The United States Transuranium and Uranium Registries as sources for actinide dosimetry and bioeffects.

The United States Transuranium and Uranium Registries (USTUR) has analysed tissues collected at autopsies of over 300 former radiation workers from actinide processing sites throughout the US, in addition to collecting the medical and radiation exposure histories of those workers. These data are included in a large USTUR database and they are available to research scientists throughout the world, either as public records or through collaborative projects with the USTUR. The USTUR also operates the National Human Radiobiological Tissue Repository (NHRTR), in which portions of tissue samples collected at autopsy are kept. These samples, frozen at -70 degrees C, may be used for molecular studies of the effects of radiation. Medical and radiation exposure histories of the tissue donors are available, as are the results of radiochemical analyses of adjacent portions of the samples. These materials are available to researchers who have collaborative agreements with the USTUR, which can be established by accessing USTUR staff members through the website, http://www.ustur.wsu.edu.

Estimation of actinide skeletal content in humans based on bone samples collected at autopsy.

The USTUR has developed simple linear and multiple regression models for estimating skeletal actinide concentrations on the basis of bone samples collected at autopsies of non-whole body tissue donors. Bone samples usually collected include a clavicle, the patella(e), one or more ribs, the sternum, and a vertebral wedge cut from within the abdominal cavity. The described models were derived by regression analyses with the analytical results from those bones and the entire skeletons of eight whole body donations to the USTUR. With the model, skeletal concentrations of 238Pu, (239+240)Pu, and 241Am can be estimated from wet or ashed actinide concentrations in one to five of the bones usually collected at autopsy and analyzed. Application of the models to a selected USTUR non-whole body donation (Case 0240) indicated that the skeletal actinide concentration estimates were reasonably precise and that there was good agreement between the results from individual bones with wet or ashed actinide concentrations. The USTUR will apply the model that is based on wet concentrations of bones to estimate skeletal concentrations of actinides in all non-whole body autopsy cases for the sake of consistency because of the large number of early cases for which ashed weights of bones were not recorded.

USTUR case 0259 whole body donation: a comprehensive test of the current ICRP models for the behavior of inhaled 238PuO2 ceramic particles. U.S. Transuranium and Uranium Registries.

An analysis of 238Pu in the whole body donation to the U.S. Transuranium and Uranium Registries (USTUR) is presented. This donor accidentally inhaled an unusual physical form of plutonium, predominantly the 238Pu isotope in the form of a highly insoluble ceramic. Along with six other workers accidentally exposed at the same time, this donor excreted little or no 238Pu in his urine for several months. Subsequently, however, and, with no further intakes, the urinary excretion of 238Pu by all of these workers increased progressively. Such a pattern of increasing urinary excretion of plutonium resulting from a single acute inhalation was unknown at the time. The subject of this study provided a unique opportunity to analyze not only the pattern of urinary excretion for 17 y following this unusual intake but also the complete distribution of 238Pu in his donated body tissues and skeleton at death. Radiochemical analyses of tissues from this whole body donation were used to perform critical tests of the applicability and accuracy of the respiratory tract model and the systemic biokinetic models for plutonium currently recommended by the International Commission on Radiological Protection. The respiratory tract model was applied to analyze the donor's long-term urinary excretion pattern. The facility provided by this model to represent progressive transformation of insoluble particles in the lungs into a more soluble form, applied in conjunction with the systemic biokinetic model, predicted the total amount of 238Pu measured in the donor's body to within 17% accuracy. The measured division of 238Pu between the donor's lungs and systemic organs was predicted to within 10%. Small adjustments to several rate constants in these models provided precise predictions of the absolute amounts of 238Pu in the lungs, thoracic lymph nodes, liver, red bone marrow, skeleton (including the distribution of 238Pu between trabecular and cortical bone matrices derived from the radiochemical analyses), kidneys, testes, and muscle. The resulting individual-specific parameters were applied to evaluate the equivalent dose rates and cumulative doses received by the donor's organs and the overall effective dose. Whereas these individual modifications to the ICRP models provided a more accurate representation of the distribution of dose between the donor's organs, it was determined that the ICRP models provided an adequate estimate of the overall effective dose.

Metabolism and dosimetry of actinide elements in occupationally-exposed personnel of Russia and the United States: a summary progress report.

The United States Transuranium and Uranium Registries (USTUR) and the Dosimetry Registry of the Mayak Industrial Association (DRMIA) have been independently collecting tissues at autopsy of plutonium workers in their respective countries for nearly 30 y. The tissues are analyzed radiochemically and the analytical data are used to develop, modify, or refine biokinetic models that describe the depositions and translocations of plutonium and transplutonium elements in the human body. The purpose of this collaborative research project is to combine the unique information on humans, gathered by the two Registries, into a joint database and perform analyses of the data. A series of project tasks are directly concerned with dosimetry in Mayak workers and involve biokinetic modeling for actinide elements. Transportability coefficients derived from in-vitro solubility measurements of actinide-containing aerosols (as measured by the DRMIA) were related to specific workplaces within Mayak facilities. The transportability coefficients of inhaled aerosols significantly affected the translocation rates of plutonium from the respiratory tract to the systemic circulation. Parameters for a simplified lung model, used by Branch No. 1, Federal Research Center Institute of Biophysics (FIB-1) and the Mayak Production Association for dose assessment at long times after inhalation of plutonium-containing aerosols, were developed on the basis of joint USTUR and DRMIA data. This model has separate sets of deposition and transfer parameters for three aerosol transportability groups, allowing work histories of the workers to be considered in the dose-assessment process. FIB-1 biokinetic models were extended to include the distributions of actinide elements in systemic organs of workers, and a relationship between the health of individual workers and plutonium distribution in tissues was determined. Workers who suffered from liver diseases generally had a smaller fraction of systemic plutonium in the liver at death and a larger fraction in the skeleton than did relatively healthy workers. Also, the fraction of total systemic plutonium excreted per day was significantly greater for workers with liver diseases than for relatively healthy workers. These observations could have a considerable effect on organ dosimetry in health-impaired workers whose dose assessments were based solely on urinary excretion rates. A comparison of this model to other biokinetic models, such as those published by the International Commission for Radiological Protection, is currently underway as is the documentation of uncertainty estimates associated with the model.

