Uranium deposition and retention in a USTUR whole body case.

This report describes a whole body donation from a person with a documented occupational intake of uranium. USTUR Case 1002 was an adult male who died from an acute cerebellar infarct at the age of 83. He worked as a power operator, utility operator, and metal operator for 28 years in a facility that processed and handled radioactive materials. Although he suffered a number of burns from hot metal and acids, cuts, abrasions, and puncture wounds during his many years of work, there were no corresponding health physics or medical records to indicate that these occurrences needed or required excision or decontamination due to the suspicion of the deposition of radioactive material. Over the course of his employment, USTUR Case 1002 submitted numerous urine samples for uranium, plutonium, and fission product analysis. The highest single uranium value measured during this time period was approximately 30 microg L(-1) recorded during the second year of his employment. A urinary bioassay sample taken before termination of employment measured 4.3 microg L(-1). The mean urinary uranium concentration per liter per year calculated from the employee's bioassay records covering the first eleven years of monitoring averaged less than 3 microg L(-1). The ratio of 234/238U activity in the lung tissue was about 1, the same as that found in natural uranium. The highest concentration of uranium was found in a tracheobronchial lymph node. The uranium content in the various tissues of the body followed a rank order lung > skeleton > liver > kidney. Concentration of uranium in the kidney tissue was approximately 1.98 ng g(-1), about 3 orders of magnitude less than the generally accepted threshold level for permanent kidney damage of 3 microg U g(-1) and roughly equal to the 1.4 ng g(-1) reported for Reference Man. The autopsy disclosed findings not uncommon in the aged: severe atherosclerosis, areas of sclerotic kidney glomeruli with stromal fibrous scarring, and moderate to severe arterionephrosclerosis. Lung sections contained parenchymal areas of acute vascular congestion and a mild degree of anthracosis.

Plutonium content of human placental tissues after occupational exposure.

The placenta and umbilical cord were obtained following a normal live delivery from a volunteer donor who had received an accidental inhalation intake of plutonium 12 years prior to her pregnancy (Case 0777). Her employer estimated the intake to be about 73 Bq Class W plutonium. Based on bioassay results and clearance models in use at that time, they calculated her body content at the beginning of pregnancy to be about 5.6 Bq with an average concentration of approximately 60 mBq kg(-1). The placenta and cord from this pregnancy, along with the placenta and cord from a donor with no known exposure to plutonium (Case 0835), were divided and assayed for plutonium by ultrasensitive fission track analysis at two collaborating laboratories. Placental 239Pu concentration values obtained by the two laboratories for Case 0777 agreed within a factor of 2 and were several-fold greater than for the control, Case 0835, as well as values that had been reported by others for unexposed populations. There was no elevated concentration of plutonium in the umbilical cord from the exposed person. The data yielded values of 0.16 and 0.27 for placental to maternal concentrations (CPl: CM) that were of the same order of magnitude as the value of 0.1 the ICRP calculated for intakes before pregnancy.

Tissue studies of persons with intakes of the actinide elements: the U.S. Transuranium and Uranium Registries.

For more than three decades, the United States Transuranium and Uranium Registries (USTUR) have studied the biokinetics, dosimetry, and biological effects of plutonium, uranium, and americium through voluntary postmortem tissues from persons with known intakes. Radiochemical analyses of tissue obtained at autopsy have shown that plutonium and americium have different biokinetics and an appreciable deposition in the soft tissues of the body as well as the known depots in skeleton and liver. Studies of whole-body Thorotrast donors to the USTUR indicate that commonly accepted risk coefficients for alpha induction of bone sarcoma may be too high while those for leukemia are a factor of six too low. This review considers these and other major contributions of the USTUR.

Causes of death in a cohort of 260 plutonium workers.

The United States Transuranium and Uranium Registries (USTUR) is a unique postmortem research study of the biokinetics, dosimetry, and possible biological effects of actinide elements in persons with occupational exposure to these radioelements. Evaluation of the causes of death in the admittedly biased self-selected cohort of the first 260 deceased participants in the USTUR revealed, in general, no apparently elevated causes of death except for six cases of mesothelioma and six cases of astrocytoma glioblastoma multiforme. The mesothelioma cases had a documented occupational exposure to asbestos, and the six brain tumor deaths all occurred at a single work site and were not radiation related but rather are likely attributable to a factor specific to the work site or surrounding area. Incidental findings in this cohort did not suggest any radiation related illness or cause of death.

A sensitive method for the determination of uranium in biological samples utilizing kinetic phosphorescence analysis (KPA).

