Office of Science, Center for Tobacco Products, U.S. Food and Drug Administration, Silver Spring, Maryland 20993, United States.
Chem Res Toxicol. 2024 Aug 19;37(8):1315-1328. doi: 10.1021/acs.chemrestox.4c00073. Epub 2024 Jul 30.
Nicotine salt-based e-liquids deliver nicotine more rapidly and efficiently to electronic nicotine delivery system (ENDS) users than freebase nicotine formulations. Nicotine salt-based products represent a substantial majority of the United States ENDS market. Despite the popularity of nicotine salt formulations, the chemical and physical characteristics of aerosols produced by nicotine salt e-liquids are still not well understood. To address this, this study reports the harmful and potentially harmful constituents (HPHCs) and particle sizes of aerosols produced by laboratory-made freebase nicotine and nicotine salt e-liquids. The nicotine salt e-liquids were formulated with benzoic acid, citric acid, lactic acid, malic acid, or oxalic acid. The nicotine salt aerosols had different HPHC profiles than the freebase nicotine aerosols, indicating that the carboxylic acids were not innocent bystanders. The polycarboxylic acid e-liquids containing citric acid, malic acid, or oxalic acid produced higher acrolein yields than the monocarboxylic acid e-liquids containing benzoic acid or lactic acid. Across most PG:VG ratios, nicotine benzoate or nicotine lactate aerosols contained the highest nicotine quantities (in %) and the highest nicotine yields (per milligram of aerosol). Additionally, the nicotine benzoate and nicotine lactate e-liquids produced the highest carboxylic acid yields under all tested conditions. The lower acid yields of the citric, malic, and oxalic acid formulations are potentially due to a combination of factors such as lower transfer efficiencies, lower thermostabilities, and greater susceptibility to side reactions because of their additional carboxyl groups serving as new sites for reactivity. For all nicotine formulations, the particle size characteristics were primarily controlled by the e-liquid solvent ratios, and there were no clear trends between nicotine salt and freebase nicotine aerosols that indicated nicotine protonation affected particle size. The carboxylic acids impacted aerosol output, nicotine delivery, and HPHC yields in distinct ways such that interchanging them in ENDS can potentially cause downstream effects.
基于尼古丁盐的电子烟液比游离碱尼古丁配方更能快速有效地将尼古丁传递给电子烟使用者。基于尼古丁盐的产品代表了美国电子烟市场的绝大部分。尽管尼古丁盐配方很受欢迎，但尼古丁盐电子烟液产生的气溶胶的化学和物理特性仍未得到很好的理解。为了解决这个问题，本研究报告了实验室制造的游离碱尼古丁和尼古丁盐电子烟液产生的气溶胶的有害和潜在有害成分（HPHC）和颗粒大小。尼古丁盐电子烟液由苯甲酸、柠檬酸、乳酸、苹果酸或草酸制成。尼古丁盐气溶胶的 HPHC 谱与游离碱尼古丁气溶胶不同，这表明羧酸不是无辜的旁观者。含有柠檬酸、苹果酸或草酸的多羧酸电子烟液比含有苯甲酸或乳酸的单羧酸电子烟液产生更高的丙烯醛产量。在大多数 PG:VG 比例下，尼古丁苯甲酸酯或尼古丁乳酸酯气溶胶含有最高的尼古丁量（以%计）和最高的尼古丁产率（每毫克气溶胶）。此外，在所有测试条件下，尼古丁苯甲酸酯和尼古丁乳酸酯电子烟液产生的羧酸产量最高。柠檬酸、苹果酸和草酸配方的酸产量较低，可能是由于多种因素的综合作用，例如较低的转移效率、较低的热稳定性以及由于额外的羧基基团成为新的反应性位点而更容易发生副反应。对于所有尼古丁配方，颗粒大小特征主要由电子烟液溶剂比控制，并且在尼古丁盐和游离碱尼古丁气溶胶之间没有明显的趋势表明尼古丁质子化会影响颗粒大小。羧酸以不同的方式影响气溶胶输出、尼古丁输送和 HPHC 产率，因此在电子烟中互换它们可能会产生下游影响。
