Nicotine and the Developing Human: A Neglected Element in the Electronic Cigarette Debate
Introduction
The rapid elimination of cigarettes and other combusted tobacco products in the U.S. would prevent tens of millions of tobacco-related deaths in the coming decades.1 Strategies proposed to reduce the size of the tobacco epidemic include aggressively strengthening established comprehensive tobacco control programs, including advertising restrictions, mass media campaigns, health warnings, smoke-free policies, restricting youth access, and price increases.1, 2 Ending death and disease caused by smoking would require implementing additional approaches.1 The Surgeon General outlined in the 50th Anniversary Report the most plausible strategies for the U.S. in the coming decade, which included reducing the nicotine content of cigarettes to non-addictive levels, restricting sales at the state or municipal level of some or all combusted products, and reducing product toxicity and appeal through regulatory standards.1 Some tobacco control advocates, stakeholders, and tobacco companies argue that the introduction of less harmful nicotine delivery devices, such as electronic cigarettes and other electronic nicotine delivery systems (ENDS), will greatly accelerate progress toward ending combustible cigarette use,1 and that the public health community should enable and encourage substitution of the these products through low or no taxes to widen the price differential in favor of less harmful products,3 tolerating public use,4 and health authority endorsement.4
Electronic cigarettes and other ENDS are battery-operated devices that heat a liquid (usually glycerin or propylene glycol) to create an aerosol. The liquid usually contains nicotine, as well as flavors, additives, and varying amounts of contaminants.5 In the U.S., the Food and Drug Administration (FDA) regulates cigarettes, cigarette tobacco, roll-your-own tobacco, and smokeless tobacco.6 Electronic cigarettes are currently unregulated. Although the FDA issued a proposed deeming rule to regulate electronic cigarettes in April 2014, developing and implementing final federal regulations can take years.7
Electronic cigarettes are currently widely available, often less expensive than combusted cigarettes, sold legally to minors in many states,8 and often contain fruit and candy flavorings such as “Snappin’ Apple,” “Cherry Crush,” and “Chocolate Treat.”9, 10 Nicotine concentrations typically range from 6 to 24 mg/mL, but products purporting to contain up to 100 mg/mL can be purchased wholesale on the Internet.11, 12 Warning labels and childproof packaging are often absent, even in products intended for consumer use. Six companies invested $60 million in electronic cigarette marketing in 2013 (twice that invested in 2012),10 using many approaches formerly employed to market cigarettes but now banned, including TV advertisements, celebrity endorsement, sponsorship of sports events and music festivals, and cartoon advertisements.9, 10, 13, 14 These marketing strategies are known to result in youth smoking initiation, and some, such as TV advertisements, have been banned for cigarettes for decades.15 Also concerning are claims that electronic cigarettes and nicotine are safe and even beneficial, which now appear frequently in the media and on company websites.16, 17, 18, 19, 20, 21 Not surprisingly, youth experimentation and recent use has increased dramatically in recent years.22, 23 Wells Fargo analysts recently predicted that, based on past sales, the consumption of electronic cigarettes “could surpass consumption of conventional cigarettes within the next decade.”24 Other marketing strategies that could appeal to youth are placement of products in easily accessible locations in stores,10 and social networking and other technical capabilities not related to use of the product.25, 26, 27
Numerous issues related to the public health consequences of widespread availability and unrestricted marketing of electronic cigarettes have been debated, including effects on youth smoking initiation, quitting, dual use among established smokers, and relapse among former smokers.28, 29 However, careful consideration of the potential adverse health effects from nicotine itself is often absent from these debates. Because the health effects of combusted products are so devastating and medicinal nicotine products approved for smoking cessation pose far fewer health risks than smoking, the effects of nicotine itself are often regarded as being of minor importance. Further exploration of the potential unintended consequences of facilitating a transition from combusted to non-combusted products is warranted, and special consideration of the effects of nicotine exposure among vulnerable populations—including pregnant women and fetuses, children, and adolescents—is urgently needed. This paper synthesizes relevant literature regarding biological properties of nicotine and its effects during development, and presents potential measures for consideration to protect the health of these vulnerable populations.
Section snippets
Biological Properties of Nicotine
Nicotine is readily absorbed through the skin and lungs and is metabolized by the lungs, liver, and kidneys.30 Nicotine exerts its physiologic effects by binding nicotinic acetyl choline receptors (nAChRs), which are expressed by both neuronal and non-neuronal cells throughout the body.31 The cholinergic system in the central nervous system is associated with cognitive function, including memory, selective attention, and emotional processing.31 Non-neuronal nAChRs are found in respiratory
Pregnant Women and Fetuses
An estimated 10% of pregnant women in the U.S. smoke cigarettes, exposing more than 400,000 fetuses annually to nicotine and other toxicants such as carbon monoxide.1 Nicotine is a developmental toxicant and adversely affects pregnancy and infant outcomes.1 Nicotine crosses the placenta and binds to nAChRs, which are widely expressed throughout the fetal nervous system.35 NAChRs regulate fetal brain maturation, and expression of nAChRs is elevated during critical periods of development.36
Children
Electronic cigarettes pose numerous risks to children. Widespread advertising of electronic cigarettes on TV could easily normalize electronic cigarette use. Because the act of using electronic cigarettes can be indistinguishable from smoking, smoking cigarettes could be re-normalized for the first time since TV advertising was banned nearly 40 years ago. Parental electronic cigarette use could result in unintended direct health risks to offspring as well. Efforts to educate parents about the
Adolescents
Electronic cigarette use increased sharply among youths between 2011 and 2013.22, 23 According to a recent national survey, more than a quarter of a million youths who had never smoked cigarettes had used electronic cigarettes and nearly half expressed intention to use conventional cigarettes in the future, compared with 22% of those who had never used electronic cigarettes.69, 90 The effects of current aggressive marketing tactics for electronic cigarettes on future youth initiation are
Acknowledgments
The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of CDC.
Terry F. Pechacek receives salary support from Pfizer Inc. for “Diffusion of Tobacco Control Fundamentals to Other Large Chinese Cities,” an effort to expand tobacco control in major cities in China. No other financial disclosures were reported by the remaining authors of this paper.
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