Institute for Radiation Protection and Nuclear Safety (IRSN)
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Fabrication and characterization of thin self-rolling film for anti-inflammatory drug delivery
No full textInternational audienceThin films have been identified as an alternative approach for targeting sensitive site as drug delivery tool. In this work, the preparation of self-rolling thin films to form tubes for wound healing and easy placement (e.g. in the colon via colonoscopy) have been studied. We explored the use of thin films as a protective dressing combined to local release of an anti-inflammatory in order to improve drug efficacy and limit the side effects of the oral route. Non-cytotoxic poly(ethylene) glycol and poly(lactic acid) photo-crosslinkable star copolymers were used for rapid UV crosslinking of bilayered films loaded with prednisolone. The films, crosslinked under UV lamp without the need of photoinitiator, are optimized and compared in terms of water uptake, swelling ratio, final tube diameter and morphology, anti-inflammatory drug loading and release. Our studies showed the spontaneous rolling of bilayer constructs directly after immersion in water. Tubular geometry allows application of the patch through minimally invasive procedures such as colonoscopy. Moreover, the rolled-up bilayers highlighted efficient release of encapsulated drug following Fickian diffusion mechanism. We also confirmed the anti-inflammatory activity of the released anti-inflammatory drug that inhibits the pro-inflammatory cytokine IL-1β in RAW 264.7 macrophages stimulated by Escherichia coli (E. coli)
“dsbandrepair” – An updated Geant4-DNA simulation tool for evaluating the radiation-induced DNA damage and its repair
No full textInternational audiencePurposeInterdisciplinary scientific communities have shown large interest to achieve a mechanistic description of radiation-induced biological damage, aiming to predict biological results produced by different radiation quality exposures. Monte Carlo track-structure simulations are suitable and reliable for the study of early DNA damage induction used as input for assessing DNA damage. This study presents the most recent improvements of a Geant4-DNA simulation tool named “dsbandrepair”.Methods“dsbandrepair” is a Monte Carlo simulation tool based on a previous code (FullSim) that estimates the induction of early DNA single-strand breaks (SSBs) and double-strand breaks (DSBs). It uses DNA geometries generated by the DNAFabric computational tool for simulating the induction of early single-strand breaks (SSBs) and double-strand breaks (DSBs). Moreover, the new tool includes some published radiobiological models for survival fraction and un-rejoined DSB. Its application for a human fibroblast cell and human umbilical vein endothelial cell containing both heterochromatin and euchromatin was conducted. In addition, this new version offers the possibility of using the new IRT-syn method for computing the chemical stage.ResultsThe direct and indirect strand breaks, SSBs, DSBs, and damage complexity obtained in this work are equivalent to those obtained with the previously published simulation tool when using the same configuration in the physical and chemical stages. Simulation results on survival fraction and un-rejoined DSB are in reasonable agreement with experimental data.Conclusions“dsbandrepair” is a tool for simulating DNA damage and repair, benchmarked against experimental data. It has been released as an advanced example in Geant4.11.2
Revisiting the thermodynamic properties of the ZrCr2 Laves phases by combined approach using experimental and simulation methods
No full textInternational audienceA comprehensive study of ZrCr2 Laves phases is important for both fundamental research and technological applications. The ZrCr2 compound is a typical precipitate observed in Zr-based alloys including the newly developed Cr-coated Zr cladding known as Accident Tolerant Fuel cladding. The brittle behavior of the Laves phases and the low melting point at the interface zone between the precipitates and the Zr matrix are considered as governing the thermomechanical behaviors of these newly developed nuclear fuel claddings for normal operating conditions but more dramatically in case of Loss Of Coolant Accident (LOCA) conditions. The aim of the present study is to investigate the various ZrCr2 Laves polymorphs and their thermodynamic features particularly where conflicts exist in the literature. Based on diffraction experiments of annealed samples, it has been established that the transformation from the C14 high-temperature form to the C15 low-temperature form is of displacive nature without the C36 polymorph forming as an intermediate phase. The stable and metastable domains of C14 and C15 and their thermodynamic properties have been determined. The specific heat of both C14 and C15 types was measured over a wide range of temperatures from 2 to 1063 K by coupling relaxation calorimetry and DSC. The experimental data were fitted using a modified Einstein model. The room temperature entropies of the C14 and C15 phases were evaluated. The enthalpy of formation was measured for the first time using drop solution calorimetry in liquid Al at 1173 K in a Tian–Calvet calorimeter. The experimental value is in good agreement with Density Functional Theory (DFT) calculations. Finally, all these new results are discussed regarding the abundant literature on the ZrCr2 Laves phases
