Physical, chemical and physiological factors influencing entry of xenobiotics into the body via the pulmonary system

The respiratory system has an extremely large surface area covered with a thin aqueous film of either mucus or a lipoprotein surfactant‐containing fluid. The large total surface area and minute separation between the air space and the blood make the lung an efficient organ for the rapid, systemic absorption of xenobiotics with a variety of physicochemical characteristics. Gases are absorbed throughout the entire respiratory system, the dominant driving force being diffusion. Highly water soluble gases are rapidly absorbed and may be cleared significantly through the surfaces of the upper respiratory tract before penetrating the deeper recesses of the lung. Inhaled particles are deposited in the respiratory system according to their size. Particles with aerodynamic diameters of 5 to 30 μm are similarly trapped in the nasopharyngeal region; those from 1 to 5 μm are largely deposited in the tracheal and bronchiolar regions, the major portion of particles smaller than 1 μm penetrate to the alveoli. Solute absorption studies indicate that the respiratory epithelium behaves like a lipoid–pore type membrane. Lipid soluble compounds are most rapidly absorbed at rates roughly related to their lipid/water partition coefficient at pH 7.4. Lipid insoluble substances are absorbed by nonsaturable diffusion with absorption rates related to the size of the molecules, i.e., the higher the molecular weight, the slower is the absorption. Organic ions can be absorbed by diffusion and by saturable, carrier‐mediated processes. Pulmonary exposure to substances known to produce lung damage, i.e., ozone, silica, or acids, can alter carrier‐mediated absorption of solutes and increase the passive absorption of lipid insoluble compounds alone or of both lipid soluble and lipid insoluble compounds. Age appears to be an important factor in absorption rate of lipid insoluble compounds. The lungs of 3‐ to 12‐day‐old rats absorb lipid insoluble compounds twice as rapidly as those of 18‐ to 27‐day‐old or adult animals. Age is unimportant, however, in the absorption of lipid soluble compounds. Species differences also exist for the absorption rates of lipid insoluble compounds but not for those of lipid soluble compounds. Mice will absorb lipid insoluble compounds 2 to 3 times more rapidly than rats, while rats absorb 1.3 to 3 times more rapidly than the rabbit.