On July 19, the 61st Annual Meeting of the Health Physics Society featured a one-day special session, “USTUR: Five-Decade Follow-Up of Plutonium and Uranium Workers.” The session was opened by Dr. Patricia Worthington, Director of the Office of Health and Safety (DOE/AU-10), and was followed by two keynote presentations. Ronald Kathren explored “where we have been and where we are going” and Eugene Carbaugh summarized the largest recorded 241Am deposition in a human. The remaining nine presentations showcased current research that is being carried out by USTUR faculty as well as national and international external collaborators. Topics included the use of chelating agents, such as DTPA, to removed plutonium from the human body, and the importance of plutonium binding in the lungs.
The special session concluded with a roundtable discussion on “50 years of USTUR history.” It was led by a panel of former directors and scientists who were involved with the Registries when its predecessor organizations were established:
- Margery Swint, USTR/USUR director (1982– 1989)
- Ronald Kathren, USTUR director (1989–1999)
- Ronald Filipy, USTUR director (1999–2005)
- Jim McInroy, in charge of USTUR radiochemistry work at LANL (1975–1992)
- Roger McClellan, SAC member (2010-present)
- Robert Bistline, SAC member (2007-2016)
Panel members introduced themselves and briefly summarized their involvement in the Registries. Conference attendees were then invited to ask questions of the roundtable panel members. The roundtable discussion was chaired by Richard Toohey (M.H. Chew & Associates).
Additionally, the USTUR hosted a two-day informational booth at the meeting. USTUR staff answered questions about the Registries, and handed out informational brochures. The booth’s purpose was to maintain the visibility of the USTUR among HPS members, and to introduce ourselves to those who were not familiar with the Registries.
KEYNOTE: The USTUR: Where we have been and where we are going
Ronald L. Kathren (WSU Tri-cities)
The evolution of the USTUR is sketched from its modest beginnings as the National Plutonium Registry in 1968 through administrative and scientifically noteworthy significant events and findings over its history, beginning with its start of operations and development of operating protocols until the present day. Administrative events discussed include formation of the parallel U.S. Uranium Registry (1978) and its ultimate amalgamation (1989) with its elder sister registry to create the USTUR; the appointment and evolving role of the Scientific Advisory Committee; the changing role of the Registries and its relationships with other programs over the years; directors; adverse publicity and investigations into USTUR operations by the General Accounting Office and the special Presidential Advisory Committee on Human Radiation Experiments. Scientific events specifically discussed are the first program description and operating protocol publications in the peer reviewed literature (1972); the results of tissue analyses from the first 30 autopsies (1975); and the radiochemical analysis of first whole body donation which led to indicated changes in the generally accepted ICRP biokinetic model and improved calibration of in vivo counting for americium. Brief mention will be made of the postmortem findings in the Hanford accidental exposure case as well as other postmortem tissue evaluations along with the implications and indications of these findings with respect to modeling and protection standards. Postmortem radiochemical analysis of tissues obtained at autopsy and from whole body contributions have led to improved understanding of the biokinetics and improved values of biokinetic constants for uranium, plutonium, and americium. Such data lead to refinement of biokinetic models underlying internal emitter safety standards and include previously unrecognized differences in soft tissue and skeletal uptake and retention of plutonium and americium; in the residence time in skeleton for uranium; distribution and bone and liver cancer and leukemia risk coefficients; and the development of a refined biokinetic model for inhaled UF6. Finally, specific current ongoing research activities of the USTUR, both intra and extramural, and potential future directions are discussed.
KEYNOTE: The Atomic Man: Case study of the largest recorded 241Am deposition in a human
Eugene H. Carbaugh (Dade Moeller)
The 1976 explosion of an ion exchange column at the Hanford Site resulted in the largest human uptake of 241Am ever recorded. The worker underwent wound debridement, extensive personal skin decontamination and long-term DTPA chelation therapy for decorporation of 241Am. Because of the contamination levels and prolonged decontamination efforts, care was provided for the first three months at a unique emergency decontamination facility with gradual transition to the patient’s home occurring over another two months. Follow-up monitoring and medical care was provided for the rest of his life. Upon his death 11 years later, from causes unrelated to the accident, the USTUR received tissue donations allowing detailed biokinetic and dose evaluation. Dubbed “the Atomic Man” by the press, USTUR Case 246 has been the subject of numerous reports and journal articles describing the accident, case management, dosimetry, and post-mortem findings. His systemic total body 241Am content was estimated to be 545 kBq at the time of death, distributed approximately 86% in the bone (primarily bone surfaces), 5% in the liver, 5% in other soft tissues, and 4% in the bone marrow. The distribution reflected the high degree of effectiveness of DTPA therapy in removing 241Am from soft tissue, and its relative ineffectiveness in removing it from bone.
