|
 
 |
| REVIEW ARTICLE |
|
| Year : 2022 | Volume
: 13
| Issue : 3 | Page : 121-126 |
|
Are smokeless tobacco products less harmful than smoking tobacco products?: A Review
Monika Srivastav1, Thayalan Dinesh Kumar2, Elizabeth C Dony1
1 Assistant Professor, Department of Oral Pathology and Microbiology, Dr.D.Y.Patil Dental College and Hospital, Dr.D.Y.Patil Vidyapeeth, Pimpri, Pune, India
2 Department of Oral Pathology and Microbiology, Reader, S.R.M Dental College and Hospital, Chennai, Tamil Nadu, India
| Date of Submission | 22-Jun-2022 |
| Date of Decision | 03-Aug-2022 |
| Date of Acceptance | 05-Aug-2022 |
| Date of Web Publication | 09-Sep-2022 |
Correspondence Address:
Dr. Monika Srivastav
2nd Floor, Department of Oral Pathology and Microbiology, Dr. DY Patil Dental College and Hospital, Dr. DY Patil Vidyapeeth, Sant Tukaram Nagar, Mahesh Nagar, Pimpri - 411 018, Pune
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/srmjrds.srmjrds_87_22
Background: The common belief amongst the consumers of smokeless tobacco products is Smokeless Tobacco Products (STPs) are not hazardous as smoking tobacco. Any form of tobacco consumed is addictive and the nicotine absorbed from these products is manifold higher than the nicotine produced and delivered from a cigarette. Aim: The aim of this narrative review is to consolidate and summarize the data from various studies to find out whether smokeless tobacco products are less harmful than smoking tobacco products or vice-versa. Method: A comprehensive literature search was conducted using various databases like EBSCO, Google scholar, Pubmed, Embase from 1957 to 2021. The keywords used for search was 'smokeless tobacco products', 'bacterial population AND smokeless tobacco products', 'water content, pH in STP'. Result: In total, 52 articles were selected to analyze the parameters, which proved increasing carcinogenicity in smokeless tobacco products. Various parameters were analyzed which include pH, water content, manufacturing procedure of STP and microbial population in smokeless tobacco products. Conclusion: The literature search suggests that the microbial population in smokeless tobacco products acts as a cascading series of events in carcinogenesis and other opportunistic infections and concludes that smokeless tobacco products are equally harmful as smoking tobacco products.
Keywords: Microbial population, smokeless tobacco products, TSNA, water content
How to cite this article:
Srivastav M, Kumar TD, Dony EC. Are smokeless tobacco products less harmful than smoking tobacco products?: A Review. SRM J Res Dent Sci 2022;13:121-6 |
How to cite this URL:
Srivastav M, Kumar TD, Dony EC. Are smokeless tobacco products less harmful than smoking tobacco products?: A Review. SRM J Res Dent Sci [serial online] 2022 [cited 2023 May 28];13:121-6. Available from: https://www.srmjrds.in/text.asp?2022/13/3/121/355831 |
| Introduction | |  |
Tobacco is the only officially permitted drug that is conscientious for killing many of its users when used exactly as intended by manufacturers. The WHO has gauged that tobacco use currently accounts for the mortality of about 6 million people across the planet every year with many of these occurring prematurely.[1] In India, The Global Adult Tobacco Survey (GATS) approximated that around 99.5 million (10.7%) are tobacco consumers and 199.4 million (21.4%) adults consume smokeless form of tobacco. In addition, it is anticipated that there will be more than 300 million smokers worldwide.[2],[3] The use of tobacco is extensive and omnipresent in the world, as it is used both in smoked forms and nonsmoked forms. Individuals consuming tobacco have an inflated risk of developing malignancies, as well as nonmalignant serious disorders such as cardiovascular and pulmonary disorders.[4]
Smoking tobacco, in the form of cigarettes or cigars, is consumed globally whereas the consumption of smokeless tobacco is confined to only specific populations or countries. The smokeless tobacco products (STPs) are more commonly used in North America, a few Scandinavian countries, Saudi Arabia, India, Bangladesh, Southeast Asia, and a few parts of Africa.[5]
