The tobacco epidemic is one of the biggest public health threats the world has ever faced, killing over 8 million people a year around the world. More than 7 million of those deaths are the result of direct tobacco use while around 1.3 million are the result of non-smokers being exposed to second-hand smoke (4).

All forms of tobacco use are harmful, and there is no safe level of exposure to tobacco. Cigarette smoking is the most common form of tobacco use worldwide. Other tobacco products include waterpipe tobacco, cigars, cigarillos, heated tobacco, roll-your-own tobacco, pipe tobacco, bidis and kreteks, and smokeless tobacco products.


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Second-hand smoke is the smoke that fills restaurants, offices, homes, or other enclosed spaces when people smoke tobacco products. There is no safe level of exposure to second-hand tobacco smoke. Second-hand smoke causes serious cardiovascular and respiratory diseases, including coronary heart disease and lung cancer, and kills around 1.3 million people prematurely every year.

The illicit trade in tobacco products poses major health, economic and security concerns around the world. It is estimated that 1 in every 10 cigarettes and tobacco products consumed globally is illicit.

Further, some toxicants found in HTP aerosols are not found in conventional cigarette smoke and may have associated health effects. Additionally, these products are highly variable and some of the toxicants found in the emissions of these products are carcinogens.

E-cigarette emissions typically contain nicotine and other toxic substances that are harmful to users and non-users who are exposed to the aerosols second-hand. Some products claiming to be nicotine-free have been found to contain nicotine.


(3) Siddiqi, K., Husain, S., Vidyasagaran, A. et al. Global burden of disease due to smokeless tobacco consumption in adults: an updated analysis of data from 127 countries. BMC Med 18, 222 (2020).

E-cigarette emissions typically contain nicotine and other toxic substances that are harmful to users and non-users who are exposed to the aerosols second-hand. Some products claiming to be nicotine-free have been found to contain nicotine.


In 2021, nearly 12 of every 100 U.S. adults aged 18 years or older (11.5%) currently* smoked cigarettes. This means an estimated 28.3 million adults in the United States currently smoke cigarettes.2 More than 16 million Americans live with a smoking-related disease.1

Cigarette smoke is a complex mixture of chemical compounds that are bound to aerosol particles or are free in the gas phase. Chemical compounds in tobacco can be distilled into smoke or can react to form other constituents that are then distilled to smoke. Researchers have estimated that cigarette smoke has 7,357 chemical compounds from many different classes (Rodgman and Perfetti 2009). In assessing the nature of tobacco smoke, scientists must consider chemical composition, concentrations of components, particle size, and particle charge (Dube and Green 1982). These characteristics vary with the cigarette design and the chemical nature of the product.

Fowles and Dybing (2003) suggested an approach to identify the chemical components in tobacco smoke with the greatest potential for toxic effects. They considered the risk for cancer, cardiovascular disease, and heart disease. Using this approach, these investigators found that 1,3-butadiene presented by far the most significant cancer risk; acrolein and acetaldehyde had the greatest potential to be respiratory irritants; and cyanide, arsenic, and the cresols were the primary sources of cardiovascular risk. Other chemical classes of concern include other metals, N-nitrosamines, and polycyclic aromatic hydrocarbons (PAHs). This evaluation, along with the Hoffmann list of biologically active chemicals (Hoffmann and Hoffmann 1998), was used to select the chemicals reviewed in this chapter. Other chemical components with potential for harm will be identified as analysis of tobacco smoke becomes more complete and cigarette design and additives change.

Smoke formation occurs when the cigarette is lit and a puff is taken or when the cigarette smolders between puffs. Mainstream smoke is released from the butt end of the burning cigarette during puffing, and sidestream smoke emanates from the burning cigarette coal when it smolders (Guerin 1980). The air in the immediate vicinity of an active smoker contains a mixture of sidestream smoke, exhaled mainstream smoke, and any smoke that passes through the porous paper surrounding the tobacco (Lfroth 1989). A greater quantity of sidestream smoke is generated when the amount of tobacco burned during smoldering increases relative to the amount burned during puffing (Johnson et al. 1973b; Perfetti et al. 1998). Thus, the way the cigarette is smoked (e.g., puff volume and time between puffs) can alter the relative levels of mainstream and sidestream smoke (Perfetti et al. 1998).

