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.

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.

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.

Measurement of thorium isotopes and 228Ra in soft tissues and bones of a deceased Thorotrast patient.

The whole body of an individual injected with Thorotrast 36 y prior to her death was analyzed for 232Th, 228Ra, 228Th, and 230Th. Measurement of these isotopes in all tissues of the body will provide data necessary to caculate the radiation dose to individual tissues and to evaluate the risk potential associated with deposition of thorium and progeny in humans. The tissues were ashed, dissolved in acid, and the thorium isolated by ion exchange and electrodeposition. The 228Ra was determined by measuring the 0.991-MeV gamma rays associated with decay of the 228Ac daughter. It was estimated that almost all of the 232Th from the original injection was retained in the body, mostly in the tissues of the reticuloendothelial system. A total of 28 kBq (0.76 microCi) of 232Th was measured in the soft tissues and bones. The body also contained 13 kBq 228Ra, 12 kBq 228Th, and 3.9 kBq 230Th. A Thorotrastoma contained about 3.5% of the total activity. Excluding the Thorotrastoma, approximately 45% of all the activity (232Th, 228Ra, 228Th, and 230Th) was retained in the liver, 13% in the spleen, 2% in muscle, 1% in skin, slightly less than 1% in the respiratory tract, 4% in all other soft tissues, and 33% in the skeleton (bone and bone marrow). Sixty to 80% of the thorium activity in bones containing red marrow was located in the marrow. Bones containing yellow marrow had less than 40% of the thorium activity in the marrow. Highest concentrations were found in the hepatic and other abdominal lymph nodes, spleen, hilar lymph nodes, liver, trachea, and bone. Approximately 60% of the 228Ra formed from the decay of the 232Th had been excreted from the body. The 228Ra and 228Th were in approximate equilibrium throughout the body.

Comparison of systemic plutonium deposition estimates from urinalysis and autopsy data in five whole-body donors.

The systemic deposition of (239 + 240)Pu was determined by postmortem radiochemical analysis of the tissues from five whole-body donors to the United States Transuranium Registry (USTR). All were males with intakes typically occurring many years prior to death. The postmortem radiochemical results were compared with estimates of systemic deposition made with 13 different biokinetic models using urinary excretion data obtained during life. In general, estimates made with older biokinetic models were severalfold greater than those obtained from radiochemical analysis of the tissues. For all five cases, agreement within a factor of two with the tissue analysis results was obtained with two of the biokinetic models evaluated: the Langham power function model as modified by Leggett and Eckerman and the two compartment exponential model proposed in ICRP Publication Nos. 19 and 30.

U.S. Transuranium Registry report on the 239Pu distribution in a human body.

The distribution of 239Pu in a human whole body is reported. The body contained 246 Bq of 239Pu of which 130 Bq (52.8%) was found in the lungs and associated lymph nodes. Of the remaining 116 Bq (47.2%) that constituted the systemic deposition, 51.2 Bq (44%) were in the skeleton, 48.6 Bq (42%) in the liver, and the remainder (14%) in the rest of the body exclusive of the lungs and associated lymph nodes. An unexpectedly high concentration was observed in the pituitary. The systemic distribution of Pu in this case, when combined with the exposure history, is suggestive of an initial partitioning ratio of 239Pu between skeleton and liver of less than unity, and a tentative initial distribution from the transfer compartment of 25% to the skeleton, 50% to the liver, and 25% to the rest of the body and early excretion is proposed for this case. Older biokinetic models, when used with the available urinalysis data for this case, typically overestimated the deposition when compared with the tissue analysis results, but more recent models provided estimates in close agreement with the autopsy results.

Simultaneous multielement analysis of diet samples by inductively coupled plasma mass spectrometry and inductively coupled plasma atomic emission spectrometry.

Diet samples were collected by a duplicated portion study for an adult male in both Mito, Japan and Los Alamos, U.S.A. The ashed samples were analyzed with inductively coupled plasma mass spectrometry (ICP-MS) and inductively coupled atomic emission spectrometry (ICP-AES) for 22 elements. The trace and ultratrace elements, Ba, Mo, Ni, Co, Cd, Cs, Tl, Pb, Bi, Th, and U were determined by ICP-MS. The major and minor elements, Na, K, P, Ca, Mg, Fe, Zn, Mn, Al, Sr, and Cu were determined by ICP-AES. Accuracy and precision for some elements were examined by analyzing National Institute of Standards and Technology (formerly National Bureau of Standards) Standard Reference Materials, 1577b Bovine Liver, and 1573 Tomato Leaves. Simultaneous multielement analyses of diet samples by using the two methods were found to be very useful.

