Disposition of Polycyclic Aromatic Hydrocarbons in the Respiratory Tract of the Beagle Dog: II. The Conducting Airways

Abstract

Physiological models have predicted that the lipophilicity of solutes such as polycyclic aromatic hydrocarbons (PAHs) will delay clearance from the respiratory tract. This clearance consists of a delayed penetration of the mucous lining layer (MLL), allowing mucociliary clearance, followed by a slow penetration of PAHs through walls of the conducting airways. To test this prediction, mucociliary clearance and retention in the mucosa of PAHs deposited in the conducting airways of the Beagle dog were measured. Mucociliary clearance of particles and dissolved PAHs was measured by instilling onto the MLL in a main stem bronchus or the distal trachea small volumes of saline containing either dissolved benzo[ a]pyrene (BaP) or phenanthrene (Phe), or a suspension of particulate solvent green (SG) or macroaggregated albumin (MAA). Sequential lavage of the mucous-retained materials followed the instillations. Retention of BaP in the airway walls of the bronchial tree was studied by instilling the hydrocarbon in an ethanol/saline solution at precise locations of the upper bronchial tree, and measuring the concentration of BaP and its major metabolites in the tissues. Results indicated that mucociliary clearance of SG and MAA particles in the trachea of the Beagle dog occurred at average rates of 27-30 mm/min. Of the two solutes, only the highly lipophilic BaP was sufficiently retained within the MLL to be transported with the mucociliary escalator. In addition, a fraction of the lipophilic materials cleared at a very rapid rate, in excess of 90 mm/min. This may indicate that one monolayer of pulmonary surfactant at the air interface is spreading out of the lungs on top of the MLL at a faster rate than mucociliary clearance. However, despite the protective properties of the MLL, fractions of BaP penetrating to the bronchial epithelium had a clearance half-time in the range of 1.4 hr, a period during which considerable metabolism of the PAH occurred. This long retention indicates a diffusion-limited uptake of BaP by the airways, and underscores the potential for local toxicity of highly lipophilic toxicants in the bronchial epithelium.