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Enhancing Nuclear Safety


Research

The effects on health of chronic contamination with a low dose of radionuclides

(juillet 2011)

RESEARCH allowing the evaluation of radionuclide-related risks and their impact on health

The ENVIRHOM-Santé experimental research programme or Understanding the effects on health of chronic contamination with a low dose of radionuclides

The brain: A new target organ to uranium

Is the xenobiotic detoxification system affected by chronic exposure to uranium ?

Chronic ingestion of caesium 137 in a post-accident situation

Chronic exposure to caesium 137: Experimental and epidemiological studies

Metabolomics: Application in radiotoxicology

The perspectives of the ENVIRHOM-Santé programme

The perspectives of the ENVIRHOM-Santé programme


Isabelle Dublineau

Head of the Experimental radiotoxicology laboratory (LRTOX) at IRSN

The perspectives of the ENVIRHOM-Santé programme


The experiments carried out at the Laboratory of experimental Radiotoxicology (LRTOX) within the scope of the ENVIRHOM research programme have shown that chronic contamination with a radionuclide, even at low doses, triggers biological effects in different organs and different physiological systems. Following the chronic ingestion of uranium, the effects on the kidneys, liver, intestine, brain, and gonads were in fact observed, leading to changes in major physiological systems:  Metabolism of iron, cholesterol, xenobiotics, vitamin D, steroid hormones and on cognitive functions, reproduction function and immunity.

These scientific results lead to a change of radiotoxicology concepts: for example, kinetics of uranium accumulation in the organs is not equivalent to that resulting from a succession of acute exposures. Furthermore, the concept of an organ as a single biological target for uranium must be reconsidered via a concept of organs and multiple target functions in the case of chronic internal contamination. Disruptions in the major metabolisms listed above coupled with cognitive and reproduction functions indicate potential non-cancerous biological effects induced by a chronic radionuclide contamination. These effects are mainly observed at molecular level (mRNA, proteins, enzymatic activity) or in the cells, and do not lead to disease development. They are observed within the limits of homeostasis and are probably due to a normal adaptive response on the part of the body following chronic internal low-dose contamination.


To date, the ENVIRHOM programme has focused primarily on three physiological systems (metabolism, central nervous system and immunity) in an experimental contamination model (healthy adult rodent) following exposure to two types of radionuclide (uranium or caesium-137). Its perspectives are now to extend research in terms of physiological systems studied (bone metabolism, vascular system), of so-called more sensitive experimental models (animals during growth periods or predisposed to a disease) and to extend these studies to other radionuclides to be present potentially in drinking water or food chain (strontium, tritium…). These new descriptive data will extend knowledge on the type and relevance of biological, non-cancerous effects caused by chronic exposure to radionuclides.

The studies presented in this report have so far been based on a single supra-environmental but non-toxic reference dose (i.e. 40 mg/L for uranium). We now have to determine the thresholds at which the biological effects appear, as a function of their level of impact. It is particularly important to determine the harmful histopathological effects (and not only the molecular effects) that are used to determine toxicity thresholds. Two thresholds will be determined: either the threshold which triggers no harmful effect (NOAEL, No Observed Adverse Effect Level) or the threshold at which the first harmful effects are observed (LOAEL = Lowest Observed Adverse Effect Level). Dose-effect studies will be undertaken with a large extensive range of radionuclide concentrations, using high and low doses to encompass the reference doses used within the ENVIRHOM-Santé programme (40 mg/L). This extension of the dose ranges is the only way to respond to expert requirements regarding the possible review of national and international standards for levels of radionuclides present in water intended for human consumption.

Furthermore, all of the effects obtained following chronic contamination with uranium or caesium indicate the induction of molecular or cellular biological effects in the numerous physiological systems, without any harmful effects and without triggering any disease. This suggests the implementation of an adaptive bodily response within the limits of homeostasis. This hypothesis will be checked, especially in a so-called reversion model, which will investigate whether the biological effects observed actually continue once contamination has been stopped.

The unexpected effects of uranium on certain physiological systems and, more particularly, on the central nervous system beg the question as to whether uranium exerts direct or indirect effects. We will therefore launch researches about these mechanisms, in order to explain the effects of this radionuclide on memory, sleep or anxiety (neurogenesis and synaptic transmission).

In conclusion, all of these studies should provide answers to the numerous questions raised at the outset of the ENVIRHOM-Santé programme, which were essentially to describe and understand the biological effects on health due to internal chronic contamination with radionuclides at low levels.

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