Estimating Uncertainty in Actinide Intake Due to Unknown Time of Exposure.

Bioassay of radiation workers handling actinides in powder form is carried out annually under routine monitoring program. In case of routine monitoring, as the day of intake is unknown, it is assumed that intake has occurred at the midpoint of monitoring interval. However, an uncertainty is introduced in intake estimation due to this assumption. In the present work, uncertainties were evaluated due to unknown time of intake of Type M and S compounds of Pu and U for annual and biennial monitoring interval. Lung and excreta monitoring methods were considered for uncertainty estimation along with the spread of ±1 month or ±2 months in measurements, at the end of monitoring interval. Annual lung monitoring is found to be the most robust and accurate method for assessment of intake of Type S compounds of Pu, Am and U when time of intake is unknown and Pu is detected using 241Am as a tracer. For Type M compounds, uncertainty was found to be higher than 3 for biennial monitoring interval. Uncertainty is found to be less than 3 for Type S compounds of Pu and U and also for Type M compounds of Pu for both, annual and biennial monitoring intervals using urine analysis. It is higher than 3 for Type M compounds of U for both the monitoring intervals. It is greater than 3 for both Type M and S compounds of Pu and U for both the monitoring intervals using fecal analysis.

Biokinetics of Americium-241 in the euryhaline diamond sturgeon Acipenser gueldenstaedtii following its uptake from water or food.

Americium-241 whole body and internal biokinetics were experimentally investigated in the euryhaline diamond sturgeon Acipenser gueldenstaedtii during its uptake from water and food, in fresh (FW) and brackish water (BW; 9 psu). Whole-body uptake rates of 241Am from water and subsequent depuration rates were quantified over 14 and 28 days, respectively, and assimilation efficiency (AE) of 241Am from diet (chironomid) was determined over 28 days. FW reduced the biological half-life of 241Am following aqueous uptake by an order of magnitude. In contrast BW greatly reduced 241Am assimilation efficiency (AE) from diet (chironomid) by several orders of magnitude (from an AE of 8.5% (FW) down to 0.003% (BW)). Hence, salinity per se is indicated as a major environmental variable in determining the radiological exposure of A. gueldenstaedtii to 241Am. During aqueous exposure BW appreciably increased 241Am activity concentrations in most body components, but aqueous or dietary exposure pathway at either salinity did not determine marked differences in how 241Am was distributed among six body components. The highly mineralized skin of A. gueldenstaedtii recurred as a major repository of 241Am in all experimental treatments, as high as 50% among body components, due to its internal transfer from diet, surface adsorption and/or active absorption from water. The indicated prominence of the aqueous, compared to the dietary, exposure pathway for 241Am accumulation by A. gueldenstaedtii suggests its radiological exposure would be enhanced by BW as it leads to its greater long-term retention, due to a much longer biological half-life.

Biokinetic Method on Simultaneous Intake of Radionuclides from Multiple Intake Scenarios for Application in Internal Exposures.

Biokinetics underlies the basis for assessment of internal exposures. This paper develops a biokinetic method on simultaneous intake of radionuclides from multiple intake scenarios in internal exposures. With numerical techniques that transform the whole biokinetics between the coupled and decoupled representations of the same problem, this method applies to coupled biokinetics with complex structures and has no restrictions of practical importance on the number of intake scenarios, the number of intake parent radionuclides and decay products, and the complexity of decay relationships between parent and progeny nuclides. For illustration, this method is applied to an assumed case of mixed inhalation and ingestion of weapon-grade plutonium material for reference workers that is focused on Pu and Am. Due to coupled biokinetics between the direct intake and ingrowth parts in different intake pathways, the multiple intake results (the contents of lungs, daily excretions, and cumulative contents) display richer behaviors as compared to single intake cases. This method benefits both the prospective and retrospective assessment of internal exposures for complex intake cases in actual applications.

Power Function Retention of Radionuclides in a Wound.