Estimation of actinide skeletal content from a single bone analysis
Sergei Y. Tolmachev (USTUR), Ronald L. Kathren (WSU Tri-cities)
Estimation of the total skeletal actinide content (Ask) is important to support biokinetic modeling of actinides. Ask is calculated as a product of radionuclide activity concentration (Crad) and skeletal weight (Wsk), Ask = Crad x Wsk. The large uncertainties are typically associated with the estimated activity, as generally only few bones are analyzed and ICRP reference weight of 10.5 kg or height-weight equation are used to estimate the skeleton weight. Several approaches are published for plutonium and americium activities estimation in a human skeleton based on the analyses of limited number of bones collected at autopsy and various assumptions on skeleton weight. Alternatively, Ask can be estimated from a single bone analysis if a fraction of total skeleton activity (deposition coefficient, Kdep) is known for this particular bone. The use of Kdep = Abone/Ask, allows simple straightforward calculation of total skeleton activity from a single bone analysis with reduced uncertainties. In addition, a linear regression equation, Ask = a x Abone + b, can be used. In this study, Kdep values were calculated for patella bone using data from 16 whole body donors to the United States Transuranium and Uranium Registries (USTUR) with known exposure to 238Pu, 239Pu, and 241Am. Total 238Pu, 239Pu, and 241Am skeletal activities were calculated using a standardized methodology. The average Kdep values (±standard deviation) for 238Pu, 239Pu, and 241Am were calculated as 0.0037 ± 0.0015, 0.0033 ± 0.0012, and 0.0040 ± 0.0013, respectively. With repeated ANOVA test, no significant difference was found among Kdep for 238Pu, 239Pu, and 241Am (p=0.126) resulting in the average Kdep = 0.0037 ± 0.0013 (n=48) for the actinides. Thus, the measured activity of plutonium or americium in patella can be reliably used to estimate the total skeletal content. Actinide total skeletal content can be simply obtained by multiplying the measured activity in the patella by 1/Kdep = 273 ± 98. Using linear regression analysis for log-transformed data (n=48), the excellent correlation, with a slope of 0.957 ± 0.023, and 2.411 ± 0.036 intercept, was found between activity in patella and that in the skeleton (r2=0.973). [USTUR-0392-16A]
Updating ICRP 70 skeleton weight vs. body height equation
Maia Avtandilashvili (USTUR), Sergei Y. Tolmachev (USTUR)
A total skeletal activity is one of the fundamental quantities for modeling biokinetics of bone-seeking radionuclides. The uncertainty in the activity estimates depends on the precision of radionuclide bone concentration measurements and the accuracy of the calculated skeleton weights. This is a challenging task, especially if only limited number of bones are collected and analyzed and no prior information on skeleton weight is available. In 1995, the International Commission on Radiological Protection (ICRP) published the skeleton weight vs. body height equation, W(kg) = 10.7 + 0.119 x H(cm), based upon data from 31 male individuals including two US Transuranium and Uranium Registries (USTUR) whole-body donors. Currently, data are available from additional USTUR whole-body donations that provide a unique opportunity to update the ICRP 70 equation. In this study, the total skeleton weights were estimated for 39 male whole-body donors, including 2 previously used by ICRP. All skeleton weights were calculated using a standardized approach and corrected for bilateral asymmetry, and possible bone mass losses during dissection. Body heights were based upon autopsy reports (when available) or medical examination records. To update the skeleton weight vs. body height correlation, original ICRP 70 and new USTUR data were combined in a set of 68 data points representing a group of 25 to 90+ year old individuals. For this group, body heights and skeleton weights ranged from 155 to 188 cm and 6.5 to 13.4 kg, respectively. Data were fitted with a linear least-square regression. A significant correlation between two parameters was observed (r = 0.55), and a new skeleton weight vs. body height equation was derived: W(kg) = 6.65 + 0.094 x H(cm). This equation will be used to estimate the skeleton weights and, ultimately, total skeletal actinide activities for biokinetic modeling of the USTUR partial-body donation cases. [USTUR-0390-16A]
