ToxSci Advance Access originally published online on April 15, 2003
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Toxicological Sciences 73, 448-456 (2003)
Copyright © 2003 by the Society of Toxicology
RESPIRATORY TOXICOLOGY |
The Effect of Lung Structure on Mucociliary Clearance and Particle Retention in Human and Rat Lungs
* Institute of Physics and Biophysics, University of Salzburg, Hellbrunner Strasse 34, A-5020 Salzburg, Austria, and
CIIT Centers for Health Research, PO Box 12137, Research Triangle Park, North Carolina 27709-2137
Mucociliary clearance velocities in human and rat bronchial airways were calculated in asymmetric, multiple-path models of the bronchial tree by solving mass transport equations based on the assumption of conservation of mucus volume and normalized to measured tracheal mucus velocities of 5.5 mm/min for humans and 1.9 mm/min for rats. Mucus velocities in single airways of the rat lung exhibited a significant statistical relationship with airway diameters but not with generation numbers, while both parameters provided equally suitable relationships for the human lung. Retention curves reflecting the combined effects of deposition and clearance were computed for unit density particles of 0.1, 1, 2, and 7 µm for resting breathing conditions. About 10 to 15% of the particles initially deposited in the human bronchial tree were still retained after 24 h, while most of the particles deposited in the rat bronchial tree were cleared after about 6 to 8 h. Snapshots of the distributions of mass retained among human bronchial airways at different times after the end of exposure indicated that the observed slow bronchial clearance may partly be attributed to delayed mucociliary clearance from particles initially deposited in the most peripheral conductive airways. If plotted as functions of airway diameter, human and rat bronchial retention patterns exhibit very similar shapes in contrast to their dependence on airway generation number. Thus, extrapolation of toxicologic response, based on local retention patterns from rat to human exposures, should be based on airway diameter rather than on generation number.
Key Words: human lung; rat lung; mucociliary clearance; particle retention; extrapolation modeling.
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