Nicotine - Public Health Consequences Of E-Cigarettes - NCBI

CONCENTRATION OF NICOTINE IN COMMERCIAL E-CIGARETTES

Although some e-cigarettes/e-liquids do not contain nicotine, most do, and the nicotine contents of e-cigarettes are variable. Based on vaping machine studies, higher nicotine concentration of e-liquids results in higher nicotine yield of any given e-cigarette (Talih et al., 2015). As with combustible tobacco cigarettes, machine-derived nicotine yield of e-cigarettes is not necessarily predictive of users' systemic exposures to nicotine. Other factors such as power of the e-cigarette and user behavior and use patterns are also critical. Nevertheless, e-liquid nicotine concentration may be a determinant of systemic nicotine exposure. Here, the committee reviews current evidence related to the range of nicotine concentrations in commercially available e-cigarettes, whether cartridges of first-generation and closed-tank e-cigarettes or refill liquids used in other open-system e-cigarettes. The committee also discusses labeling accuracy of nicotine content.

There is no consensus in the way nicotine strength is reported on labels of products or in studies. The nicotine strength on the label of some products is qualitative (e.g., zero, low, medium, high, super high) or quantitative on others. The unit of quantitative measure of nicotine strength is often reported on labels or in studies as amount per cartridge (mg), percentage per volume (e.g., 2.4 percent nicotine), concentration (mg/ml), or amount of nicotine per amount of e-liquid (µg/mg or mg/g).

A previous systematic review of the evidence evaluating chemicals in refill solutions and cartridges included studies published between January 2007 and September 2013 (Cheng, 2014). Based on 10 of the 29 studies included in this review, which reported on nicotine concentration of e-liquids, the review found that nicotine levels in e-liquids varied considerably, with a range of 0–87.2 mg/ml. For example, one study assessed the level of nicotine in popular brands of refill liquids from the United States and Western Europe (Etter et al., 2013). Among the 20 samples from 10 different brands, the range of nicotine on the labels was 6–30 mg. The range of measured nicotine concentration was 6–29.0 mg/ml; the measured concentration ranged from 85 to 107 percent of the labeled nicotine content. Another study assessed the nicotine content of 16 e-cigarette brands (20 cartridges and 15 refill liquids) based on high popularity in markets in Poland, the United Kingdom, and the United States (Goniewicz et al., 2013). Measured nicotine in cartridges ranged from 0.3 to 19 mg (per cartridge) and 0 to 25 mg in refill liquids. In another study, nicotine concentration was measured in a convenience sample of seven e-cigarette refill liquids (Cameron et al., 2014). Measured mean nicotine concentration across the seven brands ranged from 8.5 to 22.2 mg/ml, and were equivalent to or lower than labeled concentrations.

A number of studies have assessed nicotine concentration in e-liquids since the 2014 review by Cheng. Goniewicz and colleagues (2015) measured nicotine in 32, 29, and 30 popular brands of e-liquids purchased between 2013 and 2014 in the United States, South Korea, and Poland, respectively. In samples from the United States, nicotine in the e-liquid ranged from below limit of quantitation (BLQ) to 36.6 mg/ml. Of 32 samples, 9 (28 percent) had measured nicotine levels that deviated from the labeled nicotine strength by more than 20 percent. In South Korea, two-thirds of the products tested did not have detectable levels of nicotine while the higher concentration was 150 mg/ml (this product was labeled “Pure Nicotine”). The range of nicotine strength in Polish samples was BLQ to 24.7 mg/ml. Ten percent of the Polish products tested showed deviations from the label of greater than 20 percent, while none of the products labeled nicotine-free contained detectable amounts of nicotine. Lisko and colleagues (2015) measured nicotine concentration in 36 cartridge and refill e-liquids in the U.S. market that had favorable online reviews. Nicotine content ranged from undetected to 20.5 mg/g. The measured nicotine concentrations were 5.8–41.7 percent lower than the labeled nicotine content. Tierney and colleagues (2016) reported a range of 6 to 24 mg/ml in a sample of 30 cartridge and refill e-liquids.

Etter and Bugey (2017) assessed the agreement between labeled and measured nicotine content across brands and across batches within the same brand. Eighteen e-liquids from 11 frequently used brands in the United States, the United Kingdom, France, and Switzerland were purchased in 2013. Nicotine on the labels ranged from 16 to 48 mg/ml. The measured nicotine concentrations ranged from 15.5 to 52.0 mg/ml. A majority of the sample, 82 percent, had measured nicotine concentration within 10 percent of the labeled content. Differences across batches within the same brands were small (0.5 percent). By contrast, Goniewicz and colleagues (2014), in a study that measured nicotine content of e-liquids from six popular products in the United Kingdom that were purchased 4 weeks apart, found the mean difference between batches of the same brand ranged from 1 to 31 percent.

Some clinical studies have reported the nicotine content of their participants' usual brands of e-cigarettes. St.Helen and colleagues (2016a,b) characterized nicotine delivery and e-cigarette nicotine pharmacokinetic profiles among experienced e-cigarette users. Among the 13 enrolled participants, the labeled nicotine content of their usual e-liquids ranged from 6 to 24 mg/ml. The measured nicotine content ranged from 5.0 to 15.3 mg/g (note the difference in units). In another study of experienced e-cigarette users by St.Helen and colleagues (2017), the average nicotine on the label of the participants' usual e-liquids was 7.9 mg/ml (range = 3–18 mg/ml). The measured nicotine concentration averaged 7.4 mg/ml (range = 1.6–19.9 mg/ml).

The preferred nicotine strength may differ across types of e-cigarettes used, particularly based on the power of the e-cigarettes. Users of high-powered e-cigarettes tend to use e-liquids with lower nicotine concentrations. Wagener and colleagues (2017) enrolled 9 second-generation and 11 third-generation e-cigarette users in a clinical study. The average power of the second-generation e-cigarettes was 8.6 W compared with 71.6 W of the third-generation e-cigarettes. The average nicotine concentration of users of second-generation e-cigarettes was 22.3 mg/ml (range = 11–36 mg/ml) compared with 4.1 mg/ml (range = 1.5–6 mg/ml).

In summary, these studies show that nicotine content varies widely among products. Some studies show agreement between the nicotine content on the label and what was chemically measured while other studies show greater deviation of measured nicotine content from labeled content. One study showed that nicotine content is similar across batches of the same brand while another showed wider variability. Finally, the choice of preferred nicotine strength may be influenced, in part, by the characteristics of the e-cigarette used, including the power of the device.