STPs, as the name implies, are consumed without smoking (heating). They are utilized as a substitute for smoking cigarettes in spite of the strong evidence to suggest their carcinogenicity.[6] The “International Agency for Research on Cancer” (IARC) evaluates the carcinogenic risk and concludes that STPs are considered a source of malignancies in the oral cavity.[7] However, STPs appear to differ significantly in terms of their potential carcinogenicity, a characteristic attributed to the variance in carcinogenic chemical concentrations, specifically “tobacco specific N nitrosoamines (TSNAs).”[8] The STPs available in Europe and America typically contain lesser TSNAs and other chemical carcinogens than Indian brands, which may help partially explain the rise in oral cancer cases among Indians.[9]
In the past, research on the deleterious health hazards and carcinogenic consequences of STPs has mostly centered on their chemical components and the concentration of carcinogenic agents.[10] However, the probability of growth of microbial colonies in the STP is very high and could be responsible for a health risk.[11] Although it is believed that microbial composition is crucial in explaining the variance in the carcinogenicity of STPs, this idea has not been thoroughly researched.
The TSNA levels in tobacco are determined by the bacteria associated with tobacco since they are known to produce nitrite by reducing nitrates, which then combine with the alkaloids in tobacco to form TSNAs.[11],[12] Another probable risk associated with bacterial contamination is the production of metabolic by-products that may be harmful to the individuals consuming STPs.[8]
The bacterial communities discovered in STPs and their expressed activities, however, have received very little attention. The way tobacco is processed and how it has made a big impact on the microbial content remains unclear. Water content also has an impact on the microbial population since it promotes microbial growth.[13]
Earlier research on the microbiota in tobacco products has often relied on culture-based techniques, which may have overlooked the microbiome's diversity. However, only few studies have examined tobacco products using 16S rDNA metagenomic analysis, which will provide an accurate representation of the bacterial communities present.[14]
The majority of these approaches, however, have only been used to examine the hypervariable V3-V4 sections of the bacterial genome, which may provide just 60% of bacterial coverage.[14] This stands as one of the shortcomings of this approach. Compared to conventional approaches that only examine the V3-V4 region, a panel interrogating the entire V1-V9 region can enable sensitive detection and accurate representation of each species in the sample.
The leaves of plants in the Nicotiana genus are used to produce tobacco, which is then made into a variety of STPs. Almost 3000 chemical components in tobacco leaf and nearly 4000 in tobacco smoke have been carefully examined. Tobacco use is the main and perhaps most avoidable cause of premature death and illness in the world today. According to statistics, one tobacco user worldwide dies due to a cigarette-related disease every 6.5 s. Most international tobacco control (TC) propaganda is directed at cigarettes, giving smokeless tobacco and other similar products very little attention.[15]
Although the ubiquity of consuming smoking tobacco is decreased globally, there is constant and increased usage of smokeless tobacco.[16] The ubiquitous of STPs is considerably high in certain ethnic populations across the world. Approximately, 100 million consumers of Smokeless Tobacco (often as mixtures with betel leaf and areca nut) are from India and Pakistan alone.[17] From the above statistics, we can observe a sharp rise in the number of consumers of STPs. Hence, the purpose of this narrative review is to shed light on harmful effects of STPs and the microbial population present in STPs.
| Methods | | |
A comprehensive literature search was carried out using various databases such as EBSCO, Google scholar, PubMed, and Embase from 1957 to 2021. The search strategy was used with the restriction of analyzing only original studies. The keywords used for search was “STPs” OR “bacterial population AND STPs” OR “water content OR pH in STP.” The articles were selected on the basis of inclusion and exclusion criteria. Relevant articles, abstracts were screened and full text were identified and assessed. The original articles from the year 1957 to 2021 included and analyzed comprised literature on STPs. Literature review, case reports, case series were not included. The original studies published in languages other than English were not included.
