SITES OF PARTICLE RETENTION AND LUNG-TISSUE RESPONSES TO CHRONICALLY INHALED DIESEL EXHAUST AND COAL-DUST IN RATS AND CYNOMOLGUS MONKEYS

The usefulness of pulmonary carcinogenicity data from rats exposed to high concentrations of particles for quantitatively predicting lung ca ncer risk in humans exposed to much lower environmental or occupationa l concentrations has been questioned. The results of several chronic i nhalation bioassays-of poorly soluble, nonfibrous particles have sugge sted that rats may be more prone than other rodent species to develop persistent pulmonary epithelial hyperplasia, metaplasia, and tumors in response to the accumulation of inhaled particles. In addition, rats and primates differ in their pulmonary anatomy and rate of particle cl earance from the lung. This paper reviews results of recent Lovelace R espiratory Research Institute (Albuquerque, NM) investigations that di rectly compared the anatomical patterns of particle retention and the lung tissue responses of rats and monkeys exposed chronically to high occupational concentrations oi poorly soluble particles. Lung sections from male cynomolgus monkeys and F344 rats exposed 7 hr/day, 5 days/w eek for 24 months to filtered ambient air, diesel exhaust (2 mg soot/m (3)), coal dust (2 mg respirable particulate material/m(3)), or diesel exhaust and coal dust combined (1 mg soot and 1 mg respirable coal du st/m(3)) were obtained from a study conducted at the U.S. National ins titute for Occupational Safety and Health and examined histopathologic ally and morphometrically, Within each species, the sites of particle retention and lung tissue responses were the same for diesel soot, coa l dust, and combined material. Rats retained a significantly greater p ortion of the particulate material in the lumens of alveolar ducts and alveoli than monkeys. Conversely, monkeys retained a significantly gr eater portion of the particulate material in the interstitium than rat s. Rats, but not monkeys, had significant alveolar epithelial hyperpla stic, inflammatory, and septal fibrotic responses to the retained part icles. These results suggest that anatomic patterns of particle retent ion and lung tissue reactions in rats may not be predictive of retenti on patterns and tissue responses in primates that inhale poorly solubl e particles at concentrations representing high occupational exposures .