The need for regulation of carcinogenic Nnitrosamines in oral snuff

doi:10.1016/0278-6915(93)90109-C

Food and Chemical Toxicology

Volume 31, Issue 7, July 1993, Pages 497-501

https://doi.org/10.1016/0278-6915(93)90109-C Get rights and content

Abstract

Oral snuff is carcinogenic to humans and laboratory animals. The major carcinogenic agents in snuff are the N-nitrosamines, especially the tobacco-specific N-nitrosamines. During the past decade, a gradual reduction of the levels of carcinogenic N-nitrosamines was observed in the leading snuff brands in the USA and in Sweden. However, in 1990 a newly introduced snuff brand in the USA contained the highest concentration of carcinogenic N-nitrosamines ever to be determined in a commercial tobacco product. The elevated pH and relatively high levels of nitrite in this snuff favoured the formation of N-nitrosamines, 2 yr after the product first appeared, it was replaced by a new preparation of snuff under the same brand name, and, according to chemical analyses, this material would be expected to have about the same carcinogenic potential as the leading snuff products. The interdependence of the formulation and manner of preparation of snuff products with their carcinogenic potential emphasizes the need for regulation and control of the harmful substances in smokeless tobacco, especially in view of the trend of increasing consumption of snuff.

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Cited by (33)

