Chemistry:Smokeless tobacco

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Short description: Tobacco product used by means other than smoking.
A historical depiction of a man taking snuff using his thumb and forefinger.

Smokeless tobacco is a tobacco product that is used by means other than smoking.[1] Their use involves chewing, sniffing, or placing the product between gum and the cheek or lip.[1] Smokeless tobacco products are produced in various forms, such as chewing tobacco, snuff, snus, and dissolvable tobacco products.[2] Smokeless tobacco products typically contain over 3000 constituents.[3] All smokeless tobacco products contain nicotine[4] and are therefore highly addictive.[5] Quitting smokeless tobacco use is as challenging as smoking cessation.[6]

Smokeless tobacco is much lower on the risk continuum than combusted products but varies in risk within that class of products (e.g., low nitrosamine Swedish-type snus versus other smokeless tobacco with high nitrosamine levels).[7] It is estimated the safety risk of smokeless tobacco is similar to that of electronic cigarettes.[8] There is no safe level of smokeless tobacco use.[6] It is correlated with a number of adverse effects such as dental disease, oral cancer, oesophagus cancer, and pancreas cancer, as well as adverse reproductive effects including stillbirth, premature birth and low birth weight.[5] Smokeless tobacco products contain cancer-causing chemicals.[6] Approximately 28 chemical constituents present in smokeless tobacco are carcinogenic in nature, among which nitrosamine is the most prominent.[9] Smokeless tobacco accounts for an abundance of deaths globally with a significant proportion of them in Southeast Asia.[10]

Smokeless tobacco consumption is widespread throughout the world.[9] Once addicted to nicotine from smokeless tobacco use, many people, particularly young people, expand their tobacco use by smoking cigarettes.[6] Males were more likely than females to have used smokeless tobacco in the past month.[6]

Types

Dipping tobacco is placed directly in the mouth.

File:Fred Ott Sneeze 1894 remastered.webm Most smokeless tobacco use involves placing the product between the gum and the cheek or lip.[1] Smokeless tobacco is a noncombustible tobacco product.[1]

Types of smokeless tobacco include:

  • Dipping tobacco, a type of tobacco that is placed between the lower or upper lip and gums
  • Chewing tobacco, a type of tobacco that is chewed
  • Iqmik, an Alaskan tobacco product which also contains punk ash
  • Snuff, a type of tobacco that is inhaled or "snuffed" into the nasal cavity
  • Snus, similar to dipping tobacco although the tobacco is placed under the upper lip and there is no need for spitting
  • Creamy snuff, a fluid tobacco mixture marketed as a dental hygiene aid, albeit used for recreation
  • Naswar, an Afghan tobacco product similar to dipping tobacco
  • Tobacco gum, a kind of chewing gum containing tobacco
  • Gutka, a mixture of tobacco, areca nut, and various flavoring sold in South Asia
  • Dissolvable tobacco, a variation on chewing tobacco that completely dissolves in the mouth
  • Toombak and shammah, preparations found in North Africa, East Africa, and the Arabian peninsula
  • Topical tobacco paste, a paste applied to the skin and absorbed through the dermis

Since there are varied manufacturing methods, products can differ greatly in chemical arrangement and nicotine level.[11] Smokeless tobacco products typically contain over 3000 constituents which play a part in their taste as well as scent.[3]

Nicotine levels

Smokeless tobacco differs depending on the type of product, the types of tobacco used, and the amount of each tobacco type used within a product. Each variable results in different level of nicotine. Furthermore, nicotine is absorbed by the body to different degrees depending on the pH level of the product, which is known as the free nicotine or unionized nicotine level.[citation needed]

Below are some measured nicotine levels of various smokeless tobacco products from 2006 and 2007 and their corresponding free nicotine levels as calculated by the Henderson–Hasselbalch equation.[12]