Avis de l’Anses relatif à l’examen du classement de la pertinence pour le métabolite R417888 du chlorothalonil et au réexamen du classement de la pertinence pour le métabolite R471811 du chlorothalonil dans les eaux destinées à laconsommation humaine
No full textCitation suggérée : Anses. (2024). Avis de l’Anses relatif à l’examen du classement de la pertinence pour lemétabolite chlorothalonil R417888 et au réexamen du classement de la pertinence pour lemétabolite chlorothalonil R471811 dans les eaux destinées à la consommation humaine(saisines 2023-SA-0041-a et -0142-a). Maisons-Alfort : Anses, 39 p.Pour garantir la qualité des EDCH, la directive 2020/2184, transposée en droit français, fixedes valeurs paramétriques pour les concentrations en pesticides et leurs métabolites pertinents (0,1 μg.L-1 par substance individuelle1 et 0,5 μg.L-1 pour la somme des pesticides et de leurs métabolites), sans définir les critères ou les modalités d’évaluation de cette pertinence. L’arrêté du 11 janvier 2007 modifié reprend ces valeurs en tant que limites de qualité (LQ) dans les EDCH pour les pesticides et leurs métabolites pertinents.À la demande de la DGS, l’Anses a proposé le 30 janvier 2019 une méthodologie permettant l’évaluation de la pertinence des métabolites de pesticides dans les EDCH au vu des connaissances scientifiques disponibles. Elle est destinée à être mise en œuvre dans le cadre d’une expertise collective de l’Anses, en s’appuyant sur les données disponibles (dossiers d’homologation, littérature scientifique, ...). Sur la base du résultat d’une telle évaluation, et de tout autre élément considéré approprié, la DGS statue sur la pertinence des métabolites devant faire l’objet d’une attention particulière (en termes de surveillance, de limite de qualité, ...). En l’absence d’évaluation, un métabolite est considéré pertinent par défaut.Pour les métabolites non pertinents de pesticides, la directive susmentionnée demande auxÉtats membres d’établir une valeur indicative aux fins de gestion de leur présence dans les EDCH. Ainsi, l’arrêté du 11 janvier 2007 modifié fixe pour ces métabolites une valeur indicative de 0,9 μg.L, résultant de l’avis de l’Anses du 30 janvier 2019.Concernant le métabolite R 417888 du chlorothalonil :Le 15 février 2023, la DGS a saisi l’Anses pour examiner le classement de la pertinence du métabolite R417888 du chlorothalonil dans les EDCH (saisine enregistrée sous le numéro 2023-SA-0041-a). Cette demande fait suite aux résultats de la campagne nationale exploratoire menée par le laboratoire d’hydrologie de Nancy (LHN) de l’Anses entre 2020 et 2022 (Anses, 2023), et à des demandes spécifiques formulées par les agences régionales de santé (ARS).Concernant le métabolite R 471811 du chlorothalonil :À la demande de la DGS, l’Anses avait caractérisé la pertinence du métabolite R471811 dans son avis du 26 janvier 2022 (Anses, 2022). En s’appuyant sur le schéma d’évaluation établi par l’Anses pour la détermination de la pertinence dans les EDCH (Anses, 2019), ce métabolite du chlorothalonil a été proposé « pertinent dans les EDCH » par l’Anses, en raison de la proposition de classement par l’EFSA de la substance active (SA) parente en cancérogène 1B au titre du règlement « classification, labelling, packaging (CLP) » (CE) n°1272/2008 et d’un manque de données pour prouver que le métabolite ne partage pas le mode d’action de la SA parente aboutissant à des tumeurs rénales.Fin juin 2023, la société Syngenta, une des sociétés ayant commercialisé des produits à basede la SA chlorothalonil, a transmis à la DGS des éléments complémentaires (études etargumentaire) relatifs à la cancérogénicité du métabolite R471811 (§ 3.2.2.4). En raison dedifficultés persistantes de gestion de l’alimentation en eau potable, liées au classement de lapertinence de ce métabolite pour les EDCH et de l’état de contamination de ces eaux par celui-ci, la DGS a saisi l’Anses en date du 3 juillet 2023 pour une demande de réexamen du classement de la pertinence de ce métabolite dans les EDCH au regard des nouveaux éléments transmis (saisine enregistrée sous le numéro 2023-SA-0142-a
Temporal trends of plastic additive contents in sediment cores of three French rivers (Loire, Meuse and Moselle) over the last decades
