Nicotine and the Developing Human

The elimination of cigarettes and other combusted tobacco products in the U.S. would prevent tens of millions of tobacco-related deaths. It has been suggested that the introduction of less harmful nicotine delivery devices, such as electronic cigarettes or other electronic nicotine delivery systems, will accelerate progress toward ending combustible cigarette use. However, careful consideration of the potential adverse health effects from nicotine itself is often absent from public health debates. Human and animal data support that nicotine exposure during periods of developmental vulnerability (fetal through adolescent stages) has multiple adverse health consequences, including impaired fetal brain and lung development, and altered development of cerebral cortex and hippocampus in adolescents. Measures to protect the health of pregnant women and children are needed and could include (1) strong prohibitions on marketing that increase youth uptake; (2) youth access laws similar to those in effect for other tobacco products; (3) appropriate health warnings for vulnerable populations; (4) packaging to prevent accidental poisonings; (5) protection of non-users from exposure to secondhand electronic cigarette aerosol; (6) pricing that helps minimize youth initiation and use; (7) regulations to reduce product addiction potential and appeal for youth; and (8) the age of legal sale.

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.