In addition, the ratio of the levels of chemical components in sidestream smoke to their levels in mainstream smoke can be altered by differences among cigarettes (Perfetti et al. 1998). These differences are related to the tobacco blend or type, the tobacco preparation (e.g., cut width, additives, and moisture level), the dimensions of the cigarette, the weight of the tobacco rod, the porosity of the paper, the presence of a filter, and the type of filter. Studies using a machine that simulates human smoking have determined that the change in the ratio of sidestream to mainstream smoke components after introducing a filter and ventilation primarily resulted from a decrease in the amount of mainstream smoke, because the amount of sidestream smoke does not change substantially with alterations in cigarette design (Perfetti et al. 1998). Examination of chemicals with similar properties revealed that those with a low boiling point had higher ratios of levels in sidestream smoke to levels in mainstream smoke and that compounds with a high boiling point had lower ratios (Sakuma et al. 1984). Studies indicate that compared with mainstream smoke collected under standard FTC/ ISO smoking parameters, sidestream smoke has higher levels of PAHs (Grimmer et al. 1987; Evans et al. 1993); nitrosamines (Brunnemann et al. 1977a, 1980; Hoffmann et al. 1979a; Rhl et al. 1980); aza-arenes (Dong et al. 1978; Grimmer et al. 1987); aromatic amines (Patrianakos and Hoffmann 1979); carbon monoxide (CO) (Hoffmann et al. 1979b; Rickert et al. 1984); nicotine (Rickert et al. 1984; Pakhale et al. 1997); ammonia (Brunnemann and Hoffmann 1975); pyridine (Johnson et al. 1973b; Brunnemann et al. 1978; Sakuma et al. 1984); and the gas phase components 1,3-butadiene, acrolein, isoprene, benzene, and toluene (Brunnemann et al. 1990). With increased puffing intensity, the toxicant ratios of sidestream to mainstream smoke decrease (Borgerding et al. 2000).

The increase in the amount of tobacco burned during smoldering compared with tobacco burned during puffing is not the only factor influencing differences in the chemical content of sidestream and mainstream smoke. The burning conditions that generate sidestream and mainstream smoke also differ (Guerin 1987). Temperatures reach 900C during a puff and fall to about 400C between puffs (Guerin 1987). Puffing burns the tobacco on the periphery of the cigarette, and tobacco in the core burns between puffs (Johnson 1977; Hoffmann et al. 1979a). Thus, mainstream smoke depends on the chemical composition of the combustible portion of the cigarette near the periphery of the rod, whereas chemicals at higher concentrations in the central portion of the rod have higher levels in sidestream smoke than in mainstream smoke (Johnson 1977). Sidestream smoke is produced during conditions with less available oxygen (Guerin et al. 1987) and higher alkalinity and water content than those for mainstream smoke (Brunnemann and Hoffmann 1974; Adams et al. 1987; Guerin 1987). Ammonia levels are significantly higher in sidestream smoke, resulting in a more alkaline pH (Adams et al. 1987). Thus, the composition and levels of chemical species in mainstream smoke differ from those in sidestream smoke.

Levels of some compounds are higher in mainstream smoke than in sidestream smoke, and this difference may reflect chemical influences that are more complex than just changes in puff frequency. For example, mainstream smoke contains considerably more cyanide than side-stream smoke does (Johnson et al. 1973b; Brunnemann et al. 1977a; Norman et al. 1983). Sakuma and colleagues (1983) measured a series of semivolatile compounds in tobacco smoke and found that levels of phenol, cresol, xylenols, guiacol, formic acid, and acetic acid were higher in sidestream smoke, whereas levels of catechol and hydroquinone were higher in mainstream smoke. ff782bc1db

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