Areas of research to support the system of radiological protection.

This document presents the ICRP's updated vision on "Areas of Research to Support the System of Radiological Protection", which have been previously published in 2017. It aims to complement the research priorities promoted by other relevant international organisations, with the specificity of placing them in the perspective of the evolution of the System of Radiological Protection. This document contributes to the process launched by ICRP to review and revise the System of Radiological Protection that will update the 2007 General Recommendations in ICRP Publication 103.

The assessment and management of risks associated with exposures to short-range Auger- and beta-emitting radionuclides. State of the art and proposals for lines of research.

The assessment and management of risks associated with exposures to ionising radiation are defined by the general radiological protection system, proposed by the International Commission on Radiological Protection (ICRP). This system is regarded by a large majority of users as a robust system although there are a number of dissenting voices, claiming that it is not suitable for estimating the risks resulting from internal exposures. One of the specific issues of internal exposure involves short-range radiations such as Auger and beta particles. Auger- and beta-emitting radionuclides can be distributed preferentially in certain tissue structures and even in certain cellular organelles, according to their chemical nature and the vector with which they are associated. Given the limited range of the low-energy electrons in biological matter, this heterogeneous distribution can generate highly localised energy depositions and exacerbate radiotoxic responses at cellular level. These particularities in energy distribution and cellular responses are not taken into account by the conventional methods for the assessment of risk.Alternative systems have been proposed, based on dosimetry conducted at the cellular or even molecular level, whose purpose is to determine the energy deposition occurring within the DNA molecule. However, calculation of absorbed doses at the molecular level is not sufficient to ensure a better assessment of the risks incurred. Favouring such a microdosimetric approach for the risk assessments would require a comprehensive knowledge of the biological targets of radiation, the dose-response relationships at the various levels of organisation, and the mechanisms leading from cellular energy deposition to the appearance of a health detriment. The required knowledge is not fully available today and it is not yet possible to link an intracellular energy deposition to a probability of occurrence of health effects or to use methods based on cellular dosimetry directly.The imperfections of the alternative approaches proposed so far should not discourage efforts. Protection against exposure to Auger and low-energy beta emitters would benefit from mechanistic studies, dedicated to the study of energy depositions of the radionuclides in various cellular structures, but also from radiotoxicological studies to define the relative biological effectiveness of the various Auger emitters used in medicine and of certain low-energy beta emitters, whose behaviour may depend greatly on their chemical form during intake. The scientific expertise, as well as the human and physical resources needed to conduct these studies, is available. They could be now mobilised into international low-dose research programmes, in order to ultimately improve the protection of people exposed to these specific radionuclides.

Absorption of plutonium compounds in the respiratory tract.

In order to optimise the monitoring of potentially exposed workers, it is desirable to determine specific values of absorption for the compounds handled. This study derives specific values of absorption rates for different chemical forms of plutonium from in vitro and animal (monkeys, dogs, mice, rats) experiments, and from human contamination cases. Different published experimental data have been reinterpreted here to derive values for the absorption parameters, f(r), s(r) and s(s), used in the human respiratory tract model currently adopted by the International Commission on Radiological Protection (ICRP). The consequences of the use of these values were investigated by calculating related committed effective doses per unit intake. Average and median estimates were calculated for f(r), s(r), and s(s) for each plutonium compound, that can be used as default values for specific chemical forms instead of the current reference types. Nevertheless, it was shown that the use of the current ICRP reference absorption types provides reasonable approximations. Moreover, this work provides estimates of the variability in pulmonary absorption and, therefore, facilitates analyses of the uncertainties associated with assessments, either from bioassay measurements or from prospective calculations, of intake and dose.

ICRP Publication 141: Occupational Intakes of Radionuclides: Part 4.

