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.

Clinical and pathologic data were reviewed for 72 owl monkeys that died between January 1987 and May 1990 at the Center for Reproduction and Conservation of Nonhuman Primates in Iquitos, Peru. Tissue samples from 39 animals were examined. Hypertrophic cardiac disease (51% of animals examined), dilative cardiomyopathy (26%), and nephropathy (87%) were the most common diagnoses. The incidence of all three diseases appeared to increase with time in captivity. Nephropathy was less severe in colony‐born animals.

Male Wistar rats were administered 253EsC1, by intratracheal instillation and the biological effects were followed for the animals lifespan or 880 days. Three dose levels were employed; 47.2, 10.7 and 0.214 pCi/kg along with controls given pH 2 HCl by instillation. The estimated radiation dose to lung was 9800, 1900 and 38 rads, respectively. The dose to bone wa3 about + the lung dose. The earliest biological effects were dose related, e.g. impaired weight gain and death due to radiation pneumonitis. The late effects included bone and/or lung tumors in all experimental groups. The tumor site and incidence are discussed and related to similar data for plutonium compounds.EINSTEINIUM-253 (TI,, = 20.5 days; 6.6 MeV alpha) is a transuranic element formed by multiple neutron capture in the heavier actinide elements. The chemical characteristics of Es, as indicated by the behavior on ion exchange columns, are expected to be typically those of other tripositive actinides (KATZ et al., 1957). Because of the short half-life and low efficiency of production 253Es is not a radioisotope of particular biological hazard concern. It has, however, been of interest to radiation biologists because of the energetic alpha emission and the relatively short physical half-life compared to the more well known transuranic elements. Thus the unique physical properties of 253Es may be exploited in comparative biological effects studies with 239Pu (TI,, N 24,000 yr, 5.2 MeV alpha) in order to explore the effect of radiation dose rate and radiation dose distribution on the induction of latent effects such as lung and bone tumors. Studies reported here present results of preliminary investigations to determine the carcinogenicity of intratracheally instilled 263EsC1,. The intratracheal mode of administration was employed rather than the more natural inhalation route in order to facilitate the administration of accurately known amounts of radionuclide. More recent investigations which will be reported elsewhere have employed exposure by inhalation using --~ * This paper is based on research performed under United States Atomic Energy Commission Contract AT(45-1)-1830. 263Es(N0,) , aerosols and standard inhalation exposure techniques. METHODS AND MATERIALSAnimals used in this study were SPF rats of the Wistar strain obtained from Hilltop Laboratory Inc., Scottdale, Pennsylvania. Male and female animals were used, both 66 days of age, weighing 270 and 230 g, respectively. The rats were maintained in wire bottom cages with six rats in each cage initially. Food (Wayne Lab-Blox) and tap water were supplied ad libitum. Cages were changed at weekly or biweekly intervals. The animal quarters were maintained on a day-night cycle which changed at 6 a.m. and 6 p.m. Temperature and humidity were controlled at 72 f 4'F and 40-60 %, respectively.The radionuclide was administered by intratracheal instillation employing a previously described method (MORROW, 1971). A volume of 0.5 ml containing 263EsC1, in 0.01 N HCI was instilled. Control animals received th...

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.

Beagle dogs were given subcutaneous implants of plutonium in their forepaws to mimic hand wounds received by workers accidentally contaminated with plutonium. Ten dogs received 9.46 +/- 0.43 mu Ci of plutonium oxide, and eight dogs received 1.25 +/- 0.60 mu Ci of plutonium nitrate. Surviving dogs were sacrificed at 8 and 5 yr, respectively, after exposure, and radionanalyses were performed on the injection site, regional lymph nodes, liver, spleen and bone. Histopathologic and autoradiographic examinations were performed on injection sites, regional lymph nodes, livers, spleens, kidneys and grossly observed lesions. The injected paws sequestered 21 and 16%, respectively, of the injected activity from plutonium oxide and plutonium nitrate in hypocellular scar tissue. The highest concentrations of translocated radionuclides were found in the regional lymph nodes. Histopathologic and autoradiographic examinations of regional lymph nodes showed that the alpha activity was largely sequestered by scar tissue that replaced lymphoid parenchyma in the plutonium-oxide-injected dogs. In the plutonium-nitrate-injected dogs, activity was widely distributed in relatively intact regional lymph nodes. The liver had the next highest concentration for both radionuclides; activity was present as alpha stars. The spleen had the next highest concentration for plutonium-oxide-injected dogs, although concentrations in the spleen were lower than the skeleton in the plutonium-nitrate-injected dogs. Osteosarcomas and hepatomas were present in one dog injected with plutonium oxide. There does not appear to be any unique risk for dogs related to the subcutaneous route of exposure to plutonium.