NCRP Report 156 describes soluble radionuclide retention kinetics in a wound, segregated into four retention categories: weak (W), moderate (M), strong (S), and avid (A). An alternate single-parameter model, the negative power function, t, is presented in this paper to describe the time behavior of radionuclide retention. With this mathematical description, γ is a single parameter that can be used to assign the wound retention category rapidly. Using the power function description of wound retention, the various wound categories present as straight lines on log scales with different slopes corresponding to the various retention categories. Regression analysis of average retention values in NCRP 156 shows γ = 0.735 ± 0.132, 0.514 ± 0.015, 0.242 ± 0.016, and 0.053 ± 0.023 for the weak, moderate, strong, and avid categories, respectively. A case study is presented (REAC/TS Registry case 1284) where a power function is shown to fit retention data in a Pu/Am hand wound up to 2,000 d (5.4 y) post-accident.

Chelation Modeling: The Use of Ad Hoc Models and Approaches to Overcome a Dose Assessment Challenge.

Chelating agents are administered to treat significant intakes of radioactive elements such as plutonium, americium, and curium. These drugs may be used as a medical countermeasure after radiological accidents and terrorist acts. The administration of a chelating agent, such as Ca-DTPA or Zn-DTPA, affects the actinide's normal biokinetics. It enhances the actinide's rate of excretion, posing a dose assessment challenge. Thus, the standard biokinetic models cannot be directly applied to the chelation-affected bioassay data in order to assess the radiation dose. The present study reviews the scientific literature, from the early 1970s until the present, on the different studies that focused on developing new chelation models and/or modeling of bioassay data affected by chelation treatment. Although scientific progress has been achieved, there is currently no consensus chelation model available, even after almost 50 y of research. This review acknowledges the efforts made by different research groups, highlighting the different methodology used in some of these studies. Finally, this study puts into perspective where we were, where we are, and where we are heading in regards to chelation modeling.

Americium biodistribution in rats after wound contamination with different physicochemical forms in the presence or absence of plutonium: analyses using STATBIODIS.

Americium (Am) biodistribution data obtained after wound contamination in rats were analysed to evaluate and quantify the influence of different physicochemical forms of Am in the presence or absence of plutonium (Pu). The biodistribution data were individual Am daily urinary excretion and tissue retention. The data were analysed with STATBIODIS, a statistical tool developed in the laboratory and based on the R language. Non-parametric methods were selected to comply with the data characteristics. Am systemic tissue retention and urinary excretion data were much greater for contamination with soluble physicochemical forms than insoluble forms. Meanwhile, Am relative biodistribution between the main retention tissues (skeleton, liver and kidney) remained the same. Hence, after absorption into blood the radionuclide behaviour was independent of the physicochemical form. The presence of Pu did not change the Am biodistribution. Comparisons of the biodistribution data from the laboratory with mean values published by other laboratories showed that soluble to moderately soluble forms of Am resulted in similar urine excretion after contamination, whether it was intravenous, intramuscular, subcutaneous injection or incision. Findings from this work will contribute to improve the understanding and interpretation of wound contamination cases with different physicochemical forms and mixtures of actinides including Am.

Americium Systemic Biokinetic Model for Rats.

In this work, a baseline compartmental model of the distribution and retention of americium in the rat for a systemic intake was derived. The model was derived from data obtained from a study designed to evaluate the behavior of americium in the first 28 days after incorporation. A pharmacokinetic (PK)-front-end modeling approach was used to specify transfer to and from the extracellular fluids (ECF) in the various tissues in terms of vascular flow and volumes of ECF. Back-end rates representing transport into and out of the cells were determined empirically. Uncertainties in transfer rates were investigated using Markov chain Monte Carlo (MCMC). The combination of PK-front-end model and the back-end model structure used allowed for extrapolation to the earliest times with small uncertainty. This approach clearly demonstrated the rapid transfer of material from ECF to liver and bone. This model provides a baseline for modeling the action of decorporation agents, such as DTPA.

Updated biokinetic model for systemic americium.