The 2007 Recommendations (ICRP, 2007) introduced changes that affect the calculation of effective dose, and implied a revision of the dose coefficients for internal exposure, published previously in the Publication 30 series (ICRP, 1979a,b, 1980a, 1981, 1988) and Publication 68 (ICRP, 1994b). In addition, new data are now available that support an update of the radionuclide-specific information given in Publications 54 and 78 (ICRP, 1989a, 1997) for the design of monitoring programmes and retrospective assessment of occupational internal doses. Provision of new biokinetic models, dose coefficients, monitoring methods, and bioassay data was performed by Committee 2 and its task groups. A new series, the Occupational Intakes of Radionuclides (OIR) series, will replace the Publication 30 series and Publications 54, 68, and 78. OIR Part 1 (ICRP, 2015) describes the assessment of internal occupational exposure to radionuclides, biokinetic and dosimetric models, methods of individual and workplace monitoring, and general aspects of retrospective dose assessment. OIR Part 2 (ICRP, 2016), OIR Part 3 (ICRP, 2017), this current publication, and the final publication in the OIR series (OIR Part 5) provide data on individual elements and their radioisotopes, including information on chemical forms encountered in the workplace; a list of principal radioisotopes and their physical half-lives and decay modes; the parameter values of the reference biokinetic models; and data on monitoring techniques for the radioisotopes most commonly encountered in workplaces. Reviews of data on inhalation, ingestion, and systemic biokinetics are also provided for most of the elements. Dosimetric data provided in the printed publications of the OIR series include tables of committed effective dose per intake (Sv per Bq intake) for inhalation and ingestion, tables of committed effective dose per content (Sv per Bq measurement) for inhalation, and graphs of retention and excretion data per Bq intake for inhalation. These data are provided for all absorption types and for the most common isotope(s) of each element. The online electronic files that accompany the OIR series of publications contains a comprehensive set of committed effective and equivalent dose coefficients, committed effective dose per content functions, and reference bioassay functions. Data are provided for inhalation, ingestion, and direct input to blood. This fourth publication in the OIR series provides the above data for the following elements: lanthanum (La), cerium (Ce), praseodymium (Pr), neodymium (Nd), promethium (Pm), samarium (Sm), europium (Eu), gadolinium (Gd), terbium (Tb), dysprosium (Dy), holmium (Ho), erbium (Er), thulium (Tm), ytterbium (Yb), lutetium (Lu), actinium (Ac), protactinium (Pa), neptunium (Np), plutonium (Pu), americium (Am), curium (Cm), berkelium (Bk), californium (Cf), einsteinium (Es), and fermium (Fm).

Sensorimotor adaptation in Parkinson's disease: evidence for a dopamine dependent remapping disturbance.

Sensorimotor adaptation is thought to involve a remapping of the kinematic and kinetic parameters associated with movements performed within a changing environment. Patients with Parkinson's disease (PD) are known to be affected on this type of learning process, although the specific role of dopamine depletion in these deficits has not yet been elucidated. The present study was an attempt to clarify whether dopamine depletion in PD may directly affect the capacity to internally reorganize the visuomotor remapping of a distorted environment. Fourteen PD patients were tested twice, while they were treated and while they were withdrawn from their regular levodopa treatment. Fourteen control subjects were also enrolled and tested twice. Two parallel forms of the Computed Mirror Pointing Task (CMPT), requiring making a reaching movement in a visually transformed environment (mirror inversion), were administered to each participant. Each of them had to perform 40 trials at each of the 2 testing sessions. At each trial, sensorimotor adaptation was evaluated by the initial direction angle (IDA), which reflects the direction of movement before any visually guided readjustment. Results revealed no IDA difference at baseline, between control subject and PD patients, whether they were treated or not. In all group, IDA values at that time were large, reflecting a tendency to make movements according to the real life visuomotor mapping (based on the natural direct vision). However, striking differences appeared during sensorimotor learning, in that IDA reduction along trials was poorer in patient not treated with levodopa than both control subjects and the same PD patient treated with levodopa. No difference was observed between the treated PD patients and control subjects. Given that IDA is thought to reflect the internal representation of the visuomotor mapping, it is concluded that dopamine depletion in PD would affects sensorimotor adaptation, in that it facilitates old and poorly adapted movements (real life mapping), instead of new and more adapted ones (mirror transformed mapping).

