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To investigate the temporal and spatial infiltration of TRAMP-C1 tumors by myeloid-derived suppressor cells (MDSCs) after high-dose radiation therapy (RT), and to explore their effect on tumor growth.
In radiopharmaceutical therapy (RPT), a radionuclide is systemically or locally delivered with the goal of targeting and delivering radiation to cancer cells while minimizing radiation exposure to untargeted cells. Examples of current RPTs include thyroid ablation with the administration of {sup 131}I, treatment of liver cancer with {sup 90}Y microspheres, the treatment of bony metastases with {sup 223}Ra, and the treatment of neuroendocrine tumors with {sup 177}Lu-DOTATATE. New RPTs are being developed where radionuclides are incorporated into systemic targeted therapies. To assure that RPT is appropriately implemented, advances in targeting need to be matched with advances in quantitative imaging and dosimetry methods. Currently, radiopharmaceutical therapy is administered by intravenous or locoregional injection, and the treatment planning has typically been implemented like chemotherapy, where the activity administered is either fixed or based on a patient’s body weight or body surface area. RPT pharmacokinetics are measurable by quantitative imaging and are known to vary across patients, both in tumors and normal tissues. Therefore, fixed or weight-based activity prescriptions are not currently optimized to deliver a cytotoxic dose to targets while remaining within the tolerance dose of organs at risk. Methods that provide dose estimates to individual patients rather than to reference geometries are needed to assess and adjust the injected RPT dose. Accurate doses to targets and organs at risk will benefit the individual patients and decrease uncertainties in clinical trials. Imaging can be used to measure activity distribution in vivo, and this information can be used to determine patient-specific treatment plans where the dose to the targets and organs at risk can be calculated. The development and adoption of imaging-based dosimetry methods is particularly beneficial in early clinical trials. In this work we discuss dosimetric accuracy needs in modern radiation oncology, uncertainties in the dosimetry in RPT, and best approaches for imaging and dosimetry of internal radionuclide therapy.
This annual review provides the projected dose estimates of radionuclide inventories disposed in the 200 East Area Low-Level Waste Burial Grounds (LLBGs) since September 26, 1988. These estimates are calculated using the original dose methodology developed in the performance assessment (PA) analysis (WHC-SD-WM-TI-730). The estimates are compared with requirements of DOE O 435.1 Chg 1 and performance objectives defined in companion documents DOE M 435.1-1 Chg 1and DOE-STD-5002-2017). All performance objectives are currently satisfied, and operational waste acceptance criteria (HNF-EP-0063) and waste acceptance practices continue to be sufficient to maintain compliance with performance objectives. Inventory estimates and associated dose estimates from future waste disposal actions are unchanged from previous years’ evaluations that indicate potential impacts well below performance objectives; therefore, future compliance with DOE O 435.1 Chg 1 is expected. A new PA study was initiated in fiscal year (FY) 2019 for evaluation of active disposal sites within the 200 East and 200 West Areas (Trench 94 in 200 East; Trenches 31 and 34 in 200 West) due to extended time elapsing between the current annual status report and the original PA for the active disposal sites. The new PA for the active disposal sites is expected to be completed in FY 2021. Within the active burial grounds in the 200 East Area, low-level waste and mixed low-level waste will continue to be disposed of in the dedicated U.S. Navy reactor compartment trench at the 218-E-12B Burial Ground (Trench 94). During this reporting period (FY 2020, from October 1, 2019, through September 30, 2020), two reactor compartments were disposed in Trench 94. Results from sorption experiments are summarized for this reporting period to quantify the efficacy of concrete waste forms in retaining key radionuclides (e.g., technetium-99 and iodine-129). The test durations ranged from 1 to 3 months. Continued groundwater monitoring of the 200 East Area LLBGs indicates no groundwater contamination due to LLBG waste. Current assumptions about future land use at the Hanford Site are consistent with PA analysis1 assumptions of a post-closure facility that will not be degraded by human activity. The LLBGs are located in an area identified for waste management and containment of residual contamination. This area will remain after final environmental remediation and the proposed shrinkage of Hanford Site boundaries to small sections within the 200 East and 200 West Areas in the Central Plateau (DOE/EIS-0391). The current closure plan for the LLBGs (DOE/RL-2000-707) estimates that the 200 East LLBGs will be closed in the 2050 timeframe. The Disposal Authorization Statement, other technical basis documents, and the radioactive waste management basis are of continued adequacy to meet the performance objectives of DOE O 435.1 Chg 1. Overall, there are no substantive changes to primary PA assumptions nor the PA analysis conclusion; therefore, compliance with DOE O 435.1 Chg 1 and the Disposal Authorization Statement is maintained.
