Smokeless Tobacco

Ira Lamster DDS, MMSc, Editor-in-Chief, Fiona Collins BDS, MBA, MA, FPFA

TO GET C.E. CREDITS FOR THIS ARTICLE
PLEASE LOGIN OR REGISTER

Smokeless Tobacco

Tobacco products have a dramatically adverse effect on human health, including oral health.1US Department of Health and Human Services. 50 years of progress: A report of the surgeon general, 2014. Available at: http://www.surgeongeneral.gov/library/reports/50-years-of-progress/50-years-of-progress-bysection.html While generally considered less hazardous to health than smoked tobacco, smokeless tobacco (SLT) is associated with significant unfavorable effects on systemic and oral health. Recent developments, including the introduction of more novel forms of SLT and in some regions the widespread use of SLT containing betel quid and/or areca nut, are significant public health concerns.2Leon ME, Lugo A, Boffetta P, Gilmore A, Ross H, Schüz J, La Vecchia C, Gallus S. Smokeless tobacco use in Sweden and other 17 European countries. Eur J Pub Health 2016;26(5):817-21.,3Wiener RC. Association of smokeless tobacco use and smoking in adolescents in the United States. An analysis of data from the Youth Risk Behavior Surveillance System survey, 2011. J Am Dent Assoc 2013;144(8):930-8.,4Niaz K, Maqbool F, Khan F, Bahadar H, Ismail Hassan F, Abdollahi M. Smokeless tobacco (paan and gutkha) consumption, prevalence, and contribution to oral cancer. Epidemiol Health 2017;39:e2017009.

Types of Smokeless Tobacco

SLT includes tobacco that is chewed, sucked (dry or moist snuff) or sniffed (dry snuff).2Leon ME, Lugo A, Boffetta P, Gilmore A, Ross H, Schüz J, La Vecchia C, Gallus S. Smokeless tobacco use in Sweden and other 17 European countries. Eur J Pub Health 2016;26(5):817-21. Chew tobacco contains air- or fire-cured tobacco leaves that are processed with flavorings, sugars and other additives.2Leon ME, Lugo A, Boffetta P, Gilmore A, Ross H, Schüz J, La Vecchia C, Gallus S. Smokeless tobacco use in Sweden and other 17 European countries. Eur J Pub Health 2016;26(5):817-21.,3Wiener RC. Association of smokeless tobacco use and smoking in adolescents in the United States. An analysis of data from the Youth Risk Behavior Surveillance System survey, 2011. J Am Dent Assoc 2013;144(8):930-8. Dry snuff contains air- or fire-cured fermented powdered tobacco, while most moist oral snuff consists of air- or fire-cured tobacco that is processed into fine particles. The tobacco in dry and moist snuff is mixed with sugars, flavorings such as menthol or licorice, and other additives.2Leon ME, Lugo A, Boffetta P, Gilmore A, Ross H, Schüz J, La Vecchia C, Gallus S. Smokeless tobacco use in Sweden and other 17 European countries. Eur J Pub Health 2016;26(5):817-21.,5Savitz 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(11):1934-9. Swedish snus is a variant of moist oral snuff.
It contains pasteurized unfermented tobacco, does not contain sugar, and is available in cherry and other flavors that appeal to adolescents.2Leon ME, Lugo A, Boffetta P, Gilmore A, Ross H, Schüz J, La Vecchia C, Gallus S. Smokeless tobacco use in Sweden and other 17 European countries. Eur J Pub Health 2016;26(5):817-21.,3Wiener RC. Association of smokeless tobacco use and smoking in adolescents in the United States. An analysis of data from the Youth Risk Behavior Surveillance System survey, 2011. J Am Dent Assoc 2013;144(8):930-8.
Chew tobacco can be held in the vestibule of the mouth for several hours as a ‘wad,’ while dry or moist oral snuff is tucked under the upper or lower lip. Swedish snus is sold in small packets/sachets that can be placed directly under the lip. Oral SLT is also available as sticks or pellets, and is sold as a thin film that is placed on the tongue where it then dissolves.3Wiener RC. Association of smokeless tobacco use and smoking in adolescents in the United States. An analysis of data from the Youth Risk Behavior Surveillance System survey, 2011. J Am Dent Assoc 2013;144(8):930-8. (Table 1)
Table 1. Main types of SLT
Chew tobacco Air- or fire-cured tobacco leaves, flavorings, sugars and other additives
Dry snuff (sniffed) Air- or fire-cured fermented powdered tobacco
Moist snuff Air- or fire-cured tobacco as fine particles
Swedish snus Pasteurized unfermented tobacco, cherry and other flavors; no sugar
Paan Betel quid, areca nut, quenched lime, seeds and spices
Gutkha areca nut, slaked lime, spices and catechu