| Results | | |
In total, 52 original studies were selected. The parameters, which were assessed in these studies, were manufacturing procedure, pH, water content or moisture content of STPs and microbial population present in STPs, presence of nitrate reducing bacteria in STPs.
| Discussion | | |
Alarming rise in the use of smokeless tobacco products
According to GATS India Report (2009–2010), those using STPs only (163.7 million) are more than double those who are exclusive smokers (42.3 million). The law should be enforced or strengthened, to focus on control policies as the percentage of consumption has increased from 28% to 33% in males and from 12% to 18% in females 10 years (1999–2009). India has a WHO association called comprehensive TC law; the Cigarettes and other Tobacco Products (Prohibition of Advertisement and Regulation of Trade and Commerce, Production, Supply, and Distribution) Act, 2003(COTPA), whose major objective is to control regulating both smoking and smokeless forms of tobacco. Despite the implementation of population-level legislative measures, there is a dreadful increase in the use of STPs.[18]
Different forms of smokeless tobacco
There are mainly two ways by which tobacco is consumed; smoking tobacco and smokeless tobacco. Smoking tobacco is consumed by lighting or blazing it, while “STPs” are tobacco products that are used by not igniting them.”[8] These STPs are consumed through oral route or consumed by sniffing through the nasal cavity and include products such as snuff, Snus, and chewable tobacco.[19]
There are various methods of consuming STPs and are named based on the method of consumption; Chewable tobacco, Snus, and Snuff. Snus is a STP, dry or moist, mostly placed between the gingiva and upper lip. Usually, Snus consumers keep the Snus in the mouth for approximately 10–15 min before it is discarded.[20] Snuff is also finely powdered ground tobacco that is packaged in a pouch and is consumed by inhalation through the nasal cavity. Chewable tobacco, a type of STP made from cured tobacco leaves, is the preferred method of consumption. It is typically sold in the form of loose tobacco leaves, pellets, or “bits” (rolled tobacco pieces).[21],[22]
Smokeless tobacco products are less harmful – a myth
Some researchers claim that using STPs such as Snus, chewing tobacco, and snuff is less hazardous than smoking tobacco.[22] These STPs may appear to be less harmful than conventional cigarettes, but they are associated with a higher risk of several diseases, including cardiovascular disease, pancreatic cancer, oral cancer, and esophageal cancer, among others.[23] The most hazardous ingredients in STPs are nitrosamines, which are specific to tobacco. Cancer risk is directly correlated with tobacco-specific nitrosamine levels. The key ingredient included in STP, nicotine, is what contributes to addiction.[24]
The common belief among the consumers of STPs is that STPs are less hazardous than smoking tobacco products. However, any form of tobacco consumed is considered to be addictive and the nicotine absorbed from these products is manifold higher than the nicotine produced and delivered from a cigarette. In comparison to the presence of nicotine in the blood, it has been observed that nicotine in smokeless tobacco tends to stay for a longer duration than that of smoking tobacco.[25]
Bacteria present in smokeless tobacco products
Few researchers have suggested the presence of bacteria in STPs. The “carcinogens” present in “STPs” including” “tobacco-specific nitrosamines (TSNAs),” “nitrosamino acids,” and “polycyclic aromatic hydrocarbons” are responsible for the poor health outcomes. Due to the toxic effect and high abundance, TSNA is considered the most important tobacco-associated carcinogen in STPs.[26] The levels of TSNA and its toxicity are influenced by the nitrate-reducing bacteria which are present in STPs.
