Cherry-flavoured electronic cigarettes expose users to the inhalation irritant, benzaldehyde

Abstract

Many non-cigarette tobacco products, including e-cigarettes, contain various flavorings, such as fruit flavours. Although many flavorings used in e-cigarettes are generally recognized as safe when used in food products, concerns have been raised about the potential inhalation toxicity of these chemicals. Benzaldehyde, which is a key ingredient in natural fruit flavors, has been shown to cause irritation of respiratory airways in animal and occupational exposure studies. Given the potential inhalation toxicity of this compound, we measured benzaldehyde in aerosol generated in a laboratory setting from flavored e-cigarettes purchased online and detected benzaldehyde in 108 out of 145 products. The highest levels of benzaldehyde were detected in cherry flavored products. The benzaldehyde doses inhaled with 30 puffs from flavored e-cigarettes were often higher than doses inhaled from a conventional cigarette. Levels in cherry flavored products were over 1000 times lower than doses inhaled in the workplace. While e-cigarettes seem to be a promising harm reduction tool for smokers, findings indicate that using these products could result in repeated inhalation of benzaldehyde, with long-term users risking regular exposure to the substance. Given the uncertainty surrounding adverse health effects stemming from long-term inhalation of flavoring ingredients such as benzaldehyde, clinicians need to be aware of this emerging risk and ask their patients about use of flavored e-cigarettes.

To the editor

Current estimates show that 12.6% of U.S. adults report ever use of electronic cigarettes (e-cigarettes), a number which continues to rise. [1] Recent studies confirm that e-cigarettes presumably pose lower health risks to the user due to the disparity in toxic compounds found in e-cigarettes relative to tobacco cigarettes. [2] While the 2009 Family Smoking Prevention and Tobacco Control Act gave rise to a U.S. ban on added, non-menthol flavorings in cigarettes [3], currently, non-cigarette tobacco products, including e-cigarettes, are permitted to have added flavorings (ex: candy, fruit). Although many flavorings used in e-cigarettes are generally recognized as safe (GRAS) when used in food products, concerns have been raised about the potential inhalation toxicity of these chemicals [4]. The potential effects flavor compounds may have on the respiratory health of e-cigarette users is unclear. A recent report by Barrington-Trimis et al (2014) outlined the need for research on flavor additives used in e-cigarettes, noting the lack of safety data on long-term health effects from inhaling flavoring chemicals [4].

One such flavoring compound, benzaldehyde, is an aromatic aldehyde used in food and cosmetics. [5] Although data suggest little to no toxicity from oral and dermal exposure to benzaldehyde, occupational exposure has been linked to irritation of the eyes and mucous membranes of the respiratory passages. [5] Given the potential inhalation toxicity of benzaldehyde to e-cigarette users, we examined benzaldehyde levels generated from flavored e-cigarettes. We hypothesized that aerosol generated from flavored e-cigarettes would contain significant amounts of benzaldehyde.