Product Nicotine (mg/g) Free Nicotine (mg/g) Free Nicotine (% of total nicotine) pH Type Form Year
Ariva 3.90 0.70 17.95 7.36 dissolvable, dry pieces 2007
Stonewall Natural 8.19 1.17 14.23 7.24 dissolvable, dry pieces 2007
Beech-nut Chewing Tobacco 7.07 0.02 0.35 5.56 loose leaf loose 2006
Hawken Wintergreen 2.92 0.01 0.22 5.37 loose leaf cut 2007
Lancaster Premium Chewing Tobacco 8.01 0.01 0.11 5.05 loose leaf loose 2007
Levi Garrett Chewing Tobacco 5.34 0.06 1.19 6.10 loose leaf loose 2006
Red Man Chewing Tobacco 8.58 0.08 0.88 5.97 loose leaf loose 2006
Red Man Golden Chewing Tobacco 7.70 0.06 0.72 5.88 loose leaf loose 2006
Stoker Chew Apple Chewing Tobacco 3.77 0.01 0.22 5.37 loose leaf loose 2007
Taylor's Pride 6.43 0.06 0.90 5.98 plug one cut 2006
Catch Dry Eucalyptus 15.93 1.39 8.72 7.00 snuff, dry pouch 2006
Catch Dry Licorice 16.70 0.68 4.09 6.65 snuff, dry pouch 2006
Skoal Dry 11.91 2.39 20.08 7.42 snuff, dry pouch 2007
Taboka 16.73 0.36 2.14 6.36 snuff, dry pouch 2007
Taboka Green 13.01 0.48 3.66 6.60 snuff, dry pouch 2007
Bruton Scotch Snuff 17.49 0.49 2.80 6.48 snuff, dry powder 2006
Dental Sweet Snuff 11.14 0.13 1.19 6.10 snuff, dry powder 2006
Levi Garrett Snuff 16.60 0.07 0.42 5.65 snuff, dry powder 2007
Railroad Mills Plain Scotch Snuff 23.13 0.48 2.09 6.35 snuff, dry powder 2007
Red Seal Sweet Snuff 15.08 0.40 2.62 6.45 snuff, dry powder 2007
Camel Frost 13.25 4.70 35.46 7.76 snuff, moist pouch 2006
Camel Frost 14.10 4.71 33.39 7.72 snuff, moist pouch 2007
Camel Original 13.87 4.70 33.90 7.73 snuff, moist pouch 2006
Camel Original 13.49 6.20 45.98 7.95 snuff, moist pouch 2007
Camel Spice 13.16 6.65 50.58 8.03 snuff, moist pouch 2006
Camel Spice 13.16 6.65 50.58 8.03 snuff, moist pouch 2007
Cooper Long Cut Wintergreen 7.97 1.09 13.68 7.22 snuff, moist long cut 2007
Copenhagen 12.68 3.21 25.31 7.55 snuff, moist fine cut 2006
Copenhagen Long Cut 13.91 5.38 38.69 7.82 snuff, moist long cut 2006
Copenhagen Pouches 11.21 6.81 60.77 8.21 snuff, moist fine cut 2006
General Loose 7.15 1.87 26.19 7.57 snuff, moist coarse 2006
General Original Portion 8.46 5.10 60.22 8.20 snuff, moist pouch 2006
General White Portion 7.92 4.81 60.77 8.21 snuff, moist pouch 2006
Grizzly Long Cut Wintergreen 10.29 6.59 64.01 8.27 snuff, moist long cut 2006
Grizzly Long Cut Wintergreen 11.20 5.86 52.30 8.06 snuff, moist long cut 2007
Husky Fine Cut Natural 12.86 4.77 37.06 7.79 snuff, moist fine cut 2007
Kayak Long Cut Wintergreen 11.88 2.26 18.99 7.39 snuff, moist long cut 2007
Kodiak Premium Wintergreen 10.93 6.52 59.66 8.19 snuff, moist long cut 2006
Kodiak Premium Wintergreen 10.70 8.18 76.39 8.53 snuff, moist long cut 2007
Longhorn Long Cut Wintergreen 13.79 5.72 41.45 7.87 snuff, moist long cut 2007
Red Seal Fine Cut Natural 13.17 3.11 23.61 7.51 snuff, moist fine cut 2007
Renegades Wintergreen 13.36 2.40 17.95 7.36 snuff, moist pouch 2007
Skoal Fine Cut Original 13.31 3.85 28.95 7.63 snuff, moist fine cut 2006
Skoal Long Cut Cherry 12.70 1.67 13.15 7.20 snuff, moist long cut 2006
Skoal Long Cut Mint 12.93 3.68 28.47 7.62 snuff, moist long cut 2006
Skoal Long Cut Straight 13.37 3.94 29.42 7.64 snuff, moist long cut 2006
Skoal Long Cut Wintergreen 12.84 2.87 22.38 7.48 snuff, moist long cut 2006
Timberwolf Long Cut Wintergreen 14.13 5.16 36.53 7.78 snuff, moist long cut 2007

