Abstract：
Electronic cigarettes (ECs) are purported to be tobacco harm-reduction products whose degree of harm has been highly debated. EC use is considered less hazardous than smoking but is not expected to be harmless. Following the banning of e-liquid flavors in countries such as the US, Finland, Ukraine, and Hungary, there are growing concerns regarding the safety profile of e-liquid flavors used in ECs. While these are employed extensively in the food industry and are generally regarded as safe (GRAS) when ingested, GRAS status after inhalation is unclear. The aim of this review was to assess evidence from 38 reports on the adverse effects of flavored e-liquids on the respiratory system in both in vitro and in vivo studies published between 2006 and 2021. Data collected demonstrated greater detrimental effects in vitro with cinnamon (9 articles), strawberry (5 articles), and menthol (10 articles), flavors than other flavors. The most reported effects among these investigations were perturbations of pro-inflammatory biomarkers and enhanced cytotoxicity. There is sufficient evidence to support the toxicological impacts of diacetyl- and cinnamaldehyde-containing e-liquids following human inhalation; however, safety profiles on other flavors are elusive. The latter may result from inconsistencies between experimental approaches and uncertainties due to the contributions from other e-liquid constituents. Further, the relevance of the concentration ranges to human exposure levels is uncertain. Evidence indicates that an adequately controlled and consistent, systematic toxicological investigation of a broad spectrum of e-liquid flavors may be required at biologically relevant concentrations to better inform public health authorities on the risk assessment following exposure to EC flavor ingredients.
摘要：
电子烟（EC）据称是烟草减害产品，其危害程度已引起高度争议。使用EC被认为比吸烟危害小，但预计不会无害。在美国等国家禁止电子液体口味之后，芬兰,乌克兰,匈牙利,越来越多的人担心ECs中使用的电子液体香料的安全性。虽然这些在食品工业中被广泛使用，并且在摄入时通常被认为是安全的（GRAS），吸入后的GRAS状态尚不清楚。这篇综述的目的是评估2006年至2021年间发表的38份关于调味电子液体对呼吸系统的不利影响的报告的证据。收集的数据显示肉桂在体外具有更大的有害作用（9篇文章），草莓(5篇),和薄荷醇(10篇文章)，口味比其他口味。这些研究中报道最多的效果是促炎生物标志物的扰动和增强的细胞毒性。有足够的证据支持人体吸入后含有二乙酰和肉桂醛的电子液体的毒理学影响；然而，其他口味的安全性难以捉摸。后者可能是由于实验方法之间的不一致以及由于其他电子液体成分的贡献而导致的不确定性。Further,浓度范围与人体暴露水平的相关性尚不确定.证据表明，一个充分控制和一致的，可能需要对生物相关浓度下的广谱电子液体香料进行系统的毒理学调查,以便更好地告知公共卫生当局暴露于EC香料成分后的风险评估.
