Environmental Health Perspectives 105, Supplement 5, September 1997

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Sites of Particle Retention and Lung Tissue Responses to Chronically Inhaled Diesel Exhaust and Coal Dust in Rats and Cynomolgus Monkeys

Kristen J. Nikula, Kelly J. Avila, William C. Griffith, and Joe L. Mauderly

Lovelace Respiratory Research Institute, Albuquerque, New Mexico

Abstract
The usefulness of pulmonary carcinogenicity data from rats exposed to high concentrations of particles for quantitatively predicting lung cancer risk in humans exposed to much lower environmental or occupational concentrations has been questioned. The results of several chronic inhalation bioassays of poorly soluble, nonfibrous particles have suggested 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 clearance from the lung. This paper reviews results of recent Lovelace Respiratory Research Institute (Albuquerque, NM) investigations that directly compared the anatomical patterns of particle retention and the lung tissue responses of rats and monkeys exposed chronically to high occupational concentrations of poorly soluble particles. Lung sections from male cynomolgus monkeys and F344 rats exposed 7 hr/day, 5 days/week 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 dust/m 3 ) were obtained from a study conducted at the U.S. National Institute for Occupational Safety and Health and examined histopathologically and morphometrically. Within each species, the sites of particle retention and lung tissue responses were the same for diesel soot, coal dust, and combined material. Rats retained a significantly greater portion of the particulate material in the lumens of alveolar ducts and alveoli than monkeys. Conversely, monkeys retained a significantly greater portion of the particulate material in the interstitium than rats. Rats, but not monkeys, had significant alveolar epithelial hyperplastic, inflammatory, and septal fibrotic responses to the retained particles. These results suggest that anatomic patterns of particle retention and lung tissue reactions in rats may not be predictive of retention patterns and tissue responses in primates that inhale poorly soluble particles at concentrations representing high occupational exposures. -- Environ Health Perspect 105(Suppl 5):1231-1234 (1997)

Key words : diesel soot, diesel exhaust, coal dust, rats, monkeys, inhalation, inhaled particles, particle retention in lung, interspecies comparisons

This paper is based on a presentation at The Sixth International Meeting on the Toxicology of Natural and Man-Made Fibrous and Non-Fibrous Particles held 15-18 September 1996 in Lake Placid, New York. Manuscript received at EHP 26 March 1997; accepted 2 April 1997.

The substantial efforts of all the individuals who conducted the original study, especially the authors, T.R. Lewis (deceased), F.H.Y. Green, W.J. Moorman, J.R. Burg, and D.W. Lynch, are gratefully acknowledged. The authors wish to express their appreciation to V. Vallyathan, F.H.Y. Green, and F. Salomon of the National Institute for Occupational Safety and Health, who facilitated our use of these slides and provided additional information concerning the original study. This research was supported by Volkswagen AG under a Funds-In-Agreement with the U.S. Department of Energy under contract DE-AC04-76EV01013.

Address correspondence to Dr. K.J. Nikula, Lovelace Respiratory Research Institute, P.O. Box 5890, Albuquerque, NM 87185. Telephone: (505) 845-1009. Fax: (505) 845-1198. E-mail: knikula@lrri.org

Abbrevations used: AM, alveolar macrophage(s); CD, coal dust; DE, diesel exhaust; DECD, combined diesel exhaust and coal dust; FA, filtered ambient air.

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Last Update: November 17, 1997