US EPA

76041 

Journal Article 

Current information on lung overload in nonrodent mammals: contrast with rats 

Snipes, MB 

1996 

Yes 

Inhalation Toxicology
ISSN: 0895-8378
EISSN: 1091-7691 

8 

Supplement 

91-109 

Because the concept of lung overload is based primarily on the results of chronic inhalation studies in which rats inhaled large amounts of relatively non toxic, poorly soluble dusts, the extent to which biological manifestations of lung overload in rats can be extrapolated to other mammalian species, especially humans, is being questioned. Rats exhibit relatively fast pulmonary clearance of dust and appear to retain pulmonary burdens of dust predominantly in macrophages within alveoli. In contrast, larger animals and humans exhibit slower pulmonary clearance of dust and appear to retain pulmonary burdens of dust predominantly in the pulmonary interstitium. Chronic inhalation of dust by the larger species is therefore predicted to result in different dust accumulation patterns in the lungs than seen in rats. These patterns may dictate the extent to which species other than rats exhibit manifestations of lung overload. Results of several studies of coal miners, hard rock miners, and asbestos workers demonstrated that large pulmonary burdens of dust can accumulate in humans. An important unanswered question is the extent to which pulmonary clearance might have been altered during the chronic exposures of larger species and humans. It is possible for significant burdens of dust to accumulate in lungs with normal clearance. Published results of a UO2 chronic inhalation study with rats, monkeys, and dogs suggest that pulmonary clearance was not altered in monkeys and dogs under chronic exposure conditions that resulted in altered pulmonary clearance in the rats. These results strongly support the concept that relationships among species relative to lung over-load may be attributable more to differences in patterns of dust accumulation in the lung than to the amounts of accumulated dust. In summary, the available data from monkeys, dogs, and humans suggest that lung overload in rats may not be directly relevant to larger mammals and humans. However, the issue of lung overload in species other than rodents is still important and requires additional attention to determine the extent to which the various manifestations of lung overload in rats can be applied to other species, including humans.