Introduction

Tobacco use is one of the major health challenges worldwide especially in India. It’s use is one of the single largest causes of preventable death and illness worldwide.1 About 8 lakh Indians die due to consumption of tobacco products which is higher than killed by AIDS, tuberculosis and malaria combined. As per Global Adult Tobacco Survey (GATS 2) fact sheet 2016-17, there are around 28.6% (266.8 million) people in India who use smoked and/or smokeless tobacco, and among these tobacco users 42.4% are men and 14.2% are women. Smoke from someone else is called second hand smoke. Second hand tobacco smokes are also equally harmful. About 23% adults in India are exposed to second hand smoke at public places such as offices, restaurants, home, workplace etc. A large number babies and children are severely affected by the second hand smoke every year. The average age of initiation of both smoked as well as smokeless tobacco products in India is 18.

Different Forms of Tobacco Products: Broadly tobacco products are classified as smoked and smokeless tobacco (SLT) products. There are several kinds of tobacco products found in India namely Cigarette, Cigar, Bidi and Hookah. Cigarettes contain more than 4000 chemical compounds, 200 known poisons and 60 carcinogenic agents. Both Bidis and Hookahs are also harmful similar to cigarettes. Smokeless tobacco products are chewing tobacco such as Zarda, Khaini, Gutkha, Pan Masala with tobacco, Mawa, Misri, Gul etc.2 The prevalence of SLTs are higher in India compared to other countries. Among tobacco users in India, almost 60% use SLTs whereas an additional 15% use both smoked as well as SLTs. The most commonly used tobacco products in India are Khaini, Bidi and Gutkha.

Chemistry of Tobacco: The major alkaloid present in both form of tobacco is nicotine. It constitutes approximately 95% of the total alkaloid in tobacco.1bIt is highly challenging to maintain complete abstinence from tobacco use due to the addictive properties of nicotine. In addition there are other several minor alkaloids, such as, nornicotine, anabasine, anatabine and tobacco specific nitrosamines (TSNAs) present in tobacco products nornicotine, anabasine, anatabine.1^a-b,3

Nicotine is hygroscopic, colorless to yellow-brown, oily liquid. It is readily volatile in nature. Nicotine is optically active compound and has two enantiomeric forms. The naturally occurring form of nicotine is (−)-nicotine with a specific rotation of [α]D = –166.4°. The dextrorotatory form i.e. (+)-nicotine is physiologically less active than (−)-nicotine. (−)-nicotine is more toxic than (+)-nicotine. An average Cigarette yields about 2 mg of absorbed nicotine; in lesser doses of that order, the substance acts as a stimulant in mammals, while high amounts (50–100 mg) can be harmful. Nicotine’s most predominant metabolite, cotinine, suggests that some of nicotine’s psychoactive effects are mediated by cotinine. This stimulant effect is a contributing factor to the addictive properties of tobacco smoking. Beyond addiction, both short and long-term nicotine exposure have not been established as dangerous to adults. At high-enough doses, nicotine is associated with poisonings and is potentially lethal. The long-term use of nicotine in the form of Snus (Moist powder form) incurs a slight risk of cardiovascular disease compared to tobacco smoking and is not associated with cancer. There is inadequate research to show that nicotine itself is associated with cancer in humans.

Figure 1: Chemical Structures of Alkaloids found in tobacco products

Tobacco-specific nitrosamines (TSNAs) are the most studied compounds found only in tobacco and tobacco smoke.4 TSNAs contain the functional group N-N=O and are formed by nitrosation of alkaloids during fermentation, curing and burning of the tobacco leaf. The common TSNAs present in tobacco are NNN (N’-Nitrosonornicotine), NNK ((4-methylnitrosamino)-1-(3-pyridyl)-1-butanone), NAB (N’-nitrosoanabasine), NAT (N-nitrosoanatabine), NNAL ((4-methylnitrosamino)-1-(3-pyridyl)-1-butanol) (Figure 1). Among these, NNN and NNK are classified by International Agency for Research on Cancer (IACR) as the most carcinogenic compounds to humans. It causes oral, lung, oesophageal, and pancreatic cancer in humans.