Kinetic phosphorescence analysis is a technique that provides rapid, precise and accurate determination of uranium concentration in aqueous solutions. This technique utilizes a laser source to excite an aqueous solution of uranium, and measures the emission luminescence intensity over time to determine the luminescence decay profile. The lifetime of the luminescence decay profile and the linearity of the log luminescence intensity versus time profile are indications of the specificity of the technique for uranium determination. The luminescence intensity at the onset of decay (the initial luminescence intensity), which is the luminescence intensity at time zero after termination of the laser pulse used for excitation, is proportional to the uranium concentration in the sample. Calibration standards of known uranium concentrations are used to construct the calibration curve between the initial luminescence intensity and uranium concentration. This calibration curve is used to determine the uranium concentration of unknown samples from their initial luminescence intensity. We developed the sample preparation method that allows the determination of uranium concentrations in urine, plasma, kidney, liver, bone spleen and soft tissue samples. Tissue samples are subjected to dry-ashing in a muffle furnace at 600 degrees C and wet-ashing with concentrated nitric acid and hydrogen peroxide twice to destroy the organic component in the sample that may interfere with uranium determination by KPA. Samples are then solubilized in 0.82 M nitric acid prior to analysis by KPA. The assay calibration curves are linear and cover the range of uranium concentrations between 0.05 micrograms l-1 and 1000 micrograms l-1 (0.05-1000 ppb). The developed sample preparation procedures coupled with the KPA technique provide a specific, sensitive, precise and accurate method for the determination of uranium concentration in tissue samples. This method was used to quantify uranium in different tissue samples obtained over a period of 90 days following a single intraperitoneal uranium dose of 0.1 mg kg-1 in rats.

Pathway to a paradigm: the linear nonthreshold dose-response model in historical context. The American Academy of Health Physics 1995 Radiology Centennial Hartman Oration.

This paper traces the evolution of the linear nonthreshold dose-response model and its acceptance as a paradigm in radiation protection practice and risk analysis. Deterministic effects such as skin burns and even deep tissue trauma were associated with excessive exposure to x rays shortly after their discovery, and carcinogenicity was observed as early as 1902. Still, it was not until 1925 that the first protective limits were suggested. For three decades these limits were based on the concept of a tolerance dose which, if not exceeded, would result in no demonstrable harm to the individual and implicitly assumed a threshold dose below which radiation effects would be absent. After World War II, largely because of genetic concerns related to atmospheric weapons testing, radiation protection dose limits were expressed in terms of a risk based maximum permissible dose which clearly implied no threshold. The 1927 discovery by Muller of x-ray induced genetic mutations in fruit flies, linear with dose and with no apparent threshold, was an important underpinning of the standards. The linear nonthreshold dose-response model was originally used to provide an upper limit estimate of the risk, with zero being the lower limit, of low level irradiation since the dose-response curve could not be determined at low dose levels. Evidence to the contrary such as hormesis and the classic studies of the radium dial painters notwithstanding, the linear nonthreshold model gained greater acceptance and in the centennial year of the discovery of x rays stands as a paradigm although serious questions are beginning to be raised regarding its general applicability. The work includes a brief digression describing the work of x-ray protection pioneer William Rollins and concludes with a recommendation for application of a de minimis dose level in radiation protection.

A histological kidney study of uranium and non-uranium workers.

Kidney tissue sections were obtained at autopsy from seven persons with a history of low level occupational exposure to uranium and histologically compared in a blind study with similar sections obtained from six reference cases. The pathologist was unable to identify the uranium workers or any uranium-specific nephropathy. This suggests that the chronic low level of kidney uranium concentration experienced by these workers, which was an order of magnitude lower than the accepted permissible level of 3 microgram per gram, did not induce any identifiable permanent tissue damage.

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.

History of the medical uses of radiation: regulatory and voluntary standards of protection.

The main focus of this paper is on the historical development of safety standards in the use of radiation or radioactive materials in medicine. However, to provide better understanding and perspective on this history, it must be interwoven with major events and advancements in the development and use of radiation, particularly in the field of medicine. Since this history, as well as that of major events that stimulated the development of radiation protection standards, is extensive, only a very brief overview can be given here. Thus, a sufficient list of references is also provided to allow further examination of detailed historical documentation, and to provide an easier entry into further research. Also, some identification of individuals who have made important contributions to the development of standards, but who are not widely identified in either the relevant standards or the historical literature, is included. This will aid the serious historian in examining files of organizations to uncover facts or rationale that could better explain historical events or developments.

Radiation protection and medical practice with special reference to health physicists and the Health Physics Society.