In South Asia, SLT is a common and culturally significant practice, and is primarily sold as paan and gutkha. (Figure 1) Paan typically contains areca nut, betel quid, quenched lime, seeds and spices and gutkha typically contains areca nut, slaked lime, spices and catechu.4Niaz K, Maqbool F, Khan F, Bahadar H, Ismail Hassan F, Abdollahi M. Smokeless tobacco (paan and gutkha) consumption, prevalence, and contribution to oral cancer. Epidemiol Health 2017;39:e2017009. SLT used in the Middle East and South Asia variously contains ash, sodium carbonate, indigo, spices, cotton, sesame oil, and molasses.4Niaz K, Maqbool F, Khan F, Bahadar H, Ismail Hassan F, Abdollahi M. Smokeless tobacco (paan and gutkha) consumption, prevalence, and contribution to oral cancer. Epidemiol Health 2017;39:e2017009.


Figure 1.
Ingredients for Paan: betel leaves, nuts and lime
Source: Wikimedia Commons, Public Domain

Prevalence of Use

Globally, an estimated 300 million people use SLT, 90% of whom reside in South East Asia.6Freedman ND. Invited commentary: Smokeless tobacco-an important contributor to cancer, but more work is needed. Am J Epidemiol 2016;184(10):717-9. In the United States, an estimated 2.6% of American adults (4.8% of men and 0.3% of women) use SLT,7Agaku IT, King BA, Husten CG, Bunnell R, Ambrose BK, Hu SS, Holder-Hayes E, Day HR; Centers for Disease Control and Prevention (CDC). Tobacco product use among adults—United States, 2012–2013. Morb Mortal Wkly Rep 2014;63(25):542-7. and in one survey 9.9% and 1.2% of male and female high school students, respectively, reported using SLT in the prior 30 days.8Arrazola RA, Singh T, Corey CG, Husten CG, Neff LJ, Apelberg BJ, Bunnell RE, Choiniere CJ, King BA, Cox S, McAfee T, Caraballo RS; Centers for Disease Control and Prevention (CDC). Tobacco use among middle and high school students—United States, 2011–2014. Morb Mortal Wkly Rep 2015;64(14):381-5. In addition, 12.3% of the Swedish population ages 16 and over (20.7% and 3.5% of men and women, respectively) is estimated to use SLT, mainly Swedish snus, compared to 1.1% of adults across 17 other countries in Europe.2Leon ME, Lugo A, Boffetta P, Gilmore A, Ross H, Schüz J, La Vecchia C, Gallus S. Smokeless tobacco use in Sweden and other 17 European countries. Eur J Pub Health 2016;26(5):817-21. However, in India, Nepal, Myanmar and Bangladesh, SLT use ranges from 20% to 80% of the adult population, and approximately three-quarters of Pakistani school students in one study reported using SLT.4Niaz K, Maqbool F, Khan F, Bahadar H, Ismail Hassan F, Abdollahi M. Smokeless tobacco (paan and gutkha) consumption, prevalence, and contribution to oral cancer. Epidemiol Health 2017;39:e2017009.,9Eriksen M, Mackay J, Schluger N, Gomeshtapeh FI, Drope J. The tobacco atlas. 5th ed., 2015. The American Cancer Society. Available at: http://3pk43x313ggr4cy0lh3tctjh.wpengine.netdna-cdn.com/wp-content/uploads/2015/03/TA5_2015_WEB.pdf. In African and Middle Eastern countries, use of SLT among adults has been reported to range from less than 1% to 20%.9Eriksen M, Mackay J, Schluger N, Gomeshtapeh FI, Drope J. The tobacco atlas. 5th ed., 2015. The American Cancer Society. Available at: http://3pk43x313ggr4cy0lh3tctjh.wpengine.netdna-cdn.com/wp-content/uploads/2015/03/TA5_2015_WEB.pdf. (Table 2)