Prevalence

More than 300 million people are using smokeless tobacco worldwide.[13] People of many regions, including India, Pakistan, other Asian countries, and North America, have a long history of smokeless tobacco use.[9] Once addicted to nicotine from smokeless tobacco use, many people, particularly young people, expand their tobacco use by smoking cigarettes.[6] Because young people who use smokeless tobacco can become addicted to nicotine, they may be more likely to also become cigarette smokers.[14] Youth are particularly susceptible to starting smokeless tobacco use.[15]

Males were more likely than females to have used smokeless tobacco in the past month.[6] In 2014, 3.3 percent of people aged 12 or older (an estimated 8.7 million people) used smokeless tobacco in the past month. Past month smokeless tobacco use remained relatively stable between 2002 and 2014.[6] Past month smokeless tobacco use between 2002 and 2014 was mostly consistent among adults aged 26 or older.[6] There was more variability in the percentages of young adults aged 18 to 25 and adolescents aged 12 to 17 who used smokeless tobacco between 2002 and 2014.[6] Smokeless tobacco use for adolescents aged 12 to 17 was higher during the mid-2000s, but the 2014 estimates were closer to the lower levels seen in the early 2000s.[6] In 2014, an estimated 1.0 million people aged 12 or older used smokeless tobacco for the first time in the past year; this represents 0.5 percent of people who had not previously used smokeless tobacco.[6]

In 2016 about 2 of every 100 middle school students in the US (2.2%) reported current use of smokeless tobacco.[16] In 2016 nearly 6 of every 100 high school students in the US (5.8%) reported current use of smokeless tobacco.[16]

Health effects

Positions of medical organizations

(As of 2017), the World Health Organization states that "Smokeless tobacco use is a significant part of the overall world tobacco problem."[15] (As of 2015), the American Cancer Society states that "Using any kind of spit or smokeless tobacco is a major health risk. It's less lethal than smoking tobacco, but less lethal is a far cry from safe."[17] (As of 2010), the National Cancer Institute states that "because all tobacco products are harmful and cause cancer, the use of all of these products should be strongly discouraged. There is no safe level of tobacco use. People who use any type of tobacco product should be urged to quit".[18] A panel of experts convened by the National Institutes of Health (NIH) in 2006 stated that the "range of risks, including nicotine addiction, from smokeless tobacco products may vary extensively because of differing levels of nicotine, carcinogens, and other toxins in different products".[18] According to a 2002 report by the Royal College of Physicians, "As a way of using nicotine, the consumption of non-combustible tobacco is of the order of 10–1,000 times less hazardous than smoking, depending on the product".[19] As long ago as 1986, the advisory committee to the Surgeon General concluded that the use of smokeless tobacco "is not a safe substitute for smoking cigarettes. It can cause cancer and a number of noncancerous oral conditions and can lead to nicotine addiction and dependence".[18]

Smoking cessation

Quitting smokeless tobacco use is as challenging as smoking cessation.[6] There is no scientific evidence that using smokeless tobacco can help a person quit smoking.[18]

