Cultex Laboratories GmbH, Feodor-Lynen-Straße 21, 30625 Hannover, Germany.
Biomed Res Int. 2013;2013:734137. doi: 10.1155/2013/734137. Epub 2013 Feb 7.
The EU Regulation on Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) demands the implementation of alternative methods for analyzing the hazardous effects of chemicals including particulate formulations. In the field of inhalation toxicology, a variety of in vitro models have been developed for such studies. To simulate the in vivo situation, an adequate exposure device is necessary for the direct exposure of cultivated lung cells at the air-liquid interface (ALI). The CULTEX RFS fulfills these requirements and has been optimized for the exposure of cells to atomized suspensions, gases, and volatile compounds as well as micro- and nanosized particles. This study provides information on the construction and functional aspects of the exposure device. By using the Computational Fluid Dynamics (CFD) analysis, the technical design was optimized to realize a stable, reproducible, and homogeneous deposition of particles. The efficiency of the exposure procedure is demonstrated by exposing A549 cells dose dependently to lactose monohydrate, copper(II) sulfate, copper(II) oxide, and micro- and nanoparticles. All copper compounds induced cytotoxic effects, most pronounced for soluble copper(II) sulfate. Micro- and nanosized copper(II) oxide also showed a dose-dependent decrease in the cell viability, whereby the nanosized particles decreased the metabolic activity of the cells more severely.
欧盟关于化学品注册、评估、授权和限制的法规(REACH)要求替代方法来分析化学品的危险效应,包括颗粒制剂。在吸入毒理学领域,已经开发出各种体外模型来进行此类研究。为了模拟体内情况,对于在气液界面(ALI)直接暴露于培养的肺细胞,需要一个合适的暴露装置。CULTEX RFS 满足这些要求,并已针对雾化悬浮液、气体和挥发性化合物以及微纳米颗粒的暴露进行了优化。本研究提供了有关暴露装置结构和功能方面的信息。通过使用计算流体动力学(CFD)分析,对技术设计进行了优化,以实现稳定、可重复和均匀的颗粒沉积。通过以剂量依赖的方式将 A549 细胞暴露于一水乳糖、硫酸铜、氧化铜和微纳米颗粒,证明了暴露程序的效率。所有铜化合物都诱导了细胞毒性作用,可溶性硫酸铜最为明显。微纳米氧化铜也表现出细胞活力的剂量依赖性下降,其中纳米颗粒更严重地降低了细胞的代谢活性。