TOBACCO SMOKING Tobacco smoking was considered by previous IARC Working Groups in 1986, 1987 and 2002 (IARC, 1986, 1987, 2004a). Since that time, new data have become available, these have been incorporated into the Monograph, and taken into consideration in the present evaluation. 1. Exposure Data 1.2 Chemical composition of tobacco smoke 1.1 Smoked tobacco products 1.2.1 Smoke from cigarettes Smoked forms of tobacco include various One cubic cm of fresh, un-aged cigarette kinds of cigarettes (manufactured, hand-rolled, mainstream smoke [the smoke emerging from filtered, un-filtered and flavoured), cigars and the mouth end of a cigarette during smoking] pipes. While cigarette smoking, particularly has about 4 × 109 particles with a mean diameter manufactured cigarettes, is by far the main form of about 0.2 µm (Borgerding & Klus, 2005). The of tobacco smoked globally, in some countries size of the particles increases as the smoke ages. other forms of smoked tobacco are dominant Temperatures in the burning cone of the cigarette (IARC, 2004a). In India, for example, bidis are about 800 °C during the smoulder period (made of coarse and uncured tobacco) account between puffs and increase to 910–920 °C at the for about 60% of smoked tobacco products periphery of the cone during puffingBorgerding ( whereas cigarettes account for 20% (Ray & & Klus, 2005). Hydrogen is generated in the Gupta, 2009; IIPS, 2010). Water pipes, another glowing cone, resulting in an oxygen deficient form of smoked tobacco known by other various reducing atmosphere (Borgerding & Klus, 2005). names such as gaza, hookah, narghile, shisha, The approximate composition of mainstream hubble-bubble, are commonly smoked in the smoke of a plain cigarette is summarized in Table Eastern Mediterranean region, in some parts of 1.1 (Borgerding & Klus, 2005). The total particu- Asia including India, and in North Africa (Asma late matter, after subtraction of the amounts of et al., 2009). nicotine and water, is referred to as ‘tar’. Over 5300 compounds have been identi- fied in tobacco smoke Rodgman( & Perfetti, 2009). Classes of compounds include but are not limited to neutral gases, carbon and nitrogen oxides, amides, imides, lactams, carboxylic acids, lactones, esters, aldehydes, ketones, 43 IARC MONOGRAPHS – 100E humans (Group 1). Structures of some represent- Table 1.1 Approximate chemical composition ative carcinogens in cigarette smoke are shown of mainstream smoke generated by a plain in Fig. 1.1. There are other likely carcinogens in cigarette cigarette smoke that have not been evaluated Compound or class of by the IARC Monographs programme. These Relative amount w/w (%) components include, for example, PAHs with incompletely Nitrogen 58 characterized occurrence levels and carcino- Oxygen 12 genic activities; over 500 PAHs have been identi- Carbon dioxide 13 fied Rodgman( & Perfetti, 2006). Carbon monoxide 3.5 PAHs, tobacco-specific N-nitrosamines, Hydrogen, argon 0.5 Water 1 aromatic amines, aldehydes and certain volatile Volatile organic substances 5 organics likely contribute significantly to the Particulate phase 8 carcinogenic activity of tobacco smoke (Hecht, From Borgerding & Klus (2005) 2003). In the early part of the 20th century, PAHs alcohols, phenols, amines, N-nitrosamines, were identified as carcinogenic constituents of N-heterocyclics, aliphatic hydrocarbons, mono- coal tar (Phillips, 1983). They are products of cyclic and polycyclic aromatic hydrocarbons incomplete combustion of all organic matter (PAHs), nitriles, anhydrides, carbohydrates, and occur, always as complex mixtures, in tars, ethers, nitro compounds and metals (Rodgman soots, broiled foods, vehicle engine exhaust and & Perfetti, 2009). tobacco smoke. PAHs are generally locally acting The addictive properties of tobacco smoke carcinogens, and some, such as the prototypic are attributed to nicotine, the principal tobacco compound BaP, have strong carcinogenic activity alkaloid in smoke (Hukkanen et al., 2005). Minor on mouse skin and in rodent lung. Heterocyclic tobacco alkaloids include nornicotine, anatabine analogues of PAHs also occur in cigarette smoke. and anabasine (Hukkanen et al., 2005). The Concentrations of individual PAHs in main- tobacco alkaloids are not generally considered stream cigarette smoke are generally in the range carcinogenic, but are accompanied by carcino- of 1–50 ng per cigarette (IARC, 2004a). gens in each puff of smoke. Among the carcinogenic N-nitrosamines There are over 70 carcinogens in tobacco in tobacco smoke are tobacco-specific smoke that have been evaluated by the IARC N-nitrosamines, which are derived from, and Monographs programme as having sufficient structurally related to, the tobacco alkaloids. evidence for carcinogenicity in