Historically all persons working on the Nevada National Security Site (NNSS) were considered subject to worker dose limits when calculations of potential dose from the air pathway were conducted to demonstrate compliance with Title 42 United States Code (USC) Chapter 85, “The Clean Air Act,” and Title 40 Code of Federal Regulations (CFR) Part 61, Subpart H, “National Emission Standards for Hazardous Air Pollutants (NESHAP).” Calculations were also conducted for the all-pathways potential dose to demonstrate compliance with U.S. Department of Energy (DOE) Order DOE O 458.1 Chg. 3, “Radiation Protection of the Public and the Environment.” The need to evaluate environmental air sampling locations and past regulator questions about the existence of persons potentially subject to public dose limits being on the NNSS drove this assessment (letter from EPA [U.S. Environmental Protection Agency] Region 9 to DOE/Nevada Operations Office, dated September 3, 1999). This assessment also supports determining those persons subject to public dose limits from the all pathways perspective. A person that is a member of the public is subject to public dose limits.
The Second Target Station project at Oak Ridge National Laboratory will develop a cold neutron source to meet growing experimental needs. This paper describes calculations of the residual dose rates associated with the monolith shield plug and the beamline bunker, two key conventional operations and radiation safety features. While neutron production is active, the instrument hall outside the bunker must be generally accessible with dose rates of less than 0.25 mrem/h. When neutron production is halted, the bunker must be accessible for hands-on maintenance operations. Further, these two requirements form the cause for the assessments reported herein of residual dose rates caused by the monolith shield plug and residual dose rates in the bunker. The monolith shield plug was shown to not produce significant dose rates inside the bunker after a 20-year lifetime, and the residual dose rates inside the bunker for the case of an operating beamline were shown to reasonably allow for hands-on maintenance. These calculations are based on preliminary design models of the relevant systems. Additionally, an example showing the significance of considering neutron supermirror physics in transport calculations that track nuclide production and destruction rates to produce gamma sources for residual dose rate calculations is included. The example shows that if neutron supermirror physics is not considered, dose rate fields may be significantly underpredicted.
This annual review provides the projected dose estimates of radionuclide inventories disposed in the 200 East Area Low-Level Waste Burial Grounds (LLBGs) since September 26, 1988. These estimates are calculated using the original dose methodology developed in the performance assessment (PA) analysis (WHC-SD-WM-TI-730) and are compared with U.S. Department of Energy requirements (DOE O 435.1 and performance objectives defined in companion documents DOE M 435.1 and DOE-STD-5002-2017). All performance objectives are currently satisfied, and operational waste acceptance criteria (HNF-EP-0063) and waste acceptance practices continue to be sufficient to maintain compliance with performance objectives. Inventory estimates and associated dose estimates from future waste disposal actions are unchanged from previous years’ evaluations, indicating that potential impacts are well below performance objectives; therefore, future compliance with DOE O 435.1 is expected. A new PA study has been initiated in this fiscal year (FY) 2019 for evaluation of active disposal sites within the 200 West and East Areas (Trenches 31 and 34 in 200 West; Trench 94 in 200 East) because extended time has elapsed between the current annual status report and the original PA (WHC-SD-WM-TI-370) for the active disposal sites. The new PA for the active disposal sites is expected to be completed in FY 2021.
This annual review provides the projected dose estimates of radionuclide inventories disposed in the active 200 West Area Low-Level Waste Burial Grounds (LLBGs) since September 26, 1988. These estimates are calculated using the original dose methodology developed in the performance assessment (PA) analysis (WHC-EP-0645) and are compared with performance objectives defined in U.S. Department of Energy requirements (DOE O 435.1 and its companion documents DOE M 435.1-1 and DOE-STD-5002-2017). All performance objectives are currently satisfied, and operational waste acceptance criteria (HNF-EP-0063) and waste acceptance practices continue to be sufficient to maintain compliance with performance objectives. Inventory estimates and associated dose estimates from future waste disposal actions are unchanged from previous years’ evaluations, indicating that potential impacts are well below performance objectives; therefore, future compliance with DOE O 435.1 is expected.