Table 2. Prevalence of use of SLT among adults
United States 2.6%
Sweden 12.3%
Africa and The Middle East <1% to 20%
India, Nepal, Myanmar and Bangladesh 20% to 80%
In the United States, an estimated 2.6% of American adults use SLT.

Noxious Substances in SLT

SLT contains more than 30 carcinogens, including polycyclic aromatic hydrocarbons and tobacco-specific nitrosamines. Direct release of free radicals has also been demonstrated in tests of SLT extracts.10Rostron BL, Chang CM, van Bemmel DM, Xia Y, Blount BC. Nicotine and toxicant exposure among U.S. smokeless tobacco users: results from 1999 to 2012 National Health and Nutrition Examination Survey Data. Cancer Epidemiol Biomarkers Prev 2015;24(12):1829-37. doi: 10.1158/1055-9965.EPI-15-0376.,11Song MA, Marian C, Brasky TM, Reisinger S, Djordjevic M, Shields PG. Chemical and toxicological characteristics of conventional and low-TSNA moist snuff tobacco products. Toxicol Lett 2016;245:68-77.,12Lam EWN, Kelley EE, Martin SM, Buettner GR. Tobacco xenobiotics release nitric oxide. Tob Induc Dis 2003;1(3):207-11. Further, while pasteurized Swedish snus contains key carcinogens at a concentration of 601 to 5,850 ng/g, concentrations of 1,520 to 20,500 ng/g and a minimum of 295,000 ng/g, respectively, are reported for American factory-fermented snus and toombak, a compost pile-fermented SLT.7Agaku IT, King BA, Husten CG, Bunnell R, Ambrose BK, Hu SS, Holder-Hayes E, Day HR; Centers for Disease Control and Prevention (CDC). Tobacco product use among adults—United States, 2012–2013. Morb Mortal Wkly Rep 2014;63(25):542-7.
In a comparison of American ‘snus’ (moist snuff) and Swedish snus, the latter had considerably higher proportions of un-ionized nicotine
(median 81.8% vs 3.17%), a higher pH (8.68 versus 6.54), and contained 53.4% moisture versus 30.3%.13Seidenberg AB, Ayo-Yusuf OA, Rees VW. Characteristics of "American snus" and Swedish snus products for sale in Massachusetts, USA. Nicotine Tob Res 2018;20(2):262-266. doi: 10.1093/ntr/ntw334. Un-ionized nicotine is more rapidly absorbed across oral mucous membranes at the intraoral physiologic pH than ionized nicotine.14Richter P, Hodge K, Stanfill S, Zhang L, Watson C. Surveillance of moist snuff: total nicotine, moisture, pH, un-ionized nicotine, and tobacco-specific nitrosamines. Nicotine & Tobacco Res 2008;10(11):1645-52. Cadmium, nickel, nitrate, lead, chromium, ammonia, arsenic and benzo[a]pyrene may be found in moist snuff,11Song MA, Marian C, Brasky TM, Reisinger S, Djordjevic M, Shields PG. Chemical and toxicological characteristics of conventional and low-TSNA moist snuff tobacco products. Toxicol Lett 2016;245:68-77. and SLT may also contain ammonium chloride, sodium chloride, paraffin oil, glycerol and flavorings.5Savitz 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(11):1934-9. Trace amounts of vanadium, magnesium, sodium, manganese, chlorine, calcium, copper and bromine can be present in paan and gutkha.4Niaz K, Maqbool F, Khan F, Bahadar H, Ismail Hassan F, Abdollahi M. Smokeless tobacco (paan and gutkha) consumption, prevalence, and contribution to oral cancer. Epidemiol Health 2017;39:e2017009.
American snus contains key carcinogens at a concentration of 1,520 to 20,500 ng/g.