A study conducted by Dygert in 1957, investigated an unopened package of snuff and found a wide variety of bacteria including Staphylococcus aureus, Staphylococcus epidermidis, Bacillus subtilis, proteus vulgaris and Pseudomonas aeruginosa. He concluded that various bacteria present in these STPs and their variations depend on the moisture content. On consumption of these products through mouth or nose, these bacteria entered and become the source of the pathogen.[27]
In a study conducted by Han et al. in 2016, five different Bacillus species were present in chewing tobacco. Species detected are Bacillus licheniformis and Bacillus pumilus, which are responsible for causing inflammation and opportunistic infection. He concluded that colonization of bacteria in STPs depends on the temporal variation and partly by its manufacturing process.[7]
In a study conducted by Smyth et al., in 2016, on analyzing Snus and snuff, the most abundant bacteria were from the phyla Firmicutes, Proteobacteria, and Actinobacteria but different ranges of bacteria were present in different STPs. He concluded that this difference could be partially accredited to the physical characteristics and environmental conditions of “STPs” that were tested.[19]
In a study conducted by Han et al. in 2016, species identified in STPs were c, B. licheniformis, Bacillus safensis, and B. subtilis. He concluded that microbes found in these STPs may play an important role in causing opportunistic infection in tobacco consumers and these bacteria have the capacity of reducing nitrate to nitrite.[7]
The manufacturing process and its influence on bacterial growth
The curing process of tobacco formation plays a major role in bacterial growth and its colonization.[28] During the curing stage, the amount of TSNA, carcinogen obtained from the nitrosation of tobacco alkaloids, increases remarkably. The stage of fermentation in manufacturing smokeless tobacco also seems to be responsible for variations in the bacterial population of these STPs.[29]
N-Nitrosonornicotine levels are usually reduced in given circumstances:
- leaves of tobacco that is dried
- Tobacco products containing leaves that are sun-cured/fire-cured. For example, the tobacco leaves which are sun-cured and fire-cured have a lower level of nitrates than air-cured
- Smaller amounts of nitrogen-rich burley are present in tobacco
- Unfermented tobacco present in products
- Products that are processed under a high temperature to disband microbial content, and
- If products were kept in nonhumid conditions at or less than room temperature.
Various additives, for example, menthol is also added by commercial manufacturers for increasing the palatability of the product, also resulting in different nitrate levels and also influencing the bacterial composition of these products.[30]
Nitrate-reducing bacteria in smokeless tobacco products
STPs are considered highly variable products in the matter of tobacco constituents, additives, and processing. There are mainly two sources through which nitrate reducing bacteria formed in STPs which causes the fermentation.[31] In nonsterile tobacco products, the bacterial population, specifically nitrate reducing bacteria were formed in the various stages of manufacturing and may get embarked on STPs as these tobacco products might have come in contact with equipment surfaces used for manufacturing.[24]
The microbes have the capability of producing nitrite resulting in raised TSNA levels. Due to the ubiquity of pro-inflammatory biomolecules and endotoxins in these products after fermentation, a thorough knowledge of microbes influencing the chemical reaction in tobacco products is mandatory. A broad variety of microorganisms, mostly soil-borne are found in fermented STPs.[26] These nitrogen-reducing bacterial populations can reduce nitrogen which mainly contributes to the formation of “carcinogenic nitrosamines” in STPs.[32],[33]