Figure2: Chemical Structures of 14 PAHs present in tobacco smoke

Polycyclic aromatic hydrocarbons (PAHs) are a class of compounds composed of two or more fused benzenoid rings.5 These compounds are known for their carcinogenic and mutagenic properties. PAHs do not naturally occur in the tobacco plant but are formed by the incomplete combustion of tobacco and other organic components during smoking. Approximately 100 PAHs have been identified in tobacco smoke and they usually occur as complex mixtures rather than individual compounds. Benzo[a]pyrene (BaP) is classified as a Group I carcinogens by International Agency for Research on Cancer (IARC). It is the most potent carcinogen among the PAHs. The chemical structures of 14 PAHs present in tobacco smoke are shown in Figure 2.

Analysis of Alkaloids in Tobacco: A variety of methods are used to analyze the composition of tobacco products. Nicotine and related alkaloids are determined by gas chromatography with detectors such as Flame ionization detector (GC-FID), mass spectrometry (GC-MS), liquid chromatography tandem mass spectrometry (LC-MS/MS) etc.6a-b, 1a-b Tobacco specific nitrosoamines (TSNAs) are present in very low quantities and measured by liquid chromatography with quadruple mass detectors (LC-MS/MS).6c WHO TobLabNet official method SOP 05 can be used to analyse the benzo[a]pyrene in mainstream cigarette smoke.6dIn this method, the sample is extracted and analysed by GC-MS with electron ionization detection.

Health Effects: The major diseases due to tobacco use are chronic diseases such as chronic respiratory symptoms, asthma, pneumonia, tuberculosis, stroke, coronary heart disease, lung and mouth cancers. The health effects related to women using tobacco products are cancer of the cervix, infertility, low-birth weight baby’s etc.

Conclusion: Scientific data suggests that tobacco products both smoked and smokeless contain several harmful carcinogenic compounds which can cause severe health problems to human. The main alkaloid, nicotine is highly addictive component in tobacco so it is very difficult for a person to maintain abstinence from tobacco products. GATS 2 report on use of tobacco products found that most people start to use tobacco products in one or another form during their young age. Hence we must take actions in educating our young generation, about the health impact caused by use of tobacco. And to prevent the tobacco use in adults.

References:

1. (a) von Weymarn, L. B.; Thomson, N. M.; Donny, E. C.; Hatsukami, D. K.; ,Murphy, S. E.; Chem. Res. Toxicol. 2016, 29, 390.(b)Lisko, J. G.; Stanfill,S. B.; Duncan,B. W. ; Watson, C. H.;Anal. Chem.2013, 85, 3380.
2. Stanfill, S. B.; Croucher, R. E.; Gupta, P. C.; Lisko, J. G.; Lawler T. S.; Kuklenyik, P.; Dahiya, M.; Duncan B.; Kimbrell, J. B.; Peuchen, E. H.; Watson, C. H.; Food Chem. Toxicol. 2018, 118, 626.
3. Liu, B.; Chen, C.; Wu, D.; Su, Q.; J. Chromatograph. B.2008, 865, 13.
4. (a) Hecht, S. H.; Hoffmann, D.; Cariconogens, 1988, 9, 875. (b) Lipowicz , P. J.; Seeman, J. I. Chem. Res. Toxicol. 2017, 30, 1556.
5. (a) Vu, A. T.; Taylor, K. M.; Holman, M. R.; Ding, Y. S.; Hearn, B.; Watson, C. H. Chem. Res. Toxicol. 2015, 28, 1616. (b) Ding, Y. S.; Trommel, J. S.; Yan, X. J.; Ashley, D.; Watson, C. H.; Environ. Sci. Technol. 2005, 39, 471. (c) Stepanov, I.; Villalta, P. W.; Knezevich, A.; Jensen, J.; Hatsukami, D.; Heccht, S. S.; Chem. Res. Toxicol. 2010, 23, 66.
6. (a) Cai, K.; Xiang, Z.; Zhang, J.; Zhou, S.; Feng, Y.; Geng, Z.; Anal. Methods, 2012, 4, 2095; (b)Sheng, L.Q. Ding, L.; Tong, H.W.; Yong, G.P.; Zhou, X. Z.; Liu, S.M.; Chromatographia2005, 62, 63. (c) Stepanov, T.; Carmella, S. G.; Hecht, S. S.; Duca, G.; J. Agric. Food Chem, 2002, 50, 2793. (d) WHO TobLabNet official method SOP 05. Link

Relevant Reading:

1. Tobacco
2. Health Effects of Cigarette Smoking
3. The Effects of Smoking on the Body
4. 40% of Indians exposed to second hand smoke at home: WHO
5. Tobacco Free Initiative (TFI)