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The skeleton is one of the major retention sites for internally deposited actinides. Thus, an accurate estimation of the total skeleton content of these elements is important for biokinetic modeling and internal radiation dose assessment. Data from 18 whole-body donations to the US Transuranium and Uranium Registries with known plutonium intakes were used to develop a simple and reliable method for estimation of plutonium and Am activity in the total skeleton from single-bone analysis. A coefficient of deposition Kdep, defined as the ratio of actinide content in the patella to that in the skeleton, was calculated for Pu, Pu, and Am. No statistical difference was found in Kdep values among these radionuclides. Variability in Kdep values was investigated with relation to skeleton pathology (osteoporosis). The average Kdep of 0.0051 ± 0.0009 for the osteoporotic group was statistically different from Kdep of 0.0032 ± 0.0010 for nonosteoporotic individuals. The use of Kdep allows for rapid estimation of the total skeletal content of plutonium and Am with up to 35% uncertainty. To improve accuracy and precision of total skeleton activity estimates, regression analysis with power function was applied to the data. Strong correlation (r > 0.9) was found between Pu, Pu, and Am activities measured in the patella bone and total skeleton activity. The results of this study are specifically important for the optimization of bone sample collection for US Transuranium and Uranium Registries partial-body donations.

Dedication: The research of the US Transuranium and Uranium Registries relies heavily upon postmortem autopsy findings and radiochemical analysis of tissues. The enormous debt owed to those now-deceased registrants who unselfishly voluntarily participated in the US Transuranium and Uranium Registries program through postmortem donation of their tissues and to those still-living registrants who have volunteered to be future postmortem tissue donors is hereby acknowledged with gratitude. The scientific findings derived from postmortem analysis of these tissues have been instrumental in advancing our understanding of the actinide elements in humans and have led to refinement, validation, and confidence in safety standards for those who work with these elements as well as for the general public. To these generous and anonymous persons who made this ultimate contribution, this paper is dedicated with great thanks and admiration.

The US Transuranium and Uranium Registries is a human tissue program that collects tissues posthumously from former nuclear workers and radiochemically analyzes them for actinides such as plutonium, americium, and uranium. It was established in 1968 with the goal of advancing science and improving the safety of future workers. Roundtable participants recalled various aspects of this multidisciplinary research program, from establishing consistent autopsy protocols to comparing the registries' findings to those of other programs, such as the historical beagle dog studies and the Russian Radiobiological Human Tissue Repository. The importance of meeting ethical and legal requirements, including written consent forms, was emphasized, as was the need to know whether workers were exposed to nonradiological hazards such as beryllium or asbestos. At Rocky Flats, a bioassay program was established to follow workers after they terminated employment. The resulting data continue to help researchers to improve the biokinetic models that are used to estimate intakes and radiation doses. After 50 y, the US Transuranium and Uranium Registries continues to contribute to our understanding of actinides in humans, which is a testament to the vision of its founders, the generosity of its tissue donors, and the many dedicated scientists who have worked together to achieve a common goal.

Uranium content and concentrations were measured in the tissues of three Caucasian male whole body donors to the U.S. Transuranium and Uranium Registries with no known intake other than from natural environmental sources. Average total body uranium content in the three cases was 81.3 ± 22.3 μg, of which 37.2 ± 2.1 μg (46%) was in the skeleton. The skeleton had a mean concentration of 3.79 ± 0.45 μg U kg(-1) wet weight and 11.72 ± 1.49 μg U kg(-1) ash. Distribution was in bone volume and not predominately on bone surfaces. Soft tissue concentrations ranged over about an order of magnitude, averaging about 0.5 μg kg wet weight for all tissues except the thoracic lymph nodes, which averaged 32.3 times the mean for soft tissue of the three cases. Observed thyroid tissue concentrations were about an order of magnitude greater than the average soft tissue concentration in two of the three background cases, suggestive of a possible long-term depot in this organ. Kidney content of uranium averaged 0.38 ± 0.21 μg for the three cases, an order of magnitude lower than the 7 μg recommended for Reference Man. The lower content and concentration in the kidney do not support a significant long-term depot for uranium in that organ. Assuming equilibrium between intake and excretion, the tissue data suggest a transfer coefficient from blood to skeleton of 0.14 with a residence half-life in the skeleton of 4,950 d (13.56 y), significantly greater than the 1,500 d (4.1 y) half-time proposed by ICRP.