Impact on Systemic Health

Recently, a study was published examining the association of SLT with all- and specific-cause mortality.15Timberlake DS, Nikitin D, Johnson NJ, Altekruse SF. A longitudinal study of smokeless tobacco use and mortality in the United States. Int J Cancer 2017;141:264-70. Based on data from the National Longitudinal Mortality Study conducted in the United States from 1985 to 2011, the study found an increased risk of death due to coronary artery disease for male moist snuff users compared to never-users of SLT and never-smokers. No increased risk was observed for all cancers, digestive cancers or cerebrovascular disease. However, SLT is considered causal for esophageal and pancreatic cancer.6Freedman ND. Invited commentary: Smokeless tobacco-an important contributor to cancer, but more work is needed. Am J Epidemiol 2016;184(10):717-9. A second study noted a two-fold risk of hypercholesterolemia for smokers and heavy SLT users compared to nonusers of tobacco products, and in a separate review SLT use was reported as a risk factor for cardiovascular disease, as well as increased mortality.16Bolinder G. Overview of knowledge of health effects of smokeless tobacco. Increased risk of cardiovascular diseases and mortality because of snuff. Lakartidningen 1997;94(42):3725-31.,17Tucker LA. Use of smokeless tobacco, cigarette smoking, and hypercholesterolemia. Am J Public Health 1989;79(8):1048-50.

Impact on Oral Health

SLT has a significant impact on oral health, especially with respect to the risk for pre-malignant lesions and malignancies. The relationship between SLT and oral pre-malignant and malignant lesions was recently investigated in a pooled analysis of eleven US studies conducted between 1981 and 2006, with more than 6,000 cases and 8,000 controls.18Wyss AB, Hashibe M, Lee YA, Chuang S-C, Muscat J, Chen C, Schwartz SM, Smith E, Zhang Z-F, Morgenstern H, Wei Q, Li G, Kelsey KT, McClean M, Winn DM, Schantz S, Yu G-P, Gillison ML, Zevallos JP, Boffetta P, Olshan AF. Smokeless tobacco use and the risk of head and neck cancer: Pooled analysis of US studies in the INHANCE consortium. Am J Epidemiol 2016;184(10):703-16. A three-fold and approximately two-fold risk of oral cancers was found for users of snuff and chew tobacco, respectively, compared to nonusers of SLT or cigarettes. Further, a high prevalence of leukoplakia has been observed at the sites where SLT is held in the oral cavity.19Robertson PB, Walsh MM, Greene JC. Oral effects of smokeless tobacco use by professional baseball players. Adv Dent Res 1997;11(3):307-12. SLT containing sugar increases risk for dental caries, specifically, at the intraoral site where it is retained.20Going RE, Hsu SC, Pollack RL, Haugh LD. Sugar and fluoride content of various forms of tobacco. J Am Dent Assoc 1980;100:27-33.,21Tomar SL, Winn DM. Chewing tobacco use and dental caries among US men. J Am Dent Assoc 1999;130(11):1601-10. In addition, SLT is a risk factor for gingivitis, halitosis, staining and localized attachment loss.5Savitz 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(11):1934-9.,22Kallischnigg G, Weitkunat R, Lee PN. Systematic review of the relation between smokeless tobacco and non-neoplastic oral diseases in Europe and the United States. BMC Oral Health 2008;8:13. (Figures 2, 3)

An approximately two-fold risk of oral cancers has been found for users of chew tobacco, compared to nonusers of SLT or cigarettes.