USTUR Case 0785: Modeling Pu decorporation following complex exposure
Sara Dumit (USTUR), Maia Avtandilashvili (USTUR), Bastian Breustedt (Karlsruhe Institute of Technology, Germany), Sergei Y. Tolmachev (USTUR)
High levels of exposure to actinides can cause severe health effects. Individuals with significant internal contamination typically undergo treatment with chelating agents to accelerate urinary excretion and thus reduce radiation dose to sensitive tissues. The US Transuranium and Uranium Registries (USTUR) studies actinide biokinetics and tissue dosimetry by following up occupationally exposed workers. These studies are fundamental to improving the reliability of, and confidence in, radiation dose and risk assessment methods. By linking radiation exposure history, bioassay results, and medical data with post-mortem measurements of actinides in the human body, we aim to develop and parameterize a biokinetic model for plutonium decorporation therapy. USTUR Case 0785 was selected for this study. This individual was exposed to plutonium via inhalation and wounds due to an explosion at the defense nuclear facility, and underwent chelation treatment. Worksite personnel estimated his systemic deposition at 7.4 kBq. The 239Pu whole-body activity at the time of death, estimated from tissue radiochemical analysis, was 2.8 kBq. Of these, 69.7% was deposited in the skeleton, 21.7% in the liver, and 6.5% in the respiratory tract. The results confirmed that internal deposition of plutonium was caused by inhalation and wound intake, and provided additional information on material solubility type. In this preliminary study, IMBA Professional Plus software was applied to fit post-mortem plutonium activities measured in the lungs, liver and skeleton. The ICRP 130 human respiratory tract model, NCRP 156 wound model, and Leggett plutonium systemic model were used with default assumptions of material type. As small particles are typically generated due to explosion, 1 µm particle size was used instead of ICRP 130’s default value of 5 µm. Inhalation and wound intake regimes were fitted simultaneously. Results of calculations were consistent with the ICRP 68 Type S material. The residual fraction of total intake, not removed by chelation treatment, was estimated at approximately 24 kBq with 89% contributed by inhalation. This information will be used for modeling plutonium decorporation therapy. [USTUR-0391-16A]
Digital autoradiography of Am-241 spatial distribution within trabecular bone regions
George Tabatadze (USTUR), Brian W. Miller (PNNL, Univ. of Arizona), Sergei Y. Tolmachev (USTUR)
The ionizing-radiation Quantum Imaging Detector (iQID) is used at the United States Transuranium and Uranium Registries (USTUR) for imaging Alpha-emitters: Am-241, Pu-239, and Ra-226. The iQID allows visualizing the distribution of Alpha-particle events and differentiating between the surface-seeker (Am, Pu) and bone volume-seeker (Ra) radionuclides and their activity quantification. In this study, spatial distribution of metabolized Am-241 within trabecular bone regions was investigated using USTUR Case 0846 (voluntary donor). For this individual, initial Am-241 whole-body deposition was estimated to be 66.6 kBq. Post-mortem radiochemical analysis indicated that 29.6 kBq were retained in the skeleton 40 years post exposure. Bone specimens were sampled from humerus proximal end, humerus proximal shaft, and clavicle acromial end. These specimens were embedded in methyl methacrylate plastic and processed to produce multiple 100µm-thick sections. Bone sections were polished to a fine surface and anatomical structure images were taken with a digital microscope. All bone sections were imaged at 35 µm resolution for at least two weeks. In order to evaluate the radionuclide distribution and corresponding histology precisely, iQID images were co-registered and superimposed with the anatomical structure images. The Am-241 activity distributions were visualized and quantified in cortical bone and trabecular spongiosa. These two bone regions are well represented within the humerus proximal end. High activity concentration of Am-241 was measured in trabecular bone region. Activity concentration ratio was used to represent radionuclide distribution within different bone regions. The cortical bone-to-trabecular spongiosa activity concentration ratio of 1:0.7 was calculated for the humerus proximal end. This is in agreement with ratios obtained from radiochemical analysis 1:0.7 and ICRP biokinetic model predictions 1:0.5. The cortical-to-trabecular bone activity concentration ratio of 1:2.7 was in agreement with that of 1:3 obtained from radiochemical analysis. This quantitative digital autoradiography imaging approach is proven to be an effective method for micro-scale heterogeneous distribution studies, where traditional counting methods do not apply. [USTUR-0389-16A]
