10th International Aerosol Conference September 2 - September 7, 2018 America's Center Convention Complex St. Louis, Missouri, USA
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Is the Particle Deposition in a Cell Exposure Facility Comparable to the Lungs?
ERWIN KARG, George A. Ferron, Sebastian Oeder, Ralf Zimmermann, Helmholtz Zentrum München and Rostock University
Abstract Number: 165 Working Group: Aerosols and Health - Connecting the Dots
Abstract Biological endpoints from cell exposure experiments are often taken as indicators for health implications and for the impact of ambient aerosols on the lungs [1, 2]. The advantages of such experiments are their relatively short duration, good repeatability, suitable statistics and cost-effectiveness due to lab-scale facility dimensions. Additionally, with respect to the physical deposition processes, the exposure situation is supposed to be similar to the one in the lungs if particles stay airborne when provided to cells in an air-liquid-interface (ALI) system. However, geometry and air flow rates in an ALI system deviate considerably from the ones in the human respiratory tract (RT). Computer models for particle deposition were developed [3-5] and are adopted here to mimic the exposure situation, to identify the differences and to characterize the deposition patterns in both ALI and RT. As cells from different parts of the RT can be used in an ALI system, a lung deposition software has to be applied which is able to model the regional deposition in the extra-thoracic, bronchial and alveolar region. Runs of both ALI and RT model were performed for different particle size distributions, and their output was configured to provide the number of deposited particles per surface area (dose per area, DPA) of exposed cells in both the ALI and the RT regions. The built-in dichotomous human lung structure [6] in the RT model provides number, geometric diameter and length of the airway ducts and therefrom an estimate of their geometric surface area. Results show the DPA in the ALI being 4-5 orders of magnitude higher than in the alveolar region, as the surface area in the deep RT is extremely high and the inhaled particulate matter is spread out over it. In the bronchial region, however, the DPA of the ALI is found to be higher by a factor of 2-10 only and cumulated deposition is therefore much better comparable. However, hot spots may be present in the airways as lung clearance occurs along defined paths and some locations are not well cleared. Additionally, particles are deposited merely according to aerodynamic processes, and being different in size and composition. In conclusion, i) due to the high DPA, an ALI exposure experiment mimics the cumulated RT alveolar exposure of days; consequently, the experiment duration can be kept short and concentration can be kept low. And ii) if the DPA in ALI and RT should be comparable, cell lines from the bronchial or extra-thoracic region should be used as biological targets. References 1. Mülhopt, S., et al., Toxicity testing of combustion aerosols at the air–liquid interface with a self-contained and easy-to-use exposure system. Journal of Aerosol Science, 2016. 96: p. 38-55. 2. Oeder, S., et al., Particulate Matter from Both Heavy Fuel Oil and Diesel Fuel Shipping Emissions Show Strong Biological Effects on Human Lung Cells at Realistic and Comparable <italic>In Vitro</italic> Exposure Conditions. PLoS ONE, 2015. 10(6): p. e0126536. 3. Comouth, A., et al., Modelling and measurement of particle deposition for cell exposure at the air–liquid interface. Journal of Aerosol Science, 2013. 63: p. 103-114. 4. Ferron, G.A., et al., Model of the Deposition of Aerosol Particles in the Respiratory Tract of the Rat. II. Hygroscopic Particle Deposition. J Aerosol Med Pulm Drug Deliv, 2013. 26(2): p. 101-19. 5. Ferron, G.A., B. Haider, and W.G. Kreyling, Inhalation of salt aerosol particles — I. Estimation of the temperature and relative humidity of the air in the human upper airways. Journal of Aerosol Science, 1988. 19(3): p. 343-363. 6. Weibel, E.R., Morphometry of the Human Lung. 1963, Berlin: Springer Verlag. 151.