Bakand Shahnaz, Hayes Amanda
Chemical Safety and Applied Toxicology Laboratories, School of Risk and Safety Sciences, The University of New South Wales, UNSW, Sydney, 2052, Australia.
J Pharmacol Toxicol Methods. 2010 Mar-Apr;61(2):76-85. doi: 10.1016/j.vascn.2010.01.010. Epub 2010 Feb 1.
Toxicology studies of adverse effects induced by inhaled chemicals are technically challenging, due to the requirement of highly controlled experimental conditions needed to achieve reproducible and comparable results. Therefore, many considerations must be fulfilled before adopting in vitro bioassay test systems for toxicity screening of airborne materials. However, recent methodological and technical breakthroughs of in vitro methods have the potential to fulfil the essential requirements of toxicity testing for airborne chemicals. Technology has now become available that allows cells to be cultured on permeable microporous membranes in transwell or snapwell inserts providing a very close contact between target cells and test atmospheres to study the cellular interactions caused by airborne chemical exposures without any interfering culture medium. Using a direct exposure technique at the air-liquid interface, target cells can be continuously exposed to airborne chemicals on their apical side, while being nourished from their basolateral side. Test atmospheres with different physicochemical characteristics such as gases, vapours, solid and liquid aerosols and more recently nanoaerosols, can be delivered into human target cells using static and/or direct dynamic exposure methods. Therefore, toxicological risk assessments of airborne chemicals and even complex atmospheres can be achieved using in vitro test methods in parallel with real-time air monitoring techniques to fulfil the general regulatory requirements of newly developed chemical or pharmaceutical products with the potential for inhalational exposure. In this review current toxicological methods for toxicity testing of inhaled chemicals are presented. Further, to demonstrate the potential application of in vitro methods for studying inhalation toxicity, more advanced exposure techniques developed for toxicity screening of airborne chemicals are discussed.
吸入性化学物质所致不良反应的毒理学研究在技术上具有挑战性，这是因为要获得可重复且可比的结果需要高度受控的实验条件。因此，在采用体外生物测定测试系统对空气传播物质进行毒性筛选之前，必须满足许多考量因素。然而，体外方法最近在方法学和技术上的突破有潜力满足空气传播化学物质毒性测试的基本要求。现在已有技术能够使细胞在跨孔或扣盖插入物中的可渗透微孔膜上进行培养，从而使靶细胞与测试气氛紧密接触，以研究空气传播化学物质暴露所引起的细胞相互作用，而无需任何干扰性培养基。利用气液界面的直接暴露技术，靶细胞的顶侧可持续暴露于空气传播的化学物质中，同时从其基底外侧获得营养。具有不同物理化学特性的测试气氛，如气体、蒸气、固体和液体气溶胶以及最近的纳米气溶胶，可使用静态和/或直接动态暴露方法输送到人类靶细胞中。因此，结合实时空气监测技术，使用体外测试方法可以实现对空气传播化学物质甚至复杂气氛的毒理学风险评估，以满足新开发的具有吸入暴露可能性的化学或药品的一般监管要求。在本综述中，介绍了目前用于吸入性化学物质毒性测试的毒理学方法。此外，为了展示体外方法在研究吸入毒性方面的潜在应用，还讨论了为空气传播化学物质毒性筛选而开发的更先进的暴露技术。