Reanalysis of radiation and mesothelioma in the U.S. Transuranium and Uranium Registries
Joey Y. Zhou (U.S. DOE/AU-13), Stacey L. McComish (USTUR), Sergei Y. Tolmachev (USTUR)
It has been noted for years that there is an excess of mesothelioma deaths among the Registrants of the U.S. Transuranium and Uranium Registries (USTUR). The previous analyses to link the excess of mesothelioma to radiation were done inappropriately in part due to the small number of mesothelioma cases and the use of the U.S. general population as a comparison group. The reanalysis applied an internally matched case control approach to evaluate the cluster of mesothelioma cases in association with cumulative external radiation exposures. First, all causes of USTUR Registrants’ deaths were classified into 4 groups: mesothelioma cases (Meso), lung cancers (LC), other cancers (OC), and non-cancers (NC). Second, for each case of mesothelioma, controls were identified in the LC (2 ~ 3 controls per case), OC (2 ~ 5 controls per case), and NC (2 ~ 5 controls per case) groups matching gender (male), race (white), years of employment (± 2.5 years), first hire (± 5 years), birth year (±5), and age at death (±5 years). Third, a paired t-test (one sided) was used to examine whether there were statistically significant differences in cumulative external radiation doses between cases in Meso group and respective controls in LC, OC, and NC groups. In practice, a permutation paired t-test (PPTT) was developed to run the significance tests based on a large number of paired t-tests. For each paired t-test, one control for each case was randomly selected from multiple (2 ~5 controls per case) matching controls. This procedure was repeated at least 5,000 times, and the percentage of statistically significant (p < 0.05) paired t-tests was counted. Inference was reached based on whether or not 5% or more of PPTTs were statistically significant. PPTTs were not significant for Meso vs. LC, and Meso vs. OC; PPTTs were significant, however, for Meso vs. NC with larger than 9.0% of significant paired t-tests. A follow up conditional logistic regression for the Meso and NC groups showed a non-statistically significant odd ratio (OR) of 1.001 (95% CI: 0.997 ~ 1.006) between cumulative external radiation doses and mesothelioma. The internally matched case control analysis suggested that the excess of mesothelioma deaths among USTUR Registrants was not associated with cumulative external radiation exposures. [USTUR-0394-16A]
Red marrow dosimetry for former radium workers
Richard E. Toohey (M.H. Chew & Assoc.), Ronald E. Goans (MJW Corp.), Carol J. Iddins (ORISE), Nicholas Dainiak (ORISE), Stacey L. McComish (USTUR), Sergei Y. Tolmachev (USTUR)
A collaboration between the Radiation Emergency Assistance Center and Training Site (REAC/TS) at the Oak Ridge Institute for Science and Education (ORISE) in Oak Ridge, TN and the United States Transuranium and Uranium Registries (USTUR) at Washington State University in Richland, WA has resulted in the discovery of a possible long-term biodosimeter that could be useful for population screening and/or epidemiological studies. The pseudo-Pelger-Huet (pseudo-P-H) anomaly consists of characteristic bi-lobed nuclei in neutrophils that can be easily assessed by light microscopy of a peripheral blood (PB) smear. Since PB cell culture is not required (as with dicentric chromosome analysis), a marked reduction in time to obtain results is achieved. A set of 166 PB smears from former workers in the luminizing industry was provided by the USTUR from the National Human Radiobiology Tissue Repository and examined at REAC/TS; the anomaly was characterized as the percentage of pseudo-P-H cells among neutrophils. The radium intakes of most of