# Carbonyl Composition and Electrophilicity in Vaping Emissions of Flavored and Unflavored E-Liquids
###### Abstract  
It has been demonstrated that propylene glycol (PG), vegetable glycerin (VG), and flavoring chemicals can thermally degrade to form carbonyls during vaping, but less is known about carbonyl emissions produced by transformation of flavoring chemicals and the interactive effects among e-liquid constituents. This study characterized carbonyl composition and levels in vaping emissions of PG-VG (e-liquid base solvents) and four e-liquid formulations flavored with _trans_-2-hexenol, benzyl alcohol, l-(-)-menthol, or linalool. Utilizing gas chromatography (GC)- and liquid chromatography (LC)-mass spectrometry (MS) methods, 14 carbonyls were identified and quantified. PG-VG emitted highest levels of formaldehyde, acetaldehyde, and acrolein. However, flavored e-luquids contributed to the production of a wider variety of carbonyls, with some carbonyls directly corresponding to the oxidation of alcohol moieties in flavoring compounds (e.g., _trans_-2-hexenol and benzyl alcohol transformed into _trans_-2-hexenal and benzaldehyde, respectively). Detections of formaldehyde-GSH and _trans_-2-hexenal-GSH adducts signify interactions of carbonyls with biological nucleotides. The global reactivity descriptors (_I_, \(A\), \(u\), _eta_, and _o_) and condensed Fukui parameters (\(V_{k}^{0}\), \(f_{k}^{-}\), \(f_{k}^{+}\), and dual-descriptor) were computed to elucidate site reactivities of selected simple and \(\alpha\),\(\beta\)-unsaturated carbonyls found in vaping emissions. Overall, this study highlights carbonyl emissions and reactivities and their potential health risk effects associated with vaping. carboyl emissions; alcohol-containing flavoring chemicals; propylene glycol; vegetable glycerin; _trans_-2-hexenol; benzyl alcohol; l-(-)-menthol; linalool; global electrophilicity; condensed Fukui parameters 27 October 2021  
6 December 2021  
aerosols has been found to cause cytotoxicity [7], to suppress immune functions of respiratory tract cells [8], and to disrupt mitochondrial function of human bronchial epithelial cells [9]. Degradation of e-liquid constituents, such as PG, VG, and flavoring chemicals, can produce reactive compounds in vaping emissions. Studies have demonstrated that thermal decomposition of PG, VG, and flavoring chemicals can release reactive carbonyl species, including formaldehyde, acetaldehyde, acrolein, and propionaldehyde [10; 11; 12; 13]. Among commonly reported carbonyls, formaldehyde is a known human carcinogen that can cause a wide range of health implications, such as irritations and pharyngeal cancer, through inhalation exposure [14]. Carbonyls are reactive electrophiles that can form adducts with biological nucleophiles, such as glutathione (GSH) [15], protein residues [16; 17], and DNA [18; 19]. For example, as an \(\alpha\),\(\beta\)-unsaturated carbonyl, acrolein can covalently modify proteins by forming adducts with the cysteine residue via Michael addition and Schiff base formation, as well as other nucleophilic side chains (e.g., the histidine and lysine residues) and free amino terminus of proteins [20]. Reactions of carbonyls toward cellular nucleophiles can result in a wide range of adverse health effects, including oxidative DNA breakage [21], formation of protein adducts [22], decrease or loss of protein functions [23], and eventually pathogenesis. Exposure to exogenous carbonyls from cigarette smoke has been linked to DNA adduct formation and carcinogenesis [24]. [PERSON] et al. [25] detected an elevated level of formaldehyde-DNA adduct (N6-hydroxymethyldeoxyadenosine) in human leukocytes of smokers compared to nonsmokers, indicating that formaldehyde is a contributing factor of smoking-induced cancer. To model reactivity and toxicity of various carbonyls associated with vaping, computational chemistry methods, such as density functional theory and condensed Fukui functions, have been used to study global electrophilicity [26] and chemical reactivity at specific sites within a molecule [27; 28]. [PERSON] et al.