Since 1996, higher than background levels of naturally occurring radioactivity have been documented in both fossil and mineral deposits at Hagerman Fossil Beds National Monument in south-central Idaho. Radioactive fossil sites occur primarily within an elevation zone of 900-1000 m above sea level and are most commonly found associated with ancient river channels filled with sand. Fossils found in clay rich deposits do not exhibit discernable levels of radioactivity. Out of 300 randomly selected fossils, approximately three-fourths exhibit detectable levels of natural radioactivity ranging from 1 to 2 orders of magnitude above ambient background levels when surveyed with a portable hand held Geiger-Muller survey instrument. Mineral deposits in geologic strata also show above ambient background levels of radioactivity. Radiochemical lab analysis has documented the presence of numerous natural radioactive isotopes. It is postulated that ancient groundwater transported radioactive elements through sand bodies containing fossils which precipitated out of solution during the fossilization process. The elevated levels of natural radioactivity in fossils may require special precautions to ensure that exposures to personnel from stored or displayed items are kept as low as reasonably achievable (ALARA).

Title 10, Code of Federal Regulations Part 70, puts forth requirements for licensure of special nuclear material including specific risk criteria for acute intakes based on biological effects. Standards for acute oral and inhalation intakes of soluble low enrichment are proposed for the three levels of biological effects given in the regulations. These levels were developed largely from available human data and have a large measure of conservatism. The proposed threshold for life endangerment was 500 mg for acute inhalation intakes and 2,500 mg for acute ingestion intakes. Acute intakes of 1,400 mg for ingestion and 100 mg for inhalation are proposed as thresholds for irreversible or serious long lasting health effects. For minor transient health effects, the proposed levels are 410 and 30 mg, respectively, for acute ingestion and inhalation intakes. For acute intakes below these levels, no demonstrable toxicological effects are anticipated.

Many nuclear weapons complex workers were required to undergo medical x-ray examinations as a condition of their employment. To ensure that their dose reconstructions are complete, it is necessary to include the contributions from these examinations. X-ray procedures that must be evaluated include: (1) posterior-anterior and lateral radiography, and/or photofluorography, of the chest; (2) anterior-posterior, lateral and oblique lumbar, cervical and thoracic radiography of the spine; and (3) radiography of the pelvis. Each is discussed in the context of conditions that existed during the time the worker was employed. For purposes of dose reconstruction, the x-ray beam size is especially important because the dose conversion factors (DCFs) for each specific body organ depend on whether it was in, or on the periphery of, the primary beam. The approach adopted was to use the DCFs, combined with the entrance kerma, to estimate the organ doses. In cases in which beam output data or information on the primary factors influencing the dose are not available, methods to provide conservative (i.e., claimant-favorable) entrance kerma and dose estimates are adopted. These include specific default values for chest radiography. To account for uncertainties, the estimated doses due to x-ray examinations are increased by 30%.

Although human experience with uranium spans more than 200 years, the LD50 for acute intake in humans has not been well established. Large acute doses of uranium can produce death from chemical toxicity in rats, guinea pigs, and other small experimental animals, with variation in sensitivity among species. However, there has never been a death attributable to uranium poisoning in humans, and humans seem to be less sensitive to both acute and chronic toxic effects of uranium than other mammalian species studied. Highly relevant data on uranium toxicity in humans are available from the experience of persons administered large doses of uranium for therapy of diabetes and from acute accidental inhalation intakes. Although the data on which to establish oral and inhalation acute LD50 for uranium in humans are sparse, they are adequate to conclude that the LD50 for oral intake of soluble uranium compounds exceeds several grams of uranium and is at least 1.0 g for inhalation intakes. For intakes of uranium compounds of lesser solubility, acute LD50 values are likely to be significantly greater. It is suggested that 5 g be provisionally considered the acute oral LD50 for uranium in humans. For inhalation intakes of soluble compounds of uranium, 1.0 g of uranium is proposed as the provisional acute inhalation LD50.

