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International audience; Purpose To propose a new and effective dose regimen for stable potassium iodide (KI) repeated prophylaxis in case ofprolonged 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 KIbetween 174 and 1190 μg/l. The inhibition study of iodine-125 binding in the thyroid as a function of the time showedthat the protection effect of KI could be correlated to stable iodine plasma concentrations. Hence, a theoretical decreasein 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.

Individual monitoring of workers exposed to the risk of intake of actinides requires suitable methods for measuring low level of excreted activity. The current protocols used for actinides analysis in bioassay are usually complicated and highly time consuming. In this work, a protocol based on the microwave digestion of urines followed by the separation of actinides using calix[6]arene-based chromatography columns and their measurement by a quadrupole ICP-MS is developed and validated, for the first time, on urine samples containing the three actinides, U, Pu and Am. With this protocol, the total analysis time is about 2 days, including the mineralization of urine and the chromatographic separation of actinides. Detection limits of actinides in urine are determined and compared to those obtained after “dilute and shoot” ICP-MS analysis or after alpha spectrometry measurement.

International audience; Background : In the context of a nuclear reactor accident, thyroid is the main target organ of radioactive iodines. To avoid as much as possible thyroid disorders or even cancer development, it is recommended to administer a single dose of potassium iodide to people at risk of exposure. Nevertheless, the Fu-kushima Dai-ichi disaster has pointed out many questions about the conditions of stable iodine prophylaxis implementation highlighting the need for reflection further revision of the actual "iodine doctrine". Therefore, providing useful data is required notably through the implementation of animal experiments to strengthen current knowledge and to edit new recommendations. Methods : Urinary iodine constitutes a very good indicator to investigate the function of thyroid, its interpretation demands reliable analyses. Prior to perform animal experiments, two calibration methods were designed by our lab and compared together (standard addition and external calibration) to assess the urinary concentration of stable iodine in urine by ICP-MS. They were validated based on several key parameters especially linearity, accuracy and limits of detection (LOD) and quantification (LOQ). Results : The results were nicely satisfying. Indeed, both calibration methods have indicated very good coefficients of correlations, accuracies with low expanded relative uncertainties were obtained. The estimated LOD in the sample for standard addition method and external calibration were fully acceptable, 0.39 µg·L −1 and 0.35 µg·L −1 , respectively. All performance criteria have been thus fulfilled successfully. The established methods were proven to be accurate, robust and sensitive. Once validated, both calibration methods were applied to rat urine samples and the results of z-score and Wilcoxon W test concluded that there were no statistically significant differences between both methods.

International audience; 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. © 2016 Elsevier Ireland Ltd

This work falls within the context of the general pattern of individual monitoring of workers exposed to a risk of internal contamination with actinides. The aim is to propose a new procedure for analyzing Pu traces from urine media and in the presence of uranium. The extractant molecule used is a calix[6]arene bearing hydroxamic acid functions. The affinity of this molecule towards Pu(IV) and U(VI) has been studied and the possibility to separate both elements has been shown.

Individual monitoring of workers exposed to a risk of internal contamination with actinides is achieved through in vivo measurements (anthroporadiametry) and in vitro measurements (urine and feces). The procedures currently used for analyzing actinides in urine require lengthy separation associated with long counting times by alpha spectrometry due to low activity levels. Their main drawback is thus that they are time-consuming, which limits the frequency and flexibility of individual monitoring. In this context, the aim of this work, carried out by the Radiochemistry Laboratory at the Institute for Radiological Protection and Nuclear Safety (IRSN), is to propose alternative radiochemical procedures for the analysis of actinides U, Pu and Am in urine. In order to selectively extract actinides from urines, it is of interest to use calix[n]arene molecules. Indeed, the preorganized structure of these macrocyclic molecules is suitable for the complexation of ions and they can be easily functionalized to be more specific. Thus, the p-tertbutylcalix[6]arenes bearing three carboxylic acid groups or three hydroxamic acid groups are excellent extractants for uranium, and they have also a very good affinity for plutonium and americium. The extraction of actinides by these calixarene has been studied experimentally, and also by computational study for uranium. From these results, a new radiochemical procedure has been proposed for U, Pu, Am analysis in urine. For an application to bioassays laboratories, it was decided to immobilize the calix[6]arene molecules on an inert solid support, for implementation with a chromatographic column. This technique makes it possible to combine the extraction performances of the calix[6]arenes with the practical advantages of the chromatographic column. Consequently, this new radiochemical is well suited for routine analysis. Furthermore, the actinides separation is quantitative and reproducible, and is faster and easier than the current procedures.