Fisher et al. stated that nitrate-reducing bacteria are formed during the curing process and lead to the formation of TSNA. He concluded that these nitrate-reducing bacteria reduce nitrate into nitrite and TSNA is formed through the nitrosation. TSNA is the most potent cancer-causing agent which is formed in “STPs.[26]
Warek et al. in their study, cultured nitrite-reducing bacteria, which lead to an increase in the formation of TSNA. He concluded that colonization of these bacteria depends on the manufacturing procedure and storage condition.[34]
The bacterial colonies with higher levels of nitrate and low nitrate-reducing properties are needed to support the production of high levels of TSNAs in tobacco production but the colonization of bacteria also depends on the environmental condition such as pH, temperature, and moisture.[35]
Role of moisture and pH
Moisture content present in STPs are responsible for influencing the quantity of N-nitrosonornicotine nitrosamine (NNN). As the moisture content in STPs increases, it favors the microbial growth and the enzymes that reduce nitrate to nitrite and eventually promotes the nitrosation and NNN formation.[36]
There is variety of hydrocarbons such as naphthalene present in STPs. They are regarded as a significant carbon source for several bacterial communities, which are identified within STPs. They also contribute in creating the microenvironment that speeds up the growth of these microorganisms in STPs.[37],[38]
Andersen et al. stated that moisture content also depends on the curing process and storage condition of the STPs. He concluded that pH level is directly proportional to the moisture content of STPs.[39]
Richter and Spierto stated increase in moisture content and pH influence the growth of microorganisms and concluded that pH acts as the determining agent in the resorption of nicotine which is responsible for addiction in tobacco consumers.[40]
Lawler et al. stated that pH level and moisture content are directly interrelated and influence the colonization of bacterial communities in STPs. He also concluded that the higher the pH level, the higher the moisture content.[35]
Ammann et al. stated that moisture content is directly correlated to the microbial load cultured in STPs. He concluded that moisture has the capacity for the formation of NNN which is a carcinogenic component in STPs.[36]
Tobacco specific N'nitrosamines
STPs contain over 4,000 different compounds, including tobacco-specific N′nitrosamines (TSNAs). NNN, a TSNA, is formed as a result of the N-nitrosation of tobacco alkaloids, primarily during tobacco processing. IARC Group 1 has categorized NNN as one of the TSNAs that is carcinogenic to humans, and it is believed to be one of the TSNAs with the greatest concentrations in “STPs.”[42] One gram of STPs contains “1–5 μg of the tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone” and “NL′-nitrosonornicotine.” These compounds have high carcinogenicity and are most carcinogenicin the family of tobacco-specific nitrosamine.[43]
As far as poisonous and noxious substances are concerned, nicotine is regarded as the worst, and is quickly absorbed through the skin and mucosa. Nicotine is secondary amine, whereas “Nomicotine, Anabasine, and Anatabine” are tertiary amines.[44] These are the amines that are considered accountable for the formation of tobacco-specific nitrosamines (TSNAs) when they react with a nitrosating agent. Under normal physiological conditions, TSNAs are A'-nitrosamines, which are chemically stable compounds. The major-specific nitrosamines in tobacco are NNK (4-[methylnitrosamino]–abutanone), NNN (N'-nitrosonornicotine), NAT (N'-nitrosoanatabine), NAB (N'-nitrosoanabasine), NNAL (4-[methylnitrosamino]-1-[3-pyridyl]-1-butanol), iso-NNAL and iso-NNAC.[41],[42] In STPs, TSNA have been detected in urine samples of consumers of smokeless tobacco and it is also demonstrated that these cancer-causing chemical are absorbed locally, then metabolized and excreted.
