacco of popular U.S. cigarette brands have remained essentially the same (). Similarly, there is no apparent significant reduction in smoke TSNA levels over the past decade: NNN levels in the smoke of 26 brands of cigarettes analyzed as a part of the 1999 Massachusetts Benchmark Study ranged from 100 to 317 ng/cigarette, and NNK ranged from 54 to 226 ng/cigarette (summarized in 23
). Another major observation in our study is that the TSNA levels in the recently introduced new varieties of existing cigarette brands do not reflect any attempt to reduce, or at least control, the levels of these carcinogens. Thus, Marlboro Blend # 54 contains much higher levels of total TSNA than the regular Marlboro variety: 7.00 μg/g tobacco vs. 4.63 μg/g tobacco in the filler, and 572 ng/cigarette vs. 378 ng/cigarette in smoke ( and ). The levels of TSNA in the expansions of the Camel brand are also somewhat similar to the levels in regular Camel cigarettes ( and ). The overall slightly lower levels of TSNA in the cigarettes produced by R.J. Reynolds, as compared to Philip Morris’ brands, could be a consequence of the promised strategy to use low-TSNA flue-cured tobaccos.17
However, since flue-cured tobacco comprises only part of a cigarette blend, TSNA reduction in only this type of tobacco leads to not more than a modest change in total TSNA levels. In this respect, Marlboro Virginia Blend cigarettes are an exception. These cigarettes are made from a single type of flue-cured bright tobacco, and as a result, have the lowest NNN and NNK levels among all Philip Morris brands ( and ).
Figure 1 Levels of NNN and NNK in tobacco filler of a U.S. filtered cigarette at three time-points over the 30-year period. A, levels reported for an unidentified U.S. commercial filtered cigarette 5; B, average of NNN and NNK levels reported for tobacco filler (more ...)
We found a positive correlation between TSNA levels in tobacco filler and smoke of the same cigarettes (), which is consistent with previously published data. 9
Moreover, the studied brands did not differ drastically in the transfer rate of deuterium-labeled NNN and NNK from cigarette filler to smoke (). These findings indicate that TSNA levels in the smoke of cigarettes investigated here are driven primarily by the corresponding TSNA levels in cigarette filler, once again stressing the importance of changes in tobacco processing and blending approaches for the reduction of smoke deliveries of these carcinogens. As was shown for commercial Canadian and Australian cigarettes, TSNA levels in cigarette smoke can be reduced to just a few nanograms per cigarette, or even nearly eliminated 15,18
. Thus, the sum of NNN and NNK in the filler of six brands of Canadian cigarettes decreased from an average 1.2 μg/g tobacco in 2003 to an average 0.35 μg/g tobacco in 2005 (71% reduction). 15
This resulted in comparable reductions in TSNA levels in the smoke of these cigarettes, and NNN and NNK levels in cigarettes sold in 2005 averaged as low as 7 ng/cigarette and 11 ng/cigarette, respectively. U.S. cigarette manufacturers possess the necessary knowledge and tools to achieve similar reductions.
Correlation between tobacco-specific nitrosamine levels in tobacco filler and smoke of cigarettes analyzed in this study: A, NNN; B, NNK; C, Total TSNA (sum of NNN, NNK, NAT, and NAB).
TSNA are not the only carcinogens found in cigarette smoke, and it is unclear whether the reduction of their levels alone will lead to a reduction in risk of developing smoking-induced cancers. However, NNN is the most prevalent esophageal carcinogen in cigarette smoke,24
while the evidence is strong that NNK and polycyclic aromatic hydrocarbons are causative agents for lung cancer in smokers.25
Based on its historical levels in cigarette smoke and its ability to induce adenocarcinoma of the lung in three commonly used rodent models, as well as comparative lung cancer death rates from the U.S. and Australia, NNK may be partially responsible for adenocarcinoma becoming the leading type of lung cancer in the United States.26,27
Two recent reports demonstrated that higher levels of total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a biomarker of NNK exposure in smokers, are associated with a higher risk of lung cancer.28,29
Furthermore, a recent study has documented a clear relationship between urinary NNAL levels and mouth-level exposure to TSNA, showing that smokers of low-TSNA cigarettes have lower levels of NNAL in their urine.30
Taken together, the results of these studies imply that higher levels of TSNA in cigarette smoke are associated with a higher risk of cancer in smokers.
In summary, despite the available knowledge and tools, there appears to be a remarkable lack of any reduction in the levels of known human carcinogens in products being sold to millions of customers. In light of the recently granted regulatory authority to the U.S. FDA over tobacco products, regulation of TSNA levels in cigarette tobacco should be strongly considered.