Methods

We measured benzaldehyde in aerosol generated from an e-cigarette refilled with 145 flavored nicotine-containing solutions purchased from international online retailers. The solutions were classified into eight flavor groups according to labelled characteristics: berry/tropical fruit (n=40), tobacco (n=37), alcohol related/drink (n=15), chocolate/sweet flavor (n=11), coffee/tea (n=11), mint/menthol (n=10), cherry (n=10), and other, non-identifiable flavor varieties (e.g, “Indian Summer”, “Cosmopolitan”) (n=11). A refillable eGo e-cigarette (heater resistance 2.4 ohm, battery 900 mAh, 3.4 V) was used for testing. Aerosol was generated using an automatic smoking simulator following protocols used in previous studies (inhalation time 1.8 s, puff volume 70 ml, interval between puffs 17 s). [6] For each experiment, 30 puffs were taken from each e-cigarette in two series of 15 puffs, with a 5-min interval between series. Benzaldehyde from aerosol was trapped on sorbent tubes, extracted, and analyzed using a high performance liquid chromatography (HPLC) method as recommended by the U.S. Environmental Protection Agency (EPA) [7]. The lower limit of quantitation (LLOQ) was 0.025 μg/30 puffs. A Kruskal-Wallis test was performed to assess differences in the distributions of benzaldehyde levels according to flavor grouping. For each product tested, we calculated a daily inhaled dose of benzaldehyde, assuming that an experienced e-cigarette user puffs on an e-cigarette 163 times a day [8]. We compared the inhaled dose using 30 puffs from a flavored e-cigarette with an inhaled dose from a single tobacco cigarette (0.5–4.5 μg/cigarette)[9]. We also compared the inhaled dose from flavored e-cigarettes with a hypothetical dose inhaled by healthy workers who would be exposed during an 8-hr work shift to the permissible exposure limit (PEL) of benzaldehyde as defined by the U.S. Workplace Environmental Exposure Level (WEEL) Guides. [10] (90.5mg = inhalation rate 1.3 4m³/hr × 8 hrs × 8.7 mg/m³ PEL).

Results

Benzaldehyde was detected in 108 out of 145 examined products (levels above LLOQ). The highest yields of benzaldehyde were observed in cherry-flavored products (5.129 – 141.2 μg/30 puffs). Benzaldehyde yields in aerosol generated from cherry-flavored nicotine solutions were significantly higher than in other products (χ²(7)=43.70, p<0.0001; Kruskal-Wallis Test). Benzaldehyde yields in non-cherry flavored products were within the range of 0.025 to 10.27 μg/30 puffs (Table 1). The benzaldehyde doses inhaled using 30 puffs from flavored e-cigarettes were often higher than doses inhaled from a conventional cigarette. The estimated median daily inhaled dose of benzaldehyde from cherry-flavored e-cigarettes was 70.3 μg, which would be over one thousand times lower than the PEL dose for benzaldehyde concentrations in the workplace (Figure 1).

Table 1.

Yields of benzaldehyde in aerosol generated from flavored e-cigarettes (n=145)

Flavor	Number of tested products	Proportion of products with positive benzaldehyde (>LOQ)	Median benzaldehyde yield (μg/30 puffs)	Range of benzaldehyde yields (μg/30 puffs)
Fruit (other than cherry)	40	62.5%	0.050	BLQ – 2.041
Tobacco	37	78.4%	0.219	BLQ – 2.093
Alcohol related or drink	15	73.3%	0.118	BLQ – 4.499
Coffee or tea	11	81.8%	0.143	BLQ – 3.010
Chocolate or sweet flavor	11	90.9%	0.130	BLQ – 5.327
Mint or menthol	10	40.0%	0.025	BLQ – 0.237
Cherry	10	100%	12.93	5.129 – 141.2
Other	11	90.9%	0.321	BLQ – 10.27

^*BLQ – below limit of quantitation (0.025 μg/30 puffs)

Figure 1.

Discussion

By examining benzaldehyde levels in aerosols generated from a wide range of flavored nicotine solutions, our study demonstrated that elevated levels of benzaldehyde exist in cherry flavored products. Users of cherry flavored products may inhale significantly higher doses of benzaldehyde compared to users of other flavored products. Although this study has several limitations, including an arbitrarily selected testing protocol which may not reflect actual product use, this study points out a potential risk associated with using flavored e-cigarettes.

As e-cigarette popularity increases, respiratory clinicians need to be aware of potential risks that may result from use. Although e-cigarettes may be a promising harm reduction tool for smokers, findings indicate that using these products could result in repeated inhalation of benzaldehyde, with long-term users risking regular exposure to the substance. Given the uncertainty surrounding adverse health effects stemming from long-term inhalation of flavoring ingredients such as benzaldehyde, patients should be asked about use of flavored products, particularly patients with respiratory diseases.