Bacteria in smokeless tobacco products and associated disease
Various bacteria are responsible for inducing or aggravating various systemic ailments. P. aeruginosa can cause chronic bronchitis; Streptococcus sanguis and Porphyromonas gingivalis induce platelet aggregation, which leads to thrombus formation and is responsible for causing cardiovascular disorders.[44]
Han et al. stated that B. licheniformis and B. pumilus are the most abundant bacteria in STPs and are associated with inflammation and opportunistic infection. S. aureus is responsible for causing various infections, osteomyelitis, and endocarditis.[7],[45],[46]
Hiregoudar et al., on analyzing STPs, found significant colony counts of two potential human bacterial pathogens. Aerobic, Gram-positive spore-forming rods of the genus Bacillus can result in foodborne illnesses, gastroenteritis, and several opportunistic infections.[47]
Schneider et al. stated that Klebsiella isolated from gutka which is chewing tobacco is known to induce abscesses, meningitis, septicemia, pneumonia, urinary infections, and other pyogenic illnesses.[48] One of the four gutka samples had the Aspergillus fumigatus isolate.[47] In immunologically healthy individuals, this organism causes fungus balls and allergic pulmonary aspergillosis; nevertheless, it can also cause invasive infections, mainly in elderly or immunosuppressed individuals. These diseases primarily affect the lungs but can spread to other organs.[48]
Monika et al. stated that various bacteria were present in the STP even if it was stored at room temperature. Almost 2600 bacterial populations of various genera were seen. These bacteria can disseminate to other organs and can play a vital role in carcinogenesis.[49]
| Conclusion | | |
Although there is strong evidence to prove the carcinogenicity of STPs, there is a misperception that they are less hazardous. Their harmful health impacts and carcinogenic effects have been predominantly examined in terms of their chemical composition and the presence of carcinogenic chemicals. Only a little research has been done on the presence of microbes in STPs. The way tobacco is processed, the way it is made, and the amount of water present, all have a big impact on the number of microbes present. Water and pH of STPs also helps microbes to proliferate, which increases the microbial population. In preceding literature, it is already a proven fact that tobacco products contain nicotine which is the main carcinogenic product. However, many studies have already shown that STPs have a bacterial population. Both of them together can play as a carcinogen and are responsible for carcinogenesis.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Bilano V, Gilmour S, Moffiet T, d'Espaignet ET, Stevens GA, Commar A, et al. Global trends and projections for tobacco use, 1990-2025: An analysis of smoking indicators from the WHO Comprehensive Information Systems for Tobacco Control. Lancet 2015;385:966-76.  |
| 2. | Bhawna G. Burden of smoked and smokeless tobacco consumption in India-results from the global adult tobacco survey India (GATS-India)-2009-2010. Asian Pac J Cancer Prev 2013;14:3323-9. |
| 3. | Gupta PC, Ray CS. Smokeless tobacco and health in India and South Asia. Respirology 2003;8:419-31. |
| 4. | Pant NK, Pandey KC, Madabhavi I, Pandey V, Revannasiddaiah S. Evaluation of the knowledge and perceptions with regards to pictorial health warnings on tobacco products among tobacco users diagnosed with head and neck carcinoma: A study from the Kumaon Hills of India. Asian Pac J Cancer Prev 2014;15:7891-5. |
| 5. | Asplund K. The controversial snuff. J Intern Med 2014;276:74-6. |
| 6. | IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Smokeless Tobacco. In: Personal Habits and Indoor Combustions. Vol. 100. International Agency for Research on Cancer; 1987. p. 1-538. |