the subjects are given in R. E. Rowland’s publication, Radium in Humans: A Review of U.S. Studies (1994). The published intakes, based on whole-body counts, had to be modified to accommodate changes in the ICRP biokinetic model for radium since they were originally calculated. Red marrow doses were computed from the adjusted intakes of 226Ra and 228Ra by using the ingestion dose coefficients given in ICRP Publication 67. However, because many of the workers started in their teens, doses were adjusted for age at intake; the dose coefficient for a 15-year-old was used for intakes occurring before age 25, and the adult dose coefficient was used for intakes at age 25 and above. Starting dates of exposure ranged from 1914 to 1950, and ages at first exposure ranged from 13 to 40 years. Exposure durations ranged from 1 to 1800 weeks and the vast majority of these PB samples were drawn between 1973 and 1975 at the time of the whole-body counts. Calculated red marrow doses ranged from zero to 13.6 Gy-eq, computed with a radiation weighting factor of two for alpha particles producing tissue reaction effects. A companion paper by R. E. Goans et al. presents the dose-response data for the pseudo-P-H anomaly in these cases. *Acknowledgements: this work was supported by the U.S. Department of Energy under contract number DE-AC05-06OR23100 with Oak Ridge Associated Universities and award number DE-HS0000073 to Washington State University. The U.S. government retains a non-exclusive copyright on this work to use for government purposes. [USTUR-0393-16A]
The pseudo Pelger-Huet cell as a retrospective dosimeter: Analysis of a radium dial painter cohort
Ronald E. Goans (MJW Corp.), Richard E. Toohey (M.H. Chew & Assoc.), Carol J. Iddins (ORISE), Nicholas Dainiak (ORISE), Stacey L. McComish (USTUR), Sergei Y. Tolmachev (USTUR)
Recently the pseudo-Pelger Huët anomaly (PHA) in peripheral blood neutrophils was described as a new radiation-induced, stable biomarker (Goans et al. Health Phys 108(3), 2015). In this study, we have examined PHA in peripheral blood slides from a cohort of 166 former radium dial painters, 35 of whom had zero marrow dose. The slides were made available in collaboration with the US Transuranium and Uranium Registry (USTUR). Members of the radium dial painter cohort had ingestion of 226Ra and 228Ra at an early age (average age 20.6 ± 5.4 y; range 13-40 y) during the years 1914-1955. Exposure duration ranged from 1-1820 weeks with marrow dose 3-13,500 mGy-Eq. Red marrow alpha dosimetry for this study is described in a companion paper by R.E. Toohey et al. The peripheral blood slides were prepared 1960-1965 during medical follow-up and were quite suitable for light microscope evaluation after 50+ years. PHA in neutrophils is characterized by oval, symmetric bilobed nuclei which are joined by a thin mitotic bridge. PHA is known to be caused by a decreased amount of the lamin B receptor (LBR). The B-type lamins are the building blocks of the cell’s nuclear lamina and the LBR gene is known to be located on the long arm of chromosome 1, 1q42.12. PHA expressed as a percentage of total neutrophils in this cohort rises in a nonlinear fashion over five decades of red marrow dose. Six subjects in this cohort eventually developed malignancies: five osteosarcomas and one mastoid cell neoplasm. The PHA percentage in these cases rises linearly with RBE-weighted red marrow dose (r2=0.71). No sarcomas are seen for RBE-weighted red marrow dose under 10,000 mGy-Eq (500 mGy). In the context of these experiments, Receiver Operating Curve (ROC) methodology may be used to evaluate the PHA% as a binary laboratory test to determine whether there is alpha dose to bone marrow. A cut-point of 5.74% PHA is found for identification of the dose category (AUC 0.961, sensitivity 97.8%, specificity 74.2%, PPV 94.3% for this dataset). PHA from peripheral blood is therefore a reasonable dose surrogate to evaluate alpha dose to bone marrow. Acknowledgements: this work was supported by the U.S. Department of Energy under contract number DE-AC05-06OR23100 with Oak Ridge Associated Universities and award number DE-HS0000073 to Washington State University. [USTUR-0396-16A]
EURADOS intercomparison on measurements of Am-241 in 3 skull phantoms
Maria A. Lopez (CIEMAT, Spain), Pedro Nogueira (HMGU, Germany), Tomas Vrba (CTU-Prague, Czech Rep.)
