Formation of flavorant-propylene Glycol Adducts With Novel Toxicological Properties in Chemically Unstable E-Cigarette Liquids
Formation of flavorant-propylene Glycol Adducts With Novel Toxicological Properties in Chemically Unstable E-Cigarette Liquids
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DOI：
10.1093/ntr/nty192
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发表时间：
2019-09-01
影响因子：
4.7
通讯作者：
Zimmerman, Julie B.
中科院分区：
文献类型：
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作者：
Erythropel, Hanno C.;Jabba, Sairam V.;Zimmerman, Julie B.
导读：“电子烟”越来越受到年轻人的欢迎，这是由于可选择的口味种类繁多，通常使用香精醛制成。这项研究的目的是研究香精醛在电子烟液体中是否保持稳定，或者它们是否会发生化学反应，形成可能对使用者造成伤害的新化学物质。方法：采用气相色谱法测定商业电子烟产生的电子烟液和蒸汽中风味醛和反应产物的浓度。通过紫外光谱和核磁共振光谱检测反应产物在水介质中的稳定性，并通过荧光钙成像检测其对HEK-293T细胞中刺激受体的影响。结果：苯甲醛、肉桂醛、柠檬醛、乙基香兰素、香兰素等香精醛与烟油溶剂丙二醇（PG）混合后快速反应，40%以上的香精醛含量转化为香精醛PG缩醛，在商品烟油中也有检测到。电子烟实验表明，缩醛在电子烟蒸气中的残留率为50%-80%。缩醛在生理水溶液中保持稳定，半衰期超过36小时，表明使用者吸入后缩醛会持续存在。缩醛激活醛敏感的TRPA1刺激受体和醛不敏感的TRPV1刺激受体。结论：电子烟油是一种潜在的反应性化学系统，在混合成分和储存过程中可以形成新的化合物，如香精醛PG缩醛，具有意想不到的毒理学效应。出于监管目的，建议采用严格的程序来监测电子液体和电子蒸气的成分随时间的变化，以确定可能的健康危害。
Introduction: "Vaping" electronic cigarettes (e-cigarettes) is increasingly popular with youth, driven by the wide range of available flavors, often created using flavor aldehydes.The objective of this study was to examine whether flavor aldehydes remain stable in e-cigarette liquids or whether they undergo chemical reactions, forming novel chemical species that may cause harm to the user.Methods: Gas chromatography was used to determine concentrations of flavor aldehydes and reaction products in e-liquids and vapor generated from a commercial e-cigarette. Stability of the detected reaction products in aqueous media was monitored by ultraviolet spectroscopy and nuclear magnetic resonance spectroscopy, and their effects on irritant receptors determined by fluorescent calcium imaging in HEK-293T cells.Results: Flavor aldehydes including benzaldehyde, cinnamaldehyde, citral, ethylvanillin, and vanillin rapidly reacted with the e-liquid solvent propylene glycol (PG) after mixing, and upward of 40% of flavor aldehyde content was converted to flavor aldehyde PG acetals, which were also detected in commercial e-liquids. Vaping experiments showed carryover rates of 50%-80% of acetals to e-cigarette vapor. Acetals remained stable in physiological aqueous solution, with half-lives above 36 hours, suggesting they persist when inhaled by the user. Acetals activated aldehyde-sensitive TRPA1 irritant receptors and aldehyde-insensitive TRPV1 irritant receptors.Conclusions: E-liquids are potentially reactive chemical systems in which new compounds can form after mixing of constituents and during storage, as demonstrated here for flavor aldehyde PG acetals, with unexpected toxicological effects. For regulatory purposes, a rigorous process is advised to monitor the potentially changing composition of e-liquids and e-vapors over time, to identify possible health hazards.