Increased Levels of the Acrolein Metabolite 3-Hydroxypropyl Mercapturic Acid in the Urine of e-Cigarette Users

Abstract

Carcinogen and toxicant uptake by e-cigarette users have not been fully evaluated. In the study reported here, we recruited 30 e-cigarette users, 63 nonsmokers, and 33 cigarette smokers who gave monthly urine samples over a period of 4–6 months. Their product use status was confirmed by measurements of exhaled CO, urinary total nicotine equivalents, cyanoethyl mercapturic acid (CEMA), and total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol. Urinary biomarkers of exposure to the carcinogens acrolein (3-hydroxypropyl mercapturic acid, 3-HPMA), benzene (S-phenyl mercapturic acid, SPMA), acrylonitrile (CEMA), and a combination of crotonaldehyde, methyl vinyl ketone, and methacrolein (3-hydroxy-1-methylpropyl mercapturic acid, HMPMA) were quantified at each visit. Data from subject visits with CEMA > 27 pmol/mL were excluded from the statistical analysis of the results because of possible unreported exposures to volatile combustion products such as secondhand cigarette smoke or marijuana smoke exposure; this left 22 e-cigarette users with 4 or more monthly visits and all 63 nonsmokers. Geometric mean levels of 3-HPMA (1249 versus 679.3 pmol/mL urine) were significantly higher (P = 0.003) in e-cigarette users than in nonsmokers, whereas levels of SPMA, CEMA, and HMPMA did not differ between these two groups. All analytes were significantly higher in cigarette smokers than in either e-cigarette users or nonsmokers. The results of this unique multimonth longitudinal study demonstrate consistent significantly higher uptake of the carcinogen acrolein in e-cigarette users versus nonsmokers, presenting a warning signal regarding e-cigarette use.

The Tobacco Smoke Component, Acrolein, as a Major Culprit in Lung Diseases and Respiratory Cancers: Molecular Mechanisms of Acrolein Cytotoxic Activity

“…Undoubtedly, however, electronic smoking devices pose a serious threat to global health and are one of the current public health problems; it is growing at an accelerating pace and has become a public health emergency [ 41 , 42 ]. E-cigarette manufacturers convince consumers that electric smoking devices pose a lower health risk by reducing carcinogenic and harmful substances, however, the latest research indicates otherwise [ 41 , 42 , 43 , 44 ]. Heating the products in electronic cigarettes produces condensed carcinogenic hydrocarbons and products toxic to the human body.…”

“…At the same time, however, it is worth noting that the observed level of the 3HPMA metabolite in the urine of electronic cigarette users was still very high, significantly higher than in the case of non-smokers. Although e-cigarettes are likely to be less carcinogenic than tobacco cigarettes, the study results indicate that e-cigarette users have an increased risk of exposure to acrolein compared to non-smokers and are still exposed to its harmful effects [ 41 , 43 , 54 ]. In addition, Cheng et al [ 44 ], in studies using buccal cells isolated from e-cigarette smokers, clearly indicate a significant increase in the level of a carcinogen acrolein-DNA adduct 8R/S-3-(2′-deoxyribos-1′-yl)-5,6,7,8-tetrahydro-8-hydroxypyrimido [1,2-a]purine-10-(3H)-one (γ-OH-Acr-dGuo) compared to non-smokers.…”

Furan Metabolites Are Elevated in Users of Various Tobacco Products and Cannabis

“…Previous studies have reported that cannabis smokers have elevated urinary biomarker levels for other combustion products such as polycyclic aromatic hydrocarbons and acrylamide . The elevated levels of metabolites 2 and 3 in e-cigarette users contrasts to what has been reported for other volatile organic chemicals such as benzene and acrylonitrile in which e-cigarette users tend to have levels comparable to those of nonsmokers . Acrolein biomarkers, on the other hand, are elevated in exclusive e-cigarette users. , …”

“…41 The elevated levels of metabolites 2 and 3 in ecigarette users contrasts to what has been reported for other volatile organic chemicals such as benzene and acrylonitrile in which e-cigarette users tend to have levels comparable to those of nonsmokers. 42 Acrolein biomarkers, on the other hand, are elevated in exclusive e-cigarette users. 42,43 Since these metabolites are derived from the toxic metabolite of furan, BDA, they are also biomarkers of potential harm.…”

“…42 Acrolein biomarkers, on the other hand, are elevated in exclusive e-cigarette users. 42,43 Since these metabolites are derived from the toxic metabolite of furan, BDA, they are also biomarkers of potential harm. Furan is a rodent liver toxicant and carcinogen as well as a lung toxicant.…”