An international intercomparison action was organized by the Working Group 7 on Internal Dosimetry of European Radiation Dosimetry Group (EURADOS e.V. www.eurados.org) for the measurement of Americium in 3 skull phantoms using Ge detectors and gamma spectrometry. The exercise counted with the participation of 12 laboratories, 10 from Europe and 2 from North America. The main objectives were to compare the results of counting efficiency in fixed positions over each head phantom, the calculation of the activity of Americium in the skulls and to compare the phantoms it selves to check the best and appropriate features to be fulfilled by a calibration source representing the contamination of Americium in human head bone. The BfS skull was fabricated with real human bone artificially labelled with 241Am in its inner and outside sides and then covered with tissue-equivalent wax (Laurer G 1993). The BPAM phantom from USTUR (United States Transuranium and Uranium Registries) is part of the whole skeleton of a donor (USTUR Case No 102). In this case half of the skull was really contaminated due to an occupational intake of Americium by a U.S. worker, the other half is real human bone from non-contaminated person and the skull was covered by tissue equivalent material (G.S. Roessler, B. Magura. Health Physics. 49(4), 1985). Finally CSR phantom was fabricated as a simple hemisphere of equivalent bone and tissue material. The 3 phantoms differ in complexity, weight, size and shape which permitted a multi-parameter efficiency study. In case the participant counted with own calibration skull phantom, could use the laboratory calibration factor for the calculation of the activity in the 3 intercomparison phantoms. Results are discussed here. A Monte Carlo (MC) intercomparison was organized in parallel with the in-vivo monitoring exercise, using the voxel representations of the 3 physical phantoms. Three tasks were identified with increasing difficulty, starting with simple MC simulation of CSR hemisphere and the HMGU Ge detector for calculating the counting efficiency for the 59.54 keV photons of Am-241 in a predefined measurement geometry. Last step consisted in the MC simulation of the process of detection of each participant to calculate own calibration factor for his own detector system and counting geometry for a person monitoring. Conclusions of the exercise and difficulties found by the 16 participants in developing methodologies for Monte Carlo calibration are presented here.
USTUR Case 0846: Modeling americium biokinetics after intensive decorporation therapy
Bastian Breustedt (KIT, Germany), Maia Avtandilashvili (USTUR), Stacey L. McComish (USTUR), Sergei Y. Tolmachev (USTUR)
One method to avert dose after incorporation of transuranium elements is decorporation therapy with chelating agents such as diethylenetriamine pentaacetate (DTPA). Administration of the therapeutic agent temporally enhances the excretion of the radionuclides. Biokinetic models, which describe the behavior of the radionuclides in the human body, need to be adapted to take into account the effect of the therapy. In this study, biokinetic modeling of decorporation therapy following americium oxide (241AmO2) inhalation was studied using USTUR Case 0846 (voluntary donor). The modeling of this case is a challenge given that the exact date of exposure is unknown. Previously, the case was evaluated using the assumption of chronic inhalation over a 2-year period. However, a possibility of acute intake cannot be dismissed. Initial 241Am whole-body deposition was estimated to be 66,600 Bq. The Registrant was extensively treated with Ca-DTPA over a period of 7 years. A total of 313.5 g DTPA was administered in 342 i.v. injections. At the time of death, 2,740 ± 274 Bq of 241Am was measured in the lungs, 333 ± 33 in the liver, and 19,570 ± 1,957 in the skeleton by external gamma counting. Based on post-mortem radiochemical analysis results, 219.2 ± 1.9 Bq and 29,600 ± 195 Bq of 241Am were retained in the liver and the skeleton, respectively. For this study, a complete set of data including 106 fecal and 1,130 urine measurements was compiled. The CONRAD (Coordinated Network for Radiation Dosimetry) approach was applied to model americium decorporation using the excreta data only. Based on assumptions about the action and distribution of the administered DTPA, different modifications of the model were tested. To solve the compartmental model equations and fit the data, the ModelMaker4 and the SAAMII® software were used. To improve the modeling, tissue radiochemical analysis results were fitted simultaneously with the excretion data. The Bayesian approach was applied to characterize intake scenario and determine initial distribution of americium in the body prior to the therapy. This presentation provides preliminary results on americium biokinetic modeling after intensive decorporation treatment with Ca-DTPA. [USTUR-0388-16A]