Toxicology
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Highly unregulated, the sale of toxic nicotine concoctions for e-cigarette refills pose a serious threat to children.

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EMS brings in a two-year-old with vomiting and decreased mental status. According to their report, he had been doing well until he suddenly got sick en route to the hospital. He became sleepier, and, as they wheeled him in, he began to seize. His parents say he was at a relative’s house when he was found drinking from a container of some colorful liquid, which he accidently spilled on himself. Then he began to vomit. The culprit: the liquid was used to refill electronic cigarettes.

Background

Electronic cigarettes — also known as e-cigarettes or just e-cigs — are the tobacco industry’s hot new commodity. E-cigs are battery-powered devices that heat a liquid solution of nicotine, or e-liquid. Users inhale the vapors that result from heating the solution, which is known as “vaping.” The devices also have been used with other solutions, some containing cannabis. E-cigarettes were first developed in China and quickly became very popular throughout Asia and Europe. They are marketed as a “safer” cigarette that can help cigarettes users to quit smoking. 

Until recently, the Food and Drug Administration did not regulate e-cigarettes, although for several years it has had the authority to regulate tobacco products. However, under proposed regulations issued in April, the FDA would have the authority to restrict sales of e-cigarettes to anyone under 18, require manufacturers to validate claims regarding their safety and mandate warning labels. The new regulation, however, would not restrict advertising or ban flavoring the nicotine. The proposed rules are now in a public comment period.

Health Concerns

The devices themselves are generally well-made and rarely leak. Health concerns, then, often stem from the fact that many of these devices contain refillable nicotine-containing cartridges. Exposure to the nicotine solutions is dangerous because they are highly concentrated. The concentration of nicotine in these solutions can range up to 100 mg/ml. The lethal dose of nicotine is uncertain, with estimates of 30-60 mg in an adult and 10 mg in a child (Durmowicz, 2014), while some estimate the dose to be closer to 1 mg/kg (Garcia 1977). An oral LD50 of 6.5–13 mg/kg has been reported in dog models (Mayer, 2014).

Based on this LD50, the ingestion of only a few milliliters of some of the preparations is toxic. This is particularly troublesome as the solution can be bought a gallon at a time and stored in containers without safety mechanisms. Unknowingly, parents may also leave these containers anywhere around the house, in areas easy for toddlers to reach.

Liquid nicotine is readily absorbed through the skin, a risk not found with other tobacco products that require ingestion or inhalation. Lack of childproof containers, along with colorful packaging and flavorings, makes them prime targets for exploratory toddlers.

In its early clinical phase, acute nicotine poisoning is characterized by nausea, vomiting, abdominal pain, salivation, bronchorrhea, tachypnea, hypertension, tachycardia, miosis, tremor, fasciculations, and seizures. The delayed phase consists of respiratory depression, dyspnea, bradycardia, hypotension, shock, mydriasis, weakness, muscle paralysis, and coma (Metz et al., 2004). Treatment is symptom directed and includes benzodiazepines for seizures, intubation for airway and respiratory support, and atropine for bronchorrhea and bradycardia.

The CDC reports that the percentage of U.S. middle and high school students who use e-cigs more than doubled between 2011 and 2012, from 4.7% to 10%. In 2012, more than 1.78 million middle and high school students nationwide had tried e-cigarettes.

This is not surprising given the appealing packaging and flavoring that manufacturers use to make it more palatable. US Poison Centers have seen a surge in calls too, averaging 200 calls a day in early 2014 (Chatham-Stephens MMWR 2014 data). Half of those calls were for exposures in children under the age of five.

Because e-cigs do not expose the users or those around them to tar products and other products of pyrolysis they are more socially acceptable than regular cigarettes. This allows smokers to use them in places where smoking is prohibited. However, users are still exposed to nicotine so there are legitimate concerns regarding their safety. In addition to adverse effects due to its stimulant properties, vaporized nicotine may be carcinogenic, just like other forms of tobacco. Little is known about the impact of exposure to liquid nicotine from e-cigs on public health, but there is concern that this will be a gateway to use of other drugs.

Furthermore, the nicotine is dissolved in a solution containing multiple other chemicals. Although the concentration of these is very low, we still don’t have much information about the potential toxicity of these additional agents in the e-liquid. The proposed rules would require manufacturers to divulge what chemicals are included in the liquid solutions.

Liquid nicotine exposures are becoming more common. While serious exposures are uncommon and no deaths have been reported from unintentional exposures to e-liquids, there is still the potential for dangerous toxicity and close surveillance is warranted.

nicotine-gal-main

The concentration of nicotine in these solutions can range up to 100 mg/ml. The lethal dose of nicotine is uncertain, with estimates of 30-60 mg in an adult and 10 mg in a child, while some estimate the dose to be closer to 1 mg/kg. An oral LD50 of 6.5–13 mg/kg has been reported in dog models. Based on this LD50, the ingestion of only a few milliliters of some nicotine preparations is toxic. The high concentrations are particularly troublesome as the solution can be bought a gallon at a time and stored in containers without safety mechanisms.

Case Conclusion

After receiving a benzodiazepine for the seizure and a thorough scrubbing to remove any remaining liquid nicotine, your two-year-old patient slowly wakes up. He is admitted overnight for observation, and by the next morning, he is eating and playing and discharged home.

REFERENCES

Durmowicz EL (2014) The impact of electronic cigarettes on the pediatric population. Tob Control, 23, Supple 2:ii41-ii46.

Gacria-Estrada H, et al. (1977) An unusual case of nicotine poisoning. Clin Toxicol,10,391-393.

Mayer B. (2014). How much nicotine kills a human? Tracing back the generally accepted lethal dose to dubious self-experiments in the nineteenth century. Archives of Toxicology, 88, 5–7.

Metz C.N., Gregersen P.K., & Malhotra A.K. (2004). Metabolism and biochemical effects of nicotine for primary care providers. The Medical Clinics of North America, 88, 1399–1413

Chatham-Stephens K, et al. (2014) Notes from the field: calls to poison centers for exposures to electronic cigarettes-United States, September 2010-February 2014. MMWR Morb Mortal Wkly Rep,63(13):292-293.

 

Comments   

# See Allen Carr's warnings years agoGail Morris 2014-07-31 13:56
Could it not be argued that the Governments Quit program strategies have indeed encouraged smokers to resort to nicotine profducts (in all their various forms) as Nicotine Replacement Therapy - what is therapeutic about this poison?!!
It is ridiculous to suggest that taking nicotine will get smokers off nicotine - why not read Allen Carrs book 'The Nicotine Conspiracy' written in 2006 to understand the role of those involved in the promotion of this poison.
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