Figure 2. Leukoplakia
Image courtesy of the National Institutes of Health

Figure 3. Gingival recession and inflammation associated with SLT
Image courtesy of the National Institutes of Health

The development of potentially malignant oral lesions associated with the use of SLT in South Asia is a particularly ominous public health problem.4Niaz K, Maqbool F, Khan F, Bahadar H, Ismail Hassan F, Abdollahi M. Smokeless tobacco (paan and gutkha) consumption, prevalence, and contribution to oral cancer. Epidemiol Health 2017;39:e2017009.,23Seenan P, Conway D. Smokeless tobacco - a substantial risk for oral potentially malignant disorders in South Asia. Evid Based Dent 2017;18:54-5. Of further concern, as smoking has declined the use of SLT in this region has increased.24Suliankatchi RA, Sinha DN, Rath R, Aryal KK, Zaman MM, Gupta PC, Karki KB, Venugopal D. Smokeless tobacco use is 'replacing' the smoking epidemic in the South East Asia Region. Nicotine Tob Res 2017 Dec 22. doi: 15.1093/ntr/ntx272. [Epub ahead of print] Betel quid and areca nut enhance the adverse effects of SLT, and are themselves associated with pre-malignant and malignant change.5Savitz 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(11):1934-9. Other ingredients also enhance risk for oral cancer, including catechu which is strongly associated with esophageal cancer.4Niaz K, Maqbool F, Khan F, Bahadar H, Ismail Hassan F, Abdollahi M. Smokeless tobacco (paan and gutkha) consumption, prevalence, and contribution to oral cancer. Epidemiol Health 2017;39:e2017009. Paan and gutkha also result in oral submucous fibrosis (OSMF), a chronic and progressive inflammatory precancerous condition involving fibrosis of connective tissues.4Niaz K, Maqbool F, Khan F, Bahadar H, Ismail Hassan F, Abdollahi M. Smokeless tobacco (paan and gutkha) consumption, prevalence, and contribution to oral cancer. Epidemiol Health 2017;39:e2017009. The reported incidence for OSMF is 75% after 4.5 years of paan use. In addition, lime contained in SLT can trigger tissue irritation and hyperplasia.

Betel quid and areca nut are themselves associated with pre-malignant and malignant change.

Implications for Oral Health Professionals

SLT significantly impacts systemic health and oral health, yet patients may consider SLT a safe alternative to smoked tobacco. The proposed use of Swedish snus for smoking cessation is also a concern, since recent data suggests that snus may be a gateway for future smoking, and nicotine addiction. Additionally, as the prevalence of smoking has declined the use of SLT has increased.2Leon ME, Lugo A, Boffetta P, Gilmore A, Ross H, Schüz J, La Vecchia C, Gallus S. Smokeless tobacco use in Sweden and other 17 European countries. Eur J Pub Health 2016;26(5):817-21.,4Niaz K, Maqbool F, Khan F, Bahadar H, Ismail Hassan F, Abdollahi M. Smokeless tobacco (paan and gutkha) consumption, prevalence, and contribution to oral cancer. Epidemiol Health 2017;39:e2017009. It is crucial that dental professionals educate patients on the dangers of SLT, including the associated risk of oral cancer and other detrimental effects to health.
It is also important to consider the broader implications of the significant global variation in the preferred type of SLT. In addition, individuals using paan and gutkha often believe that this habit confers health benefits and are unaware of the risk of oral cancer.4Niaz K, Maqbool F, Khan F, Bahadar H, Ismail Hassan F, Abdollahi M. Smokeless tobacco (paan and gutkha) consumption, prevalence, and contribution to oral cancer. Epidemiol Health 2017;39:e2017009. While use of paan and gutkha is most prevalent in South Asia, their use is also widespread among immigrants from this region now living in Europe and North America.4Niaz K, Maqbool F, Khan F, Bahadar H, Ismail Hassan F, Abdollahi M. Smokeless tobacco (paan and gutkha) consumption, prevalence, and contribution to oral cancer. Epidemiol Health 2017;39:e2017009. Dental professionals across the globe should consider this when educating patients on SLT.