Harm reduction

(As of 2017), the World Health Organization states that "There is no evidence to recommend that any smokeless tobacco product should be used as part of a harm reduction strategy."[15] Tobacco companies that sell smokeless tobacco products promote them as harm reduction products and a less harmful substitute to cigarettes.[20]

Safety

Smokeless tobacco products vary extensively worldwide in both form and health hazards, with some evidently toxic forms such as from South Asia, and some forms with less hazards such as snus from Sweden.[21] It is correlated with a number of adverse effects such as dental disease, oral cancer, oesophagus cancer, and pancreatic cancer, cardiovascular disease, asthma, and deformities in the female reproductive system.[9] A correlation was identified between smokeless tobacco and risk of fatal coronary artery disease and fatal stroke.[5] Use of smokeless tobacco also seems to greatly raise the risk of non-fatal ischaemic heart disease among users in Asia, although not in Europe.[5]

It is estimated the safety risk of smokeless tobacco is similar to that of electronic cigarettes, which has about 1% of the mortality risk of traditional cigarettes.[8] Smokeless tobacco is not a healthy alternative to cigarette smoking.[6] There is no safe level of smokeless tobacco use.[6] The declines in smokeless tobacco initiation among adolescents and young adults is particularly relevant to improving the health of the nation because smokeless tobacco use is often linked to subsequent cigarette initiation.[6] Smokeless tobacco users can experience these negative health consequences at any age.[6] Smokeless tobacco accounts for an abundance of deaths globally with a significant proportion of them attributed to Southeast Asia.[10] Youth use of tobacco in any form is unsafe.[16]

Carcinogenicity

Graphic from the 2016 Centers for Disease Control and Prevention report entitled Smokeless Tobacco: Health Effects. The text states, "Smokeless tobacco, like chew and dip, can cause CANCER of the MOUTH, ESOPHAGUS, AND PANCREAS."
Graphic from the 2016 Centers for Disease Control and Prevention report entitled Smokeless Tobacco: Health Effects.[14]

All tobacco products contain toxicants, and smokeless tobacco products contain cancer-causing chemicals.[6] The carcinogenic compounds occurring in smokeless tobacco vary widely, which rely upon the kind of product and how it was manufactured.[4] A 2017 review found "Overall, 28 carcinogens have been rigorously identified across a range of major smokeless tobacco products, primarily from 3 groups of compounds: nonvolatile, alkaloid-derived TSNAs; N-nitrosoamino acids; and volatile N-nitrosamines. Among these carcinogens, researchers identify TSNAs as the most abundant in smokeless tobacco and the most carcinogenic."[4] The amounts of nicotine in saliva from using smokeless tobacco could be at amounts that can cause cytotoxicity, according to in vitro studies.[22]

Other chemicals found in tobacco can also cause cancer.[14] These include: A radioactive element (polonium-210) found in tobacco fertilizer.[14] Chemicals formed when tobacco is cured with heat (polynuclear aromatic hydrocarbons—also known as polycyclic aromatic hydrocarbons).[14] Harmful metals (arsenic, beryllium, cadmium, chromium, cobalt, lead, nickel, mercury).[14] Products such as 3-(methylnitrosamino)-proprionitrile, nitrosamines, and nicotine initiate the production of reactive oxygen species in smokeless tobacco, eventually leading to fibroblast, DNA, and RNA damage with carcinogenic effects in the mouth of tobacco consumers.[9] The metabolic activation of nitrosamine in tobacco by cytochrome P450 enzymes may lead to the formation of N-nitrosonornicotine, a major carcinogen, and micronuclei, which are an indicator of genotoxicity. These effects lead to further DNA damage and, eventually, oral cancer.[9] Smokeless tobacco can cause white or gray patches inside the mouth (leukoplakia) that can lead to cancer.[14] The World Health Organization has classified smokeless tobacco products as human carcinogenic compounds, in particular tobacco-specific nitrosamines, which account for 76 to 91% of the total N-nitroso compound (NOC) burden.[9] A 2014 review found there is "a number of ethnically linked smokeless tobacco types that contain areca nut, a Group 1 carcinogen. Use of areca nut-containing smokeless tobacco is known to cause oral cancer, yet despite this, prevalence is increasing in the Western Pacific."[3] N-nitrosonornicotine and ketone are group 1 carcinogens to humans.[20] These two nitrosamines found in smokeless tobacco products are the main agents for the majority of cancers in smokeless tobacco users.[20]

