correspondence

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tries, companies, and professions most directly involved have an incentive to work together to help ensure that clinical genetics technology is accurate-ly and ethically introduced into medical practice.George J. Annas, J.D., M.P.H.Boston University School of Public Health Boston, MA

Sherman Elias, M.D.Northwestern University Feinberg School of Medicine Chicago, IL

Since publication of their article, the authors report no fur-ther potential conflict of interest.

DOI: 10.1056/NEJMc1404692

Nicotine Poisoning in an Infant

To the Editor: Reports to U.S. poison control centers of possible nicotine toxicity tripled from 2012 to 2013.1,2 Although nicotine toxicity is not a new phenomenon, the emergence of electronic cigarettes (e-cigarettes) has spawned a market for highly concentrated liquid nicotine. This phe-nomenon has resulted in unprecedented access to potentially toxic doses of nicotine and other harmful compounds in the home. We report a case of a child who was poisoned by e-cigarette refill liquid (e-liquid).

Vomiting, tachycardia, grunting respirations, and truncal ataxia developed in a 10-month-old boy after he ingested a small amount of e-liquid nicotine. The vaping (or vape) shop that com-pounded the product reported that it contained a nicotine concentration of 1.8% (18 mg per milliliter) and unknown concentrations of oil of wintergreen (methyl salicylate), glycerin, and propylene glycol.

Multiple toxidromes that could have been as-sociated with ingestion of this type of product include cholinergic crisis and salicylism. Low dos-es of nicotine frequently have stimulant effects (e.g., tachycardia). Vomiting is common with en-teral exposures. Signs of central nervous system toxicity include ataxia and seizures. As doses increase, loss of nicotinic receptor specificity may occur and result in signs of muscarinic cho-linergic toxicity, including extreme secretions and gastrointestinal disturbance. The highest levels of poisoning can result in neuromuscular block-ade, respiratory failure, and death. Small inges-tions could be deadly. With an estimated median lethal dose between 1 and 13 mg per kilogram of body weight, 1 teaspoon (5 ml) of a 1.8% nico-tine solution could be lethal to a 90-kg person.3,4

Fortunately, our patients levels of conscious-ness, hemoglobin oxygen, and serum salicylate, as well as findings on chest radiography and his

basic metabolic profile, were all normal. The boy did not require antidote therapy (usually at-ropine or scopolamine to combat cholinergic activity) and recovered baseline health 6 hours after ingesting the poison.

The Food and Drug Administration does not currently regulate nontherapeutic nicotine; this raises concern that in the ballooning unregu-lated liquid nicotine market there may be vari-ability in nicotine dosing and introduction of unintended toxic ingredients. Lack of regulatory oversight has resulted in inconsistent labeling, insufficient or nonexistent child protective pack-aging, and product design and flavoring that may encourage children to explore and ingest these products. Figure 1 shows labeling that contains suggestions of edible ingredients (lem-onade), visually appealing cartoons, and hand-written labels of uncertain reliability.

Figure 1. Three Examples of Over-the-Counter Liquid Nicotine Products.

The nicotine concentration in the vials (left and center) is 1.8%. The hand-labeled container on the right was found next to the patient described in our letter.

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T h e n e w e ngl a nd j o u r na l o f m e dic i n e

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With the growing use of e-cigarettes, physi-cians need to be alert for nicotine poisoning. They also need to educate patients and parents about this danger and advocate for measures that will help prevent potentially fatal liquid nico-tine poisoning of infants and young children.

Robert A. Bassett, D.O.Einstein Medical Center Philadelphia, PA bassettr@einstein.edu

Kevin Osterhoudt, M.D.Childrens Hospital of Philadelphia Philadelphia, PA

Tecla Brabazon, D.O.Abington Health Lansdale Hospital Lansdale, PA

Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org.

This letter was published on May 7, 2014, at NEJM.org.

1. Bronstein AC, Spyker DA, Cantilena LR Jr, Rumack BH, Dart RC. 2011 Annual report of the American Association of Poison Control Centers National Poison Data System (NPDS): 29th An-nual Report. Clin Toxicol (Phila) 2012;50:911-1164.2. Mowry JB, Spyker DA, Cantilena LR Jr, Bailey JE, Ford M. 2012 Annual report of the American Association of Poison Con-trol Centers National Poison Data System (NPDS): 30th Annual Report. Clin Toxicol (Phila) 2013;51:949-1229.3. Soghian S. Nicotine. In: Nelson LS, Lewin NA, Howland MA, Hoffman RS, Goldfrank LR, Flomenbaum NE, eds. Gold-franks toxicologic emergencies. 9th ed. New York: McGraw-Hill, 2011:1185-9.4. Mayer B. How much nicotine kills a human? Tracing back the generally accepted lethal dose to dubious self-experiments in the nineteenth century. Arch Toxicol 2014;88:5-7.

DOI: 10.1056/NEJMc1403843

Figure 1 (facing page). Levels and Patterns of Chemicals in Various Brands of Cherry-, Grape-, and Apple-Flavored Candies, Kool-Aid Drink Mix, and Tobacco Products.

Panel A shows that the cherry-flavored products con-tain the chemicals benzaldehyde, benzyl alcohol, and other cherry chemicals. The cherryvanilla pairing (with vanillin, ethyl vanillin, or both) was detected in all the cherry-flavored tobacco products examined. As shown in Panel B, all grape products tested were found to contain methyl anthranilate; several of the tobacco products were found to include raspberry ketone (a berry flavor chemical), vanillin, or both. The cherry-flavor chemical benzyl alcohol was detected in the grape-flavored Phillies Blunt cigar, Kayak snuff, and Zig-Zag wraps. As shown in Panel C, all apple products were found to contain 1-hexanol. Other six-carbon flavor compounds (e.g., [Z]-3-hexen-1-ol) were detected in multiple products. Pairing with vanilla was detected in every apple tobacco product exam-ined. Pairing with the cherry-flavor chemical benzyl alcohol was detected in the apple-flavored Kayak snuff, Skoal snuff, and Zig-Zag wraps.

Candy Flavorings in Tobacco

To the Editor: Flavored tobacco products are marketed worldwide (see the Supplementary Appendix, available with the full text of this letter at NEJM.org). A 2007 World Health Organization (WHO) report1 states, In view of the little re-search that has been conducted on flavoured tobacco, the WHO Study Group on Tobacco Product Regulation . . . urges health authori-ties to consider public health initiatives to re-duce the marketing and use of flavoured tobacco products.

In the United States, the Food and Drug Ad-ministration reports, Almost 90 percent of adult smokers start smoking as teenagers. . . . f la-vored cigarettes are a gateway for many children and young adults to become regular smokers.2

The Family Smoking Prevention and Tobacco Control Act of 2009 banned U.S. sales of ciga-rettes with characterizing flavors other than menthol. However, that ban does not extend to the many products that are not categorized as cigarettes under U.S. tax law. These products include cigarette-like small and large cigars, cigarillos, blunts (large cigars composed of a tobacco-based paper overwrap holding shredded tobacco [such as a Phillies Blunt cigar]), con-ventional rolled-leaf cigars, roll-your-own to-bacco, blunt wraps (i.e., tobacco-based wraps often flavored that are related to the wraps used on a blunt cigar and are often used to roll

cannabis), hookah tobacco, moist snuff for dip-ping, dissolvables such as Camel Orbs, and electronic cigarettes. Some cannabis smokers use the shell of a blunt cigar to roll a blunt; this creates a nexus of tobacco use with canna-bis use.3 Blunt wraps provide just a tobacco wrap in a ready-to-roll form. Because some cigars are now structurally very similar to cigarettes (see

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