This annual review provides the projected dose estimates of radionuclide inventories disposed in the active 200 West Area Low-Level Waste Burial Grounds (LLBGs) since September 26, 1988. These estimates are calculated using the original dose methodology developed in the performance assessment (PA) analysis (WHC-EP-0645). The estimates are compared with the performance objectives defined in U.S. Department of Energy requirements (DOE O 435.1 and its companion documents DOE M 435.1-1 and DOE-STD-5002-2017). All performance objectives are currently satisfied, and operational waste acceptance criteria (HNF-EP-0063) and waste acceptance practices continue to be sufficient to maintain compliance with performance objectives. Inventory estimates and associated dose estimates from future waste disposal actions are unchanged from previous years’ evaluations that indicate potential impacts well below performance objectives; therefore, future compliance with DOE O 435.1 is expected. Within the active burial grounds, low-level and mixed low-level waste currently may be disposed only in two lined trenches in the 218-W-5 Burial Ground (Trenches 31 and 34) until they are either filled or a decision is made to close these trenches. Some mixed low-level waste is also disposed at the Environmental Restoration Disposal Facility in the 200 West Area (which is covered under a separate PA). During this (fiscal year 2022) reporting period (October 1, 2021, through September 30, 2022), waste was disposed to the 200 West Area LLBGs. Continued groundwater monitoring of the 200 West Area LLBGs indicates no groundwater contamination due to LLBG waste. Current assumptions about future land use at the Hanford Site are consistent with PA analysis assumptions of a postclosure facility that will not be degraded by human activity. The LLBGs are in an area identified for waste management and containment of residual contamination (DOE/EIS-0391). The current closure plan for the LLBGs (DOE/RL-2000-70) estimates that the 200 West LLBGs will be closed in the 2050 timeframe. The Disposal Authorization Statement, other technical basis documents, and the radioactive waste management basis are of continued adequacy to meet the performance objectives of DOE O 435.1. Overall, there are no substantive changes to primary PA assumptions and no changes to the PA analysis conclusion; therefore, compliance with DOE O 435.1 and the Disposal Authorization Statement is maintained. A new PA to evaluate the long-term impacts of three disposal trenches that are currently active within the 200 East and 200 West Areas (Trench 94 in the 200 East Area and Trenches 31 and 34 in the 200 West Area) was initiated in fiscal year 2019 and completed in fiscal year 2022. Corrective actions addressing 3 key issues and 31 secondary issues identified during the review process were developed and submitted to the Low-Level Waste Disposal Facility Federal Review Group Co-Chairs for review and approval. This PA provides additional technical basis for the continued adequacy of the existing Operating Disposal Authorization Statement.
This annual review provides the projected dose estimates of radionuclide inventories disposed in the active 200 West Area Low-Level Waste Burial Grounds (LLBGs) since September 26, 1988. These estimates are calculated using the original dose methodology developed in the performance assessment (PA) analysis (WHC-EP-0645). The estimates are compared with the performance objectives defined in U.S. Department of Energy requirements (DOE O 435.1 and its companion documents DOE M 435.1-1 and DOE-STD-5002-2017). All performance objectives are currently satisfied, and operational waste acceptance criteria (HNF-EP-0063). and waste acceptance practices continue to be sufficient to maintain compliance with performance objectives. Inventory estimates and associated dose estimates from future waste disposal actions are unchanged from previous years’ evaluations that indicate potential impacts well below performance objectives; therefore, future compliance with DOE O 435.1 is expected.
This annual review provides the projected dose estimates of radionuclide inventories disposed in the 200 East Area Low-Level Waste Burial Grounds (LLBGs) since September 26, 1988. These estimates are calculated using the original dose methodology developed in the performance assessment (PA) analysis (WHC-SD-WM-TI-730). The estimates are compared with the performance objectives defined in U.S. Department of Energy requirements (DOE O 435.1 and its companion documents DOE M 435.1-1 and DOE-STD-5002-2017). All performance objectives are currently satisfied, and operational waste acceptance criteria (HNF-EP-0063) and waste acceptance practices continue to be sufficient to maintain compliance with performance objectives. Inventory estimates and associated dose estimates from future waste disposal actions are unchanged from previous years’ evaluations that indicate potential impacts well below performance objectives; therefore, future compliance with DOE O 435.1 is expected.
