Flavoring Chemicals in E-Cigarettes: Diacetyl, 2,3-Pentanedione, and Acetoin in a Sample of 51 Products, Including Fruit-, Candy-, and Cocktail-Flavored E-Cigarettes

Abstract

Background:There are > 7,000 e-cigarette flavors currently marketed. Flavoring chemicals gained notoriety in the early 2000s when inhalation exposure of the flavoring chemical diacetyl was found to be associated with a disease that became known as “popcorn lung.” There has been limited research on flavoring chemicals in e-cigarettes.Objective:We aimed to determine if the flavoring chemical diacetyl and two other high-priority flavoring chemicals, 2,3-pentanedione and acetoin, are present in a convenience sample of flavored e-cigarettes.Methods:We selected 51 types of flavored e-cigarettes sold by leading e-cigarette brands and flavors we deemed were appealing to youth. E-cigarette contents were fully discharged and the air stream was captured and analyzed for total mass of diacetyl, 2,3-pentanedione, and acetoin, according to OSHA method 1012.Results:At least one flavoring chemical was detected in 47 of 51 unique flavors tested. Diacetyl was detected above the laboratory limit of detection in 39 of the 51 flavors tested, ranging from below the limit of quantification to 239 μg/e-cigarette. 2,3-Pentanedione and acetoin were detected in 23 and 46 of the 51 flavors tested at concentrations up to 64 and 529 μg/e-cigarette, respectively.Conclusion:Because of the associations between diacetyl and bronchiolitis obliterans and other severe respiratory diseases observed in workers, urgent action is recommended to further evaluate this potentially widespread exposure via flavored e-cigarettes.Citation:Allen JG, Flanigan SS, LeBlanc M, Vallarino J, MacNaughton P, Stewart JH, Christiani DC. 2016. Flavoring chemicals in e-cigarettes: diacetyl, 2,3-pentanedione, and acetoin in a sample of 51 products, including fruit-, candy-, and cocktail-flavored e-cigarettes. Environ Health Perspect 124:733–739; http://dx.doi.org/10.1289/ehp.1510185

Accumulation of Ubiquitin and Sequestosome-1 Implicate Protein Damage in Diacetyl-Induced Cytotoxicity

“…72 Because our study demonstrates that diacetyl alters proteostasis and cigarette smoke contains diacetyl, 74,75 the results suggest that diacetyl may play a role in chronic obstructive pulmonary disease in addition to its role in flavorings-related lung disease. 11,12 In addition, during autophagy, SQSTM1 is phosphorylated, a process that activates the Kelch-like ECHassociated protein 1 (Keap1)enuclear factor E2erelated factor 2 (Nrf2) pathway. 62 Thus, our finding of SQSTM1 accumulation and autophagy may explain the recently described nuclear accumulation of NRF2 in the transitional and respiratory epithelium of the nose of diacetyl-exposed rats.…”

“…Additional high-concentration diacetyl inhalation exposures occur in traditional cigarette smokers and e-cigarette vapers. 11,12 Diacetyl is a four-carbon compound with adjacent carbonyl carbons, putting it into a class of compounds known as a-dicarbonyl compounds. The adjacent carbonyl groups tend to increase the chemical reactivity of a-dicarbonyl compounds.…”

Electronic Cigarette (E-Cigarette) Using: Toxicological Aspects

“…At the beginning of the year 2000, diacetyl was associated with a disease named "Popcorn Lung". The amount of diacetyl, 2,3-pentanedione, and acetone, which are the most commonly used flavoring substances, was tried to be determined in a study conducted by Allen et al (50) in 51 e-cigarette cartridges with fruit, sugar, and cocktail flavors that are sold in markets. While the diacetyl limit of quantification (LOQ) value was found to be 239 μg/e-cigarette, LOQ for 2,3-pentanedione and acetone were found as 64 and 529 μg/e-cigarette.…”

Electronic cigarettes and lung toxicity

“…In addition, the flavoring chemicals in e-cigarettes, especially sweet or cinnamon e-liquid, can contain diacetyl, a compound linked to respiratory injury. 9 The long term effects of exposure are unknown, and documented acute adverse effects on the lungs from e-liquid exposure have been limited to infrequent case reports and abstracts (Table). Three individual case reports have described a temporal association between subacute bronchiolitis, pleuritic chest pain with associated bilateral pleural effusions, and acute hypersensitivity pneumonitis with the use of e-cigarettes.…”