The distribution and effects of inhaled 239Pu(NO3)4 deposited in the liver of dogs.

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.

Changes in soft tissue concentrations of plutonium and americium with time after human occupational exposure.

Concentrations of 239 + 240Pu and 241Am in human soft tissues (testes, thyroid gland, kidneys, spleen, heart, skeletal muscle, brain, and pancreas) were compared to those in livers of the same subjects. The subjects were volunteer donors with occupational exposures to plutonium and americium autopsied as part of the United States Transuranium and Uranium Registries program. The temporal distributions of tissue-to-liver ratios were compared to liver uptake fractions assumed on the basis of current models to estimate the initial uptake fractions for each tissue studied. Regressions of the ratios were used to compare tissue retention half-times to those of the liver. Effective half-times for plutonium and americium in the tissues studied were similar to those for the liver with three exceptions: (1) the clearance half-time for plutonium in kidneys is shorter than that of liver; (2) the retention half-time for plutonium in testes is longer than that of liver; and (3) the retention half-time for americium in skeletal muscle was longer than in the liver. Next to liver, the greatest initial uptake of systemic actinides was in skeletal muscle and the greatest initial concentrations were in the spleen. The uptake fraction of plutonium in the testes proposed by the ICRP was verified.

Deterministic effects of 241Am exposure in the Hanford Americium accident case.

Lifetime follow-up of USTUR Case 246 demonstrated the lack of severe biological effects resulting from his exposure to 241Am. Deterministic effects observed were limited to hematological changes, including lymphopenia and thrombocytopenia. These hematological changes were consistent with those observed in experimental animals following actinide exposure. Cataracts were removed from the left and right eyes at 547 and 1,030 d after the accident, respectively, but were considered to be trauma-induced rather than radiation-induced. No abnormal findings were reported from gross or histological examinations of tissue samples removed at autopsy, other than those resulting from the subject's preexisting cardiovascular disease.

Soft tissue concentrations of plutonium and americium in occupationally-exposed humans.

Human tissues, obtained at autopsy from 82 volunteer donors with a history of occupational exposure, were analyzed for 238Pu, 239 + 240Pu, and 241Am by chemical separation and subsequent alpha spectrometry. Concentrations of these actinide nuclides in soft tissues (testes, thyroid gland, spleen, kidneys, heart, and skeletal muscle) were compared to those of the livers in the same subjects. Tissue:liver concentration ratios were essentially constant over a wide range of liver concentrations. The spleen had consistently high actinide concentrations relative to liver; however, the heart had the greatest concentration ratio for 241Am. Testes had relatively high concentration ratios of the plutonium nuclides but low concentrations of 241Am. Skeletal muscle had low concentrations of plutonium relative to liver but high concentrations of 241Am. In the tissues studied, concentration ratios of 241Am were greater than those of the plutonium nuclides, most likely a result of more rapid excretion of that nuclide than the plutonium nuclides by the liver.

Microdistribution and microdosimetry of thorium deposited in the liver.

The distribution of thorium in the liver of a patient 36 y after injection with Thorotrast was examined with autoradiographic and scanning electron microscope backscatter image techniques. Autoradiographic examination of randomly selected histologic sections of the liver showed a total alpha activity calculated at 33.7 Bq g-1, with the highest concentration of alpha activity sequestered in subcapsular scare tissue. Subcapsular scare tissue received 4.8 cGy d-1 of alpha radiation, periportal areas were accumulating 1.4 cGy d-1, and the hepatic cord areas 0.09 cGy d-1 of alpha radiation at the time of death. The concentration of dose in periportal areas correlates with higher incidence of bile duct tumors (than hepatocellular carcinomas) found in patients exposed to Thorotrast. The backscatter technique was demonstrated as useful for identifying thorium in liver specimens.

Tobacco smoke inhalation studies: a dosimetric comparison of different cigarette types.

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.

Clinical and pathological effects of cigarette smoke exposure in beagle dogs.

To compare the clinical and pathological effects of high and low nicotine cigarette smoke 12 young adult male beagles were separated into four equal groups and exposed to smoke from high (4.6 mg) or low (1.4 mg) nicotine cigarettes, administered in six or 12 cigarettes per day. Two control groups, sham-exposed and nontracheostomized, consisted of three dogs each. The dogs were exposed seven days per week for five months. Tracheobronchitis developed in smoke-exposed dogs; gross lesions were generally confined to the lungs and tracheobronchial lymph nodes. Histopathological changes were found in all smoke-exposed dogs, with slightly more severe or extensive lesions in the dogs exposed to 12 cigarettes per day. The incidence and severity of rhinitis, turbinate basal epithelial cell hyperplasia, and squamous metaplasia were increased among dogs in the high nicotine cigarette groups.

Pulmonary hyalinosis in dogs.

Pulmonary hyalinosis occurred in Beagles exposed to radon daughters with uranium ore dust. The lesion was composed of alveolar cells distended with material positive for periodic acid-Schiff (PAS) and oil red O that ultrastructurally consisted of a whorled arrangement of lamellar membranes suggestive of a storage disease. The high incidence in exposed dogs and the ultrastructural appearance suggested the material originated endogenously as a degenerative response to injury.