Dataset Information

Analytical and toxicological evaluation of flavor chemicals in electronic cigarette refill fluids.

ABSTRACT: Thousands of electronic cigarette refill fluids are commercially available. The concentrations of nicotine and the solvents, but not the flavor chemicals, are often disclosed on product labels. The purpose of this study was to identify and quantify flavor chemicals in 39 commercial refill fluids that were previously evaluated for toxicity. Twelve flavor chemicals were identified with concentrations ?1?mg/ml: cinnamaldehyde, menthol, benzyl alcohol, vanillin, eugenol, p-anisaldehyde, ethyl cinnamate, maltol, ethyl maltol, triacetin, benzaldehyde, and menthone. Transfer of these flavor chemicals into aerosols made at 3V and 5V was efficient (mean transfer?=?98%). We produced lab-made refill fluids containing authentic standards of each flavor chemical and analyzed the toxicity of their aerosols produced at 3V and 5V using a tank Box Mod device. Over 50% of the refill fluids in our sample contained high concentrations of flavor chemicals that transferred efficiently to aerosols at concentrations that produce cytotoxicity. When tested with two types of human lung cells, the aerosols made at 5V were generally more toxic than those made at 3V. These data will be valuable for consumers, physicians, public health officials, and regulatory agencies when discussing potential health concerns relating to flavor chemicals in electronic cigarette products.

SUBMITTER: Behar RZ

PROVIDER: S-EPMC5974410 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Analytical and toxicological evaluation of flavor chemicals in electronic cigarette refill fluids.

Behar Rachel Z RZ Luo Wentai W McWhirter Kevin J KJ Pankow James F JF Talbot Prue P

Scientific reports 20180529 1

Thousands of electronic cigarette refill fluids are commercially available. The concentrations of nicotine and the solvents, but not the flavor chemicals, are often disclosed on product labels. The purpose of this study was to identify and quantify flavor chemicals in 39 commercial refill fluids that were previously evaluated for toxicity. Twelve flavor chemicals were identified with concentrations ≥1 mg/ml: cinnamaldehyde, menthol, benzyl alcohol, vanillin, eugenol, p-anisaldehyde, ethyl cinnam ...[more]

PMID: 29844439

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Project description:Flavor chemicals in electronic cigarette (EC) fluids, which may negatively impact human health, have been studied in a limited number of countries/locations. To gain an understanding of how the composition and concentrations of flavor chemicals in ECs are influenced by product sale location, we evaluated refill fluids manufactured by one company (Ritchy LTD) and purchased worldwide. Flavor chemicals were identified and quantified using gas chromatography/mass spectrometry (GC/MS). We then screened the fluids for their effects on cytotoxicity (MTT assay) and proliferation (live-cell imaging) and tested authentic standards of specific flavor chemicals to identify those that were cytotoxic at concentrations found in refill fluids. A total of 126 flavor chemicals were detected in 103 bottles of refill fluid, and their number per/bottle ranged from 1-50 based on our target list. Two products had none of the flavor chemicals on our target list, nor did they have any nontargeted flavor chemicals. A total of 28 flavor chemicals were present at concentrations ≥1 mg/mL in at least one product, and 6 of these were present at concentrations ≥10 mg/mL. The total flavor chemical concentration was ≥1 mg/mL in 70% of the refill fluids and ≥10 mg/mL in 26%. For sub-brand duplicate bottles purchased in different countries, flavor chemical concentrations were similar and induced similar responses in the in vitro assays (cytotoxicity and cell growth inhibition). The levels of furaneol, benzyl alcohol, ethyl maltol, ethyl vanillin, corylone, and vanillin were significantly correlated with cytotoxicity. The margin of exposure calculations showed that pulegone and estragole levels were high enough in some products to present a nontrivial calculated risk for cancer. Flavor chemical concentrations in refill fluids often exceeded concentrations permitted in other consumer products. These data support the regulation of flavor chemicals in EC products to reduce their potential for producing both cancer and noncancer toxicological effects.

Project description:Rationale: The use of electronic cigarettes (e-cigarettes) has rapidly increased in the United States, and thousands of e-cigarette flavors are available. However, there remains a dearth of evidence on e-cigarette flavor use patterns among older e-cigarette users.Objectives: This longitudinal study examined changes in flavor use patterns in long-term e-cigarette users, assessed self-reported adverse reactions, and evaluated users' anticipated reactions to possible U.S. Food and Drug Administration e-cigarette flavor regulatory scenarios.Methods: The study population was 383 adult participants who completed two online e-cigarette surveys in 2012-2014 (baseline survey) and in 2017-2019 (follow-up survey). In both surveys, participants were asked, "Thinking about your preferred liquid, what is the name of this liquid flavor?" and to list all flavors used in the past 30 days. Flavor preference was classified using the Penn State Three-Step Flavor Classification method. Participants reported adverse events (open-ended description) with the associated flavor. Regulatory scenarios were presented, and participants selected perceived actions from among a list of 15 options.Results: Participants' age averaged 44?±?12 years; 86% were exclusive e-cigarette users, and 13% reported "poly-use" (i.e., e-cigarette and other tobacco product use). E-cigarette flavor preference migration occurred in all demographic groups: only 36-44% maintained a preference for their original flavor. Preference for tobacco and menthol or mint decreased over time (40% baseline vs. 22% follow-up); preference for fruit remained stable (23% baseline and follow-up), but chocolate/candy or other sweets preference significantly increased (16% baseline vs. 29% follow-up), and other flavors increased slightly. Migration to sweet flavors was more noticeable in younger adults (18-45 yr); exclusive e-cigarette users preferred sweet flavors more commonly than poly-users did (31% vs. 19%). Flavor-associated adverse reactions, mainly respiratory irritations, were reported by 26 (6.9%) participants. Nearly 50% of the participants reported that they would "find a way" to buy their preferred flavor or add flavoring agents themselves if nontobacco flavors were banned.Conclusions: Flavor migration toward sweet flavors occurred in long-term e-cigarette users, a trend most pronounced in younger and exclusive e-cigarette users. The anticipated maintenance of access to flavors despite regulation suggests an element of e-cigarette-related dependence that requires further evaluation. This information could help clinicians understand the health impacts of e-cigarette flavors, develop appropriate strategies for smoking cessation, and inform the U.S. Food and Drug Administration to plan future regulation of e-cigarette flavors.

Dataset Information

Analytical and toxicological evaluation of flavor chemicals in electronic cigarette refill fluids.

Publications

Analytical and toxicological evaluation of flavor chemicals in electronic cigarette refill fluids.

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