| 7. | Han J, Sanad YM, Deck J, Sutherland JB, Li Z, Walters MJ, et al. Bacterial populations associated with smokeless tobacco products. Appl Environ Microbiol 2016;82:6273-83. |
| 8. | Al-Hebshi NN, Alharbi FA, Mahri M, Chen T. Differences in the bacteriome of smokeless tobacco products with different oral carcinogenicity: Compositional and predicted functional analysis. Genes (Basel) 2017;8:106. |
| 9. | Muwonge R, Ramadas K, Sankila R, Thara S, Thomas G, Vinoda J, et al. Role of tobacco smoking, chewing and alcohol drinking in the risk of oral cancer in Trivandrum, India: A nested case-control design using incident cancer cases. Oral Oncol 2008;44:446-54. |
| 10. | Borgerding MF, Bodnar JA, Curtin GM, Swauger JE. The chemical composition of smokeless tobacco: A survey of products sold in the United States in 2006 and 2007. Regul Toxicol Pharmacol 2012;64:367-87. |
| 11. | Wei X, Deng X, Cai D, Ji Z, Wang C, Yu J, et al. Decreased tobacco-specific nitrosamines by microbial treatment with Bacillus amyloliquefaciens DA9 during the air-curing process of burley tobacco. J Agric Food Chem 2014;62:12701-6. |
| 12. | Ammann JR, Lovejoy KS, Walters MJ, Holman MR. A survey of N′-nitrosonornicotine (NNN) and total water content in select smokeless tobacco products purchased in the United States in 2015. J Agric Food Chem 2015;62:12701-6. |
| 13. | Vishwakarma A, Verma D. Microorganisms: Crucial players of smokeless tobacco for several health attributes. Appl Microbiol Biotechnol 2021;105:6123-32. |
| 14. | Sajid M, Srivastava S, Joshi L, Bharadwaj M. Impact of smokeless tobacco-associated bacteriome in oral carcinogenesis. Anaerobe 2021;70:102400. |
| 15. | Etu ES, Gemeda DH, Hussen MA. Prevalence and factors that influence smokeless tobacco use among adults in pastoralist communities of Borena Zone, Ethiopia: mixed method study. Tob Induc Dis 2017;15:1. |
| 16. | Syamlal G, King BA, Mazurek JM. Tobacco use among working adults – United States, 2014-2016. MMWR Morb Mortal Wkly Rep 2017;66:1130-5. |
| 17. | Stanisce L, Levin K, Ahmad N, Koshkareva Y. Reviewing smokeless tobacco epidemiology, carcinogenesis, and cessation strategy for otolaryngologists. Laryngoscope 2018;128:2067-71. |
| 18. | Arora M, Madhu R. Banning smokeless tobacco in India: Policy analysis. Indian J Cancer 2012;49:336-41. [ PUBMED] [Full text] |
| 19. | Smyth EM, Kulkarni P, Claye E, Stanfill S, Tyx R, Maddox C, et al. Smokeless tobacco products harbor diverse bacterial microbiota that differ across products and brands. Appl Microbiol Biotechnol 2017;101:5391-403. |
| 20. | Foulds J, Ramstrom L, Burke M, Fagerström K. Effect of smokeless tobacco (snus) on smoking and public health in Sweden. Tob Control 2003;12:349-59. |
| 21. | Boffetta P, Hecht S, Gray N, Gupta P, Straif K. Smokeless tobacco and cancer. Lancet Oncol 2008;9:667-75. |
| 22. | Cogliano V, Straif K, Baan R, Grosse Y, Secretan B, El Ghissassi F, et al. Smokeless tobacco and tobacco-related nitrosamines. Lancet Oncol 2004;5:708. |
| 23. | Adkison SE, Bansal-Travers M, Smith DM, O'Connor RJ, Hyland AJ. Impact of smokeless tobacco packaging on perceptions and beliefs among youth, young adults, and adults in the U.S: Findings from an internet-based cross-sectional survey. Harm Reduct J 2014;11:2. |
| 24. | Janbaz KH, Qadir MI, Basser HT, Bokhari TH, Ahmad B. Risk for oral cancer from smokeless tobacco. Contemp Oncol (Pozn) 2014;18:160-4. |
| 25. | Delnevo CD, Wackowski OA, Giovenco DP, Manderski MT, Hrywna M, Ling PM. Examining market trends in the United States smokeless tobacco use: 2005-2011. Tob Control 2014;23:107-12. |
| 26. | Fisher MT, Bennett CB, Hayes A, Kargalioglu Y, Knox BL, Xu D, et al. Sources of and technical approaches for the abatement of tobacco specific nitrosamine formation in moist smokeless tobacco products. Food Chem Toxicol 2012;50:942-8. |
| 27. | Dygert HP. Snuff-a source of pathogenic bacteria in chronic bronchitis. N Engl J Med 1957;257:311-3. |
