Assessment of the effects of repeated doses of potassium iodide intake during pregnancy on male and female rat offspring using metabolomics and lipidomics.

Preparedness for nuclear accident responsiveness includes interventions to protect pregnancies against prolonged exposure to radioactive iodine. The aim of this study was to investigate a new design consisting of repeated administration of potassium iodide (KI, 1 mg/kg) for 8 days in late pregnancy gestational day 9-16 (GD9-GD16) in rats. The later-life effects of this early-life iodine thyroid blocking (ITB) strategy were assessed in offspring two months afterbirth. Functional behavioral tests including forced swimming test (FST) and rotarod test (RRT) in rats of both genders showed lower FST performance in KI-treated females and lower RRT performance in KI-treated male pups. This performance decline was associated with metabolic disruptions in cortex involving amino acid metabolism, tyrosine metabolism, as well as docosahexaenoic acid (DHA) lipids and signaling lipids in males and females. Beyond these behavior-associated metabolic changes, a portion of the captured metabolome (17-25%) and lipidome (3.7-7.35%) remained sensitive to in utero KI prophylactic treatment in both cortex and plasma of post-weaning rats, with some gender-related variance. Only part of these disruptions was attributed to lower levels of TSH and T4 (males only). The KI-induced metabolic shifts involved a broad spectrum of functions encompassing metabolic and cell homeostasis and cell signaling functions. Irrespective Regardless of gender and tissues, the predominant effects of KI affected neurotransmitters, amino acid metabolism, and omega-3 DHA metabolism. Taken together, data demonstrated that repeated daily KI administration at 1 mg/kg/day for 8 days during late pregnancy failed to protect the mother-fetus against nuclear accident radiation. Abbreviations: CV-ANOVA: Cross-validation analysis of variance; DHA: Docosahexaenoic acid; FST: Forced swimming test; FT3: plasma free triiodothyronine; FT4: plasma free thyroxine; GD: Gestational day; ITB: Iodine thyroid blocking; KI: potassium iodide; LC/MS: Liquid chromatography coupled with mass spectrometry; MTBE: Methyl tert-butyl ether; m/z: mass-to-charge ratio; PLS-DA: Partial least squares-discriminant analysis; PRIODAC: Repeated stable iodide prophylaxis in accidental radioactive releases; RRT: Rotarod test; TSH: Thyroid-stimulating hormone; VIP: Variable importance in projection.

Mutagenic potential assessment associated with human exposure to natural radioactivity.

Lucrécia city, known to harbor a high cancer rate, is located in a semiarid region characterized by the presence of mineral reservoirs, facing a high exposure to metal and natural radioactivity. The present study aimed to assess the environmental scenario at a semiarid region located in Northeastern Brazil. Metal concentration, alpha and beta radiation, and cyanobacteria content in tap water along with indoor radon and gamma emitters (U, K and Th) concentrations were measured. In addition, mutagenic and nuclear instability effects were assessed using buccal micronucleus cytome assay. The study included five samplings corresponding to a period between 2007 and 2009. Drinking water from Lucrécia city presented levels of Mn, Ni and Cr along with cyanobacteria in concentrations one to four times higher than regulatory guidelines considered. Furthermore, high levels of all the tested radionuclides were found. A high percentage of the houses included in this study presented indoor radon concentrations over 100 Bq m-3. The mean annual effective dose from Lucrécia houses was six times higher than observed in a control region. The levels of exposure in most of the Lucrécia houses were classified as middle to high. A significant mutagenic effect, represented as an increase of micronuclei (MN) frequency and nuclear abnormalities as nuclear buds (NB), binucleated cells (BN), and pyknotic cells (PYC) were found. The results obtained highlight the role of high background radioactivity on the observed mutagenic effect and could help to explain the exacerbated cancer rate reported in this locality.

Lognormal distribution of cellular uptake of radioactivity: Monte Carlo simulation of irradiation and cell killing in 3-dimensional populations in carbon scaffolds.