Uranium in the tissues of an occupationally exposed individual.

Uranium concentrations were radiochemically determined in samples of lung, kidney, liver and bone collected at autopsy from an occupationally exposed individual. Levels of U in these tissues were clearly in excess of those expected from environmental exposure. Deposition followed the pattern: skeleton greater than liver greater than kidney, with ratios of 63:2.8:1. The data suggest there is an important long-term storage depot in the skeleton, but the fraction transferred to this compartment, as proposed by ICRP 30, may be too small. In vivo chest counts obtained over about a 10-y period prior to death indicated about a factor of 2 greater in total U content and 235U enrichment than deposition estimates made at autopsy for the lungs and associated lymph nodes.

Comparative skeletal distribution of Am and Pu in man, monkey, and baboon.

The skeletal distribution of Am and Pu in four human cases was compared with the skeletal distributions of these radioelements in baboons and monkeys. Excellent agreement was noted among the four human cases; data were available for Am in all four and Pu in three. A statistically significant correlation was found between the 241Am and 239Pu + 240Pu skeletal distributions in the humans and those in nonhuman primates. Trabecular bone had the highest concentrations of 241Am and 239+240Pu in humans, baboons, and monkeys. Scaling factors are proposed to convert the percentages of skeletal activity in animal bones to the corresponding percentages in the bones of the human skeleton.

Estimation of human gonadal Pu and Ce concentrations from animal data.

Data were obtained from the literature for gonad and body weights and for the Pu or Ce content of the gonads and body at death for several laboratory animal species, five human Pu injection cases, and 731 human adults exposed environmentally to Pu in fallout. Data for Pu concentration in gonads, liver, and bone samples of 59 male and five female occupational Pu cases (including four completely analyzed whole bodies) were obtained from the U.S. Transuranium Registry. A logarithmic function was used to relate fractional Pu or Ce concentration in testes and ovaries to body weight of the animals and to predict fractional Pu or Ce concentrations in human gonads, [Pu]G . PuB-1 = aBWb, where [Pu]G or [Ce]G is the nuclide concentration in gonads (Bq g-1 of wet weight), PuB or CeB is the nuclide content of the body at death, and BW is body weight (kg). The fractional Pu and Ce concentrations in both the testes and ovaries are inverse and nearly linear functions of body weight. The regression lines of fractional Pu or Ce concentration in testes and ovaries have similar slopes (b = -1.07 +/- 0.14); however, the nuclide concentrations (coefficient a) in ovaries are six times greater than in testes. Extrapolation of the animal data yielded fractional Pu concentrations in human testes and ovaries that agree with those calculated for the occupational cases and those recommended by the International Commission on Radiological Protection. The good agreement between the fractional concentrations of Pu and Ce in the testes and in the ovaries suggests that these data can be substituted in metabolic models of chemically similar elements for which gonadal data are scarce.

Determination of U in human tissues by delayed neutron activation analysis.

A rapid, sensitive and highly selective technique using Delayed Neutron Activation Analysis (DNAA) has been used to determine U concentrations in human tissues. Two different sample preparation techniques were compared: one involves total matrix destruction to a dry ash while the other is a nondestructive preparation of the wet sample. The data obtained from the analyses of the same sample by DNAA of wet tissues, DNAA of ashed tissues and from radiochemical analyses using alpha spectroscopy (a standard method of U determination) were statistically equivalent on the basis of variance analysis at the p = 0.05 level.

Partitioning of 238Pu, 239Pu and 241Am in skeleton and liver of U.S. Transuranium Registry autopsy cases.