| 28. | Ogidi OI, Tobia PE, Adigwe PC. Microbial contamination of snuff sold in selected markets in Yenagoa, Bayelsa State, Nigeria. Int J Adv Sci 2018;3:2455-4227. |
| 29. | Brunnemann KD, Qi J, Hoffmann D. Chemical profile of two types of oral snuff tobacco. Food Chem Toxicol 2002;40:1699-703. |
| 30. | Di Giacomo M, Paolino M, Silvestro D, Vigliotta G, Imperi F, Visca P, et al. Microbial community structure and dynamics of dark fire-cured tobacco fermentation. Appl Environ Microbiol 2007;73:825-37. |
| 31. | Villanti AC, Richardson A, Vallone DM, Rath JM. Flavored tobacco product use among U.S. young adults. Am J Prev Med 2013;44:388-91. |
| 32. | Klus H, Kunze M, König S, Pöschl E. Smokeless tobacco – An overview. Beitr Tab Int 2009;23:248-76. |
| 33. | Melikian AA, Hoffmann D. Smokeless tobacco: A gateway to smoking or a way away from smoking. Biomarkers 2009;14 Suppl 1:85-9. |
| 34. | Warek U, Nielsen MT, Xu D, Cui M, Luo X, Jin X, et al. Nitrite-degrading and TSNA-degrading bacteria and methods of making and using. J Agric Food Chem 2019;10:88-9. |
| 35. | Lawler TS, Stanfill SB, Zhang L, Ashley DL, Watson CH. Chemical characterization of domestic oral tobacco products: Total nicotine, pH, unprotonated nicotine and tobacco-specific N-nitrosamines. Food Chem Toxicol 2013;57:380-6. |
| 36. | Ammann JR, Lovejoy KS, Walters MJ, Holman MR. A survey of N-nitrosonornicotine (NNN) and total water content in select smokeless tobacco products purchased in the United States in 2015. J Agric Food Chem 2016;64:4400-6. |
| 37. | McAdam KG, Faizi A, Kimpton H, Porter A, Rodu B. Polycyclic aromatic hydrocarbons in US and Swedish smokeless tobacco products. Chem Cent J 2013;7:151. |
| 38. | Orisakwe OE, Igweze ZN, Okolo KO, Udowelle NA. Human health hazards of poly aromatic hydrocarbons in Nigerian smokeless tobacco. Toxicol Rep 2015;2:1019-23. |
| 39. | Andersen RA, Fleming PD, Hamilton-Kemp TR, Hildebrand DF. pH changes in smokeless tobaccos undergoing nitrosation during prolonged storage: Effects of moisture, temperature, and duration. J Agric Food Chem 1994;41:968-72. |
| 40. | Richter P, Spierto FW. Surveillance of smokeless tobacco nicotine, pH, moisture, and unprotonated nicotine content. Nicotine Tob Res 2008;10:1645-52. |
| 41. | Hatsukami DK, Stepanov I, Severson H, Jensen JA, Lindgren BR, Horn K, et al. Evidence supporting product standards for carcinogens in smokeless tobacco products. Cancer Prev Res (Phila) 2015;8:20-6. |
| 42. | Chamberlain WJ, Schlotzhauer WS, Chortyk OT. Chemical composition of nonsmoking tobacco products. J Agric Food Chem 1988;8:20-6. |
| 43. | Konstantinou E, Fotopoulou F, Drosos A, Dimakopoulou N, Zagoriti Z, Niarchos A, et al. Tobacco-specific nitrosamines: A literature review. Food Chem Toxicol 2018;118:198-203. |
| 44. | Savitz DA, Meyer RE, Tanzer JM, Mirvish SS, Lewin F. Public health implications of smokeless tobacco use as a harm reduction strategy. Am J Public Health 2006;96:1934-9. |
| 45. | Zhou J, Michaud DS, Langevin SM, McClean MD, Eliot M, Kelsey KT. Smokeless tobacco and risk of head and neck cancer: Evidence from a case-control study in New England. Int J Cancer 2013;132:1911-7. |
| 46. | Li X, Kolltveit KM, Tronstad L, Olsen I. Systemic diseases caused by oral infection. Clin Microbiol Rev 2000;13:547-58. |
| 47. | Hiregoudar M, Subramaniam R, Prashant GS, Chandu GN. In vitro effect of smokeless tobacco extracts on the growth of Streptococcus mutans in relation to Nicotine and Sugar contents. J Indian Assoc Public Health Dent 2010;8:174-8. [Full text] |
| 48. | Schneider KR, Parish ME, Goodrich RM, Cookingham T. Preventing Foodborne Illness: Bacillus Cereus and Bacillus anthracis. Vol. 8. United State: Florida Cooperative Extension Services, University of Florida; 2005. p. 190-9. |
| 49. | Monika S, Dineshkumar T, Priyadharini S, Niveditha T, Sk P, Rajkumar K. Smokeless tobacco products (STPs) harbour bacterial populations with potential for oral carcinogenicity. Asian Pac J Cancer Prev 2020;21:815-24. |
|
Search Pubmed for