The biokinetic model for systemic americium (Am) currently recommended by the International Commission on Radiological Protection (ICRP) for application to occupational intake of Am is based on information available through the early 1990s. Much additional information on Am biokinetics has been developed in the past 25 y, including measurements of retention and excretion of 241Am in many workers with 241Am burdens and post mortem measurements of 241Am in tissues of some of those workers. The ICRP's current Am model is reasonably consistent with the updated information, with the main exception that the current model apparently overestimates 24-hour urinary Am as a fraction of skeletal or systemic Am at late times after intake. This paper provides an overview of current information on the systemic kinetics of Am in adult human subjects and laboratory animals and presents an updated biokinetic model for systemic Am that addresses the discrepancies between the current database and current ICRP systemic model for Am. This model is applied in Part 4 (to appear) of an ICRP series of reports on intake of radionuclides by workers called the OIR (Occupational Intake of Radionuclides) series.

A quick and simple in vitro assay to predict bioavailability of actinides following accidental exposure.

Physicochemical properties of actinides highly influence internal intake and biodistribution. An a priori knowledge of the dissolution properties of compounds involved in accidental exposure would be of great help in early dose assessment. However, this information is rarely available, leading to difficulties in interpreting excretion data from contaminated victims. We developed an in vitro acellular assay to predict in vivo bioavailability of actinides and improve medical handling of the victims. Various actinides of different physicochemical properties were used to validate the reliability of the assay to mimic in vivo behavior of the contaminants. Our assay was designed as a dynamic muticompartmental system in which an agarose gel represents the retention compartment of actinides and a dynamic phase the transfer compartment. Relevant physiological conditions were obtained by introducing various components both in the static and dynamic phases. The proposed model may provide a good prediction of in vivo behavior and could be used as a first assessment to predict the fraction of actinides that could be potentially transferred from retention compartments, as well as the fraction available to chelating drugs.

Mapping 241Am Spatial Distribution Within Anatomical Bone Structures Using Digital Autoradiography.

Digital autoradiography with the ionizing radiation quantum imaging detector is used at the US Transuranium and Uranium Registries for visualizing the microdistribution of alpha particles from Am and quantifying the activity. The radionuclide spatial distribution was investigated within cortical and trabecular regions of bone samples from US Transuranium and Uranium Registries case 0846. Multiple specimens from the humerus proximal end, humerus proximal shaft, and clavicle acromial end were embedded in plastic, and 100-µm-thick sections were taken and imaged using the ionizing radiation quantum imaging detector. The detector images were superimposed on the anatomical structure images to visualize Am distribution in cortical bone, trabecular bone, and trabecular spongiosa. Activity concentration ratios were used to characterize Am distribution within different bone regions. The trabecular-to-cortical bone and trabecular-spongiosa-to-cortical bone activity concentration ratios were quantified in both humerus and clavicle. The ionizing radiation quantum imaging detector results were in agreement with those obtained from radiochemical analysis of the remaining bone specimens. The results were compared with International Commission on Radiological Protection default biokinetic model predictions. Digital autoradiography was proven to be an effective method for microscale heterogeneous distribution studies where traditional counting methods are impractical.

Application of the ICRP 67 and NCRP 156 Biokinetic Models to 241 Am Wound Data from Nonhuman Primates.

Distribution, retention, and excretion of intramuscularly injected Am citrate have been investigated in cynomolgus and rhesus nonhuman primates (NHP). Bioassay and retention data, obtained from experiments done by Patricia Durbin and her colleagues at Lawrence Berkeley National Laboratory, were evaluated against the International Commission on Radiological Protection (ICRP 67) Am systemic model coupled with to the National Council on Radiation Protection and Measurement wound model (NCRP 156). The default transfer rates suggested in these models were used with the urine and feces excretion data to predict the intake as well as liver and skeleton tissue contents at the time of death. The default models adequately predict the animals' urine bioassay data, but the injected activities were overpredicted by as much 4.41 times and underpredicted by as much as 0.99 times. Poor prediction has been observed in all cases using fecal excretion. The retained activity in the liver and skeleton were investigated using the same approach. It appears that the models predict the amount of the activity retention in the skeleton more accurately than in the liver. The fraction of predicted to measured activity at the time of death in the skeleton was over 1.0 in most cases, and accurate predictions were obtained in seven cases. The predicted activity in skeleton for these cases ranged from 2.7 to 17% overestimated activity and from 9 to 14% underestimated activity. NHPs' urine data and organ retention were compared with data from previously modeled baboons and beagle dogs. About 6% of the injected activity in baboons and beagle dog was excreted in urine and approximately 0.1% in feces in the first 24 h. The results from NHP are not different from excreta analysis in these other species. Urinary excretion in the cynomolgus, rhesus, and baboon NHP is the dominant pathway of Am clearance; however, fecal excretion is considered dominant in beagle dogs. The comparison between NHPs and humans is difficult due to the differences in the number of activities translocated or deposited in the liver tissue and nonliver tissues (primarily skeleton), in addition to the physiological differences between the NHPs and humans.