This paper broadly examines the historical development of radiation protection in medical practice through an examination of the interactions of those concerned with radiation protection and medical practice with emphasis on the last half century and on the role played by health physicists and the Health Physics Society. Included is a brief discussion of the relevant activities of various federal agencies and other organizations including the Atomic Energy Commission and successors and the U.S. Public Health Service; the National Council on Radiation Protection and Measurements and International Commission on Radiological Protection; and the Health Physics Society, American Board of Health Physics, American Association of Physicists in Medicine, Society of Nuclear Medicine, and Conference of Radiation Control Program Directors and related scientific and professional bodies.

Overview and dosimetry of the Hanford Americium accident case.

Postmortem examinations of selected tissues from an individual who received a massive internal exposure to 241Am and succumbed to pre-existing cardiovascular disease 11 y later are summarized. Significant findings include acellularity of the marrow, marked peritrabecular fibrosis, and a lack of bone surface remodeling, confirmed by bone-surface alpha-spectrometry; tissue concentrations of 241Am that indicate bone and liver as the primary deposition sites, in general agreement with the new ICRP model, but not with the older models; a distribution of 241Am in soft tissues in general agreement with that observed in animals; and the absence of any other gross or microscopic pathological findings attributable to the exposure. Cumulative absorbed doses to the bone, bone surface, liver, and lung were 18, 520, 8, and 1.6 Gy, respectively. The probability of not observing a fatal cancer based on BEIR-IV risk factors for these absorbed doses was 12%.

Postmortem tissue contents of 241Am in a person with a massive acute exposure.

241Am was determined radiochemically in the tissues of USTUR Case 246, a 76-y-old man who died of cardiovascular disease 11 y after massive percutaneous exposure following a chemical explosion in a glove box. This worker was treated extensively with a chelation drug, DTPA, for over 4 y after exposure. The estimated 241Am deposition at the time of death was 540 kBq, of which 90% was in the skeleton, 5.1% in the liver, and 3.5% in muscle and fat. Among the soft tissues, the highest concentrations were observed in liver (22 Bq g-1), certain cartilaginous structures such as the larynx (15 Bq g-1) and the red marrow (9.7 Bq g-1), as compared with the mean soft tissue concentration of approximately 1 Bq g-1. Concentration in muscle was approximately that of the soft tissue average, while concentrations in the pancreas, a hilar lymph node and fat were less than the average. Concentrations in bone ash were inversely related to the ratio of ash weight to wet weight, a surrogate for bone volume-to-surface ratio. The distribution of activity in this case is reasonably consistent with that observed in another human case, when allowance is made for chelation therapy, and also tends to support more recent models of 241Am metabolism.

Histopathology and 241Am microdistribution in skeletal USTER Case 246.

Histopathology and qualitative autoradiography studies were undertaken on bone removed at autopsy from USTUR Case 246. The histopathology examination revealed extensive bone marrow peritrabecular fibrosis and decreased cellularity in most samples. In addition, histological indicators suggest that bone cell turnover was suppressed at most sites, although turnover was found to be essentially normal in a vertebral body sample. The autoradiographic studies showed that bone turnover that had occurred resulted in the redistribution of americium within bone. However, surface deposits of americium remained conspicuous at many sites, particularly those with low bone growth activity. A few percent of the americium was present in the bone marrow. The dosimetric and toxicology findings indicate that current assumptions about the metabolic behavior of bone-seeking radionuclides are likely to be unrealistically simplistic.

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.

Alpha radiation risk coefficients for liver cancer, bone sarcomas, and leukemia.

This study compares published risk coefficients with those determined from dose rates established by postmortem radiochemical analysis of tissues from two whole body donors to the U. S. Transuranium and Uranium Registries, both of whom had been injected with Thorotrast approximately four decades prior to death. The dose data from these cases were used in combination with published latent periods and epidemiologic study results to calculate the following risk coefficients: 0.020 liver cancers Gy-1, 0.002 bone sarcomas Gy-1, and 0.032 leukemias Gy-1. These compare with the ranges of 0.013 to 0.074 liver cancers Gy-1, 0.0016 to 0.0120 bone sarcomas Gy-1, and 0.005 to 0.060 leukemias Gy-1 reported in the literature. The results of this study are generally consistent with previously reported values with two exceptions: the values for bone sarcomas fall below the range given by BEIR IV and the values for leukemia are a factor of 6 greater than those reported by BEIR IV. This suggests that the BEIR IV risk coefficient for bone sarcomas may be too high, and that for leukemia may be too low.