We report that Dibenzo[def,p]chrysene (DBC) is an environmental polycyclic aromatic hydrocarbon (PAH) that causes tumors in mice and has been classified as a probable human carcinogen by the International Agency for Research on Cancer. Animal toxicity studies often utilize higher doses than are found in relevant human exposures. Additionally, like many PAHs, DBC requires metabolic bioactivation to form the ultimate toxicant, and species differences in DBC and DBC metabolite metabolism have been observed. To understand the implications of dose and species differences, a physiologically based pharmacokinetic model (PBPK) for DBC and major metabolites was developed in mice and humans. Metabolism parameters used in the model were obtained from experimental in vitro metabolism assays using mice and human hepatic microsomes. PBPK model simulations were evaluated against mice dosed with 15 mg/kg DBC by oral gavage and human volunteers orally microdosed with 29 ng of DBC. DBC and its primary metabolite DBC-11,12-diol were measured in blood of mice and humans, while in urine, the majority of DBC metabolites were obeserved as conjugated DBC-11,12-diol, conjugated DBC tetrols, and unconjugated DBC tetrols. The PBPK model was able to predict the time course concentrations of DBC, DBC-11,12-diol, and other DBC metabolites in blood and urine of human volunteers and mice with reasonable accuracy. Agreement between model simulations and measured pharmacokinetic data in mice and human studies demonstrate the success and versatility of our model for interspecies extrapolation and applicability for different doses. Furthermore, our simulations show that internal dose metrics used for risk assessment do not necessarily scale allometrically, and that PBPK modeling provides a reliable approach to appropriately account for interspecies differences in metabolism and physiology.
The Enrico Fermi Atomic Power Plant Unit 1 (Fermi-1) was a sodium-cooled fast breeder reactor located in Monroe County, Michigan. The reactor was powered by a core of enriched uranium metal alloy driver fuel, which was enveloped by an axial and radial blanket material consisting of depleted uranium metal alloyed with 3 wt.% molybdenum. There are 406 axial and 559 radial irradiated sodium-bonded Fermi-1 blanket assemblies in storage at INL, totaling 34 metric tons of heavy metal. Disposal of the Fermi-1 blanket material directly into a geological repository is prohibited due to the reactive characteristic of its bond sodium. A melt drain evaporate (MEDE) process can effectively remove bond sodium from Fermi-1 blanket material. Consequently, planning is underway to apply a MEDE process to treat the 34 metric tons of heavy metal of irradiated Fermi-1 blanket material. Given the irradiated Fermi-1 blanket material’s relatively low power history and 50+ years of decay, it can be treated in a shielded glovebox. To assess the requisite shielding, the dose rates of the Fermi-1 blanket elements in various process configurations are needed. The method to perform the dose rate calculations is to first generate an average source term and associated photon source spectra for the Fermi-1 blanket material in SCALE and then use the associated photon spectra to calculate dose rates using MCNP6.2 in seven representative geometries. Dose rates in rem/h were calculated on contact (1 cm from outer geometry surface), 30 cm away from outer geometry surface, and 1 m from outer geometry surface at axial heights spanning the length of the blanket material within the geometry. The maximum average dose rate for the single Fermi-1 radial blanket element is ~0.60 rem/h, for the Fermi-1 radial blanket assembly ~1.10 rem/h, for the single Fermi-1 axial blanket element ~0.5 rem/h, for the Fermi-1 axial blanket assembly ~1.01 rem/h, for the MEDE can ~ 0.98 rem/h, for the Fermi Storage Canister ~ 0.83 rem/h, and for the MEDE cans in the DOE Standard Canister ~0.51 rem/h. Based on these maximum average values, the bounding dose rates are assumed to be 3× the average dose rates calculated for the axial blanket material and 7.6× the average dose rates calculated for the radial blanket material, based on the distribution of Fermi-1 blanket material assembly burnup.
Our purpose was to assess the use of machine learning methods and Mobius 3D (M3D) dose calculation software to reduce the number of physical ion chamber (IC) dose measurements required for patient-specific quality assurance during corona virus disease 2019.
This paper presents a comprehensive characterization study of the microstructural responses to ion irradiation of the oxide dispersion strengthened (ODS) ferritic alloy MA957 using atom probe tomography (APT). The MA957 specimens were irradiated by 1.8 MeV Cr3+ ions to doses and temperatures relevant to advanced fast reactors (100 and 500 dpa at 400-500 °C). The average sizes of the YTiO particles decreased slightly after irradiation at all temperatures, with the most pronounced change at 400 °C. The particle number densities for 400 and 500 °C were slightly below number densities for the unirradiated condition, while the values were slightly higher at 420 and 450 °C. This behavior is consistent with the Nelson-Hudson-Mazey rate theory model that considers the competing effects between recombination and dissolution. An increase in the Y/Ti ratio of the YTiO particles was observed at the two lower temperatures. The formation of Cr-rich precipitates (a') was observed in specimens irradiated at temperatures up to 450 °C. Irradiation-induced segregation on grain boundaries was also investigated. Grain boundary element concentration profiles and ion maps demonstrate differences among the irradiation temperatures, with most datasets differing from the unirradiated condition. A key focus of this ion irradiation study is the high-dose response, and this quantitative assessment revealed relatively small but distinct effects of irradiation on microstructure evolution. Overall, these results showing minor second phase evolution suggest that MA957 should retain mechanical performance generally well up to 500 dpa for the irradiation temperatures studied.