The content of 238Pu, 239Pu and 241Am in the liver and skeleton was estimated from radiochemical analysis of human liver and bone samples obtained at autopsy from former actinide workers whose occupational histories were suggestive of chronic inhalation exposures, with minor skin contamination and wounds documented in a few individuals. For times estimated to be several years to a few decades post intake, 75.8 +/- 15.3% of the total 241Am in the skeleton and liver was found in the skeleton (25 cases) as compared with 63.4 +/- 24.1% for 238Pu (36 cases) and 53.2 +/- 18.2% for 239Pu (43 cases). These differences are significant at the 95% confidence level. Of these cases, 34 included data on both 238Pu and 239Pu and were divided into high and low activity subgroups. The difference in the fractionation of the two Pu isotopes was apparent only in the low activity subgroup, suggesting that the difference observed between the Pu isotopes may be an artifact of the data. The different partitioning of these three nuclides suggests that the ALIs for 238Pu and 241Am may be high by about 25-50% if only the dose to bone is considered and may be high by 12-13%, based on the weighted committed dose equivalent in target organs or tissues.

Actinide distribution in the human skeleton.

Radiochemical analysis of two half skeletons donated to the United States Transuranium Registry from individuals with occupationally incurred depositions, one of 241Am and the other of 239Pu, revealed an inverse proportionality between the concentration of actinide in the bone ash and the fraction of ash (or the calcium content of the ash). A similar relationship was observed in a third case suffering from osteoporosis, but the slope was shallower. These results suggest that accurate estimates of the total skeletal content of actinide can be made from radiochemical analysis of only a few bone samples.

The U.S. Transuranium Registry report of the 241Am content of a whole body. Part IV: Preparation and analysis of the tissues and bones.

Los Alamos National Laboratory has analyzed autopsy tissue for the USTR, as a part of its study of the uptake, distribution and retention of Pu and other transuranic elements in occupationally exposed workers since 1978. In April 1979, Los Alamos received the internal organs and bone samples from the first whole-body donation to the USTR. The donor was known to have an internal deposition of 241Am. All soft tissue, the bones from the right half of the skeleton, and the odd-numbered vertebrae were received at Los Alamos in February 1980. The bones were subdivided along anatomical areas of interest. All soft tissues and bone specimens were analyzed for their 241Am content. A total deposition of 147.4 nCi 241Am was measured. Approximately 18% of the 241Am remaining in the body (disregarding that in the left hand), was found in the soft tissues, and 82% was in the bones and teeth. The soft tissues and organs containing the largest amounts of 241Am were the combined soft tissue (striated muscle, connective tissue and skin) 8.8%; liver, 6.4% and respiratory tract, 1.5%. The remaining organs accounted for 0.9% of the systemic burden.

Plutonium in gonads: a summary of the current status.

A review of the literature was carried out to investigate the following: the fraction of Pu in the body that was in the gonads; the necessity for a localization factor in calculating the genetic dose to humans; and the possibility that an unexpectedly high relative biological effectiveness (RBE) causing genetic effects could occur for alpha particles. Human autopsy data from both occupationally exposed persons and the public were relied on to determine the amount of Pu in the gonads. It was found that an average fraction of 3 X 10(-3) of the Pu in the body was in the ovaries and testes but there was a wide variation among individuals. While a localization factor over the average of 2.5-4 is needed to calculate the dose to the sensitive cells for rodents, no such factor is required for the human. Information on the RBE for various genetic effects shows RBEs for Pu alpha's about as would be expected from neutron irradiation. The usual quality factor applied in calculating dose equivalent is appropriate and may be conservative, particularly for females.

Plutonium partitioning among internal organs.

An estimate of partitioning of plutonium among skeleton, liver, and other organs is needed to estimate the radiation dose to individual organs. This review was done to provide an analysis of the coefficients currently used for the translocation of plutonium from blood to other organs and excreta. Data from both experimental animals and human autopsy cases were used in our analysis. The analysis of data from 257 experimental animal and 169 human subjects led to a conclusion that a 70-30% split of plutonium distribution between skeleton and liver, respectively, would be appropriate for use in plutonium organ distribution models. Analysis of data from other organs and early excreta indicated that these other compartments generally comprised less than 3% of the total early body burden. The variability of plutonium distribution within all compartments is emphasized, with the conclusion that the coefficients of uptake to individual organs are adequate to estimate average organ doses for an exposed population but use for estimating doses for an individual will lead to uncertain results.