[Development of a job exposure matrix for the epidemiological follow-up of workers in the French nuclear industry]. / Construction d'une matrice emplois--expositions pour le suivi épidémiologique des travailleurs de l'industrie nucléaire en France. Résultats d'une étude pilote.

BACKGROUND: A pilot study was carried out in the AREVA NC Pierrelatte nuclear facility in order to investigate a possible carcinogenic effect of internal radiation exposure among nuclear workers in France. The objective of this study was to develop a method for retrospective reconstruction of the occupational exposure to internal radiation from uranium and associated chemical exposures. METHODS: A plant- and period-specific job exposure matrix (JEM) was designed. Job groups and exposure agents groups including uranium compounds and other chemical agents known as being carcinogenic, mutagenic or toxic were defined by an expert committee. Exposure was evaluated by active and retired workers included in the evaluator committee. A quantitative assignment of quantity and frequency of handling (both coded from 0 to 3) was performed for each agent groups using a method derived from the Delphi technique. RESULTS: In all, 23 experts and 353 evaluators participated to the JEM elaboration. A final JEM involved 232 "job-periods" presenting throughout the plant period 1960-2006 and 22 exposure agents groups in use at the plant. Six of them involved uranium compounds classified by their blood-transferability and toxicity characteristics. A first validation of the JEM by experts in radiological protection and industrial hygiene showed an acceptable internal consistency. CONCLUSION: In the context of missing past exposure measurement data, the plant- and period-specific job exposure matrices may be considered as a valid alternative for exposure estimation. This method may be applied to other nuclear plants and offers allowance to investigate a possible carcinogenic effect of internal radiation exposure among nuclear workers.

ICRP Task Group 95: internal dose coefficients.

Internal doses are calculated using biokinetic and dosimetric models. These models describe the behaviour of the radionuclides after ingestion, inhalation, and absorption to the blood, and the absorption of the energy resulting from their nuclear transformations. The International Commission on Radiological Protection (ICRP) develops such models and applies them to provide dose coefficients and bioassay functions for the calculation of equivalent or effective dose from knowledge of intakes and/or measurements of activity in bioassay samples. Over the past few years, ICRP has devoted a considerable amount of effort to the revision and improvement of models to make them more physiologically realistic representations of uptake and retention in organs and tissues, and of excretion. Provision of new biokinetic models, dose coefficients, monitoring methods, and bioassay data is the responsibility of Committee 2 and its task groups. Three publications in a series of documents replacing the ICRP Publication 30 series and ICRP Publications 54, 68, and 78 have been issued [Occupational Intakes of Radionuclides (OIR) Parts 1-3]. OIR Part 1 describes the assessment of internal occupational exposure to radionuclides, biokinetic and dosimetric models, methods of individual and workplace monitoring, and general aspects of retrospective dose assessment. OIR Parts 2-5 provide data on individual elements and their radioisotopes. Work is also in progress on revision of dose coefficients for radionuclide intakes by members of the public.

Effect of acetaminophen administration to rats chronically exposed to depleted uranium.

The extensive use of depleted uranium (DU) in both civilian and military applications results in the increase of the number of human beings exposed to this compound. We previously found that DU chronic exposure induces the expression of CYP enzymes involved in the metabolism of xenobiotics (drugs). In order to evaluate the consequences of these changes on the metabolism of a drug, rats chronically exposed to DU (40mg/l) were treated by acetaminophen (APAP, 400mg/kg) at the end of the 9-month contamination. Acetaminophen is considered as a safe drug within the therapeutic range but in the case of overdose or in sensitive animals, hepatotoxicity and nephrotoxicity could occur. In the present work, plasma concentration of APAP was higher in the DU group compared to the non-contaminated group. In addition, administration of APAP to the DU-exposed rats increased plasma ALT (p<0.01) and AST (p<0.05) more rapidly than in the control group. Nevertheless, no histological alteration of the liver was observed but renal injury characterized by incomplete proximal tubular cell necrosis was higher for the DU-exposed rats. Moreover, in the kidney, CYP2E1 gene expression, an important CYP responsible for APAP bioactivation and toxicity, is increased (p<0.01) in the DU-exposed group compared to the control group. In the liver, CYP's activities were decreased between control and DU-exposed rats. These results could explain the worse elimination of APAP in the plasma and confirm our hypothesis of a modification of the drug metabolism following a DU chronic contamination.