UNLABELLED: The biologic response of tissue exposed to radiation emitted by internal radioactivity is often correlated with the mean absorbed dose to a tissue element. However, studies show that even when the macroscopic absorbed dose to the tissue element is constant, the response of the cell population within the tissue element can vary significantly, depending on the distribution of radioactivity at the cellular and multicellular levels. These variations are believed to be the consequence of nonuniform distributions of activity among the cells or subcellular compartments that comprise the tissue element. Furthermore, the self-dose received by a cell containing radioactivity can be more radiotoxic than the cross-dose from neighboring cells. To study how the nonuniformity of activity among cells can affect the dose response, a 3-dimensional model of cells in a heterogeneous carbon scaffold was used to assess response. METHODS: A theoretic model of a 3-dimensional cell culture was constructed, and Monte Carlo radiation transport was performed to assess self- and cross-doses for each cell nucleus in a population of 10(6) cells. On the basis of these individual doses and on empiric models of radiation-induced cell death (i.e., reproductive failure), survival curves were simulated with different electron energies and activity distributions among the cells. RESULTS: Nonuniformity of cell activities are responsible for nonuniformity of the dose at the cellular level, which in turn causes a change in the surviving fraction of the cell population from that expected on the basis of uniform activity and dose. CONCLUSION: The macroscopic dose received by a tissue cannot be used to anticipate its biologic response. The dose distribution among individual cells, because of both their nonuniform activity and geometric environment, is an important factor in determining biologic response of the tissue at the macroscopic level.

Reactor-based management of used nuclear fuel: assessment of major options.

This paper discusses the current status of the ongoing Advanced Fuel Cycle Initiative (AFCI) program in the U.S. Department of Energy that is investigating the potential for using the processing and recycling of used nuclear fuel to improve radioactive waste management, including used fuel. A key element of the strategies is to use nuclear reactors for further irradiation of recovered chemical elements to transmute certain long-lived highly-radioactive isotopes into less hazardous isotopes. Both thermal and fast neutron spectrum reactors are being studied as part of integrated nuclear energy systems where separations, transmutation, and disposal are considered. Radiotoxicity is being used as one of the metrics for estimating the hazard of used fuel and the processing of wastes resulting from separations and recycle-fuel fabrication. Decay heat from the used fuel and/or wastes destined for disposal is used as a metric for use of a geologic repository. Results to date indicate that the most promising options appear to be those using fast reactors in a repeated recycle mode to limit buildup of higher actinides, since the transuranic elements are a key contributor to the radiotoxicity and decay heat. Using such an approach, there could be much lower environmental impact from the high-level waste as compared to direct disposal of the used fuel, but there would likely be greater generation of low-level wastes that will also require disposal. An additional potential waste management benefit is having the ability to tailor waste forms and contents to one or more targeted disposal environments (i.e., to be able to put waste in environments best-suited for the waste contents and forms).

Human health risk assessment of environmental and dietary exposure to natural radionuclides in the Catalan stretch of the Ebro River, Spain.

This study was aimed at assessing the levels of 210Pb and 210Po concentrations as well as gross alpha and beta activities in environmental monitors from the Catalan stretch of the Ebro River (Spain), potentially influenced by the presence of sediments with high concentrations of 238U and its decay chain daughters in the Flix reservoir. The chronic daily intake of 210Pb and 210Po through ingestion and inhalation of soils was evaluated, and the derived non-carcinogenic and carcinogenic risks were characterized. The low concentration of radioisotopes in soils resulted in a negligible annual effective dose. The levels of 210Pb and 210Po were determined in various groups of highly consumed food (fish and seafood, vegetables, fruits, and rice), and their dietary intake was calculated. The annual effective dose for the adult people from food intake was estimated in 3.3×10(-2) mSv, mostly due to 210Po. Overall, the current radioactivity levels in the Catalan stretch of the Ebro River should not mean any additional health risk for the population living nearby. However, an integral assessment of the risks derived from exposure to other pollutants (e.g., metals and organochlorine compounds) jointly with radionuclides could be of great interest.