No full text(IF 8.2; Q1)International audienceSediment cores from three major French watersheds (Loire, Meuse and Moselle) have been dated by 137Cs and 210Pbxs from 1910 (Loire), 1947 (Meuse) and 1930 (Moselle) until the present in order to reconstruct trajectories of plastic additive contaminants including nine phthalate esters (PAEs) and seven organophosphate esters (OPEs), measured by gas chromatography–mass spectrometer (GC–MS–MS). Historical levels of ∑PAEs were higher than those of ∑OPEs in the Loire and the Moselle sediments, while ∑PAEs and ∑OPEs contents were of the same order of magnitude in the Meuse sediments. Although increases in concentrations do not evolve linearly, our results clearly indicate an increase in OPEs and PAEs concentrations from the 1950–1970 period onwards, compared with the first half of the 20th century. Our results show that, ∑OPE contents increase gradually over time in the Loire and Meuse rivers but evolve more randomly in the Moselle River. Trajectories of ∑PAEs depend on the river and no generality can be established, suggesting sedimentary reworking and/or local contamination. Data from this study allowed comparisons of contents of ∑OPEs and ∑PAEs between rivers, with ∑OPE concentrations in the Moselle River > Meuse River > Loire River, and concentrations of ∑PAEs in the Loire River > Moselle River > Meuse River. Among all PAEs, di(2-ethylhexyl) phthalate (DEHP) was the most abundant in all sediment samples, followed by diisobutyl phthalate (DiBP). Tris (2-chloroisopropyl) phosphate (TCPP) was the most abundant OPE in sediments of the three rivers. In addition, strong positive Pearson correlations were observed between organic matter (OM) parameters and OPE concentrations, and to a lesser extent, between OM parameters and PAE concentrations. This is particularly true for the Moselle River and for the Loire River, but less so for the Meuse River
Reactivity and bioconcentration of stable cesium in a hyperturbid fluvial-estuarine continuum: A combination of field observations and geochemical modeling
No full textInternational audienceEffective, post-accidental management needs an accurate understanding of the biogeochemical behavior of radionuclides in surface environments at a regional scale. Studies on stable isotopes (element homologs) can improve this knowledge. This work focuses on the biogeochemical behavior of stable cesium (Cs) along a major European fluvial-estuarine system, the Gironde Estuary (SW France). We present results obtained from (i) a long-term monitoring (2014–2017) of dissolved (Csd) and particulate (Csp) Cs concentrations at five sites along the freshwater continuum of the Garonne watershed, (ii) Csd and Csp concentrations during four oceanographic campaigns at contrasting hydrological conditions along longitudinal profiles of the estuarine system, (iii) a 24 h cycle of Csp at the estuary mouth, and (iv) a historical trend of Cs bioconcentration in wild oysters at the estuary mouth (RNO/ROCCH, 1984–2017). In addition, we model the partitioning of Cs within the estuarine environment for clay mineral interactions via PhreeqC. At fluvial sites, we observe a geogenic dependence of the Csp and a seasonal variability of Csd, with a downstream increase of the solid-liquid partitioning (log10 Kd values from 3.64 to 6.75 L kg−1) for suspended particulate matter (SPM) < 200 mg L−1. Along the estuarine salinity gradients, Cs shows a non-conservative behavior where fresh SPM (defined as Cs-depleted particles recently put in contact with Csd) act as a Cs sink during both flood and low discharge (drought) conditions. This sorption behavior was explained by the geochemical model, highlighting the relevance of ionic strength, water and SPM residence times. However, at high salinities, the overall log10 Kd value decreases from 6.02 to 5.20 for SPM ∼300–350 mg L−1 due to the Csd oceanic endmember. Despite wild oysters showing low bioconcentration factors (∼1220 L kg−1) at the estuary mouth, they are sensitive organisms to Cs fluxes
Intergenerational effects of ionizing radiation: review of recent studies from human data (2018–2021)
No full textInternational audiencePurpose: The purpose of this paper was to conduct a review of the studies published between 2018 and 2022 to investigate radiation-related effects in the offspring of human individuals exposed to ionizing radiation.Methods: The search identified 807 publications, from which 9 studies were selected for detailed analysis to examine for effects in children whose parents were exposed to various types and doses of radiation.Results: The review does not yield substantial evidence supporting intergenerational effects of radiation exposure in humans. However, caution is required when interpreting the results due to limitations in the majority of the published articles.Conclusion: This review, covering the period 2018-2022, serves as an extension of the previous systematic review conducted by Stephens et al. (2024), which encompassed the years 1988-2018. Together, these two papers offer a comprehensive overview of the available evidence regarding the intergenerational effects of parental pre-conceptional exposure to ionizing radiation. Overall, the findings do not provide strong evidence supporting a significant association between adverse (or other) outcomes in unexposed children and parental preconception radiation exposure
On the use of new vs. heated sample carriers for luminescence measurements
