INITIAL EVALUATION OF INDIVIDUAL DOSES IN THE EARLY PHASE OF A NUCLEAR REACTOR ACCIDENT BASED ON IN-VIVO MONITORING DATA AND SIMULATED RADIOLOGICAL CONSEQUENCES.

In the early phase of a nuclear reactor accident, in-vivo monitoring of impacted population would be highly useful to detect potential contamination during the passage of the cloud and to estimate the dose from inhalation of measured radionuclides. However, it would be important to take into account other exposure components: (1) inhalation of unmeasured radionuclides and (2) external irradiation from the plume and from the radionuclides deposited on the soil. This article presents a methodology to calculate coefficients used to convert in-vivo measurement results directly into doses, not only from the measured radionuclides but from all sources of exposure according to model-based projected doses. This early interpretation of in-vivo measurements will provide an initial indication of individual exposure levels. As an illustration, the methodology is applied to two scenarios of accidents affecting a nuclear power plant: a loss-of-coolant accident leading to core meltdown and a steam generator tube rupture accident.

Repeated KI Prophylaxis in Case of Prolonged Exposure to Iodine Radioisotopes: Pharmacokinetic Studies in Adult Rats.

PURPOSE: To propose a new and effective dose regimen for stable potassium iodide (KI) repeated prophylaxis in case of prolonged exposure to radioactive iodine. METHODS: The pharmacokinetics of iodine was determined in rats by compartmental analyses after intravenous and oral administrations of the optimal dose of 1 mg/kg KI, which was previously selected in a dose-effect study. The thyroid protection against iodine-125 incorporation was followed during 24 h after a single oral dosing of KI. A repeated KI prophylaxis was modeled using initial estimates of iodine pharmacokinetic parameters. RESULTS: A dose regimen consisting in administrations of 1 mg/kg daily for 8 days was selected and studied. Plasma iodine concentrations predicted by simulation were verified by experimental data and varied after the third dose of KI between 174 and 1190 µg/l. The inhibition study of iodine-125 binding in the thyroid as a function of the time showed that the protection effect of KI could be correlated to stable iodine plasma concentrations. Hence, a theoretical decrease in iodine-125 thyroid uptake from 63 to 88% could be achieved in a 24 h-interval between two KI doses. CONCLUSION: Given the satisfactory levels of thyroid protection, this dose regimen could be envisaged in order to extent KI indications for repeated prophylaxis.

Optimal KI Prophylactic Dose Determination for Thyroid Radiation Protection After a Single Administration in Adult Rats.

A dose-response study was performed in adult rats to select an optimal stable potassium iodide (KI) dose which could be implemented in repeated prophylaxis, in case of prolonged exposure to radioactive iodine. Increasing doses of KI were given orally to rats 1 hour before internal exposure simulated by I-125 injection. I-125 incorporation in the thyroid was measured by γ-spectrometry, and KI protection effect was modeled by pharmacological functions. The measurement method by inductively coupled plasma mass spectrometry previously developed for the quantification of stable iodine in urine was adapted to correlate KI effect with its distribution in the thyroid. More than 75% blockade of iodine I-125 incorporation in the thyroid was achieved for KI single doses above 0.5 to 0.7 mg/kg. Stable iodine content in the thyroid 24 hours after KI administration displayed a biphasic response, with a maximum level for a dose around 1 mg/kg. Besides, the urinary excretion of stable iodine is described by a sigmoid function. The change in the rate of iodine excretion for doses above 1 mg/kg KI suggests a body overload in iodine and corroborates a possible saturation of the thyroid. The results show that 1 mg/kg KI could be regarded as an optimal dose for thyroid protection.

Compared in vivo efficiency of nanoemulsions unloaded and loaded with calixarene and soapy water in the treatment of superficial wounds contaminated by uranium.

No emergency decontamination treatment is currently available in the case of radiological skin contamination by uranium compounds. First responders in the workplace or during an industrial nuclear accident must be able to treat internal contamination through skin. For this purpose, a calixarene nanoemulsion was developed for the treatment of intact skin or superficial wounds contaminated by uranium, and the decontamination efficiency of this nanoemulsion was investigated in vitro and ex vivo. The present work addresses the in vivo decontamination efficiency of this nanoemulsion, using a rat model. This efficiency is compared to the radio-decontaminant soapy water currently used in France (Trait rouge®) in the workplace. The results showed that both calixarene-loaded nanoemulsion and non-loaded nanoemulsion allowed a significant decontamination efficiency compared to the treatment with soapy water. Early application of the nanoemulsions on contaminated excoriated rat skin allowed decreasing the uranium content by around 85% in femurs, 95% in kidneys and 93% in urines. For skin wounded by microneedles, mimicking wounds by microstings, nanoemulsions allowed approximately a 94% decrease in the uranium retention in kidneys. However, specific chelation of uranium by calixarene molecules within the nanoemulsion was not statistically significant, probably because of the limited calixarene-to-uranium molar ratio in these experiment conditions. Moreover, these studies showed that the soapy water treatment potentiates the transcutaneous passage of uranium, thus making it bioavailable, in particular when the skin is superficially wounded.

Cellular dosimetry calculations for Strontium-90 using Monte Carlo code PENELOPE.