either laboratory Two of the most important of these are NNK and animals or humans (IARC, 2004a). The different NNN (Hecht & Hoffmann, 1988). Levels of NNK chemical classes of carcinogens and representa- and NNN in cigarette smoke vary depending on tives of each are presented in Table 1.2 (IARC, tobacco type and other factors, but are frequently 2004a). Sixteen of these – benzo[a]pyrene in the range of 50–200 ng per cigarette (IARC, (BaP), 4-(methylnitrosamino)-1-(3-pyridyl)-1- 2004a). butanone (NNK) and N′-nitrosonornicotine Aromatic amines were first identified as (NNN), 2-naphthylamine, 4-aminobiphenyl, human carcinogens from industrial expo- formaldehyde, 1,3-butadiene, benzene, vinyl sures in the dye industry in the early part of chloride, ethylene oxide, arsenic, beryllium, the 20th century. They include the well known nickel compounds, chromium VI, cadmium, and human bladder carcinogens 2-naphthylamine polonium-210 – are classified as carcinogenic to and 4-aminobiphenyl which, along with other 44 Tobacco smoking Table 1.2 Tobacco smoke carcinogens evaluated in the IARC Monographs Chemical Class Number of Carcinogens Representative Carcinogens Polycyclic aromatic hydrocarbons (PAHs) 15 Benzo[a]pyrene (BaP) and their heterocyclic analogues Dibenz[a,h]anthracene N-Nitrosamines 8 4-(Methylnitrosamino)-1-(3-pyridyl)-1- butanone (NNK) N′-Nitrosonornicotine (NNN) Aromatic amines 12 4-Aminobiphenyl 2-Naphthylamine Aldehydes 2 Formaldehyde Acetaldehyde Phenols 2 Catechol Caffeic acid Volatile hydrocarbons 3 Benzene 1,3-Butadiene Isoprene Other organics 12 Ethylene oxide Acrylonitrile Inorganic compounds 8 Cadmium Polonium-210 There are many other carcinogens in cigarette smoke that have not been evaluated in an IARC Monograph. From IARC (2004a) isomers, are found in cigarette smoke, but their compounds including multiple toxicants and levels are generally quite low (1–20 ng per ciga- carcinogens. rette) (IARC, 2004a). Aldehydes such as formaldehyde and 1.2.2 Smoke from other tobacco products acetaldehyde occur widely in the human envi- ronment and are also found in human blood. Some constituents have been measured in Concentrations of acetaldehyde and formal- roll-your-own cigarettes, and their levels are dehyde in cigarette smoke are far higher than comparable to or higher than those in commer- those of PAHs, N-nitrosamines or aromatic cial brands. Carcinogen and toxicant levels amines but their carcinogenic activities are weak expressed per unit are higher in cigars than in (Hecht, 2003). Cigarette mainstream smoke typi- cigarettes because of their larger size, and in cally contains 10–30 µg formaldehyde/cigarette some instances are also higher per litre of smoke. and 800–900 µg acetaldehyde/cigarette (IARC, Levels of nicotine and tobacco-specific nitro- 2004a). samines were comparable in bidis and commer- Volatile hydrocarbons in cigarette smoke cial Indian cigarettes; bidis also contain high include 1,3-butadiene, a powerful multi- levels of eugenol, as do kreteks. Levels of NNK organ carcinogen in the mouse, and benzene, and NNN in chuttas were considerably higher a known human leukaemogen. 1,3-Butadiene than in standard cigarettes (IARC, 2004a). (20–40 µg/cigarette) and benzene (12–50 µg/ciga- rette) are two of the most prevalent strong carcin- ogens in cigarette smoke (IARC, 2004a). In summary, cigarette smoke is an exceed- ingly complex mixture which contains over 5300 45 IARC MONOGRAPHS – 100E Fig. 1.1 Structures of some representative tobacco smoke carcinogens 46 Tobacco smoking Fig. 1.2 Proportion of adult smokers by WHO region in 2009 From WHO (2011) 1.3 Prevalence of tobacco smoking Region; AFRO, African Region; WPRO, Western Pacific Region; SEARO, South East Asian Region; 1.3.1 Data collection and methods AMRO, Region of the Americas. A listing of the Data on smoking tobacco are available from countries in each region can be viewed at http:// WHO’s Global Infobase (www.who.int/infobase) www.who.int/about/structure/en/index.html. and the WHO Global Health Observatory (www. who.int/gho/en) – repositories of information 1.3.2 Distribution of smokers by WHO region on tobacco use and other risk factors in young and country people (13–15 years old) and adults (aged 15 years WHO estimates that in 2009, there was about and over). The data span several years and are 1.1 billion adult smokers worldwide, representing acquired from government reports, journals and nearly a quarter (22%) of the global adult popula- unpublished sources. WHO has in the recent tion (WHO, 2011). A disaggregation by the six past used and modelled these data to produce WHO regions (Fig. 1.2) shows that over a third estimates of tobacco smoking prevalence, of smokers worldwide live in WPRO (highly published in the WHO Reports on the Global