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U.S. Transuranium and Uranium Registries Conference Contributions

Health Physics Society Meeting, Spokane, WA, July 17-21, 2022

The 2022 Health Physics Society meeting was held in Spokane, WA. The USTUR hosted an exhibitor booth, where staff provided information about the Registries and the unique research opportunities available there. Eight members of the USTUR faculty and staff attended the meeting, and USTUR faculty were authors on six presentations in three different sessions: internal dosimetry, radiobiology and biological response, and a special session on Department of Energy (DOE) health studies.

U.S. Transuranium and Uranium Registries: 2010 – 2022 research accomplishments and collaborative efforts

Sergei Tolmachev (USTUR)

The United States Transuranium and Uranium Registries (USTUR), and the associated National Human Radiobiology Tissue Repository (NHRTR), is a federal-grant program funded by U.S. Department of Energy and operated by College of Pharmacy and Pharmaceutical Sciences at Washington State University in Richland, Washington, USA. The Registries was established in 1968 to study the biokinetics and internal dosimetry of actinides (uranium, plutonium, and americium) in occupationally-exposed Registrants who volunteered portions of their bodies, or their whole bodies, for scientific use posthumously. The USTUR is the only program worldwide that can comprehensively study biokinetics and dosimetry of internally deposited actinides. The USTUR serves as a source for both scientific research and public information regarding the biokinetics and tissue dosimetry of the actinide elements in humans. Since 1992, eight PhD and eight MS students have used USTUR data to complete the research requirements of their studies. Currently, USTUR research focuses on: (i) estimation of uncertainties in radiation dose assessment for internally deposited actinides, (ii) biokinetic modeling of individual cases, (iii) development of actinide chelation models, (iv) study of post-mortem distribution of actinides in the human body, and (v) study of occupational exposure to non-radioactive materials associated with the nuclear industry. The USTUR core operational functions are: (i) accepting and processing Registrant donations, (ii) completing radiochemical analysis of donated tissue samples, and (iii) completing the development and population of the USTUR databases. Currently, the Registries holds records and data for 364 deceased and 22 living Registrants. The USTUR/NHRTR data and materials are available to qualified scientists for their research upon request. The USTUR maintains well-established collaborations with national and international scientists and institutions, and develops new collaborative relationships. Since its establishment, the USTUR has published over 350 peer-reviewed manuscripts, and has contributed to six National Council on Radiation Protection and Measurements reports and nine International Commission on Radiological Protection publications. [USTUR-0538-20A]

Presentation Slides

Beryllium in tissues of former nuclear workers

Maia Avtandilashvili (USTUR), Dominic Larivière (Laval University, Canada), Noriyuki Momoshima (Kyushu Environmental Evaluation Association, Japan), Dana Wegge (University of Missouri), John D. Brockman (University of Missouri), Sergei Y. Tolmachev (USTUR)

Beryllium and beryllium compounds widely used in nuclear power industry and weapons production are known to be human carcinogens. Currently, there is limited published data on beryllium concentrations and distribution in the human body. The US Transuranium and Uranium Registries (USTUR), established in 1968 to study the biokinetics and internal dosimetry of actinides by following up former nuclear workers with documented intakes of these elements, who volunteered their bodies for scientific use posthumously, holds detailed work history, radiation exposure, and industrial hygiene records including self-reported information on beryllium exposure. Out of 364 deceased USTUR Registrants, 92 self-reported working with beryllium, but only 73 individuals reported years of beryllium work ranging from 1 to 45 years with the average of 17 ± 13 years. Beryllium concentrations were measured using inductively-coupled plasma mass spectrometry in tissue samples from 13 USTUR cases with beryllium exposure duration ranging from 3 to 39 years. A total of 149 tissues was analyzed including 105 tissues from a whole-body donor who was potentially exposed to beryllium for 6 years. The highest concentrations were measured in thoracic lymph nodes with the range of 6 – 334 µg kg-1 (median: 59.1 µg kg-1). For other tissues, beryllium median concentration followed the order: liver (6.84 µg kg-1) > kidney (0.55 µg kg-1) > lung (0.30 µg kg-1) > skeleton (0.16 µg kg-1). For analyzed whole-body case, the total beryllium content was estimated to be 54.8 µg, including 5.8 µg retained in the respiratory tract 22 years post-exposure. It was found that systemic beryllium primarily accumulated in the skeleton (27.3 µg), followed by the liver (11.3 µg) and other soft tissues (10.4 µg). Beryllium concentration in the liver (10.2 µg kg-1) was three times higher than the average concentration in the skeleton (3.0 µg kg-1 and 42 times higher than that in other soft tissues (0.24 µg kg-1). [USTUR-0537-20A]

