Morphometric and morphologic evaluation of pulmonary lesions in beagle dogs chronically exposed to high ambient levels of air pollutants.

Beagle dogs (104) comprising one control and seven treatment groups were exposed 16 hours daily for 68 months to filtered air, raw or photochemically reacted auto exhaust, oxides of sulfur or nitrogen, or their combinations. After a further 32 to 36 months in clean air, morphologic examination of lungs by light microscopy, scanning electron microscopy, and transmission electron microscopy revealed two important exposure-related lesions. They were enlargement of air spaces in proximal acinar regions, with and without increases in the number and size of interalveolar pores, and hyperplasia of nonciliated bronchiolar cells. Proximal enlargment of air spaces was most severe, both subjectively and morphometrically, in those dogs exposed to oxides of nitrogen, oxides of sulfur, or oxides of sulfur with photochemically reacted auto exhause. In contrast, hyperplasia of nonciliated bronchiolar cells was most severe in dogs exposed to raw auto exhaust alone or with oxides of sulfur. The air space enlargement and hyperplasia of bronchiolar epithelium correlated with functional impairment reported as occurring in these dogs. Foci of ciliary loss with and without squamous metaplasia were occasionally observed in trachea and bronchi. The observations indicate that enlargement of proximal acinar air spaces with some loss of interalveolar septa can develop in the absence of alveolar fenestrations. The persistnt nature of bronchiolar cell proliferations in such circumstances was also demonstrated. Two major toxicologic implications are (1) the production of permanent lung damage by much lower concentrations of pollutants than previously reported and (2) the apparent lack of additive or synergistic effects between oxidant gases and sulfur oxides.