Behavior of Americium in Simulated Wounds in Nonhuman Primates.

An americium solution injected intramuscularly into several nonhuman primates (NHPs) was found to behave differently than predicted by the wound models described in the NCRP Report 156. This was because the injection was made along with a citrate solution, which is known to be more soluble than chlorides, oxides, or nitrates on which the NCRP Report was based. A multi-exponential wound model specific to the injected americium solution was developed based on the retention in the intramuscular sites. The model was coupled with the americium systemic model to interpret the urinary excretion data and assess the intake, and it was determined that the models were adequate to predict early urinary excretion in most cases but unable to predict late urinary excretion. This was attributed to the differences in the systemic handling of americium between humans and nonhuman primates. Information on the type of wounds, solubility, particle size, mass, chemical form, etc., should always be considered when performing wound dosimetry.

ICRP 67 Biokinetic Models for AM-241 Applied to Nonhuman Primates.

Between 1960 and 1985, Patricia Durbin and colleagues performed studies on the distribution of intravenously and intramuscularly injected Am citrate with dosages ranging from 16 to 32 kBq kg in 30 male and female non-human primates (NHP). Dr. Durbin died unexpectedly in March of 2009, leaving much of the extensive serial blood, bioassay, and autopsy data from these NHP studies unanalyzed. As part of the experimental design, serial blood samples were taken, and urine and feces samples were collected separately for the duration of the study. The measurements of urine, fecal excretion, blood samples, and organ burden data obtained from the animals were used to evaluate the transfer rates of the ICRP 67 biokinetic model for Am. Seven cases, in which the primates were administered Am citrate by intravenous injection, were evaluated using the ICRP 67 systemic model. There were differences ranging from 51.4% underestimated to 102.7% overestimated activity between the predicted intake, which was calculated using IMBA Professional Plus software and based upon the urine bioassay data and the actual activity. The difference between the predicted activity at the time of death in the liver and skeleton using IMBA professional software and the value of the measured activity at the time of death were also compared. Generally, the ratios of predicted activity in the liver and skeleton at the time of death to the measured activity were consistently more than 1. However, the ratios were less than 1 in the skeleton for animals that were sacrificed 2,199 and 973 d post injection. The posterior probability distributions for model parameters derived using WeLMoS method were inconsistent with the ICRP 67 default parameters. The prediction made based on the posterior probability distributions for model parameters derived using WeLMoS gave the best fit to these data; however, the modified parameters overestimated the activity in almost all cases. The difference between the predicted Am activity and the value of the measured activity may be due to the physiological age-related characteristics relative to the age of the animal at the time of the injection and early and long scarified time.

241Am INGROWTH AND ITS EFFECT ON INTERNAL DOSE.

Generally, plutonium has been manufactured to support commercial and military applications involving heat sources, weapons, and reactor fuel. This work focuses on three typical plutonium mixtures while observing the potential of Am ingrowth and its effect on internal dose. The term "ingrowth" is used to describe Am production due solely to the decay of Pu as part of a plutonium mixture, where it is initially absent or present in a smaller quantity. Dose calculation models do not account for Am ingrowth unless the Pu quantity is specified. This work suggested that Am ingrowth be considered in bioassay analysis when there is a potential of a 10% increase to the individual's committed effective dose. It was determined that plutonium fuel mixtures, initially absent of Am, would likely exceed 10% for typical reactor grade fuel aged less than 30 y; however, heat source grade and aged weapons grade fuel would normally fall below this threshold. Although this work addresses typical plutonium mixtures following separation, it may be extended to irradiated commercial uranium fuel and is expected to be a concern in the recycling of spent fuel.

Influence of DTPA Treatment on Internal Dose Estimates.