Effects during pregnancy

It is correlated with adverse reproductive effects including stillbirth, premature birth, low birth weight.[5] Using smokeless tobacco during pregnancy can increase the risk for early delivery and stillbirth.[14] Nicotine in smokeless tobacco products that are used during pregnancy can affect how a baby's brain develops before birth.[14]

Management

Due to smokeless tobacco harms, it should be treated. some medications shows some benefits are varenicline, nicotine lozenges.[23] some behavioural interventions may help, however a cochrane review mentioned that there components need to be clearer.[23]

History

Smokeless tobacco was first discussed in the English language in 1683 as a powdered tobacco for breathing into the nose.[24] People have used it for over a thousand years.[24] Cigarette manufacturers have penetrated the smokeless tobacco market.[25]

Public perceptions

Many people who use smokeless tobacco may think it is safer than smoking, but all tobacco products contain toxicants, and use of smokeless tobacco poses its own significant health risks.[6] In South and South-East Asia these products are considered part of the cultural heritage and there is little enthusiasm for regulation. Around 80% of users live in these regions.[26]

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 "Smokeless Tobacco Products, Including Dip, Snuff, Snus, and Chewing Tobacco". United States Food and Drug Administration. 7 May 2018. https://www.fda.gov/TobaccoProducts/Labeling/ProductsIngredientsComponents/ucm482582.htm.  This article incorporates text from this source, which is in the public domain.
  2. ↑ Czoli, Christine D; Fong, Geoffrey T; Mays, Darren; Hammond, David (2016). "How do consumers perceive differences in risk across nicotine products? A review of relative risk perceptions across smokeless tobacco, e-cigarettes, nicotine replacement therapy and combustible cigarettes". Tobacco Control 26 (e1): tobaccocontrol–2016–053060. doi:10.1136/tobaccocontrol-2016-053060. ISSN 0964-4563. PMID 27625408. 
  3. ↑ 3.0 3.1 3.2 Lauterstein, Dana; Hoshino, Risa; Gordon, Terry; Watkins, Beverly-Xaviera; Weitzman, Michael; Zelikoff, Judith (2014). "The Changing Face of Tobacco Use Among United States Youth". Current Drug Abuse Reviews 7 (1): 29–43. doi:10.2174/1874473707666141015220110. ISSN 1874-4737. PMID 25323124. 
  4. ↑ 4.0 4.1 4.2 Drope, Jeffrey; Cahn, Zachary; Kennedy, Rosemary; Liber, Alex C.; Stoklosa, Michal; Henson, Rosemarie; Douglas, Clifford E.; Drope, Jacqui (2017). "Key issues surrounding the health impacts of electronic nicotine delivery systems (ENDS) and other sources of nicotine". CA: A Cancer Journal for Clinicians 67 (6): 449–471. doi:10.3322/caac.21413. ISSN 0007-9235. PMID 28961314. 
  5. ↑ 5.0 5.1 5.2 5.3 5.4 Vidyasagaran, A. L.; Siddiqi, K.; Kanaan, M. (2016). "Use of smokeless tobacco and risk of cardiovascular disease: A systematic review and meta-analysis". European Journal of Preventive Cardiology 23 (18): 1970–1981. doi:10.1177/2047487316654026. ISSN 2047-4873. PMID 27256827. http://eprints.whiterose.ac.uk/101100/1/EJPC_D_16_00085_R1_2016.pdf. 
