The Regulatory Challenge of Electronic Cigarettes Electronic cigarettes (e-cigarettes or electronic

nicotine delivery systems) heat a nicotine solution to generate vapor that is inhaled, without the combus-tion of tobacco and its toxic constituents. Use of e-cigarettes is increasing in the United States and around the world. Current smokers in the United States report an 11.4 % prevalence of ever use of e-cigarettes and 4.1 % use in past 30 days.1 They likely pose less direct hazard to the individual smoker than tobacco cigarettes and might help smokers quit smok-ing or reduce harm by smoking fewer tobacco ciga-rettes. On the other hand, there are potential harms, including promoting continued smoking of cigarettes and renormalizing cigarette smoking behaviors. The Food and Drug Administration (FDA) is authorized to regulate tobacco products, and in 2011 the agency announced plans to regulate e-cigarettes as tobacco products.2 The FDA will need to make a number of regulatory decisions about product safety that could have major effects on public health and will face many challenges. The e-Cigarette as a Nicotine Delivery System The delivery of nicotine to the lungs via inhalation, with rapid absorption into the circulation, is critical to the addictiveness of cigarette smoking.3 The adverse health consequences of cigarette smoking are caused primarily by inhalation of toxic tobacco constituents and organic combustion products. Nicotine per se con-tributes to some smoking-related diseases, but its contribution is considered to be much smaller than that of combustion products.3 The provision of clean nicotine (without combustion products or other tobacco plant toxins) in the form of nicotine replace-ment therapies (NRTs) has been in use for nearly 30 years and has proven to be a safe way to facilitate smoking cessation. Currently available NRT products are not as satisfying and are less acceptable to smok-ers compared with inhaling and absorbing nicotine from cigarette smoke. The possibility of an inhaled clean nicotine device has been discussed by health researchers for many years as a potentially more effec-tive way to promote smoking cessation. Although not yet proven safe or effective for smoking cessation, the e-cigarette has been positioned as such an inhaled nicotine delivery device and has gained popularity through this perception.