Conclusions

Dental professionals must be strong advocates for avoidance of all tobacco products, including SLT. Given the known oral and systemic health risks associated with SLT, policies should be introduced and strengthened to reduce SLT usage and to prevent it replacing smoked tobacco.24Suliankatchi RA, Sinha DN, Rath R, Aryal KK, Zaman MM, Gupta PC, Karki KB, Venugopal D. Smokeless tobacco use is 'replacing' the smoking epidemic in the South East Asia Region. Nicotine Tob Res 2017 Dec 22. doi: 15.1093/ntr/ntx272. [Epub ahead of print] In addition, more research is required to fully assess the adverse health effects associated with use of SLT,6Freedman ND. Invited commentary: Smokeless tobacco-an important contributor to cancer, but more work is needed. Am J Epidemiol 2016;184(10):717-9. alone as well as in combination with other tobacco products.6Freedman ND. Invited commentary: Smokeless tobacco-an important contributor to cancer, but more work is needed. Am J Epidemiol 2016;184(10):717-9.,18Wyss AB, Hashibe M, Lee YA, Chuang S-C, Muscat J, Chen C, Schwartz SM, Smith E, Zhang Z-F, Morgenstern H, Wei Q, Li G, Kelsey KT, McClean M, Winn DM, Schantz S, Yu G-P, Gillison ML, Zevallos JP, Boffetta P, Olshan AF. Smokeless tobacco use and the risk of head and neck cancer: Pooled analysis of US studies in the INHANCE consortium. Am J Epidemiol 2016;184(10):703-16.

