Department of Environmental Health, Center for Nanotechnology and Nanotoxicology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts 02115, USA.
Department of Environmental and Population Health Bio-Sciences, Environmental Occupational Health Sciences Institute, School of Public Health, Rutgers University, Piscataway, New Jersey 08854, USA.
Toxicol Sci. 2022 May 26;187(2):279-297. doi: 10.1093/toxsci/kfac047.
The 2019 United States outbreak of E-cigarette (e-cig), or Vaping, Associated Acute Lung Injury (EVALI) has been linked to presence of vitamin E acetate (VEA) in Δ8tetrahydrocannabinol (Δ8THC)-containing e-liquids, as supported by VEA detection in patient biological samples. However, the pathogenesis of EVALI and the complex physicochemical properties of e-cig emissions remain unclear, raising concerns on health risks of vaping. This study investigates the effect of Δ8THC/VEA e-liquids and e-cig operational voltage on in vitro toxicity of e-cig aerosols. A novel E-cigExposure Generation System platform was used to generate and characterize e-cig aerosols from a panel of Δ8THC/VEA or nicotine-based e-liquids at 3.7 or 5 V. Human lung Calu-3 cells and THP-1 monocytes were exposed to cell culture media conditioned with collected e-cig aerosol condensate at doses of 85 and 257 puffs/m2 lung surface for 24 h, whereafter specific toxicological endpoints were assessed (including cytotoxicity, metabolic activity, reactive oxygen species generation, apoptosis, and inflammatory cytokines). Higher concentrations of gaseous volatile organic compounds were emitted from Δ8THC/VEA compared with nicotine-based e-liquids, especially at 5 V. Emitted PM2.5 concentrations in aerosol were higher for Δ8THC/VEA at 5 V and averagely for nicotine-based e-liquids at 3.7 V. Overall, aerosols from nicotine-based e-liquids showed higher bioactivity than Δ8THC/VEA aerosols in THP-1 cells, with no apparent differences in Calu-3 cells. Importantly, presence of VEA in Δ8THC and menthol flavoring in nicotine-based e-liquids increased cytotoxicity of aerosols across both cell lines, especially at 5 V. This study systematically investigates the physicochemical and toxicological properties of a model of Δ8THC/VEA and nicotine e-cigarette condensate exposure demonstrating that pyrolysis of these mixtures can generate hazardous toxicants whose synergistic actions potentially drive acute lung injury upon inhalation.
2019 年美国电子烟（e-cig）或蒸气相关的急性肺损伤（EVALI）爆发与含有 Δ8-四氢大麻酚（Δ8-THC）的电子烟液中存在维生素 E 醋酸酯（VEA）有关，这一点得到了患者生物样本中 VEA 检测的支持。然而，EVALI 的发病机制和电子烟排放的复杂物理化学性质仍不清楚，这引起了人们对蒸气健康风险的关注。本研究调查了 Δ8-THC/VEA 电子烟液和电子烟工作电压对电子烟气溶胶体外毒性的影响。使用新型电子烟暴露产生系统平台，从一组 Δ8-THC/VEA 或尼古丁电子烟液中产生并表征电子烟气溶胶，工作电压分别为 3.7 或 5 V。人肺 Calu-3 细胞和 THP-1 单核细胞暴露于收集的电子烟气溶胶冷凝物中，在 85 和 257 口/平方米肺表面剂量下培养 24 小时，然后评估特定的毒理学终点（包括细胞毒性、代谢活性、活性氧生成、细胞凋亡和炎症细胞因子）。与基于尼古丁的电子烟液相比，Δ8-THC/VEA 电子烟液释放的气态挥发性有机化合物浓度更高，尤其是在 5 V 时。在 5 V 时，Δ8-THC/VEA 气溶胶中 PM2.5 浓度更高，而在 3.7 V 时，基于尼古丁的电子烟液中 PM2.5 浓度平均更高。总体而言，基于尼古丁的电子烟液气溶胶在 THP-1 细胞中的生物活性高于 Δ8-THC/VEA 气溶胶，而在 Calu-3 细胞中则没有明显差异。重要的是，Δ8-THC 中的 VEA 和尼古丁电子烟液中的薄荷醇调味剂增加了两种细胞系中气溶胶的细胞毒性，尤其是在 5 V 时。本研究系统地调查了 Δ8-THC/VEA 和尼古丁电子烟冷凝物暴露的模型的物理化学和毒理学特性，证明这些混合物的热解可以产生有害的有毒物质，这些物质的协同作用可能会在吸入时导致急性肺损伤。