Grass roots approach to control levels of carcinogenic nitrosamines, NNN and NNK in smokeless tobacco products
2019, Food and Chemical Toxicology
Citation Excerpt :
Levels of NNN and NNK in tobacco are governed by numerous factors like plant genetics, growth factors, cultivation practices, processing, blending and storage conditions (Niaz et al., 2017). In Sweden, careful manipulation of these factors has led to a decrease in the levels of carcinogenic nitrosamines by about 85% over a 20-year period (Gray et al., 2008; Djordjevic et al., 1993a; Borgerding et al., 2012). But NNN values for most US SLT brands ranged from 3.76 to 6.86 as compared to 1.66 for Swedish snus which has lowest NNN content than any other SLT product in the world (Osterdahl and Slorach, 1983).
Due to the extensive ban on public smoking, tobacco companies focused their business on new smokeless tobacco (SLT) products promoting them as a harm reduction strategy and a safer alternative to cigarettes. Two nitrosamines, N′-nitrosonornicotine (NNN) and nicotine-derived nitrosamine ketone (NNK), present in SLT, listed as group 1 human carcinogens by the International Agency for Research on Cancer, are found to be the prime agents for most of cancers in SLT users. This review illustrates the mechanism of cancer induction by NNN and NNK in humans along with factors influencing the formation of NNN and NNK at various stages of tobacco manufacturing. It reveals the high levels and wide variations of NNN and NNK found among the diverse variety of SLT products sold worldwide. According to a recent report by FDA- Centre for Tobacco Products, reducing levels of nitrosamines in SLT products could greatly enhance the quality of life by reducing mortality, morbidity and medical expenditures due to cancer. For the first time, grass root approaches to minimize the levels of NNN and NNK in tobacco, from plant growth to the finished products, have been systematically compiled as they have the potential to contribute to reducing tobacco related disease burden.
Le snus
2012, Presse Medicale
The use of snus (smokeless tobacco) can be detrimental to health. Containing carcinogenic nitrosamines (Swedish snus do not contain nitrosamine). Snus delivers rapidly high doses of nicotine which can lead to dependence. It do not induce bronchial carcinoma differently smoked tobacco.
Lesions usually develop in the area of the mouth where the snus is placed. Non-malignant oral lesions include leukoedema, hyperkeratotic lesions of the oral mucosa and localised periodontal disease. The most frequently occurring premalignant lesion is leukoplakia. Studies reveal conflicting evidence about the risk of oral and gastroesophageal cancer with regard to snus users. However, the use of snus has proved to be a risk factor in developing pancreatic cancer and increases the risk of fatal myocardial infarction and ischemic stroke.
During pregnancy, snus is associated with an increased risk of pre-eclampsia and premature delivery.
Nicotine substitution therapy and bupropion and varenicline reduce withdrawal symptoms and tobacco craving during snus cessation. However, they have not been shown to assist in long-term abstinence. Information concerning potential hazards of using snus products must be incorporated into health educational programmes in order to discourage its use. Snus is not a recommended product to help in stopping to smoke.
L’utilisation du snus (tabac non fumé) peut être néfaste pour la santé ; il contient des nitrosamines carcinogènes (en Suède, il est « dénitrosaminé »). Il délivre rapidement des doses importantes de nicotine et induit dépendance et morbidité, mais à la différence du tabac fumé, il ne provoque pas de cancer bronchique.
Des lésions buccales inconstantes peuvent se développer au niveau des zones de placement. Les lésions non cancéreuses comportent le leuco-œdème et l’hyperkératose de la muqueuse buccale. La lésion précancéreuse la plus fréquente est la leucoplasie. Les études sur le risque de cancer buccal et œsogastrique sont discordantes. En revanche, la consommation de snus est un facteur de risque avéré du cancer du pancréas, d’infarctus du myocarde et d’accident vasculaire cérébral mortels.
Pendant la grossesse, le snus est associé à une augmentation du risque de pré-éclampsie et d’accouchement prématuré.
Les substituts nicotiniques, le bupropion et la varénicline diminuent les symptômes de sevrage et le craving lors de la tentative d’arrêt du snus sans modifier l’abstinence à long terme. L’information sur les dangers du snus doit être intégrée dans les programmes d’éducation à la santé, afin d’éviter son usage. Il ne représente pas un produit de substitution au tabac fumé.
Smokeless tobacco
2011, Revue des Maladies Respiratoires
L’utilisation du tabac non fumé (TNF) (tabac mâché et snuff) peut avoir des conséquences néfastes pour la santé. Le TNF, qui contient des nitrosamines carcinogènes, délivre rapidement des doses importantes de nicotine et peut induire dépendance et morbidité. Les lésions buccales se développent en général au niveau des zones de placement du TNF. Les lésions non cancéreuses comportent le leuco-œdème et l’hyperkératose de la muqueuse buccale. Les lésions précancéreuses sont la leucoplasie, l’érythroplasie, la fibrose buccale sous-muqueuse et le lichen plan. Le bétel mâché avec ou sans tabac augmente l’incidence du cancer de la bouche. Chez les consommateurs de snuff, les études sur le risque de cancer buccal et oesogastrique sont discordantes. La consommation actuelle de TNF est un facteur de risque du cancer du pancréas. Le TNF augmente le risque d’infarctus du myocarde et d’accident vasculaire cérébral mortels. Pendant la grossesse, le TNF est associé à une augmentation du risque de pré-éclampsie, d’accouchement prématuré et de mortinatalité. Les substituts nicotiniques et le bupropion diminuent les symptômes de sevrage et la craving à l’arrêt du TNF mais ne modifient pas l’abstinence à long terme. Des informations sur les dangers du TNF doivent être intégrées dans les programmes d’éducation à la santé afin d’éviter son usage, d’aider les utilisateurs à arrêter leur consommation. Le TNF ne représente donc pas un produit de substitution au tabac fumé.
