The Toxicity of Depleted Uranium

Depleted uranium (DU) is an emerging environmental pollutant that is introduced into the environment primarily by military activity. While depleted uranium is less radioactive than natural uranium, it still retains all the chemical toxicity associated with the original element. In large doses the kidney is the target organ for the acute chemical toxicity of this metal, producing potentially lethal tubular necrosis. In contrast, chronic low dose exposure to depleted uranium may not produce a clear and defined set of symptoms. Chronic low-dose, or subacute, exposure to depleted uranium alters the appearance of milestones in developing organisms. Adult animals that were exposed to depleted uranium during development display persistent alterations in behavior, even after cessation of depleted uranium exposure. Adult animals exposed to depleted uranium demonstrate altered behaviors and a variety of alterations to brain chemistry. Despite its reduced level of radioactivity evidence continues to accumulate that depleted uranium, if ingested, may pose a radiologic hazard. The current state of knowledge concerning DU is discussed

Assessment of the Central Effects of Natural Uranium via Behavioural Performances and the Cerebrospinal Fluid Metabolome

International audienceNatural uranium (NU), a component of the earth's crust, is not only a heavy metal but also an alpha particle emitter, with chemical and radiological toxicity. Populations may therefore be chronically exposed to NU through drinking water and food. Since the central nervous system is known to be sensitive to pollutants during its development, we assessed the effects on the behaviour and the cerebrospinal fluid (CSF) metabolome of rats exposed for 9 months from birth to NU via lactation and drinking water (1.5, 10, or 40 mg⋅L −1 for male rats and 40 mg⋅L −1 for female rats). Medium-term memory decreased in comparison to controls in male rats exposed to 1.5, 10, or 40 mg⋅L −1 NU. In male rats, spatial working memory and anxiety-and depressive-like behaviour were only altered by exposure to 40 mg⋅L −1 NU and any significant effect was observed on locomotor activity. In female rats exposed to NU, only locomotor activity was significantly increased in comparison with controls. LC-MS metabolomics of CSF discriminated the fingerprints of the male and/or female NU-exposed and control groups. This study suggests that exposure to environmental doses of NU from development to adulthood can have an impact on rat brain function

Effect of repetitive potassium iodide on elderly rat’s thyroid

Background: Nuclear power plant emergencies had often been accompanied by radioactivity release into the environment, thyroid cancer is one of the major health consequences due to the effect of radioactive iodine (131I) that emits ϒ ray and β particles resulting in thyroid DNA damage and late onset thyroid cancer. Intake of a single dose of potassium iodide (KI) is recommended to reduce this risk. However in case of prolonged radioiodine release as noticed during Chernobyl and Fukushima accidents, more than one dose of KI may be basic to ensure adequate protection [1]. Whereas a single dose of KI is admitted to be safe, knowledge about the effects of repeated KI administration are scarce, few studies demonstrated the potential efficiency of repetitive KI intake in humans [2] and non-human primates [3] without hormonal variations. These studies are relevant in the field of radiation protection and give a base evidence of the possible use of repetitive KI. On the other hand, we have studies on rodents that showed an impact of chronic iodine excess on pituitary thyroid axis function [4]. Our previous work on adult male rats demonstrated the safety of repeated administration of KI over 8 days [5]. Indeed in the elderly persons KI administration in case of nuclear emergency remains a topic of debate, because of the possible impact in cardiovascular diseases. Thyroid hormones are well-known for their profound effects on cardiovascular function and metabolism; myocardial and vascular endothelial tissues have receptors for thyroid hormones and are sensitive even to subtle changes in the concentrations of circulating pituitary and/or thyroid hormones i.e. subclinical hypothyroidism and hyperthyroidism. It is well established that hyperthyroidism induces a hyper-dynamic cardiovascular state, which is associated with a faster heart rate, enhanced left ventricular systolic and diastolic function whereas hypothyroidism is characterized by the opposite changes. Atrial fibrillation is the most common cardiac arrhythmia in the elderly, the prevalence and incidence increase with advancing age [6]. Several interventional trials showed that treatment of subclinical thyroid diseases improves cardiovascular risk factors, which implies potential benefits for reducing cardiovascular events. Objective: The aim of this study is to assess the effects of repeated KI intake on the thyroid function of aged male rats. Methods: A twelve months old male rats were subjected to either KI or saline solution over 8 days. Clinical biochemistry, pituitary and thyroid hormones level, and thyroid genes expression were analyzed 30 days after the treatment discontinuation. Findings: urinary assessment shows a subtle increase of some parameters (Creatinin, Uric Acid, Urea, Glucose, Potassium, Sodium and Chlorine), plasma biochemistry reveals a subtle variation of some parameters (an increase of Creatinin, Glucose and phosphorus; and a decrease of Chlorine level). Regarding pituitary-thyroid hormones we get a significant decrease of TSH level without thyroid hormones variation. At the molecular level, we observe a significant increase of TPO (+100%), AIT (+299%) and Tg (+38%) mRNA expression. On the other hand we get a significant decrease of TSHR (-51%) mRNA expression. Conclusion and perspectives: Our first results indicate that repeated KI intake affects the clinical biochemistry and the pituitary-thyroid axis function in elderly rats. To go further we are investigating the impact of these variations on the cardiovascular function and its parameters. Cardiac output data, cardiovascular gene expression, oxidative stress and inflammatory analysis are being processed. This study will contribute to the evolution of iodine policy and the harmonization of the current KI guidelines

