Context and objectives
Research area and results
Reactor core accidents at nuclear power plants can lead to radioactive substances being released into the environment in the form of gas and aerosols, particularly caesium-134, caesium-137, iodine-131 and other short-lived isotopes of iodine. These particles and aerosols can be inhaled or ingested by populations exposed to the plume. The authorities have various measures for mitigating this risk: evacuation, sheltering indoors, dietary restrictions and stable iodine prophylaxis.
Radioactive iodine species can accumulate very quickly in the thyroid, which can lead to an increased cancer risk for the most vulnerable, especially infants and children. This exposure/effect relationship was demonstrated after 1991 in the areas most severely contaminated by fallout from the Chernobyl disaster, in Belarus, Russia and Ukraine. In France, the “iodine policy” recommends a single administration of potassium iodide (KI) tablets, which can be repeated once if it is impossible to evacuate the population. To be effective, these have to be given ideally between two hours before exposure and up to six hours after. Until now the marketing authorisation (MA) for the iodine tablets has not allowed for repeated administration of iodine beyond two doses.
Since the Fukushima accident, it seems necessary to consider the possibility of repeated administration of stable iodine for people in an area with repeated or prolonged radioactive releases while awaiting evacuation, or where evacuation is impossible. This is what the PRIODAC programme seeks to address.
Its focuses have been undergirded by the research needs identified by the World Health Organization (WHO) in its 2017 guidelines (1).
Since its launch in March 2014, the PRIODAC project has (2):
- built on scientific knowledge of the Wolff-Chaikoff effect (reduction in thyroid hormone production following a very large influx of iodine) and the role of some of the species involved (Na+/I- Symporter (NIS) and SLC5A8, which transports iodine from the apical membrane of thyrocytes). Our studies demonstrated that the Wolff-Chaikoff effect (3), (4), (5), (6), (12) and its escape mechanism occur after prolonged saturation of the thyroid.
- determined the procedures for the repeated administration of stable iodine among four representative age groups of the population (adults including pregnant women, foetuses, neonates and the elderly). Bio-kinetic studies (7), (8) were used to define an optimal effective dose for the daily administration of potassium iodide (KI) over an 8-day period thanks to several experiments conducted on rats and mice;
- ensured that there are no significant side effects on an adult Wistar rat model for the selected dosage regimen (9), (11). Wistar rats of different age categories have been studied in order to simulate the response of different categories of the population (adults, the elderly, pregnant women, neonates, children). Side effects were examined on various organs: the thyroid, as well as the cardiovascular system, central nervous system, immune system and renal system. However, our studies conducted on an experimental in utero model in a pregnant Wistar rat (mimicking a pregnant woman) revealed significant adverse effects on the offspring and effects on the central nervous system in particular (10), (13), (14). Unlike for adult individuals, the conditions for repeated optimal prophylaxis without toxicity for this category of the population have therefore yet to be defined;
- conducted regulatory toxicology studies using Good Laboratory Practices (GLP) on two adult animal species, rats and dogs, with the Pharmacie Centrale des Armées;
- obtained a marketing authorisation variation (MAV) from the French National Agency for Medicine and Health Product Safety (ANSM). The new dose regimen proposed for adults and children over 12 is 130 mg of potassium iodide per day for up to 7 days.
The authorities responsible for defining the iodine policy are and will continue to be informed of the results of the project. These new French recommendations derived from the PRIODAC project could serve as an example for harmonising "iodine policies" at both European and international levels.
Progress of the PRIODAC project
A PRIODAC project extension granted by the ANR (2019-2022) will make it possible to determine whether repeated prophylaxis is possible for pregnant women, and define the appropriate dosage regiment. Given the marketing authorisation variation granted in early 2020, conditions for the paediatric population still need to be approved following regulatory toxicology tests.