Presentation Slides

The neutrophil to lymphocyte ratio shows evidence for chronic inflammation in a radium dial painter cohort

Ronald E. Goans (MJW Corporation and REAC/TS), Richard E. Toohey (REAC/TS), Carol J. Iddins (REAC/TS), Michael Mumma (International Epidemiology Institute), Stacey L. McComish (USTUR), Sergei Y. Tolmachev (USTUR)

The neutrophil to lymphocyte ratio (NLR) is widely regarded in clinical medicine as a nonspecific marker of inflammation. In a collaborative effort with the US Transuranium and Uranium Registries (USTUR) and with the NCRP Million Person Study, it has been possible to evaluate NLR from medical records of a cohort of 166 former radium dial painters previously evaluated at Argonne National Laboratory. The radium dial painters (RDP) are a well-described group of predominantly young women who incidentally ingested 226Ra and 228Ra as they painted luminescent watch dials in the first part of the twentieth century. Members of the cohort had ingestion of radium at an early age (mean age 20.6 ± 5.4 y). Exposure duration ranged from 1-1,820 weeks with red marrow dose 1.5 mGy – 10.52 Gy. Two subsets (n=7 each; marrow dose > 50 cGy) were derived from this cohort: one set consists of those RDP without a history of radium-induced sarcoma (average red marrow dose 164 cGy) and another set of RDP with a history of treated sarcoma (average marrow dose 371 cGy). In addition, a set of normal unirradiated controls (n=125) was obtained. NLR is found to be the same in the RDP subset without sarcoma as in controls (2.06 ± 0.062 vs. 2.07 ± 0.12; mean ± SEM; p=0.43 NS, Mann-Whitney Rank Sum Test). However, NLR in the treated sarcoma group is markedly higher (3.17 ± 0.25), significant at p<0.001 using Mann-Whitney. This observation suggests a possible state of chronic inflammation in those patients previously treated for radium-induced osteosarcoma. [USTUR-0604-22A]

Misclassification of causes of death among USTUR Registrants: Death certificates vs. autopsy reports

Stacey L. McComish (USTUR), Xirui Liu (Weill Cornell Medicine), Florencio T. Martinez (USTUR), Joey Y. Zhou (DOE), Sergei Y. Tolmachev (USTUR)

The USTUR performs autopsies on each of its Registrants as a part of its mission to follow up occupationally-exposed individuals. This provides a unique opportunity to explore death certificate misclassification errors among this small population of former nuclear workers. Underlying causes of death (UCOD) from death certificates and autopsy reports were coded using the 10th revision of the International Classification of Diseases (ICD-10). These codes were then used to quantify misclassification rates among 240 individuals for whom both death certificates and autopsy reports were available. ICD-10 categorizes diseases using 22 chapters. Death certificates incorrectly identified the UCOD ICD-10 disease chapter in 28.3% of cases. The misclassification rates for the most common disease chapters were: 13.8% neoplasms, 15.0% circulatory, 64.0% respiratory, 23.5% external causes, and 40.0% nervous system. Death certificates often include fields that indicate if the autopsy report was used to determine the cause of death. The misclassification rate was 18.4% for death certificates that used the autopsy report to determine the UCOD, 38.0% for those that did not, and 23.1% for those where use was unknown. The difference between the misclassification rate for death certificates that used the autopsy report to determine the UCOD and those that did not was statistically significant. [USTUR-0603-22A]