Nickel-63 microirradiators.

Here we report the fabrication of two types of microirradiators, consisting of a recessed disk and protruding wire with low-beta-energy radionuclide Ni-63 electrodeposited onto a 25 microm diameter Pt wire. Ni-63 is constricted to a small surface area of the microelectrode; hence, this tool provides a means of delivery of localized, large dose density of beta radiation to the object but a minimal dose exposure to the user. The activity levels of Ni-63 emitted from the recessed disk and protruding wire are 0.25 and 1 Bq, respectively. The corresponding beta particles flux levels emitted from the recessed disk and protruding wire are 51 and 11 kBq/cm(2), respectively. These values, measured experimentally using liquid scintillation counting, fit very well the expected values of activity for each microirradiator, calculated considering the self-absorption effect, typical for low-energy beta particles. In order to determine the optimal configuration the dose rates for varying distances from the object were calculated.

Development of site profiles for dose reconstruction used in worker compensation claims.

For the purpose of dose reconstruction, personal dosimeter data and measured intakes through bioassay analysis (i.e., in-vivo and in-vitro measurements) should be used whenever possible and given precedence over area monitoring data, survey data, or source term data. However, this is not always possible. A worker's exposure record may be incomplete or missing, or, based on directives and guidelines at the time, a worker may not have been monitored during his or her time of employment. In an effort to recognize, analyze, and incorporate all possible considerations of potential exposures, the National Institute for Occupational Safety and Health Radiation Dose Reconstruction Program developed "site profiles" for all of the major U.S. Department of Energy sites and Atomic Weapons Employer sites. Site profiles are technical documents that (1) provide a brief, general overview of the site; (2) identify the facilities on site with a brief description of the processes and radionuclides used in these processes; (3) contain detailed information on the historical detection limits for film, thermoluminescent dosimeter, and bioassay measurements that are used by the dose reconstructor to interpret a worker's available monitoring records; and (4) provide important supporting information for the dose reconstructor to use if the monitoring data are inadequate or unavailable. When a complete set of monitoring data for an individual is unavailable, it is the parameters in the site profile that are of the most use to the dose reconstructor. These parameters include facility monitoring data (by radionuclide, mechanism of intake, year of exposure, location within a facility); occupational medical x rays and techniques used; environmental measurements (by area on site, radiation type, energy range); minimum detectable activities of the types and kinds of instruments used to detect the different radionuclides; specific source terms (quantities of material and their molecular form) within each facility or process; and specifics of the overall dosimetry programs as they evolved over time. An additional benefit of having a site profile for a site is that it promotes consistency among the numerous health physicists that are working on the project. Resources used in the development of site profiles include technical basis documents for external and internal dosimetry programs, facility descriptions, environmental reports, safety analysis reports, input from past and present site workers, and other reports that have been written to describe the workplace environments within the facilities.

Internal dose reconstruction under Part B of the energy employees compensation act.

The reconstruction of internal doses under Part B of the Energy Employees Occupational Illness Compensation Program Act differs in multiple ways from that used in a typical operational setting. There are, for example, no limits at or above which doses must be assessed; all doses, including unmonitored or potentially undetected doses, must be reconstructed. In addition, the primary dose of concern is that delivered to the organ in which the cancer originated, and only the dose delivered to that organ prior to the time the cancer was diagnosed is relevant. Additional challenges are presented in the requirement to partition dose by radiation type and energy rather than by radionuclide, the need to include any potential dose that could have been received but was unmonitored or undetected, the inability to collect follow-up samples, and, in many cases, a general lack of information regarding the employee's work history, such as specific duties or location within a site. To overcome these challenges, the NIOSH dose reconstruction program has adopted a set of default values that include assumptions that are favorable to the claimant when there is more than one plausible choice. Due to the large number of claims that must be reconstructed, efforts are continuously underway to expedite the rate at which they can be processed. This is being achieved by taking advantage of situations in which it can be documented that more detailed evaluations would not change the outcome of the adjudication of the claim.

