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Enhancing Nuclear Safety


Research

Thesis vivas

Stable iodine toxicology: in vivo study of the biological effect of repeated potassium iodide prophylaxis


 

Dalila Lebsir will defend her thesis

on Friday 16th November 2018 at 2:00 pm

at IRSN auditorium

31 avenue de la Division Leclerc

92260 Fontenay-aux-Roses

France


 

Jury

 

François Coudore, Professor (Paris-Sud University), President

Armelle Baeza, Professor (Paris Diderot University), Reporter

France Massicot, PhD (Paris Descartes University), Reporter

Karine Gauthier-Vanacker, PhD (ENS Lyon), Examiner

Thierry Pourcher, PhD (Nice Sophia Antipolis University), Examiner

Philippe Lestaevel, PhD (IRSN), Examiner

Maâmar Souidi, PhD (IRSN), Thesis Supervisor


 

Abstract

Following nuclear accidents, uranium fission products such as radioactive iodines are released into the environment. Humans are likely to be exposed to these elements mainly through inhalation of air and / or ingestion of contaminated food. Iodine 131 is known to be responsible for increasing the incidence of thyroid cancer. One of the available countermeasures is the ingestion of a single dose of potassium iodide (KI) tablets to saturate the thyroid gland with stable iodine and thus prevent the uptake of the radioactive isotope. Repeated releases of radioactive iodine during the two major accidents Chernobyl and Fukushima have highlighted the weaknesses of this measure, repeated intake of KI maybe necessary. In the literature there is little clinical and preclinical data on the repeated intake of stable iodine, its use has poorly been described. The iodine doctrine as well as the Marketing Authorization (MA) of the KI considers only the single taking, to renew exceptionally in the adult population. Iodine is known to be a key component of thyroid function, playing a dual role as both a substrate and a regulator of the thyroid. If its presence is essential for the synthesis of thyroid hormones, its excess exerts a transient inhibitory effect on this synthesis known as the Wolff-Chaikoff effect. Thyroid hormones affect the development and function of almost all organs of the body (brain, heart, bones ...), the slightest variation in their level can impact the homeostasis of the body. Hence, the toughness of applying repeated KI intake in the absence of biological and toxicological data.
 

To fill this gap and find a solution in the event of repeated exposure, the French research program PRIODAC: repeated potassium iodide prophylaxis in accidental situation (ANR / RSNR), of which this thesis is part, aims to define the modalities of repeated administration of KI in all age groups (in utero, adult and elderly), and evaluate the biological consequences on the the body's major physiological functions. Three models of Wistar rats were used in this work : the reference model adult rat (3 months), the first sensitive model offspring (exposed during gestation) and another sensitive model the older rat (12 months ), these three models received 8 consecutive intakes of KI 1mg / kg / 24h. And the effects were assessed at long-term (30 days post-prophylaxis). On the reference model, there was no long-term adverse impact of repeated KI intake. On the other hand, sensitive models reveal several long-term effects; the offspring exhibited impaired motor coordination and variation of the expression of some key brain genes. And in the elderly rat urinary biochemistry, expression of some key genes involved in the cardiovascular function, as well as the renin-angiotensin-aldosterone system were significantly impacted by the treatment. In conclusion, the results obtained shown the toxicological safety of KI at 1 mg / kg every 24 hours for 8 days in the adult model, and the harm of this prophylactic scheme in sensitive models in utero and elderly. These results were sent to the French central pharmacy of armies and served as input data for good laboratory practice studies that eventually will contribute to the evolution of the iodine doctrine and KI MA.



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