Sites for uptake of inhaled vapors in beagle dogs

The site of uptake of inhaled vapors profoundly influences which respiratory tract tissues receive the highest doses. How the site of uptake depends on the physicochemical properties of inhaled vapors has been the subject of experiment and speculation for decades, but remains undefined. Using techniques that distinguish between vapor uptake in the nose and lung during cyclic breathing by Beagle dogs, we examined uptake of the vapors of 2,4-dimethypentane (DMP), propyl ether, butanone, dioxolane, and ethanol. These compounds have blood/air partition coefficients ranging from 1 to 2000. The effect of altering respiratory rates on vapor uptake was examined for DMP and dioxolane vapors. Deposition of vapors in the nasal cavity during inhalation was highly dependent on the partition coefficient. Vapor deposited in the nasal mucosa during inhalation was desorbed to a substantial extent during exhalation. Lung uptake of total inhaled vapor was limited by the amount available after passage through the nose, but in no case did it exceed 50% of the available amount. The data suggest that the diffusion of vapor molecules through the tissue barrier separating the air/tissue interface from the tissue/blood interface constitutes a significant resistance for both nasal uptake and lung uptake of many inhaled vapors. The data were used to validate a mathematical model describing nasal uptake of vapors. The model is described in the companion paper.