DISPOSITION OF POLYCYCLIC AROMATIC-HYDROCARBONS IN THE RESPIRATORY-TRACT OF THE BEAGLE DOG .1. THE ALVEOLAR REGION

Clearance of polycyclic aromatic hydrocarbons (PAHs) from the respiratory tract follows a biphasic pattern, with a rapid clearance of most of the PAH followed by a slower clearance of a small fraction. In previously published models, it was predicted that the rapid phase represents clearance through the thin epithelial barriers in the alveoli, the slow clearance is through the thicker epithelium of the airways, and the rate of clearance from either region will be slowed if the PAH has a high degee of lipophilicity. The objective of this first study in a series of three was to validate model predictions for rates of alveolar clearance of PAHs of different lipophilicities. A new method was developed to exposure dogs to a bolus of aerosolized crystals of either benzo[a] pyrene (BaP) or phenanthrene (Phe) in a single breath. A bolus of PAH crystals was formed by condensation from a heated vapor and was injected into the pulmonary region. The bloodborne clearance of the PAHs was monitored by repeatedly sampling blood through catheters in the ascending aorta and the right atrium of the dog. Half of the Phe and the BaP cleared within 1 min and 2.4 min, respectively. The data indicated that the clearance of the highly lipophilic BaP was limited by diffusion of the PAH through the alveolar septa, while clearance of the moderately lipophilic Phe was limited mostly by the rate of perfusion of the blood. The results indicate that inhaled PAHs of sufficient lipophilicity to limit diffusion through cells have a greater potential for toxicity to the lung than less lipophilic PAHs. Because of thicker epithelia, bronchi should be a greater risk than the alveoli for PAH-induced toxicity exerted at the portal of entry. © 1994 Academic Press. All rights reserved.