Interspecies comparisons of lung responses to inhaled particles and gases.
Two important challenges for inhalation toxicologists involve the elucidation of mechanisms of lung toxicity caused by inhalation of chemicals or particulate materials, as well as the extrapolation of animal data to humans. Because risk estimates of toxicity generally are dependent upon experimental data for which a variety of species are utilized, a fundamental knowledge of species similarities and differences in lung anatomy, physiology, biochemistry, cell biology, and corresponding disease processes is essential. In the present review, the known mechanisms of particle deposition and clearance among various species have been highlighted and related to structure/function relationships and pathogenetic responses to some selected inhaled toxicants. In the aggregate, there is remarkable homogeneity in form and function among the species. Morphologic aspects of the respiratory tract and lung defense mechanisms are qualitatively similar among species. On the other hand, quantitative differences between humans and experimental animals are known to exist with respect to deposition and mucociliary clearance of inhaled particulates, and these factors are likely to influence the dose that is delivered to specific target sites in the lung. It is interesting to consider that pathologic cellular events following asbestos, ozone, and nitrogen dioxide exposure are likely to occur at similar sites in humans, nonhuman primates, and rodents. In this respect, it has been demonstrated that the early lesions of asbestos-induced lung disease in both rats and humans are initiated at similar anatomical sites, i.e., the junctions of terminal airways and alveolar regions. PMs and complement-mediated mechanisms have been implicated in the development of asbestosis in rats; however, it remains to be determined whether complement activation plays an important role in human asbestosis, although pulmonary and interstitial macrophages clearly are associated with the fibrogenic process associated with this restrictive lung disease. The toxic pulmonary effects following ozone exposure have been well studied in rodents and nonhuman primates. It has been established that distal airway and alveolar epithelial cells are principal targets of oxidant pollutants, and this is well supported by dosimetry considerations, morphologic observations, and morphometric analyses. Chronic ozone exposure in rats and monkeys causes epithelial injury at the level of the terminal bronchiole and proximal alveolar regions of the lung.(ABSTRACT TRUNCATED AT 400 WORDS)
Warheit
D B
DB
Department of Acute and Developmental Toxicology, E. I. duPont de Nemours and Company, Inc., Newark, Delaware.
D000280:Administration, Inhalation; D000818:Animals; D005739:Gas Poisoning / Q000503:physiopathology*; D006801:Humans; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D008171:Lung Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D013045:Species Specificity