Unexpected Lack of Deleterious Effects of Uranium on Physiological Systems following a Chronic Oral Intake in Adult Rat

Uranium level in drinking water is usually in the range of microgram-per-liter, but this value may be as much as 100 to 1000 times higher in some areas, which may raise question about the health consequences for human populations living in these areas. Our purpose was to improve knowledge of chemical effects of uranium following chronic ingestion. Experiments were performed on rats contaminated for 9 months via drinking water containing depleted uranium (0.2, 2, 5, 10, 20, 40, or 120 mg/L). Blood biochemical and hematological indicators were measured and several different types of investigations (molecular, functional, and structural) were conducted in organs (intestine, liver, kidneys, hematopoietic cells, and brain). The specific sensitivity of the organs to uranium was deduced from nondeleterious biological effects, with the following thresholds (in mg/L): 0.2 for brain, >2 for liver, >10 for kidneys, and >20 for intestine, indicating a NOAEL (No-Observed-Adverse-Effect Level) threshold for uranium superior to 120 m g/L. Based on the chemical uranium toxicity, the tolerable daily intake calculation yields a guideline value for humans of 1350 μg/L. This value was higher than the WHO value of 30 μg/L, indicating that this WHO guideline for uranium content in drinking water is very protective and might be reconsidered

Concerns regarding nanosized titanium dioxide nasal exposure and neurotoxicity study by Ze et al.

International audienceScientific articles dealing with nanotoxicology are particularly awaited and important, as in the field of nanotechnology, a relatively new domain; they likely have a significant impact not only on our perception of the risk and danger potentially associated with nanomaterials but also on regulatory decisions with regard to their use in consumer products. Because nanotoxicology refers to the work of researchers from different domains of expertise, it appears also more difficult to secure accurate review and thus accurate conclusions. In that context, particular attention must be drawn on these studies. Still for the readers of such articles, of which most of are not experts in several aspects of nanotoxicology it would be tempting to take the messages for granted, thinking the studies are well conducted and reported with accuracy. In the case of the article by Ze and colleagues, we have noticed a certain number of critical comments that should be brought to the attention of the readers of J. Biomed Mater res A, because this study presents several problems. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A 103A 2198-2200, 2015. © 2014 Wiley Periodicals, Inc

The Challenges of 21st Century Neurotoxicology: The Case of Neurotoxicology Applied to Nanomaterials

International audienceAfter a short background discussing engineered nanomaterials (ENMs) and their physicochemical properties and applications, the present perspective paper highlights the main specific points that need to be considered when examining the question of neurotoxicity of nanomaterials. It underlines the necessity to integrate parameters, specific tools, and tests from multiple sources that make neurotoxicology when applied to nanomaterials particularly complex. Bringing together the knowledge of multiple disciplines e.g., nanotoxicology to neurotoxicology, is necessary to build integrated neurotoxicology for the third decade of the 21st Century. This article focuses on the greatest challenges and opportunities offered by this specific field. It highlights the scientific, methodological, political, regulatory, and educational issues. Scientific and methodological challenges include the determination of ENMs physicochemical parameters, the lack of information about protein corona modes of action, target organs, and cells and dose-response functions of ENMs. The need of standardization of data collection and harmonization of dedicated neurotoxicological protocols are also addressed. This article highlights how to address those challenges through innovative methods and tools, and our work also ventures to sketch the first list of substances that should be urgently prioritized for human modern neurotoxicology. Finally, political support with dedicated funding at the national and international levels must also be used to engage the communities concerned to set up dedicated educational program on this novel field

The Challenges of 21st Century Neurotoxicology: The Case of Neurotoxicology Applied to Nanomaterials

After a short background discussing engineered nanomaterials (ENMs) and their physicochemical properties and applications, the present perspective paper highlights the main specific points that need to be considered when examining the question of neurotoxicity of nanomaterials. It underlines the necessity to integrate parameters, specific tools, and tests from multiple sources that make neurotoxicology when applied to nanomaterials particularly complex. Bringing together the knowledge of multiple disciplines e.g., nanotoxicology to neurotoxicology, is necessary to build integrated neurotoxicology for the third decade of the 21st Century. This article focuses on the greatest challenges and opportunities offered by this specific field. It highlights the scientific, methodological, political, regulatory, and educational issues. Scientific and methodological challenges include the determination of ENMs physicochemical parameters, the lack of information about protein corona modes of action, target organs, and cells and dose– response functions of ENMs. The need of standardization of data collection and harmonization of dedicated neurotoxicological protocols are also addressed. This article highlights how to address those challenges through innovative methods and tools, and our work also ventures to sketch the first list of substances that should be urgently prioritized for human modern neurotoxicology. Finally, political support with dedicated funding at the national and international levels must also be used to engage the communities concerned to set up dedicated educational program on this novel field.</jats:p