References

  • 1.US Department of Health and Human Services. 50 years of progress: A report of the surgeon general, 2014. Available at: http://www.surgeongeneral.gov/library/reports/50-years-of-progress/50-years-of-progress-bysection.html
  • 2.Leon ME, Lugo A, Boffetta P, Gilmore A, Ross H, Schüz J, La Vecchia C, Gallus S. Smokeless tobacco use in Sweden and other 17 European countries. Eur J Pub Health 2016;26(5):817-21.
  • 3.Wiener RC. Association of smokeless tobacco use and smoking in adolescents in the United States. An analysis of data from the Youth Risk Behavior Surveillance System survey, 2011. J Am Dent Assoc 2013;144(8):930-8.
  • 4.Niaz K, Maqbool F, Khan F, Bahadar H, Ismail Hassan F, Abdollahi M. Smokeless tobacco (paan and gutkha) consumption, prevalence, and contribution to oral cancer. Epidemiol Health 2017;39:e2017009.
  • 5.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(11):1934-9.
  • 6.Freedman ND. Invited commentary: Smokeless tobacco-an important contributor to cancer, but more work is needed. Am J Epidemiol 2016;184(10):717-9.
  • 7.Agaku IT, King BA, Husten CG, Bunnell R, Ambrose BK, Hu SS, Holder-Hayes E, Day HR; Centers for Disease Control and Prevention (CDC). Tobacco product use among adults—United States, 2012–2013. Morb Mortal Wkly Rep 2014;63(25):542-7.
  • 8.Arrazola RA, Singh T, Corey CG, Husten CG, Neff LJ, Apelberg BJ, Bunnell RE, Choiniere CJ, King BA, Cox S, McAfee T, Caraballo RS; Centers for Disease Control and Prevention (CDC). Tobacco use among middle and high school students—United States, 2011–2014. Morb Mortal Wkly Rep 2015;64(14):381-5.
  • 9.Eriksen M, Mackay J, Schluger N, Gomeshtapeh FI, Drope J. The tobacco atlas. 5th ed., 2015. The American Cancer Society. Available at: http://3pk43x313ggr4cy0lh3tctjh.wpengine.netdna-cdn.com/wp-content/uploads/2015/03/TA5_2015_WEB.pdf.
  • 10.Rostron BL, Chang CM, van Bemmel DM, Xia Y, Blount BC. Nicotine and toxicant exposure among U.S. smokeless tobacco users: results from 1999 to 2012 National Health and Nutrition Examination Survey Data. Cancer Epidemiol Biomarkers Prev 2015;24(12):1829-37. doi: 10.1158/1055-9965.EPI-15-0376.
  • 11.Song MA, Marian C, Brasky TM, Reisinger S, Djordjevic M, Shields PG. Chemical and toxicological characteristics of conventional and low-TSNA moist snuff tobacco products. Toxicol Lett 2016;245:68-77.
  • 12.Lam EWN, Kelley EE, Martin SM, Buettner GR. Tobacco xenobiotics release nitric oxide. Tob Induc Dis 2003;1(3):207-11.
  • 13.Seidenberg AB, Ayo-Yusuf OA, Rees VW. Characteristics of "American snus" and Swedish snus products for sale in Massachusetts, USA. Nicotine Tob Res 2018;20(2):262-266. doi: 10.1093/ntr/ntw334.
  • 14.Richter P, Hodge K, Stanfill S, Zhang L, Watson C. Surveillance of moist snuff: total nicotine, moisture, pH, un-ionized nicotine, and tobacco-specific nitrosamines. Nicotine & Tobacco Res 2008;10(11):1645-52.
  • 15.Timberlake DS, Nikitin D, Johnson NJ, Altekruse SF. A longitudinal study of smokeless tobacco use and mortality in the United States. Int J Cancer 2017;141:264-70.
  • 16.Bolinder G. Overview of knowledge of health effects of smokeless tobacco. Increased risk of cardiovascular diseases and mortality because of snuff. Lakartidningen 1997;94(42):3725-31.
  • 17.Tucker LA. Use of smokeless tobacco, cigarette smoking, and hypercholesterolemia. Am J Public Health 1989;79(8):1048-50.
  • 18.Wyss AB, Hashibe M, Lee YA, Chuang S-C, Muscat J, Chen C, Schwartz SM, Smith E, Zhang Z-F, Morgenstern H, Wei Q, Li G, Kelsey KT, McClean M, Winn DM, Schantz S, Yu G-P, Gillison ML, Zevallos JP, Boffetta P, Olshan AF. Smokeless tobacco use and the risk of head and neck cancer: Pooled analysis of US studies in the INHANCE consortium. Am J Epidemiol 2016;184(10):703-16.
  • 19.Robertson PB, Walsh MM, Greene JC. Oral effects of smokeless tobacco use by professional baseball players. Adv Dent Res 1997;11(3):307-12.
  • 20.Going RE, Hsu SC, Pollack RL, Haugh LD. Sugar and fluoride content of various forms of tobacco. J Am Dent Assoc 1980;100:27-33.
  • 21.Tomar SL, Winn DM. Chewing tobacco use and dental caries among US men. J Am Dent Assoc 1999;130(11):1601-10.
  • 22.Kallischnigg G, Weitkunat R, Lee PN. Systematic review of the relation between smokeless tobacco and non-neoplastic oral diseases in Europe and the United States. BMC Oral Health 2008;8:13.
  • 23.Seenan P, Conway D. Smokeless tobacco - a substantial risk for oral potentially malignant disorders in South Asia. Evid Based Dent 2017;18:54-5.
  • 24.Suliankatchi RA, Sinha DN, Rath R, Aryal KK, Zaman MM, Gupta PC, Karki KB, Venugopal D. Smokeless tobacco use is 'replacing' the smoking epidemic in the South East Asia Region. Nicotine Tob Res 2017 Dec 22. doi: 15.1093/ntr/ntx272. [Epub ahead of print]