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首页> 外文期刊>Applied in vitro toxicology. >Establishment of a Human 3D Tissue-Based Assay for Upper Respiratory Tract Absorption
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Establishment of a Human 3D Tissue-Based Assay for Upper Respiratory Tract Absorption

机译：建立一个人类3 d组织分析上呼吸道吸收

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摘要

Regulatory human health risk assessment of chemicals ideally requires integration of toxicokinetic absorption, distribution, metabolism, and excretion where the respiratory system is a principal exposure route and threshold site for absorption. This study evaluated the permeability capacity of an in vitro human airway epithelium cell model (MucilAir?). Initially, definition of the in vitro method, including development of standard operating procedure confirmation of transferability and assurance of reproducible performance, was established in a preliminary phase involving two independent laboratories using six chemicals (propranolol, atenolol, nicotine, cadmium dichloride, cobalt chloride, and ammonium hexachloroplatinate). A follow-up investigation of method relevance, measuring relative permeability of 30 chemicals, in 1 laboratory is also reported. Absorption through the lung barrier model was determined as apparent permeability coefficient (Papp) following apical and basolateral exposure to nontoxic concentrations. Papp was calculated from chemical concentrations crossing the cell barrier at appropriate time intervals. Comparative permeability of nasal and bronchial epithelium is also reported. Overall, the results demonstrate that MucilAir is an effective barrier model for assessing the permeability of different classes of compounds across the human airway epithelium. Results indicate a generally higher permeability of the airway epithelium for organic compounds compared to inorganic chemicals, with a low-protein-mediated efflux as permeability mechanism. The in vitro test system provides a robust and transferable method for determination of pulmonary absorption, relevant to toxicokinetic modeling and integration into risk assessment of chemicals.
机译：监管的人类健康风险评估化学物质理想需要集成毒性动力学吸收,分布,呼吸代谢和排泄系统是一个主要暴露途径和阈值网站吸收。评估的渗透能力体外人工气道上皮细胞模型(MucilAir吗?)体外方法,包括标准的发展操作程序的确认可转移性和可再生的保证性能,初步建立了阶段包括两个独立的实验室使用六个化学品(普萘洛尔、阿替洛尔尼古丁、二氯化镉,氯化钴,和hexachloroplatinate铵)。相关性的调查方法,测量相对渗透率30的化学物质,在1实验室也报道。肺屏障模型被确定为明显渗透系数(Papp)顶端基底和无毒浓度。浓度穿越细胞屏障适当的时间间隔。鼻的渗透性和支气管上皮细胞也报道。, MucilAir模型是一种有效的屏障评估不同类别的渗透性化合物的人工气道上皮细胞。结果表明普遍较高的渗透率气道上皮的有机化合物相比,无机化学,low-protein-mediated流出的渗透率机制。健壮和可转让的方法测定肺吸收有关毒性动力学建模和集成到风险评估化学物质。

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