In case of internal contamination with plutonium materials, a treatment with diethylene triamine pentaacetic acid (DTPA) can be administered in order to reduce plutonium body burden and consequently avoid some radiation dose. DTPA intravenous injections or inhalation can start almost immediately after intake, in parallel with urinary and fecal bioassay sampling for dosimetric follow-up. However, urine and feces excretion will be significantly enhanced by the DTPA treatment. As internal dose is calculated from bioassay results, the DTPA effect on excretion has to be taken into account. A common method to correct bioassay data is to divide it by a factor representing the excretion enhancement under DTPA treatment by intravenous injection. Its value may be based on a nominal reference or observed after a break in the treatment. The aim of this study was to estimate the influence of this factor on internal dose by comparing the dose estimated using default or upper and lower values of the enhancement factor for 11 contamination cases. The observed upper and lower values of the enhancement factor were 18.7 and 63.0 for plutonium and 24.9 and 28.8 for americium. For americium, a default factor of 25 is proposed. This work demonstrates that the use of a default DTPA enhancement factor allows the determination of the magnitude of the contamination because dose estimated could vary by a factor of 2 depending on the value of the individual DTPA enhancement factor. In case of significant intake, an individual enhancement factor should be determined to obtain a more reliable dose assessment.

Synthesis and Physicochemical Characterization of a Diethyl Ester Prodrug of DTPA and Its Investigation as an Oral Decorporation Agent in Rats.

The increasing threats of nuclear terrorism have made the development of medical countermeasures a priority for international security. Injectable formulations of diethylenetriaminepentaacetic acid (DTPA) have been approved by the FDA; however, an oral formulation is more amenable in a mass casualty situation. Here, the diethyl ester of DTPA, named C2E2, is investigated for potential as an oral treatment for internal radionuclide contamination. C2E2 was synthesized and characterized using NMR, MS, and elemental analysis. The physiochemical properties of solubility, lipophilicity, and stability were investigated in order to predict its oral bioavailability. Finally, an animal efficacy study was conducted in Sprague Dawley rats pre-contaminated by intramuscular injection with (241)Am(NO3)3 to establish effectiveness of the therapy via the oral route. Synthesis of C2E2 yielded a crystalline powder with high solubility and improved lipophilicity over DTPA. The ester was stable in both simulated gastric and intestinal fluids over the anticipated time course of absorption. Capsules containing C2E2 were demonstrated to be stable for 12 months under accelerated stability conditions. After a single dose, C2E2 enhanced the elimination of (241)Am in a dose-dependent manner. Significant improvement was seen in both total (241)Am decorporation and reduction of (241)Am liver and skeletal burden. C2E2 was concluded to be effective when orally administered to (241)Am-contaminated rats. It may therefore have potential for medical countermeasure in treating humans contaminated with (241)Am or other transuranic elements. An oral capsule or powder for reconstitution may be suitable formulations for future development based on the physiochemical properties and anticipated dose required for efficacy.

Speciation of americium in seawater and accumulation in the marine sponge Aplysina cavernicola.

The fate of radionuclides in the environment is a cause of great concern for modern society, seen especially in 2011 after the Fukushima accident. Among the environmental compartments, seawater covers most of the earth's surface and may be directly or indirectly impacted. The interaction between radionuclides and the marine compartment is therefore essential for better understanding the transfer mechanisms from the hydrosphere to the biosphere. This information allows for the evaluation of the impact on humans via our interaction with the biotope that has been largely undocumented up to now. In this report, we attempt to make a link between the speciation of heavy elements in natural seawater and their uptake by a model marine organism. More specifically, because the interaction of actinides with marine invertebrates has been poorly studied, the accumulation in a representative member of the Mediterranean coralligenous habitat, the sponge Aplysina cavernicola, was investigated and its uptake curve exposed to a radiotracer (241)Am was estimated using a high-purity Ge gamma spectrometer. But in order to go beyond the phenomenological accumulation rate, the speciation of americium(III) in seawater must be assessed. The speciation of (241)Am (and natural europium as its chemically stable surrogate) in seawater was determined using a combination of different techniques: Time-Resolved Laser-Induced Fluorescence (TRLIF), Extended X-ray Absorption Fine Structure (EXAFS) at the LIII edge, Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy and Scanning Electron Microscopy (SEM) and the resulting data were compared with the speciation modeling. In seawater, the americium(III) complex (as well as the corresponding europium complex, although with conformational differences) was identified as a ternary sodium biscarbonato complex, whose formula can be tentatively written as NaAm(CO3)2·nH2O. It is therefore this chemical form of americium that is accumulated by the sponge A. cavernicola.

