Feasibility of Dose Adjustment Based on Difference in Long-Term Clearance Rates of Inhaled Particulate Matter in Humans and Laboratory Animals

摘要

Long-term pulmonary clearance rates were evaluated for several laboratory animal species, dogs, and humans to determine if differences among species exist, and if so, the adequacy of the data for dose adjustment. Within each species, large variations in clearance rates were seen, probably as a result of differences in solubility of the aerosol particles, differences in measurement techniques, possible lung damage, transport to lung-associated lymph nodes, and binding of dissolved chemicals to cellular macromolecules in the lung. While few direct comparisons among species using the same aerosol were available, mechanical clearance of particles from the alveolar regions of dogs and humans was generally slower than in most laboratory species, with t1/2 values several-fold longer. Particle clearance rate variations of the magnitude were shown to induce potentially large differences in bioavailability. This can result in large errors in assessing human risk from animal studies unless a dose adjustment is made.