The development of pulmonary lesions in beagle dogs was studied following chronic inhalation exposures to radon (at 105 % 20 nCi/l), radon daughters (at 605 k 169 WL), uranium ore dust (at 12.9 5 6.7 mglm') and cigarette smoke. Chronic exposures to mixtures of these agents caused significant lifespan shortening when compared with controls. Survival times of controls and smoke-exposed dogs were equivalent during the 4 to 5-yr mean survival time of the dogs exposed to radon-daughter and ore-dust mixtures (with or without added cigarette smoke).Animals with tumors of the respiratory tract generally had cumulative radon-daughter exposures exceeding 13,000 WLM, and their survival time was longer than the survival time of nontumor-bearing animals. Under the conditions of the experiment, exposure to cigarette smoke was found to have a mitigating effect on radon daughter-induced tumors. It is uncertain whether this would be a general finding applicable to other levels of exposure to radon daughters, uranium ore dust and cigarette smoke. tract lesions. However, exposure to 20 cigarettedd, 7 d/wk resulted in pulmonary emphysema, fibrosis and chronic bronchitis and bronchiolitis.Emphysema and fibrosis were much more prevalent and severe in the dogs exposed to mixtures which included radon daughters and uranium ore dust. These dogs also had adenomatous lesions which progressed to squamous metaplasia of aleveolar epithelium, epidermoid carcinoma and bronchioloalveolar carcinoma. Pathologic changes in the airways of these dogs were most prominent in the nasal mucosa, and included a few squamous carcinomas in the nasal cavity.We conclude that the beagle dog is a useful animal for modeling pulmonary lesions produced by uranium mine air contaminants. Tumors were produced at levels that did not greatly exceed some exposures reported for uranium miners. These tumors, found after approx. 50mo of exposure, might partially account for the absence of tumors in experiments where exposures terminated before 50 mo.
As part of a long-term inhalation bioassay study of cigarette smoke in rats, a detailed dosimetric comparison of three groups of rats exposed to smoke from different cigarette types was performed. Groups of 20 female F-344 rats were exposed, in Maddox-ORNL smoking machines, to 14C-dotriacontane-labeled smoke from three types of research cigarettes: high tar-low nicotine, low tar-high nicotine, and high tar-high nicotine. Analyses of lung tissues revealed similar deposition amounts and patterns of particulate matter for all three cigarette types even though the chamber smoke concentrations varied substantially. These results suggested that for rats exposed to different types of cigarette smoke, the amount of particulate material deposited may not be a function of concentration only. The authors conclude that when comparing cigarette smoke inhalation studies of different cigarette types, exposure parameters and smoke composition may both influence the amount of smoke inhaled and deposited in the lung and other organs.
The distribution and effects of inhaled 239Pu(NO3)4 deposited in the liver of dogs were studied in five groups of 20 beagles exposed to initial lung depositions ranging from 1.0 to 520 Bq g(-1) lung. Following life-span observations, the liver contained 40 +/- 1% of the final body deposition of plutonium, second only to the skeleton. The liver-to-skeleton ratio of deposited plutonium for total organ was 0.8, or 3.5 when expressed on a per-gram basis. There was no effect of exposure level on liver-to-skeleton ratios. Autoradiographs showed that the dose rate delivered to parenchymal cells was higher than evident from radiochemical analysis of the whole organ. Elevated levels of serum liver enzymes were observed in groups with mean liver concentrations of 1.3 Bq g(-1) and liver doses of 3 Gy or higher. Nodular hyperplasia of liver and bile-duct hyperplasia were observed. Liver tumors, principally of bile-duct epithelium, were late-occurring and were observed at lower exposure levels at which life span was not shortened by lung or bone tumors.
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