The lungs provide a portal of entry into the bloodstream for numerous airborne materials including aerosolized drugs, cosmetics, household products, insecticides, herbicides, industrial chemical dusts, and various other potentially toxic environmental agents. Accordingly, it is important to know how rapidly and to what extent aerosols are absorbed into the blood after inhalation by humans and also by animals intended for use as food by humans.
The specific aim of the present proposal is to develop a small animal model for predicting pulmonary absorption rates of aerosolized substances in various mammalian species. The overall long-term objective of this investigation is to develop a combined small animal and mathematical model by which this information can be extrapolated to large animals including man. Water solutions of non-metabolized, nonvolatile organic test compounds will be introduced into the lungs of anesthetized animals either as a liquid aerosol of known particle size or as a small volume of intratracheally-injected fluid. The aerosol or injected fluid will enter the lungs through a tight-fitting tracheal cannula so that absorption into the bloodstream can occur from the lungs but not from extrapulmonary sites, and so that mucocilliary clearance of substances is prevented. Thus the rate at which a substance disappears from the lungs as measured by specific chemical assay of lung tissue will provide an accurate measure of its rate of absorption into the bloodstream. Absorption rates for the various test substances will be compared in anesthetized animals of different body size: mice, rats and rabbits. Based on preliminary results, there is a high probability of finding in each species a constant ratio between the absorption rates seen after intratracheal injection and those obtained after inhalation of an aerosol of specified particle size. Moreover, based on preliminary results, there is a high probability of finding a constant ratio between absorption rates seen in one species and those obtained in another species provided that aerosol particle size is kept constant. Thus, with knowledge of the above sets of ratios, it should be possible to measure the absorption rate of a substance by the simple intratracheal injection technique in a small, inexpensive animal (mouse or rat) and then extrapolate the result to an aerosol of known particle size in larger animals.
| Schanker, L S; Mitchell, E W; Brown Jr, R A (1986) Species comparison of drug absorption from the lung after aerosol inhalation or intratracheal injection. Drug Metab Dispos 14:79-88 |
| Schanker, L S; Mitchell, E W; Brown Jr, R A (1986) Pulmonary absorption of drugs in the dog: comparison with other species. Pharmacology 32:176-80 |