In 2005, the Health Physics Society celebrates its 50th anniversary. During its half century of existence, the Society has evolved from a small group of operationally oriented radiation protection scientists into an organization of several thousand with a recognized and respected peer reviewed journal. The bold decision to form an organization devoted to radiation safety in the United States spurred the formation of such societies in other countries and led to the formation of an international confederation of national societies, which has facilitated scientific communication and exchange worldwide. It also led to the formation of a separate body for the certification of health physicists, which in turn has grown into an academy with more than 1,000 members, and was instrumental in providing basic information establishing the need for a registry of radiation protection technologists.

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.

This paper briefly reviews the contributions made by human tissue studies to improved understanding of the biokinetics, dosimetry and potential bioeffects of plutonium in man. It includes consideration of tissue donations from both environmental and occupational populations, along with a brief history of human experience with plutonium and consideration of the bioethical aspects of post-mortem human tissue sampling.

A 38-y-old Caucasian male who suffered an acute accidental inhalation intake of 6.3 kBq of 241Am was monitored over 2,135 d using periodic in vivo measurements of the activity in the lungs, liver, and skeleton. Lung clearance was described by a two-compartment exponential model with half-times of 110 d and 10,000 d. The observed uptake of 241Am in the liver (72 Bq) and skeleton (170 Bq) was significantly greater than predicted by the ICRP models for liver (5 Bq) and skeleton (8 Bq). The half-time in the liver was approximately 850 d. Estimates of skeletal activity based on head, wrist, and knee counts generally agreed within 25% over the course of the monitoring period. The half-time in the skeleton was approximately 20,000 d.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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%.

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.

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.

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.

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.

Volume and uranium content were determined in individual urine voids over a 76-h (3.25-d) period from six unexposed normal male subjects and three male uranium workers. Uranium analyses were accomplished by a newly developed high-precision kinetic phosphorescence analysis technique with a lower level of detection of 0.007 ng mL-1. Urinary uranium concentrations in individual voids varied by a factor of 2 or less for any one unexposed subject, although there was an order of magnitude variation among the group of unexposed men. The fractional urinary volume excreted in the "standard" so-called simulated 24-h sample was the same for both the unexposed and exposed groups and averaged 0.42 +/- 0.13 of the total daily urine volume. The fraction of uranium in the simulated 24-h samples was 0.43 +/- 0.15 in the unexposed group but only 0.31 +/- 0.13 in the uranium worker group, suggesting that the use of the simulated 24-h urine sample would underestimate the total daily urinary uranium output by approximately a factor of 2 in the uranium workers. Daily urinary excretion relative to intake from drinking water (essentially equal to the gastrointestinal uptake fraction) among the unexposed group ranged from 0.002-0.028, averaging 0.011 +/- 0.008, with an indication that the gastrointestinal uptake factor was inversely proportional to total intake via drinking water.

Results are presented of postmortem human tissue sampling and analysis for plutonium of Hanford Site workers, residents of the nearby Tri-Cities, and individuals residing farther away from the Hanford Site for the period 1970-1975. The majority of Hanford Site workers and nearby residents coming to autopsy had tissue concentrations of plutonium no larger than those who lived farther away from Hanford and whose likely source of plutonium was limited to nuclear weapons testing fallout. Thus, Hanford operations up to that time apparently had made no significant addition to plutonium in those individuals sampled postmortem.

Radioactive measurements and histopathologic findings are described in a patient administered Thorotrast, a radiographic contrast agent, 36 y prior to death and compared with cancer risks noted in epidemiologic studies. This person [designated as U.S. Uranium Registry (USUR) Case 1001] had prearranged for donation of her body to the USUR and the National Cancer Institute for study. Elevated levels of radioactivity were noted in those organs in which excess cancers have been reported in epidemiologic surveys of Thorotrast-exposed subjects. Hepatic tissue in USUR Case 1001 was estimated to have received an average lifetime absorbed dose of 16.2 Gy, based on radiochemical analyses, consistent with the high risks for liver tumors reported in all studied populations. Thorotrast was present throughout the bone marrow of USUR Case 1001, who died secondary to complications of refractory anemia with excess blasts (RAEB). Elevated risks for acute myeloid leukemia have been noted in Thorotrast patients, and more recently, cases of RAEB and RAEB in transformation have been reported. The thorium decay series includes the bone-seeking radionuclides 224Ra and 228Ra, which have been associated with high risks for osteosarcomas, although the association between Thorotrast and bone cancer is not as convincing. The skeleton of USUR Case 1001, however, contained significant levels of radioactivity. Other tissues evaluated in USUR Case 1001 included lung, eye, kidney, and breast, which did not contain elevated levels of radioactivity.

