Comparative toxicology of the respiratory tract

It is difficult to extrapolate observations and results from one species to another and from animals to humans because of interspecies differences. A complete and systematic description of such differences among commonly used laboratory animals is lacking. We have reviewed the relevance of deposition, clearance, and the type and magnitude of biological response to inhaled aerosols. Current predictions on the probability of deposition of inhaled aerosols differ, but the fraction of aerosol that is actually deposited in the respiratory tract appears independent of body size. Different species of animals breathing the same aerosol do not receive identical lung doses, and thus exposure concentration is not an adequate description of lung dose. Parameters that affect the magnitude of local doses include changes in ventilation, collection efficiency, lung anatomy, and clearance mechanisms. Apart from these variations, the interspecies differences in substance metabolism and innate biological responsiveness make it unlikely that the extent of lung damage will be identical even in cases where lung doses are equal. We need a comprehensive view of species differences with predictive power.