Parental exposure to enriched uranium induced delayed hyperactivity in rat offspring.

Several recent reports suggest that chronic exposure to uranium could induce behavioural effects in adult rats. As the immature brains are known to be more susceptible to toxic effects, rats were observed in an open field, in a Y-maze and in an elevated plus-maze at 2, 5 and 9 months old after exposure to enriched uranium (40 mg l-1) during gestation and lactation. The rats exposed to enriched uranium showed a significant decrease in alternation in the Y-maze at 2 months old which reflects a slight decrease in the spatial working memory capacities as previously described in adult rats. However, the main result was a delayed hyperactivity in the rats exposed to enriched uranium, which appeared to a slight extent at 5 months old and was more evident at 9 months old. Although this effect could not be directly explained by some uranium accumulation in the target organs, this experiment showed that early exposure to enriched uranium can induce a very late effect on the rat behaviour and that such studies should not be restricted to the effects observed on young rats.

Comparison of the effects of enriched uranium and 137-cesium on the behaviour of rats after chronic exposure.

PURPOSE: A radionuclide that accumulates in the central nervous system is likely to exert both a chemical and a radiological effect. The present study aimed at assessing the behavioral effect of two radionuclides previously shown to accumulate in the central nervous system after chronic exposure--uranium and cesium. MATERIALS AND METHODS: Rats were exposed for 9 months to drinking water contaminated with either enriched uranium at a dosage of 40 mg U x l(-1) or 137-cesium at a dosage of 6500 Bq x l(-1), which correspond to the highest concentrations measured in some wells in the south of Finland (uranium) or in the milk in Belarus in the year following the Chernobyl accident (137-cesium). RESULTS: At this level of exposure, 137-cesium had no effect on the locomotor activity measured in an open-field, on immobility time in a forced swimming test, on spontaneous alternation in a Y-maze and on novel object exploration in an object recognition test. Enriched uranium exposure specifically reduced the spontaneous alternation measured in the Y-maze after 3 and 9 months exposure although it did not affect the other parameters. CONCLUSION: Enriched uranium exposure altered the spatial working memory capacities and this effect was correlated with previously described accumulation of uranium in the hippocampus which is one of the cerebral areas involved in this memory system.

Effects of chronic 137Cs ingestion on barrier properties of jejunal epithelium in rats.

Environmental contamination by 137Cs is of particular public health interest because of the various sources of fallout originating from nuclear weapons, radiological source disruptions, and the Chernobyl disaster. This dispersion may lead to a chronic ecosystem contamination and subsequent ingestion of contaminated foodstuffs. The aim of this study was to thus determine the impact of a chronic ingestion of low-dose 137Cs on small intestine functions in rats. The animals received 150 Bq per day in drinking water over 3 mo. At these environmental doses, 137Cs contamination did not modify the crypt and villus architecture. In addition, epithelial integrity was maintained following the chronic ingestion of 137Cs, as demonstrated by histological analyses (no breakdown of the surface mucosa) and electrical transepithelial parameters (no change in potential difference and tissue conductance). Furthermore, cesium contamination seemed to induce contradictory effects on the apoptosis pathway, with an increase in the gene expression of Fas/FasL and a decrease in the apoptotic cell number present in intestinal mucosa. No marked inflammation was observed following chronic ingestion of 137Cs, as indicated by neutrophil infiltration and gene expression of cytokines and chemokines. Results indicated no imbalance in the Th1/Th2 response induced by cesium at low doses. Finally, evaluation of the functionality of the jejunal epithelium in rats contaminated chronically with 137Cs did not demonstrate changes in the maximal response to carbachol, nor in the cholinergic sensitivity of rat jejunal epithelium. In conclusion, this study shows that chronic ingestion of 137Cs over 3 mo at postaccidental doses exerts few biological effects on the epithelium of rat jejunum with regard to morphology, inflammation status, apoptosis/proliferation processes, and secretory functions.