Uncertainties in radiation dose assessment for internally deposited plutonium in support of radiation epidemiology

Martin Šefl (USTUR), Joey Y. Zhou (DOE), Maia Avtandilashvili (USTUR), Stacey L. McComish (USTUR), George Tabatadze (USTUR), Sergei Y. Tolmachev (USTUR)

Since its establishment in 1968, the United States Transuranium and Uranium Registries (USTUR) has received 317 partial- and 47 whole-body donations for scientific research from former nuclear workers who had accidental intakes of actinide radionuclides. These individuals typically have well-documented work history, exposure, bioassay monitoring, and medical records. Among 349 cases with completed radiochemical analysis, 59 cases with recorded 239Pu intake(s) were selected for evaluation of uncertainties in the radiation dose assessment for radiation epidemiology. These individuals were not extensively treated with chelation therapy and had at least five 239Pu urine measurements exceeding the contemporary detection limit, as well as 239Pu concentrations in the skeleton and liver greater than 0.1 Bq kg-1 and 1 Bq kg-1, respectively. The objectives were to compare: (i) predicted 239Pu activities in the skeleton and liver, based upon urine bioassays, with measured post-mortem activities in the skeleton and liver; (ii) dose estimates calculated from urine data alone with those based on both urine data and post-mortem radiochemical analyses. Taurus internal dosimetry software was used to model individual cases using default ICRP biokinetic model assumptions. Biases for the predicted and measured post-mortem organ activities and calculated radiation doses were studied as a pilot study of 11 former Manhattan Project workers. Current biokinetic model predictions for the liver+skeleton retention appear to be on average within 5% of the measured organ activities. On the other hand, the use of early urine bioassay data collected during the exposure period in the 1940s overestimated the liver+skeleton activity on average by a factor of 2.5. This demonstrates the importance of a long-term collection of bioassays as a part of follow-up. Analysis of the remaining cases are in progress. [USTUR-0539-20A]

Presentation Slides

Revision of the ICRP 141 Pu systemic model to incorporate the HAT Model and the hepatic portal vein

Daniel J. Strom (USTUR), Maia Avtandilashvili (USTUR), Alan S. Felsot (WSU), Stacey L. McComish (USTUR), Martin Šefl (USTUR), George Tabatadze (USTUR), Sergei Y. Tolmachev (USTUR)

The human liver typically receives about 25% of systemic blood circulation. The liver is unusual in that it has two separate input streams of blood: the hepatic artery supplies oxygenated blood and about 20% of blood flowing into the liver; and the hepatic portal vein brings nutrient-rich oxygen-depleted blood from the alimentary tract and associated secretory organs, and accounts for about 80% of the blood flowing into the liver. After the liver processes nutrients and other material from the digestive system, the streams combine and exit the liver via the hepatic vein. While the ICRP 100 human alimentary tract (HAT) model explicitly includes the HPV, the ICRP 141 models for actinides and for plutonium do not, and in fact show uptake from the small intestine directly to blood. The fact that all blood from the HAT first passes through the liver before mixing with systemic circulation is critical for understanding the metabolism and toxicity of chemicals, as well as understanding the processing of all materials entering from the gut. The liver selectively removes plutonium from blood and retains a significant fraction of a body’s systemic Pu. This paper proposes a modification to the ICRP 141 Pu systemic model to harmonize the entire ICRP 100 HAT model with the systemic model, explicitly modeling the first stop in the liver for all blood containing Pu. Since it is doubtful whether existing data can be used to determine all the new model parameters, some simplification may be required, but the product of such efforts must retain the fundamental fact that any uptake of Pu from the HAT first visits the liver. It is unknown if this anatomically and physiologically improved model would provide a better understanding of Pu biokinetics, and we pose several questions regarding how inclusion of the HPV may impact the kinetics of Pu in the liver. [USTUR-0605-22A]