The distribution of radioactivity and the associated doses were evaluated postmortem for USUR Case 1001, a female who had been injected with Thorotrast some 36 y prior to death. The distribution was determined for four nuclides: 232Th and its decay products, 228Ra and 228Th; and 230Th, a contaminant associated with Thorotrast. More than 90% of the activity was associated with the reticuloendothelial system. Approximately 32% of the total activity was found in the total skeleton (mineral bone and bone marrow), which is somewhat higher than expected from the literature. The 44% found in the liver and 12% in the spleen were somewhat lower than expected. This difference may be attributable, in part, to the initial deposition as influenced by colloidal particle size and to the radiation-induced hyposplenism, splenic atrophy, and slight hepatic atrophy observed at autopsy. In addition, roughly 3% of the activity was found in the Thorotrastoma and surrounding carotid artery tissue. Estimated lifetime absorbed doses from the 232Th series were 15 Gy to the liver, 121 Gy to the spleen, 4 Gy to the skeleton, and 16 Gy to the Thorotrastoma. Comparable dose equivalents to these tissues are 300, 2420, 80, and 320 Sv, respectively, assuming a quality factor of 20 for alpha irradiation.

For several decades, thousands of people received Thorotrast during the course of angiography and other radiologic procedures. Eventually, as the hazards of this radioactive, radiographic contrast agent became apparent, research was initiated to further evaluate its associated adverse effects. In 1988 and 1989, Charles W. Mays, together with colleagues at a variety of sites, developed a detailed protocol for the comprehensive postmortem evaluation of one subject who had been administered Thorotrast 36 y previously. This case represents the first holistic approach to the analysis of Thorotrast in a whole body, simultaneously assembling clinical and autopsy findings with dosimetric, radiochemical, autoradiographic, and molecular evaluations.

Samples of bone containing cellular and fatty bone marrow were removed at autopsy from the body of a woman who, following an automobile accident, had been injected with approximately 25 mL of the radiographic contrast medium Thorotrast. The woman survived for 36 y after the accident and died at age 72 y following bone marrow failure. The samples were analyzed to determine their thorium content by x-ray fluorescence and by image analysis. In addition, Thorotrast was visualized in the different bones examined by light microscopy and by backscattered electron imaging with a scanning electron microscope. The results showed Thorotrast to be largely restricted to areas of cellular bone marrow. In such regions, Thorotrast was present throughout the marrow tissue and was also concentrated within cells that were commonly aggregated within focalized areas of the marrow. Overall the results suggest a rather uniform pattern of Thorotrast uptake by the red bone marrow at different skeletal sites. Significant deposits of Thorotrast were not found in fatty yellow marrow. We conclude that Thorotrast-derived risk estimates for human leukemia following high LET, alpha irradiation may be used for calculating the risks of alpha exposure, but with caution.

We analyzed six different tissue DNA samples from a leukemic individual who received an injection of Thorotrast for alterations in proto-oncogene or tumor-suppressor gene structure. Our examination of the DNA indicated an alteration of the c-fms gene in the blood sample from this individual. This locus showed a deletion in which the 3' end of the deleted region maps between exons 11 and 12. In this particular case, the type of leukemia is unknown but myeloid leukemia is a neoplasm associated with individuals injected with Thorotrast. It is possible that the alteration in the c-fms gene of this individual is a consequence of the radiation exposure. No apparent alterations in the c-mos gene were observed in any of the tissues from the individual. This is in contrast to previous studies that described alterations in methylation patterns associated with the c-mos locus in radium-exposed individuals. A number of the individuals exposed to radium also had alterations of the retinoblastoma gene while no such alterations were observed in any tissue DNA samples from this Thorotrast case. It is possible that our inability to detect alterations of the c-mos and retinoblastoma gene may be attributable to the nature of alpha-emitting radionuclides or their distribution, or to the limited set of tissues available for analysis.