  6. ↑ 6.00 6.01 6.02 6.03 6.04 6.05 6.06 6.07 6.08 6.09 6.10 6.11 6.12 6.13 6.14 6.15 6.16 6.17 6.18 Lipari, R. N; Van Horn, S. L (31 May 2017). Trends in Smokeless Tobacco Use and Initiation: 2002 to 2014. Substance Abuse and Mental Health Services Administration. PMID 28636307.  This article incorporates text from this source, which is in the public domain.
  7. ↑ Abrams, David B.; Glasser, Allison M.; Pearson, Jennifer L.; Villanti, Andrea C.; Collins, Lauren K.; Niaura, Raymond S. (2018). "Harm Minimization and Tobacco Control: Reframing Societal Views of Nicotine Use to Rapidly Save Lives". Annual Review of Public Health 39 (1): 193–213. doi:10.1146/annurev-publhealth-040617-013849. ISSN 0163-7525. PMID 29323611.  This article incorporates text by David B. Abrams, Allison M. Glasser, Jennifer L. Pearson, Andrea C. Villanti, Lauren K. Collins, and Raymond S. Niaura available under the CC BY 4.0 license.
  8. ↑ 8.0 8.1 Caponnetto, P.; Russo, C.; Bruno, C.M.; Alamo, A.; Amaradio, M.D.; Polosa, R. (March 2013). "Electronic cigarette: a possible substitute for cigarette dependence". Monaldi Archives for Chest Disease 79 (1): 12–19. doi:10.4081/monaldi.2013.104. ISSN 1122-0643. PMID 23741941. 
  9. ↑ 9.0 9.1 9.2 9.3 9.4 9.5 9.6 Niaz, Kamal; Maqbool, Faheem; Khan, Fazlullah; Bahadar, Haji; Ismail Hassan, Fatima; Abdollahi, Mohammad (2017). "Smokeless tobacco (paan and gutkha) consumption, prevalence, and contribution to oral cancer". Epidemiology and Health 39: e2017009. doi:10.4178/epih.e2017009. ISSN 2092-7193. PMID 28292008.  This article incorporates text by Kamal Niaz, Faheem Maqbool, Fazlullah Khan, Haji Bahadar, Fatima Ismail Hassan, Mohammad Abdollahi available under the CC BY 4.0 license.
  10. ↑ 10.0 10.1 Sinha, Dhirendra N; Suliankatchi, Rizwan A; Gupta, Prakash C; Thamarangsi, Thaksaphon; Agarwal, Naveen; Parascandola, Mark; Mehrotra, Ravi (2016). "Global burden of all-cause and cause-specific mortality due to smokeless tobacco use: systematic review and meta-analysis". Tobacco Control 27 (1): tobaccocontrol–2016–053302. doi:10.1136/tobaccocontrol-2016-053302. ISSN 0964-4563. PMID 27903956. 
  11. ↑ Cervellin, Gianfranco; Borghi, Loris; Mattiuzzi, Camilla; Meschi, Tiziana; Favaloro, Emmanuel; Lippi, Giuseppe (2013). "E-Cigarettes and Cardiovascular Risk: Beyond Science and Mysticism". Seminars in Thrombosis and Hemostasis 40 (1): 060–065. doi:10.1055/s-0033-1363468. ISSN 0094-6176. PMID 24343348. 
  12. ↑ Borgerding M F, Bodnar J A, Curtin , Swauger (2012). "The chemical composition of smokeless tobacco: A survey of products sold in the United States in 2006 and 2007". Regulatory Toxicology and Pharmacology 64 (3): 367–387. doi:10.1016/j.yrtph.2012.09.003. PMID 23000415. 
  13. ↑ Rostron, Brian L; Chang, Joanne T; Anic, Gabriella M; Tanwar, Manju; Chang, Cindy M; Corey, Catherine G (2018). "Smokeless tobacco use and circulatory disease risk: a systematic review and meta-analysis". Open Heart 5 (2): e000846. doi:10.1136/openhrt-2018-000846. ISSN 2053-3624. PMID 30364426. 
  14. ↑ 14.0 14.1 14.2 14.3 14.4 14.5 14.6 14.7 14.8 "Smokeless Tobacco: Health Effects". Centers for Disease Control and Prevention. 1 December 2016. https://www.cdc.gov/tobacco/data_statistics/fact_sheets/smokeless/health_effects/index.htm.  This article incorporates text from this source, which is in the public domain.
