Histopathologic, Morphometric And Physiologic Investigation Of Lungs Of Dogs Exposed To Uranium Ore Dust

INTRODUCTION During the last decade, several studies in France (e.g., Perraud et al. , 1970; Chameaud et al., 1974, 1979 and 1980) and the United States (e.g., Stuart et al., 1978; Cross et al., 1978, 1980 and 1981) have demonstrated the systematic production of emphysema, fibrosis and tumors in the lungs of animals exposed to radon daughters alone or to mixtures of uranium-mine air contaminants. The studies in beagle dogs have been particularly interesting because of the uncertain etiology of the disease and the (apparently) diverse results of the studies at the University of Rochester and the Pacific Northwest Laboratory (PNL). In the Rochester studies, reported by Morken (1973), beagle dogs were exposed to "normal" room air dust loads and radon daughters from 200 to 10,000 WLM*, delivered in 1 to 50 days (rate of delivery, about 200 WLM per day of exposure). Histological examination of tissues was conducted at 1, 2 and 3 years after exposure for all exposure levels. No cancers were noted in these dogs that received estimated alveolar doses of 34 to 1700 rad (0.34 to 17 Gy). Pathologic changes were found only in the alveolar and bronchiolar regions of the lung. These changes were small, subtle, variable, and widely separated, involving only a very small fraction of lung tissue. Lesions appeared as focal thickening of alveolar septa, with some metaplasia of alveolar cells and some hyperplasia of bronchial epithelium. In the PNL experiments reported by Cross et al. (1978), beagle dogs were exposed in lifespan studies to mixtures of radon daughters (rate of delivery, about 14 WLM per day of exposure), uranium ore dust and cigarette smoke. One group of dogs was exposed to cigarette smoke alone. Except in control and smoke-only groups, the dogs died within 4' years of the first radon daughter exposure, or were killed when death appeared imminent because of pulmonary insufficiency (characterized by rapid, shallow breathing). Control and smoke-only animals were killed at periods corresponding to highmortality periods in the groups exposed to radon daughters and mixtures of uranium ore dust and cigarette smoke. Emphysema and fibrosis were much more prevalent and severe in the lungs of dogs exposed to the mixtures. These dogs also had adenomatous lesions, which progressed to squamous metaplasia of alveolar epithelium, epidermoid carcinoma and bronchioloalveolar carcinoma. Pathologic changes in the upper airways of these dogs were most prominent in the nasal mucosa, and included a few squamous carcinomas in the nasal cavity. Respiratory tract neoplasia was noted after ~4 years exposure and at cumulative exposures exceeding approximately 12,000 WLM. Apart from differences in associated carrier aerosol (room air dust vs. uranium ore dust) and radon-daughter exposure rate (200 WLM/day, shortduration exposure vs. 14 WLM/day, long-duration exposure), the most obvious difference in the Rochester and PNL studies was the observation time following exposure (3 years maximum vs. >4 years). Although neoplasia may not have been observed in the Rochester animals because of the earlier termination of the experiments, it is surprising that other lesions, such as prominent fibrosis and emphysema, were not reported. A follow-up study (reported here) is currently in progress at PNL to determine the pathogenic role of uranium ore dust alone and, in particular, to clarify the role of the ore dust in the production of the massive pulmonary fibrosis observed in the earlier study. Pulmonary function testing (a recently acquired capability) was included in the follow-up study as an indicator of progressive change in lung tissue. MATERIALS AND METHODS Chronic (4 hr/day, 5 days/week) exposures began when the dogs were about 2 1/2 years old. Two identical exposure chambers provided space for simultaneous, head-only exposure of 24 dogs to ~l5 mg/m3 carnotite uranium ore dust. An aerosol diffusion system was incorporated in each chamber in order to channel fresh aerosol past each dog's head; uranium ore dust was added to the inlet room air with Wright Dust Feed Mechanisms* (WDFM). Uranium ore dust and condensation nuclei concentrations were measured daily; chamber aerosols were monitored occasionally for particle-size distributions as described for previous hamster experiments (Cross et al., 1981). The carnotite ore used in these experiments, from the Mitten mine in Utah, was furnished in 1970 through the Grand Junction, CO Office of the (then) U.S. Atomic Energy Commission (now the Department