Abstract
Bangladesh exhibits the second highest rate of smokeless tobacco (SLT) product usage in the world, and this has been associated with the high upper aerodigestive tract cancer incidence in this country. The goal of the present study was to examine the levels of the highly carcinogenic tobacco-specific nitrosamines (TSNAs) in Bangladeshi SLT products and compare these levels to that observed in SLT brands from southeast Asia and the USA. The levels of TSNAs and nicotine were determined by LC-MS/MS in twenty-eight SLT brands and several tobacco additives from Bangladesh, as well as several SLT brands from India, Pakistan and the USA. The levels of N-nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N-nitrosoanatabine (NAT) and N-nitrosoanabasine (NAB) in Bangladeshi SLT brands ranged from 1.1–59, 0.15–34, 0.79–45, and 0.037–13 μg/g SLT powder, respectively. The mean levels of the highly carcinogenic TSNAs (NNN+NNK) were 7.4-, 2.4-, and 63-fold higher in Bangladeshi SLT products as compared to SLT brands from the USA, India and Pakistan, respectively; these trends were also observed for NAT and NAB. Similar mean levels of nicotine were observed in the Bangladeshi brands (31 mg/g powder) versus brands from the USA (25 mg/g powder) and India (20 mg/g powder); they were 3-fold higher than brands from Pakistan (10 mg/g powder). Gul SLT brands exhibited the highest pH and the highest levels of unprotonated nicotine. The high levels of TSNAs in Bangladeshi SLT brands may be an important factor contributing to the high rates of upper aerodigestive tract cancer in Bangladesh.
Highlights
Tobacco use has long been recognized as a contributing factor for cancers of the aerodigestive tract [1,2,3,4] and is strongly associated with many other diseases including chronic obstructive pulmonary disease and cardiovascular disease [5,6,7,8]
The representative LC-MS/MS chromatograms shown in Fig 1 demonstrate the effective separation of individual tobacco-specific nitrosamines (TSNAs) as well as nicotine in a representative Bangladeshi smokeless tobacco (SLT) product (Akiz zarda)
The TSNA values obtained in the present study for the reference tobacco products were consistent with the certified reference values (TSNA range for certified reference products (CRP) 1.1 were NNN: 0.13– 0.42 μg/g SLT powder, NNK: 0.032–0.078 μg/g SLT powder, NAT: 0.083–0.20 μg/g SLT powder, NAB: 0.014–0.004 μg/g SLT powder, nicotine: 4.9–8.2 mg/g SLT powder; CRP 2.1 were NNN: 2.9–7.3 μg/g SLT powder, NNK: 1.7–2.4 μg/g SLT powder, NAT: 3.8–4.9 μg/g SLT powder and NAB: 0.22–0.56 μg/g SLT powder, nicotine: 8.0–13 mg/g SLT powder; Table 1) provided by the Cooperation Centre for Scientific Research Relative to Tobacco (CORESTA)
Summary
Tobacco use has long been recognized as a contributing factor for cancers of the aerodigestive tract [1,2,3,4] and is strongly associated with many other diseases including chronic obstructive pulmonary disease and cardiovascular disease [5,6,7,8]. Tobacco is consumed in several forms in developed and developing countries worldwide as both a smoked or smokeless product. Levels of tobacco specific nitrosamines in Bangladeshi smokeless tobacco products many forms including snus, chew, toombak (fermented tobacco), zarda (flavored tobacco flakes), gul (powdered tobacco), sada pata (tobacco leaf), and khaini (flavored tobacco flakes mixed with slaked lime). Smokeless tobacco is placed in contact with mucus membranes, either placed inside the mouth between the cheek and gums or chewed, and has long been associated with squamous cell carcinoma in various head and neck (H&N) tissues [9,10,11,12]
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