  15. ↑ 15.0 15.1 15.2 "Recommendation on smokeless tobacco products". World Health Organization. 2017. pp. 1–9. http://apps.who.int/iris/bitstream/10665/42658/1/9241590556.pdf. 
  16. ↑ 16.0 16.1 16.2 "Youth and Tobacco Use". Centers for Disease Control and Prevention. 20 September 2017. https://www.cdc.gov/tobacco/data_statistics/fact_sheets/youth_data/tobacco_use/index.htm.  This article incorporates text from this source, which is in the public domain.
  17. ↑ "Health Risks of Smokeless Tobacco". American Cancer Society. 13 November 2015. https://www.cancer.org/cancer/cancer-causes/tobacco-and-cancer/smokeless-tobacco.html. 
  18. ↑ 18.0 18.1 18.2 18.3 "Smokeless Tobacco and Cancer". United States Department of Health and Human Services. 25 October 2010. https://www.cancer.gov/about-cancer/causes-prevention/risk/tobacco/smokeless-fact-sheet.  This article incorporates text from this source, which is in the public domain.
  19. ↑ Royal College of Physicians of London. Tobacco Advisory Group (2002). Protecting Smokers, Saving Lives: The Case for a Tobacco and Nicotine Regulatory Authority. Royal College of Physicians. pp. 5–. ISBN 978-1-86016-177-3. https://books.google.com/books?id=fpUgCBGb5SwC&pg=PA5. 
  20. ↑ 20.0 20.1 20.2 Gupta, Alpana K.; Tulsyan, Sonam; Bharadwaj, Mausumi; Mehrotra, Ravi (2019). "Grass roots approach to control levels of carcinogenic nitrosamines, NNN and NNK in smokeless tobacco products". Food and Chemical Toxicology 124: 359–366. doi:10.1016/j.fct.2018.12.011. ISSN 0278-6915. PMID 30543893. 
  21. ↑ O'Connor, RJ (March 2012). "Non-cigarette tobacco products: what have we learnt and where are we headed?". Tobacco Control 21 (2): 181–90. doi:10.1136/tobaccocontrol-2011-050281. PMID 22345243. 
  22. ↑ Holliday, Richard S; Campbell, James; Preshaw, Philip M. (2019). "Effect of nicotine on human gingival, periodontal ligament and oral epithelial cells. A systematic review of the literature". Journal of Dentistry 86: 81–88. doi:10.1016/j.jdent.2019.05.030. ISSN 0300-5712. PMID 31136818. 
  23. ↑ 23.0 23.1 Ebbert, JO; Elrashidi, MY; Stead, LF (26 October 2015). "Interventions for smokeless tobacco use cessation.". The Cochrane Database of Systematic Reviews 2015 (10): CD004306. doi:10.1002/14651858.CD004306.pub5. PMID 26501380. 
  24. ↑ 24.0 24.1 Schivo, Michael; Avdalovic, Mark V.; Murin, Susan (February 2014). "Non-Cigarette Tobacco and the Lung". Clinical Reviews in Allergy & Immunology 46 (1): 34–53. doi:10.1007/s12016-013-8372-0. ISSN 1080-0549. PMID 23673789. 
  25. ↑ Levy, David T.; Cummings, K. Michael; Villanti, Andrea C.; Niaura, Ray; Abrams, David B.; Fong, Geoffrey T.; Borland, Ron (2017). "A framework for evaluating the public health impact of e-cigarettes and other vaporized nicotine products". Addiction 112 (1): 8–17. doi:10.1111/add.13394. ISSN 0965-2140. PMID 27109256. 
  26. ↑ Siddiqi, Kamran (5 April 2019). "Smokeless tobacco products flying under the radar of regulation in many countries". The Conversation. https://theconversation.com/smokeless-tobacco-products-flying-under-the-radar-of-regulation-in-many-countries-114680. 



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