No full textInternational audienceTo ensure precise luminescence measurements, it is crucial to carry out measurements on clean sample carriers. Moreover, it is essential to ensure that the light emitted by the studied sample is reproducibly reflected towards the detector, particularly when the sample exhibits dim luminescence. This study reports observations made by three laboratories working in the field of retrospective dosimetry. The study discusses the results obtained using new sample carriers (made of stainless steel), instead of sample carriers previously heated to a temperature of 450 ◦C. The article describes the cleaning protocols routinely used by each laboratory and the treatment with distilled water that effectively removed spurious signals. When measuring TL signals of resistors using new sample carriers, a signal reduction of 10% was observed in the second measurement compared to the initial TL. For display glass samples from a mobile phone, a signal reduction between 15% and 32% was observed. However, there was negligible change in reproducibility when using the previously heated sample carriers. The reflectance of the sample carrier surface was indirectly measured using breakthrough signal measurements using violet or blue LEDs. A signal reduction of 12–14 % was observed when heating was applied for 20 new, unheated sample carriers using violet LEDs. The impact on dose estimation is discussed, and some recommendations are provided to guarantee precise luminescence measurements
Comparative Study of Radiation Mapping Technologies for Nuclear Disaster Assessment
No full textInternational audienceThe distribution of the ambient dose equivalent rate (i.e., air dose rate) after a nuclear disaster is crucial for zoning contaminated areas to facilitate authorities’ effective decision making. Several countries are considering a gradual characterization strategy where airborne measurement is performed first followed by ground measurement (i.e., via manborne or carborne surveys). Nonetheless, potential differences might emerge in country-specific air dose rate assessment methods. Explaining these discrepancies can improve and converge existing methodologies. The Japan Atomic Energy Agency (JAEA) and the French Institute for Radiological Protection and Nuclear Safety (IRSN), which are organizations involved in post-nuclear accident crisis management, jointly performed air dose rate measurements in 2019 at contaminated sites around the Fukushima Daiichi Nuclear Power Station. The similarities and differences between the two organizations’ methods and results were quantitatively assessed by comparing the average air dose rates obtained within a grid created with a geographic information system, and the reasons for the differences between the organizations’ results were investigated. The air dose rates obtained by the manborne measurements varied depending on the calibration method. Comparing the air dose rate assessment methods and mapping techniques used in different countries will contribute to developing international guidelines for recommending the best method for determining air dose rates
Classical and Bayesian statistical methods for low-level metrology
No full textInternational audienceThis document presents the statistical methods used to process low-level measurements in the presence of noise. These methods can be classical or Bayesian. The question is placed in the general framework of the problem of nuisance parameters, one of the canonical problems of statistical inference. By using a simple criterion proposed by Bolstad (2007), it is possible to define statistically significant results during a measurement process (act of measuring in the vocabulary of metrology). This result is similar for a classic paradigm (called “frequentist”) or Bayesian: the presence of zero in the interval considered (confidence or credibility). It is shown that in the case of homoskedastic Gaussians, the commonly used results are found. The case of Poisson distributions is then considered. In the case of heteroscedastic Gaussians, which is that of radioactivity measurement, we can consider them as Poisson laws in the limit of large counts. The results are different from those commonly used, and in particular those from standards (ISO 11929). Their statistical performances, characterized by simulation, are better and are well verified experimentally. This is confirmed theoretically by the use of the Neyman-Pearson lemma which makes it possible to formally determine the statistical tests with the best performances. These results also make it possible to understand the paradox of the possible divergence of the detection limit. It is also formally shown that the confidence intervals thus calculated by getting rid of the nuisance parameter according to established methods result in the commonly used confidence interval. To our knowledge, this constitutes the first formal derivation of these confidence intervals.This method is based on keeping the measurement results whether they are significant or not (not censoring them). This is recommended in several standards or documents, is compatible with the ISO 11929 standard and is in line with recent proposals in the field of statistics. On the other hand, all the information necessary to determine whether a measurement result is significant or not remains available. The conservation and restitution of all results is currently applied in the USA. The textbook case of the WIPP incident makes it possible to ensure favorable public perception.The implications and applications of this method in different fields are finally discussed