Incorporation and distribution of uranium in rats after a contamination on intact or wounded skin.

Uranium uptake can occur accidentally by inhalation, ingestion, injection, or absorption through intact or wounded skin. Intact or wounded skin routes of absorption of uranium have received little attention. The aims of our work were (1) to evaluate the influence of the type of wound contamination on the short term distribution and excretion of uranium in rats and (2) to generate data to assess the time available to treat contamination of intact or wounded skin before significant uptake of uranium occurs. Biokinetic data presented in the present paper are based on an in vivo rat model. This study shows that a significant uptake of a uranyl nitrate solution through intact skin can occur within the first 6 h of exposure. Absorption of a uranyl nitrate solution through excoriated skin is significant after only 30 min of exposure. After a 24-h exposure, uranium uptake through intact skin and excoriated skin represents about 0.4% and 38% of the initial deposit of uranium, respectively. Contaminated serious chemical skin burns induced by HNO3 or NaOH are paradoxically less important in terms of uranium uptake risk because 99% of the incorporated uranium remains trapped at the wound site and its incorporation is delayed for at least 6 h after the beginning of contamination. These results confirm that the biokinetics of a given physicochemical form of uranium incorporated after wound contamination depend largely on the physiological evolution of the considered wound. Each type of wound, with its corresponding biokinetics of a uranium species, is a particular case.

Updating the ICRP human respiratory tract model.

The ICRP Task Group on Internal Dosimetry is developing new Occupational Intakes of Radionuclides (OIR) documents. Application of the Human Respiratory Tract Model (HRTM) requires a review of the lung-to-blood absorption characteristics of inhaled compounds of importance in radiological protection. Where appropriate, material-specific absorption parameter values will be given, and for other compounds, assignments to default Types will be made on current information. Publication of the OIR provides an opportunity for updating the HRTM in the light of experience and new information. The main possibilities under consideration relate to the two main clearance pathways. Recent studies provide important new data on rates of particle transport from the nasal passages, bronchial tree (slow phase) and alveolar region. The review of absorption rates provides a database of parameter values from which consideration can be given to deriving typical values for default Types F, M and S materials, and element-specific rapid dissolution rates.

Percutaneous penetration of uranium in rats after a contamination on intact or wounded skin.

The aim of this work is to assess in vivo in a hairless rat model, the percutaneous diffusion of uranium through intact or wounded rat skin. Six types of wounds were simulated by excoriation and burns with 10 N HF, 2, 5 and 14 N HNO3 and 10 N NaOH on anaesthetised hairless rats. Percutaneous penetration through wounded skin towards blood and subsequent urinary excretion of uranium was followed in vivo during 24 h. The influence of the physicochemical form (solution or powder) of uranyl nitrate (UN) on its percutaneous diffusion was also investigated. UN, even as a powder, can diffuse through intact skin. The presence of uranium in blood is more persistent and its urinary elimination is slower after an HF burn than after an HNO3 burn. Excoriation increases dramatically percutaneous absorption of UN. Thus, percutaneous diffusion of UN is largely dependent on skin barrier integrity with a particular importance of stratum corneum.

Dose coefficients calculated using the new ICRP model for the human alimentary tract.

Publication 100 of the International Commission on Radiological Protection (ICRP) provides a Human Alimentary Tract Model (HATM) to replace the gastrointestinal (GI) model described in Publication 30. The HATM will be used for future calculations of dose coefficients and bioassay predictions, first in a series of publications on occupational intakes of radionuclides, and subsequently in revision of dose coefficients for public exposures. This paper compares dose coefficients calculated using the new model with current values calculated using the GI model for a range of radionuclides. Colon doses are lower using the HATM in all cases considered, in some cases by significant factors. Stomach doses tend to be lower, but are in some cases higher under HATM. The extent to which these changes in doses to gut tissues impacts upon the effective dose varies among nuclides, but there is a tendency for lower effective doses. Special-case applications of the HATM are also described, considering retention on teeth or in the walls of the small intestine. Although the effect of such retention on the regional tissue dose can be large, the effective dose is not greatly changed.