Use of smokeless tobacco (ST) (chewing tobacco and snuff) can lead to a number of consequences detrimental to health. ST rapidly delivers high doses of nicotine, which can lead to dependence and is also a source of carcinogenic nitrosamines. Changes usually develop in the mouth area where the ST is most often placed. Non-malignant oral lesions include leuko-oedema, hyperkeratotic lesions of the oral mucosa and localised periodontal disease. Oral premalignant lesions are leukoplakia, erythroplakia, submucosal fibrosis and lichen planus. Betel chewing, with or without tobacco, may increase the incidence of oral cancer. There is conflicting evidence with regard to snuff users about the risk of oral and gastro-oesophageal cancer. ST use is a risk factor for pancreatic cancer and may increase the risk of fatal myocardial infarction and ischemic stroke. During pregnancy, ST is associated with an increase in pre-eclampsia, preterm delivery and stillbirth. Nicotine replacement therapy and bupropion reduce withdrawal symptoms and tobacco craving during ST cessation. However, they have not been shown to help long-term abstinence. Information concerning the potential hazards of ST products should be incorporated into educational programmes to discourage its use and to help users to quit. Smokeless tobacco is not recommended to help smoking cessation.
Gastric DNA damage through tobacco chewing: In vitro mechanistic studies of DNA nitrite attack
2006, Cancer Letters
Smokeless chewing tobacco or snuff has been linked to carcinogenic effects in upper aerodigestive organs. The presence of nitrite within the tobacco product is suspected to foster carcinogenic DNA mechanisms at lower pH. We studied the impact of sodium nitrite on DNA damage at single-strand conformers or hairpin loops, known to be present at fragile sites that have been shown to cause methyltransferase stalling and that can lead to chromosomal breakage. At a pH of 4.2, two base-damage products could be demonstrated at significant levels (1–5% of total nucleotides), with greater sensitivity to hairpin loops compared to a control Watson–Crick duplex. Pyrimidine-rich strands (CCG, CTG) were more reactive than purine-rich strands (CAG, CGG). The data support a mechanism for allele-specific predisposition to DNA damage. This mechanism may be of significance in gastric cancer initiation due to chewing tobacco.
Chemical profile of two types of oral snuff tobacco
2002, Food and Chemical Toxicology
The chemical-analytical profile of two US brands of oral moist snuff was determined. These two brands were bought in five geographical locations (NY, MA, CO, CA and KY in the US). They were mixed thoroughly to yield representative samples. Brand A had a pH of 5.84 and nicotine content of 0.42%, while brand B had a pH of 7.99 and nicotine content of 2.73%. At pH 5.84, only 1% of the nicotine is present as a free base while 59% of nicotine is present in unprotonated form at pH 7.99. It is the unprotonated form of nicotine that is most readily absorbed through the mucous membrane in the oral cavity. Snuff A contained also significantly lower levels of moisture, nitrate, nitrite and tobacco-specific nitrosamines than snuff B. The University of Kentucky reference snuff 1S3 was analyzed as an external control sample. These two snuff brands are currently being assayed with rats in a short-term and in long-term bioassays to test the concept that the tobacco-specific N-nitrosamines are major contributors to the carcinogenic activity of oral snuff.
Smokeless tobacco as a possible risk factor for myocardial infarction: A population-based study in middle-aged men
1999, Journal of the American College of Cardiology
OBJECTIVES
To explore whether the use of snuff affects the risk of myocardial infarction (MI).
BACKGROUND
Snuff and other forms of smokeless tobacco are widely used in some populations. Possible health hazards associated with the use of smokeless tobacco remain controversial.
METHODS
In a population-based study within the framework of the Northern Sweden center of the World Health Organization Multinational Monitoring of Trend and Determinants in Cardiovascular Disease (WHO MONICA) Project, tobacco habits were compared in 25- to 64-year-old men with first-time fatal or nonfatal MI and referent subjects matched for age and place of living (687 cases, 687 referents).
RESULTS
The unadjusted odds ratio (OR) for MI in regular cigarette smokers as compared with men who never used tobacco was 3.65 (95% confidence interval [CI] 2.67 to 4.99). When nonsmoking regular snuff dippers were compared with never-users of tobacco, the unadjusted OR was 0.96 (0.65 to 1.41). After adjustment for multiple cardiovascular risk factors, the OR was 3.53 (95% CI 2.48 to 5.03) for regular smoking and 0.58 (95% CI 0.35 to 0.94) for regular snuff dipping. Restricting the analyses to fatal cases of myocardial (including sudden death) showed a tendency towards increased risk among snuff dippers 1.50 (95% CI 0.45 to 5.03).
CONCLUSIONS
The risk of MI is not increased in snuff dippers. Nicotine is probably not an important contributor to ischemic heart disease in smokers. A possible small or modest detrimental effect of snuff dipping on the risk for sudden death could not be excluded in this study due to a limited number of fatal cases.

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The need for regulation of carcinogenic Nnitrosamines in oral snuff

Abstract

Deep Sea Research

Food and Cosmetics Toxicology

Absorption of nicotine in cigarette and cigar smoke

Nature, London

Analytical studies on N-nitrosamines in tobacco and tobacco smoke

Recent Advances in Tobacco Science

Decreased concentrations of N-nitrosodiethanolamine and N-nitrosomorpholine in commercial tobacco products

Journal of Agricultural and Food Chemistry

Improved method for the quantification of nitrite in plant material

Analytical Letters

Identification and analysis of a nicotine-derived N-nitrosamino acid and other nitrosamino acids in tobacco

Carcinogenesis

Identification and quantitative analysis of new N-nitrosamino acids in snuff tobacco

Assessment of major carcinogens and alkaloids in the tobacco and mainstream smoke of USSR cigarettes

International Journal of Cancer

Induction of oral cavity tumors in F344 rats by tobacco-specific nitrosamines and snuff

Cancer Research

On the control of toxic substances in smokeless tobacco

Lung cancer and the changing cigarette