The nuclear power industry has growing interest in qualifying powder metallurgy with hot isostatic pressing (PM-HIP) to replace traditional alloy fabrication methods for reactor structural components. But there is little known about the response of PM-HIP alloys to reactor conditions. This study directly compares the response of PM-HIP to forged Ni-base Alloy 625 under neutron irradiation doses ~0.5–1 displacements per atom (dpa) at temperatures ranging ~321–385 °C. Post-irradiation examination involves microstructure characterization, ASTM E8 uniaxial tensile testing, and fractography. Up through 1 dpa, PM-HIP Alloy 625 appears more resistant to irradiation-induced cavity nucleation than its forged counterpart, and consequently experiences significantly less hardening. This observed difference in performance can be explained by the higher initial dislocation density of the forged material, which represents an interstitial-biased sink that leaves a vacancy supersaturation to nucleate cavities. These findings show promise for qualification of PM-HIP Alloy 625 for nuclear applications, although higher dose studies are needed to assess the steady-state irradiated microstructure.
ORIGEN is one of the main transmutation software packages used in nuclear engineering Modeling Tungsten Boride Neutronics in ORIGEN for Z-Facilityproblems. For the case of this study, tungsten borides are studied using a coupled framework between MCNP and the ORIGEN package of scale. The input used four compositions of tungsten boride: WB with natural boron- 10 abundance, WB with 80wt% B-10 per isotope of boron, WB4 with natural boron-10 abundance, and WB4 with 80wt% B-10 per isotope of boron. Isotopic inventories were produced for WB which show the time dependent change up to 2 years after a 6-Month irradiation. This will allow for further studies of the materials to assess things material composition changes, dose contribution, and waste management requirements.
Abstract Chemical exposure estimation through the dermal route is an underemphasized area of ecological risk assessment for terrestrial animals. Currently, there are efforts to create exposure models to estimate doses from this pathway for use in ecological risk assessment. One significant limitation has been insufficient published data to characterize exposure and to support the selection and parameterization of appropriate models, particularly for amphibians in terrestrial habitats. Recent publications measuring pesticide doses to terrestrial‐phase amphibians have begun to rectify this situation. We collated and summarized available measurements of terrestrial amphibian dermal exposure to pesticides from 11 studies in which researchers measured tissue concentrations associated with known pesticide experimental application rates. This data set included tissue concentrations in 11 amphibian species and 14 different pesticides. We then compared the results of two screening exposure models that differed based on surface area scaling approaches as a function of body weight (one based on birds as surrogates for amphibians and another amphibian‐specific) to the measured tissue residue concentrations. We define a false‐negative rate for each screening model as the proportion of amphibians for which the predicted concentration is less than the observed concentration (i.e., underestimate), contrary to the intent of screening models, which are intended to have a bias for higher exposure concentrations. The screening model that uses birds as surrogates did not have any instances where estimated expected avian doses were less than measured amphibian body burdens. When using the amphibian‐specific exposure model that corrected for differences between avian and amphibian surface area, measured concentrations were greater than model estimates for 11.3% of the 1158 comparisons. The database of measured pesticide concentrations in terrestrial amphibians is provided for use in calculating bioconcentration factors and for future amphibian dermal exposure model development. Integr Environ Assess Manag 2023;19:9–16. © 2022 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
Abstract Whether low-dose ionizing radiation can cause cancer is a critical and long-debated question in radiation protection. Since the Biological Effects of Ionizing Radiation report by the National Academies in 2006, new publications from large, well-powered epidemiological studies of low doses have reported positive dose-response relationships. It has been suggested, however, that biases could explain these findings. We conducted a systematic review of epidemiological studies with mean doses less than 100 mGy published 2006–2017. We required individualized doses and dose-response estimates with confidence intervals. We identified 26 eligible studies (eight environmental, four medical, and 14 occupational), including 91 000 solid cancers and 13 000 leukemias. Mean doses ranged from 0.1 to 82 mGy. The excess relative risk at 100 mGy was positive for 16 of 22 solid cancer studies and 17 of 20 leukemia studies. The aim of this monograph was to systematically review the potential biases in these studies (including dose uncertainty, confounding, and outcome misclassification) and to assess whether the subset of minimally biased studies provides evidence for cancer risks from low-dose radiation. Here, we describe the framework for the systematic bias review and provide an overview of the eligible studies.