Feasibility of dose adjustment based on differences in long-term clearance rates of inhaled particulate matter in humans and laboratory animals.
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 this 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. It is suggested that despite limitations on available data, a two- to threefold adjustment of dose when extrapolating from small laboratory animals to humans, for quantitative risk assessment, should be considered, unless solubility half-times are very short.
Pepelko
W E
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Office of Health and Environmental Assessment, U.S. Environmental Protection Agency, Washington, D.C. 20460.
D000393:Air Pollutants / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D006801:Humans; D013045:Species Specificity
D000393:Air Pollutants