External dose reconstruction under Part B of the energy employees compensation act.

External doses reconstructed under Part B of the Energy Employees Occupational Illness Compensation Program Act include not only those that were recorded by personal dosimeters, but also those that were not recorded. Recorded doses may require corrections to account for measurement bias or limitations in the dosimeters' capabilities. Unrecorded doses that have been reconstructed include (1) those missed due to limits of detection associated with personal dosimeters, (2) external ambient doses that may have been inadvertently omitted from the monitoring results (or were not monitored altogether in the case of nonradiation workers), and (3) doses incurred as a result of medical x-ray examinations required by employers. Additionally, some workers were not monitored (or their dosimetry data are not available) even though there was a potential for exposure; doses to such workers are typically assigned based on the records of coworkers who performed the same, or similar, tasks. Additional issues that complicate the dose reconstruction process include the requirements that (1) all external doses must be partitioned according to radiation type and energy, and (2) the accompanying doses to specific body organs must be estimated. Since the external dose reconstruction process typically incorporates many claimant-favorable methodologies, parameters, and assumptions, the doses assigned do not necessarily reflect either realistic or actual estimates of the doses received, and external doses assigned to workers under the Act often are substantially higher than those contained in the dosimetry records.

Dynamic model for the assessment of radiological exposure to marine biota.

A generic approach has been developed to simulate dynamically the uptake and turnover of radionuclides by marine biota. The approach incorporates a three-compartment biokinetic model based on first order linear kinetics, with interchange rates between the organism and its surrounding environment. Model rate constants are deduced as a function of known parameters: biological half-lives of elimination, concentration factors and a sample point of the retention curve, allowing for the representation of multi-component release. The new methodology has been tested and validated in respect of non-dynamic assessment models developed for regulatory purposes. The approach has also been successfully tested against research dynamic models developed to represent the uptake of technetium and radioiodine by lobsters and winkles. Assessments conducted on two realistic test scenarios demonstrated the importance of simulating time-dependency for ecosystems in which environmental levels of radionuclides are not in equilibrium.

Distribution coefficients (Kd's) for use in risk assessment models of the Kara Sea.

As a prerequisite for most evaluations of radionuclide transport pathways in marine systems, it is necessary to obtain basic information on the sorption potential of contaminants onto particulate matter. Kd values for use in modeling radionuclide dispersion in the Kara Sea have been determined as part of several international programs addressing the problem of radioactive debris residing in Arctic Seas. Field and laboratory Kd experiments were conducted for the following radionuclides associated with nuclear waste: americium, europium, plutonium, cobalt, cesium and strontium. Emphasis has been placed on two regions in the Kara Sea: (i) the Novaya Zemlya Trough (NZT) and (ii) the mixing zones of the Ob and Yenisey Rivers (RMZ). Short-term batch Kd experiments were performed at-sea on ambient water column samples and on samples prepared both at-sea and in the laboratory by mixing filtered bottom water with small amounts of surficial bottom sediments (particle concentrations in samples = 1-30 mg/l). Within both regions, Kd values for individual radionuclides vary over two to three orders of magnitude. The relative particle affinities for radionuclides in the two regions are americium approximately equal to europium > plutonium > cobalt > cesium > strontium. The values determined in this study agree with minimum values given in the IAEA Technical Report [IAEA, 1985. Sediment Kd's and Concentration Factors for Radionuclides in the Marine Environment. Technical Report No. 247. International Atomic Energy Agency, Vienna.]. Given the importance of Kd's in assessments of critical transport pathways for radionuclide contaminants, we recommend that Kd ranges of values for specific elements rather than single mean values be incorporated into model simulations of radionuclide dispersion.