ICRP Publication 137: Occupational Intakes of Radionuclides: Part 3.

Abstract ­: The 2007 Recommendations of the International Commission on Radiological Protection (ICRP, 2007) introduced changes that affect the calculation of effective dose, and implied a revision of the dose coefficients for internal exposure, published previously in the Publication 30 series (ICRP, 1979, 1980, 1981, 1988) and Publication 68 (ICRP, 1994). In addition, new data are now available that support an update of the radionuclide-specific information given in Publications 54 and 78 (ICRP, 1988a, 1997b) for the design of monitoring programmes and retrospective assessment of occupational internal doses. Provision of new biokinetic models, dose coefficients, monitoring methods, and bioassay data was performed by Committee 2, Task Group 21 on Internal Dosimetry, and Task Group 4 on Dose Calculations. A new series, the Occupational Intakes of Radionuclides (OIR) series, will replace the Publication 30 series and Publications 54, 68, and 78. OIR Part 1 has been issued (ICRP, 2015), and describes the assessment of internal occupational exposure to radionuclides, biokinetic and dosimetric models, methods of individual and workplace monitoring, and general aspects of retrospective dose assessment. OIR Part 2 (ICRP, 2016), this current publication and upcoming publications in the OIR series (Parts 4 and 5) provide data on individual elements and their radioisotopes, including information on chemical forms encountered in the workplace; a list of principal radioisotopes and their physical half-lives and decay modes; the parameter values of the reference biokinetic model; and data on monitoring techniques for the radioisotopes encountered most commonly in workplaces. Reviews of data on inhalation, ingestion, and systemic biokinetics are also provided for most of the elements. Dosimetric data provided in the printed publications of the OIR series include tables of committed effective dose per intake (Sv Bq−1 intake) for inhalation and ingestion, tables of committed effective dose per content (Sv Bq−1 measurement) for inhalation, and graphs of retention and excretion data per Bq intake for inhalation. These data are provided for all absorption types and for the most common isotope(s) of each element. The electronic annex that accompanies the OIR series of publications contains a comprehensive set of committed effective and equivalent dose coefficients, committed effective dose per content functions, and reference bioassay functions. Data are provided for inhalation, ingestion, and direct input to blood. This third publication in the series provides the above data for the following elements: ruthenium (Ru), antimony (Sb), tellurium (Te), iodine (I), caesium (Cs), barium (Ba), iridium (Ir), lead (Pb), bismuth (Bi), polonium (Po), radon (Rn), radium (Ra), thorium (Th), and uranium (U).

Chronic contamination with 137Cesium affects Vitamin D3 metabolism in rats.

Twenty years after Chernobyl disaster, many people are still chronically exposed to low dose of (137)Cs, mainly through the food consumption. A large variety of diseases have been described in highly exposed people with (137)Cs, which include bone disorders. The aim of this work was to investigate the biological effects of a chronic exposure to (137)Cs on Vitamin D(3) metabolism, a hormone essential in bone homeostasis. Rats were exposed to (137)Cs in their drinking water for 3 months at a dose of 6500 Bq/l (approximately 150 Bq/rat/day), a similar concentration ingested by the population living in contaminated territories in the former USSR countries. Cytochromes P450 enzymes involved in Vitamin D(3) metabolism, related nuclear receptors and Vitamin D(3) target genes were assessed by real time PCR in liver, kidney and brain. Vitamin D, PTH, calcium and phosphate levels were measured in plasma. An increase in the expression level of cyp2r1 (40%, p<0.05) was observed in the liver of (137)Cs-exposed rats. However a significant decrease of Vitamin D (1,25(OH)D(3)) plasma level (53%, p=0.02) was observed. In brain, cyp2r1 mRNA level was decreased by 20% (p<0.05), while the expression level of cyp27b1 is increased (35%, p<0.05) after (137)Cs contamination. In conclusion, this study showed for the first time that chronic exposure with post-accidental doses of (137)Cs affects Vitamin D(3) active form level and induces molecular modifications of CYPs enzymes involved its metabolism in liver and brain, without leading to mineral homeostasis disorders.

