Carcinogenic tobacco-specific N-nitrosamines in US cigarettes: Three decades of remarkable neglect by the tobacco industry

Masonic Cancer Center and Tobacco Use Research Programs, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Tobacco control (Impact Factor: 5.93). 05/2011; 21(1):44-8. DOI: 10.1136/tc.2010.042192
Source: PubMed

ABSTRACT Modification of tobacco curing methods and other changes in cigarette manufacturing techniques could substantially reduce the levels of tobacco-specific nitrosamines (TSNA), a group of potent carcinogens, in cigarette smoke. In 1999, two major US cigarette manufacturers stated their intent to move towards using tobaccos low in TSNA. There is no information available on current TSNA levels in tobacco of various cigarettes available in the US, particularly in the newer varieties introduced over the past decade.
Seventeen brands of cigarettes were purchased in April of 2010 from retail stores in Minnesota. TSNA levels were measured in the tobacco filler and smoke of these cigarettes.
In all brands, the sum of two potent carcinogenic TSNA--4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and N'-nitrosonornicotine--in cigarette filler averaged 2.54 (± 1.05) μg/g tobacco. This value is virtually identical to the sum of these two carcinogens reported for the tobacco of a US filtered cigarette in 1979. TSNA levels in smoke positively correlated with those in tobacco filler of the same cigarettes.
We found no indication that any meaningful attempt was made to reduce or at least control TSNA levels in the new varieties of the popular brands Marlboro and Camel introduced over the last decade. In light of the recently granted regulatory authority to the FDA over tobacco products, regulation of TSNA levels in cigarette tobacco should be strongly considered to reduce the levels of these potent carcinogens in cigarette smoke.

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    • "We identified 14 published studies that met the data inclusion criteria (Adams et al., 1987; Brunnemann and Hoffmann, 1991; Brunnemann et al., 1996; Counts et al., 2005, 2006; Djordjevic et al., 1991; Hecht et al., 1979; Hoffmann et al., 1979, 1982, 1994; Patskan et al., 2008; Roemer et al., 2004; Stepanov et al., 2012; Swauger et al., 2002). Table 1 presents cigarette product identifications, levels of MS smoke tar (mg/cigarette), NNK (ng/cigarette ), and NNN (ng/cigarette), and sources of the data presented in this review. "
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    ABSTRACT: This paper characterizes historical and current tobacco specific nitrosamine (TSNA) levels in mainstream (MS) cigarette smoke of US commercial cigarettes. To conduct this analysis, we gathered 35 years of published data of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N-nitrosonornicotine (NNN) levels in MS cigarette smoke. We also assessed internal data of MS smoke NNK and NNN levels generated from various market monitoring initiatives and from control cigarettes used in a multi-year program for testing cigarette ingredients. In all, we analyzed machine smoking data from 401 cigarette samples representing a wide range of products and design characteristics from multiple manufacturers and market leaders. There was no indication that TSNA levels systematically increased in cigarette MS smoke over the 35-year analysis period. In particular, TSNA levels expressed as either per cigarette or normalized for tar suggest a downward trend in MS smoke over the past 10 years. The apparent downward trend in TSNA levels in MS smoke may reflect industry and agricultural community efforts to reduce levels of TSNAs in tobacco and cigarette smoke.
    Regulatory Toxicology and Pharmacology 04/2013; 66(2). DOI:10.1016/j.yrtph.2013.03.013 · 2.03 Impact Factor
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    • "TSNAs smoke delivery. The transfer rate (the ratio of the amount of the compound in burnt tobacco to the amount of the compound present in mainstream smoke) of TSNAs is well established (Fischer et al., 1990); about 10.7% of deuterated NNN and 11.1% of deuterated NNK when added to American blend cigarettes are found to transfer to smoke (Stepanov et al., 2011). The rapid reaction of NO x with smoke components to yield nitrosamines is well documented. "
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    ABSTRACT: The WHO TobReg proposed mandating ceilings on selected smoke constituents determined from the market-specific median of nicotine-normalized yield distributions. Data validating this regulatory concept were obtained from essentially single-blend surveys. This process is strongly impacted by inverse correlations among yields. In the present study, 18 priority WHO smoke constituent yields (nicotine-normalized) were determined (using 2 smoking regimens) from 262 commercial brands including American, Virginia and local blends from 13 countries. Principal Component Analysis was used to identify yields patterns, clustering of blend types and the inverse correlations causing these clusters. Three principal components explain about 75% of total data variability. PC(1) was sensitive to the relative levels of gas- and particle-phase compounds. PC(2) and PC(3) cluster American- and Virginia-blends, revealing inverse correlations: Nitrogen oxides and amino- or nitroso-aromatic compounds inversely correlate to either formaldehyde and acrolein, or benzo(a)pyrene and di-hydroxybenzenes. These results can be explained by reviewing the processes determining each components smoke delivery. Regulatory initiatives simultaneously targeting selected smoke constituents in markets with mixed blend styles will be strongly impacted by the inverse correlations described. It is difficult to predict the ultimate impact of such regulations on public health, considering the complex chemistry of cigarette smoke formation.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 01/2013; 55. DOI:10.1016/j.fct.2013.01.016 · 2.90 Impact Factor
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    ABSTRACT: Tobacco-specific nitrosamine (TSNA) formation in tobacco is influenced by alkaloid levels and the availability of nitrosating agents. Tobacco types differ in their potential for TSNA accumulation due to genetic, agronomic, and curing factors. Highest TSNA concentrations are typically measured in burley tobaccos. One of the main genetic differences between burley and all other tobacco types is that this tobacco type is homozygous for recessive mutant alleles at the Yellow Burley 1 (Yb(1)) and Yellow Burley 2 (Yb(2)) loci. In addition, burley tobacco is typically fertilized at higher nitrogen (N) rates than most other tobacco types. This study utilized nearly isogenic lines (NILs) differing for the presence of dominant or recessive alleles at the Yb(1) and Yb(2) loci to investigate the potential influence of genes at these loci on TSNA accumulation. Three pairs of NILs were evaluated at three different nitrogen fertilization rates for alkaloid levels, nitrogen physiology measures, and TSNA accumulation after air-curing. As previously observed by others, positive correlations were observed between N application rates and TSNA accumulation. Recessive alleles at Yb(1) and Yb(2) were associated with increased alkaloid levels, reduced nitrogen use efficiency, reduced nitrogen utilization efficiency, and increased leaf nitrate nitrogen (NO(3)-N). Acting together, these factors contributed to significantly greater TSNA levels in genotypes possessing the recessive alleles at these two loci relative to those carrying the dominant alleles. The chlorophyll-deficient phenotype conferred by the recessive yb(1) and yb(2) alleles probably contributes in a substantial way to increase available NO(3)-N during curing and, consequently, increased potential for TSNA formation.
    Journal of Agricultural and Food Chemistry 06/2012; 60(25):6454-61. DOI:10.1021/jf2053614 · 2.91 Impact Factor
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