Troubleshooting methods for toxicity testing of airborne chemicals in vitro

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.