An approach to testing undiluted e-cigarette aerosol in vitro using 3D reconstituted human airway epithelium
An approach to testing undiluted e-cigarette aerosol in vitro using 3D reconstituted human airway epithelium
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DOI：
10.1016/j.tiv.2018.01.010
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发表时间：
2019-02-01
影响因子：
3.2
通讯作者：
Gaca, M.
中科院分区：
文献类型：
--
作者：
Bishop, E.;Haswell, L.;Gaca, M.
这里提供的数据表明，为了提供相对细胞毒性的估计，因此可以使用未稀释的气溶胶技术。随着电子尼古丁输送系统的出现，需要适合目的的体外筛选方法。使用Vitrocell VC 10，将重构的3D人体气道上皮暴露于气液界面处的未稀释气溶胶。评估TEER、纤毛搏动频率和细胞毒性反应。使用两种吸烟方案（ISO和HCI），3R 4F参考香烟分别产生5.2和2.1 min的IC（50）s，1458 ng/mL和1640 ng/mL尼古丁。使用开罐电子烟装置，获得完整的细胞毒性剂量-响应曲线，其给出30分钟的IC 50，相应的尼古丁为10，957 ng/mL，比香烟烟雾的细胞毒性小6-14倍。将常用的电子液体香料肉桂醛和已知的皮肤致敏剂添加到标准电子液体制剂中，并用作雾化的阳性对照，分别以0.1、0.025、0.02在体外递送未稀释的气溶胶导致方法灵敏度、通量和定量电子烟比较增加。从“安全”电子液体基准生成的阳性对照气雾剂可以为可支持的风味成分水平的风险评估提供信息。
The data presented here show that to provide an estimate of the relative cytotoxicity and therefore potency of e-cigarettes, undiluted aerosol techniques can be used. With the emergence of electronic nicotine delivery systems, fit-for-purpose in vitro screening methods are required.Reconstituted 3D human airway epithelium, was exposed to undiluted aerosols at the air-liquid interface, using a Vitrocell VC 10. TEER, cilia beat frequency and cytotoxic responses were assessed. Using two smoking regimes (ISO and HCI) a 3R4F reference cigarette, produced IC(50)s of 5.2 and 2.1 min, 1458 ng/mL and 1640 ng/mL nicotine respectively. Using an open tank e-cigarette device, a full cytotoxicity dose-response curve was obtained giving an IC50 of 30 min with corresponding nicotine of 10,957 ng/mL, 6-14 times less cytotoxic than cigarette smoke.A commonly used e-liquid flavourant cinnamaldehyde and known skin sensitizer was added to the standard e-liquid formulation and used as an aerosolised positive control, at 0.1, 0.025, 0.01 and 0%, demonstrating a full dose response.The delivery of undiluted aerosols in vitro has resulted in increased method sensitivity, throughput and quantitative e-cigarette comparisons. A positive control aerosol generated from a 'safe' e-liquid benchmark can inform risk assessments on supportable levels of flavour ingredients.