Decorporation of systemically distributed americium by a novel orally administered diethylenetriaminepentaacetic acid (DTPA) formulation in beagle dogs.

Novel decorporation agents are being developed to protect against radiological accidents and terrorists attacks. Radioactive americium is a significant component of nuclear fallout. Removal of large radioactive materials, such as 241Am, from exposed persons is a subject of significant interest due to the hazards they pose. The objective of this study was to evaluate the dose-related efficacy of daily doses of NanoDTPA™ Capsules for decorporating Am administered intravenously as a soluble citrate complex to male and female beagle dogs. In addition, the efficacy of the NanoDTPA™ Capsules for decorporating 241Am was directly compared to intravenously administered saline and DTPA. Animals received a single IV administration of 241Am(III)-citrate on Day 0. One day after radionuclide administration, one of four different doses of NanoDTPA™ Capsules [1, 2, or 6 capsules d(-1) (30 mg, 60 mg, or 180 mg DTPA) or 2 capsules BID], IV Zn-DTPA (5 mg kg(-1) pentetate zinc trisodium) as a positive control, or IV saline as a placebo were administered. NanoDTPA™ Capsules, IV Zn-DTPA, or IV saline was administered on study days 1-14. Animals were euthanized on day 21. A full necropsy was conducted, and liver, spleen, kidneys, lungs and trachea, tracheobronchial lymph nodes (TBLN), muscle samples (right and left quadriceps), gastrointestinal (GI) tract (stomach plus esophagus, upper and lower intestine), gonads, two femurs, lumbar vertebrae (L1-L4), and all other soft tissue remains were collected. Urinary and fecal excretion profiles were increased approximately 10-fold compared to those for untreated animals. Tissue contents were decreased compared to untreated controls. In particular, liver content was decreased by approximately eightfold compared to untreated animals. The results from this study further demonstrate that oral NanoDTPA™ Capsules are equally efficient compared to IV Zn-DTPA in decorporation of actinides.

Skull counting in late stages after internal contamination by actinides.

Monitoring preparation for internal contamination with actinides (e.g. Pu and Am) is required to assess internal doses at nuclear fuel cycle-related facilities. In this paper, the authors focus on skull counting in case of single-incident inhalation of (241)Am and propose an effective procedure for skull counting with an existing system, taking into account the biokinetic behaviour of (241)Am in the human body. The predicted response of the system to skull counting under a certain counting geometry was found to be only ∼1.0 × 10(-5) cps Bq(-1) 1y after intake. However, this disadvantage could be remedied by repeated measurements of the skull during the late stage of the intake due to the predicted response reaching a plateau at about the 1000th day after exposure and exceeding that in the lung counting. Further studies are needed for the development of a new detection system with higher sensitivity to perform reliable internal dose estimations based on direct measurements.

30-y follow-up of a Pu/Am inhalation case.

In 1983, a young man inhaled accidentally a large amount of plutonium and americium. This case was carefully followed until 2013. Since no decorporation measures had been taken, the undisturbed metabolism of Pu and Am can be derived from the data. First objective was to determine the amount of inhaled radionuclides and to estimate committed effective dose. In vivo and excretion measurements started immediately after the inhalation, and for quality assurance, all types of measurements were performed by different labs in Europe and the USA. After dose assessment by various international groups were completed, the measurements were continued to produce scientific data for model validation. The data have been analysed here to estimate lung absorption parameter values for the inhaled plutonium and americium oxide using the proposed new ICRP Human Respiratory Tract Model. As supplement to the biokinetic modelling, biological data from three different cytogenetic markers have been added. The estimated committed effective dose is in the order of 1 Sv. The subject is 30 y after the inhalation, of good health, according to a recent medical check-up.