Electronic cigarette-generated aldehydes: The contribution of e-liquid components to their formation and the use of urinary aldehyde metabolites as biomarkers of exposure

Abstract

Electronic cigarettes (e-cigarette) have emerged as a popular electronic nicotine delivery system (ENDS) in the last decade. Despite the absence of combustion products and toxins such as carbon monoxide (CO) and tobacco-specific nitrosamines (TSNA), carbonyls including short-chain, toxic aldehydes have been detected in e-cigarette-derived aerosols up to levels found in tobacco smoke. Given the health concerns regarding exposures to toxic aldehydes, understanding both aldehyde generation in e-cigarette and e-cigarette exposure is critical. Thus, we measured aldehydes generated in aerosols derived from propylene glycol (PG):vegetable glycerin (VG) mixtures and from commercial e-liquids with flavorants using a state-of-the-art carbonyl trap and mass spectrometry. To track e-cigarette exposure in mice, we measured urinary metabolites of 4 aldehydes using ULPC-MS/MS or GC-MS. Aldehyde levels, regardless of abundance (saturated: formaldehyde, acetaldehyde >> unsaturated: acrolein, crotonaldehyde), were dependent on the PG:VG ratio and the presence of flavorants. The metabolites of 3 aldehydes - formate, acetate and 3-hydroxypropyl mercapturic acid (3-HPMA; acrolein metabolite) -- were increased in urine after e-cigarette aerosol and mainstream cigarette smoke (MCS) exposures, but the crotonaldehyde metabolite (3-hydroxy-1-methylpropylmercapturic acid, HPMMA) was increased only after MCS exposure. Interestingly, exposure to menthol-flavored e-cigarette aerosol increased the levels of urinary 3-HPMA and sum of nicotine exposure (nicotine, cotinine, trans-3’-hydroxycotinine) relative to exposure to a Classic Tobacco-flavored e-cigarette aerosol. Comparing these findings with aerosols of other ENDS and by measuring aldehyde-derived metabolites in human urine following exposure to e-cigarette aerosols will further our understanding of the relationship between ENDS use, aldehyde exposure and health risk.

Comparison of Systemic Exposure to Toxic and/or Carcinogenic Volatile Organic Compounds (VOC) during Vaping, Smoking, and Abstention

“…We found no evidence of significant differences in exposure to the other VOCs, including acrolein, across device types. This observation regarding acrolein was surprising because vaping machine studies have reported substantial acrolein generation from e-cigarettes, particularly at higher power settings (38)(39)(40). However, it is possible that background exposure to acrolein, primarily from food sources through thermal breakdown of animal and vegetable fats, carbohydrates, and amino acids, or even endogenous production of acrolein (41), could overwhelm the contribution of e-cigarettes to acrolein exposure.…”

A 6-month inhalation toxicology study in Apoe−/− mice demonstrates substantially lower effects of e-vapor aerosol compared with cigarette smoke in the respiratory tract

“…Other studies have reported that e-cigarette devices could generate carbonyl compounds, thus increasing pulmonary oxidative stress and inflammation (Cirillo et al 2019 ; Ong et al 2012 ). Carbonyl levels are device specific, depending on the puffing regimen or device setup (Margham et al 2016 ; Thomson and Lewis 2015 ) the applied voltage and temperature of the heater coil (El-Hellani et al 2018 ; Gillman et al 2016 ; Kosmider et al 2014 ; Sleiman et al 2016 ), and the chemical composition of the liquids in the e-cigarette devices (Conklin et al 2018 ). In CS, carbonyls are generated during pyrolysis, combustion and distillation of the tobacco smoke product, which reaches temperatures up to 900℃ (Baker et al 2004 ).…”

Acetaldehyde Induces an Endothelium-Dependent Relaxation of Superior Mesenteric Artery: Potential Role in Postprandial Hyperemia

“…As acetate is the primary urinary metabolite of AA, it was measured by GC-MS in electron ionization (EI) mode as described previously (Kage et al, 2004; Lamarre et al, 2014) with modifications (Conklin et al, 2018). Briefly, urine (50 μL) was mixed with sodium phosphate (20 μL 0.5M, pH 8.0) containing an internal standard ( 13 C 1 D 3 -acetate, 2.3 mM).…”