In 1992, the US Environmental Protection Agency classified environmental tobacco smoke as one of the most dangerous cancer-causing agents in humans, a Group A carcinogen. Tobacco smoke consists of more than 4000 chemical compounds and approximately 60 known carcinogens. Half of these compounds occur naturally in the green tobacco leaf, where the remainder is generated when the tobacco is burned. The complex mixture of chemicals in tobacco smoke includes carbon monoxide, hydrogen cyanide, benzene, formaldehyde, nicotine, phenol, polycyclic aromatic hydrocarbons (PAHs) and tobacco-specific nitrosamines (TSNAs). It should be noted that only the particulate phase, approximately 5% of the cigarette's total output, is visible.

For risk assessment, tobacco smoke has been classified as either mainstream or sidestream. Mainstream smoke is that which is inhaled through the column of the cigarette and filter tip. In contrast, sidestream smoke is emitted from a burning cigarette between puffs and inhaled by nonsmokers. Although the chemical composition of mainstream and sidestream smoke is similar, the concentration of many constituents is higher in sidestream, or “passive,” smoke.

Nicotine, the second most abundant constituent of tobacco smoke, is responsible for the addictive properties of tobacco and represents a major source of TSNAs.³ Nicotine is present in both mainstream and sidestream smoke and is rapidly absorbed by the alveoli of the lungs. Nicotine concentrates in the pulmonary veins as a bolus and circulates throughout the body. Subsequent release of dopamine via activation of cholinergic receptors in the brain and modulation of hormones such as epinephrine and cortisol is believed to lead to nicotine dependence. The effect of polymorphisms in the dopamine transporter (SLC6A3) and dopamine D2 receptor (DRD2) genes on smoking initiation and nicotine dependence remains controversial and a subject of intense investigation.