PURPOSE: To improve risk assessments associated with chronic exposure to Strontium-90 (Sr-90), for both the environment and human health, it is necessary to know the energy distribution in specific cells or tissue. Monte Carlo (MC) simulation codes are extremely useful tools for calculating deposition energy. The present work was focused on the validation of the MC code PENetration and Energy LOss of Positrons and Electrons (PENELOPE) and the assessment of dose distribution to bone marrow cells from punctual Sr-90 source localized within the cortical bone part. MATERIALS AND METHODS: S-values (absorbed dose per unit cumulated activity) calculations using Monte Carlo simulations were performed by using PENELOPE and Monte Carlo N-Particle eXtended (MCNPX). Cytoplasm, nucleus, cell surface, mouse femur bone and Sr-90 radiation source were simulated. Cells are assumed to be spherical with the radii of the cell and cell nucleus ranging from 2-10 µm. The Sr-90 source is assumed to be uniformly distributed in cell nucleus, cytoplasm and cell surface. RESULTS: The comparison of S-values calculated with PENELOPE to MCNPX results and the Medical Internal Radiation Dose (MIRD) values agreed very well since the relative deviations were less than 4.5%. The dose distribution to mouse bone marrow cells showed that the cells localized near the cortical part received the maximum dose. CONCLUSION: The MC code PENELOPE may prove useful for cellular dosimetry involving radiation transport through materials other than water, or for complex distributions of radionuclides and geometries.

Texturing formulations for uranium skin decontamination.

CONTEXT: Since no specific treatment exists in case of cutaneous contamination by radionuclides such as uranium, a nanoemulsion comprising calixarene molecules, known for their good chelation properties, was previously designed. However, this fluid topical form may be not suitable for optimal application on the skin or wounds. OBJECTIVE: To develop a texturing pharmaceutical form for the treatment of wounded skins contaminated by uranium. MATERIALS AND METHODS: The formulations consisted in oil-in-water (O/W) nanoemulsions, loaded with calixarene molecules. The external phase of the initial liquid nanoemulsion was modified with a combination of thermosensitive gelifying polymers: Poloxamer and HydroxyPropylMethylcellulose (HPMC) or methylcellulose (MC). These new formulations were characterized then tested by ex vivo experiments on Franz cells to prevent uranyl ions diffusion through excoriated pig ear skin explants. RESULTS: Despite strong changes in rheological properties, the physico-chemical characteristics of the new nanoemulsions, such as the size and the zeta potential as well as macroscopic aspect were preserved. In addition, on wounded skin, diffusion of uranyl ions, measured by ICP-MS, was limited to less than 5% for both HPMC and MC nanoemulsions. CONCLUSIONS: These results demonstrated that a hybrid formulation of nanoemulsion in hydrogel is efficient to treat uranium skin contamination.

Calixarene cleansing formulation for uranium skin contamination.

An oil-in-water cleansing emulsion containing calixarene molecule, an actinide specific chelating agent, was formulated in order to improve the decontamination of uranium from the skin. Commonly commercialized cosmetic ingredients such as surfactants, mineral oil, or viscosifying agents were used in preparing the calixarene emulsion. The formulation was characterized in terms of size and apparent viscosity measurements and then was tested for its ability to limit uranyl ion permeation through excoriated pig-ear skin explants in 24-h penetration studies. Calixarene emulsion effectiveness was compared with two other reference treatments consisting of DTPA and EHBP solutions. Application of calixarene emulsion induced the highest decontamination effect with an 87% decrease in uranium diffusion flux. By contrast, EHBP and DTPA solutions only allowed a 50% and 55% reduction of uranium permeation, respectively, and had the same effect as a simple dilution of the contamination by pure water. Uranium diffusion decrease was attributed to uranyl ion-specific chelation by calixarene within the formulation, since no significant effect was obtained after application of the same emulsion without calixarene. Thus, calixarene cleansing emulsion could be considered as a promising treatment in case of accidental contamination of the skin by highly diffusible uranium compounds.

Uranium microdistribution in renal cortex of rats after chronic exposure: a study by secondary ion mass spectrometry microscopy.

For a few years, the biological effects on ecosystems and the public of the bioaccumulation of radionuclides in situations of chronic exposures have been studied. This work, in keeping with the ENVIRHOM French research program, presents the uranium microdistribution by secondary ion mass spectrometry (SIMS) technique in the renal cortex of rats following chronic exposure to this low level element in the drinking water (40 mg/L) as a function to exposure duration (6, 9, 12, and 18 months). The SIMS mass spectra and 238U+ ion images produced with a SIMS CAMECA 4F-E7 show the kinetic of uranium accumulation in the different structures of the kidney. For the rats contaminated up to 12 months, the radioelement is mainly fixed in the proximal tubules; then after 18 exposure months, uranium is detected in all the segments of the nephron. This work has also shown that ion microscopy is an analytical method to detect trace elements and give elemental cartography at the micrometer scale.

Ex vivo decrease in uranium diffusion through intact and excoriated pig ear skin by a calixarene nanoemulsion.

Cutaneous contamination by radionuclides is a major concern in the nuclear industry. In case of skin exposure to uranium, no efficient emergency treatment is available to remove the actinide from the skin. For this purpose, we developed a nanoemulsion containing calixarene molecules displaying good chelating properties towards uranium. In this paper, we describe the ability of this formulation to trap uranium and limit its transfer from the cutaneous contaminated site into the blood. Uranium percutaneous diffusion kinetics was assessed with Franz cells over 24 h through intact and excoriated pig ear skin biopsies, after or without application of the nanoemulsion. Uranium distribution in the skin layers was analysed by SIMS microscopy. The results showed that prompt application of the calixarene nanoemulsion allows a 94% and 98% reduction of the amount of uranium diffused respectively through intact and excoriated skin. The formulation is still efficient in case of delayed application up to 30 minutes since the 24 h-uranium transfer through excoriated skin is reduced by 71%. Besides, no accumulation of uranium or uranium-calixarene chelate was observed in the different skin layers. In conclusion, this study demonstrated the efficiency of the calixarene nanoemulsion, which can be regarded as a promising treatment for uranium cutaneous contamination.