Chronic ingestion of uranyl nitrate perturbs acetylcholinesterase activity and monoamine metabolism in male rat brain.

Recent animal studies have shown that uranium can reach the brain after chronic exposure. However, little information is available on the neurological effects of chronic long-term exposure to uranium. In the present study, the effects during 1.5, 6 and 9-month periods of chronic ingestion of uranyl nitrate (UN) in drinking water (40 mg of uranium per litre) on cholinergic acetylcholinesterase (AChE) activity and on dopaminergic and serotoninergic metabolisms were investigated in several areas of male Srague Dawley rat brains. Uranium brain accumulation and distribution was also investigated after 1.5 and 9 months. Both after 1.5, 6 and 9 months of exposure, AChE activity was unaffected in the striatum, hippocampus and frontal cortex. Nevertheless, AChE activity was transitionally perturbed in the cerebellum after 6 months of exposure. After 1.5 months of exposure, DA level increased in hypothalamus. After 6 months of exposure, a tiny but significant modification of the DAergic turnover ratio was detected in the frontal cortex. And after 9 months, UN produced a significant decrease in the 5HIAA level and the 5HTergic turn-over ratio in the frontal cortex and also a decrease in the DOPAC level and DAergic turn-over ratio in the striatum. Uranium brain accumulation was statistically significant in striatum after 1.5 months and in striatum, hippocampus and frontal cortex after 9 months of exposure. Although neurochemical changes did not always correlated with increased accumulation of uranium in specific areas, these results suggest that chronic ingestion of UN can cause chronic and progressive perturbations of physiological level of neurotransmitter systems. Considering previous reports on behavioural uranium-induced effects and the involvement of neurotransmitters in various behavioural processes, it would be crucial to determine whether these neurochemical disorders were accompanied by neurobehavioral deficits even at 40 mg of uranium per litre exposure.

Short-term effects of depleted uranium on immune status in rat intestine.

In the event of ingestion, the digestive tract is the first biological system exposed to depleted uranium (DU) intake via the intestinal lumen. However, little research has addressed the biological consequences of a contamination with depleted uranium on intestinal properties such as the barrier function and/or the immune status of this tissue. The aim of this study was to determine if the ingestion of depleted uranium led to changes in the gut immune system of the intestine. The experiments were performed at 1 and 3 d following a per os administration of DU to rats at sublethal dose (204 mg/kg). Several parameters referring to the immune status, such as gene and protein expressions of cytokines and chemokines, and localization and density of immune cell populations, were assessed in the intestine. In addition, the overall toxicity of DU on the small intestine was estimated in this study, with histological appearance, proliferation rate, differentiation pattern, and apoptosis process. Firstly, the results of this study indicated that DU was not toxic for the intestine, as measured by the proliferation, differentiation, and apoptosis processes. Concerning the immune properties of the intestine, the ingestion of depleted uranium induced some changes in the production of chemokines and in the expression of cytokines. A diminished production of monocyte chemoattractant protein-1 (MCP-1) was noted at 1 day post exposure. At 3 d, the increased gene expression of interferon gamma (IFNgamma) was associated with an enhanced mRNA level of Fas ligand, suggesting an activation of the apoptosis pathway. However, no increased apoptotic cells were observed at 3 d in the contaminated animals. There were no changes in the localization and density of neutrophils, helper T lymphocytes, and cytotoxic T lymphocytes after DU administration. In conclusion, these results suggest that depleted uranium is not toxic for the intestine after acute exposure. Nevertheless, DU seems to modulate the expression and/or production of cytokines (IFNgamma) and chemokines (MCP-1) in the intestine. Further experiments need to be performed to determine if a chronic contamination at low dose leads in the long term to modifications of cytokines/chemokines patterns, and to subsequent changes in immune response of the intestine.