Survey on national practices regarding iodine thyroid blocking in 2016-2017.

Severe nuclear accidents may lead to a release of radioactivity, including radioactive iodine, into the environment. The thyroid gland in the human body needs natural or stable iodine to function properly and this iodine is normally absorbed in small quantities from food. Following a release of radioactive iodine from a nuclear or radiological accident, the body will absorb and accumulate the radioactive iodine in the thyroid gland. This increases the risk of thyroid cancer, especially in children. Since the thyroid gland cannot distinguish between radioactive and stable iodine, stable iodine can be taken to prevent the absorption of radioiodine by the thyroid in the event of a nuclear emergency. This is referred to as Iodine Thyroid Blocking (ITB). In 2017, the World Health Organization published revised guidelines entitled 'Iodine Thyroid Blocking: guidelines for use in planning for and responding to radiological and nuclear emergencies'. The purpose of these guidelines is to support Member States in planning for and implementation of ITB before and during a radiation emergency. To enable the monitoring and measurement of the impact of a specific recommended intervention, a baseline should be established against which the impact will be measured over a certain period of time. With that in mind, a global WHO survey of national policies on ITB was carried out in 2016-2017. Here, an overview of some core findings of this survey is provided.

Introduction

When a severe nuclear or radiological accident occurs, radioactive isotopes of iodine may be released into the surrounding environment and dispersed in the atmosphere over long distances, presenting a health hazard to people through different exposure pathways. Radioiodine can also be deposited on the ground and vegetation, and get into water sources, thereby contaminating the environment and entering the food chain. Radioiodine may enter the human body as a result of inhalation of radioiodine in the air or ingestion of contaminated food and water, as well as through wounds and to some extent even through intact skin on which it has been deposited, resulting in an internal contamination (WHO, 2017). A well-known example of an accident where radioiodine was released, is the nuclear reactor accident in Chernobyl that occurred on 26 April 1986. From the damaged reactor, a large amount of radionuclides was released into the atmosphere, including the radiologically significant short-lived iodine-131, tellurium-132, iodine-133, and long-lived caesium-134 and caesium-137 (UNSCEAR, 2011). Although there were other exposure pathways with typically small contributions to the thyroid dose, for most individuals exposed after the Chernobyl accident, the thyroid dose was mainly due to Iodine-131 (Drozdovitch, 2021).

Once inside the body, iodine is actively extracted from the blood stream by the thyroid gland and also, to a lesser extent, by other organs and tissues such as the salivary glands and breast tissue (EC, 2010). Uptake of radioactive iodine can occur in the breast tissue of both non-lactating and lactating women (Bakheet and Hammami, 1994; Hammami and Bakheet, 1996). The thyroid gland stores iodine in the organ's follicles as part of the normal production process of thyroid hormones and does not distinguish between the different iodine isotopes. If iodine is radioactive, the thyroid itself and the surrounding organs and tissues will be irradiated, which may cause thyroid disorders, in particular thyroid cancer (WHO, 2017).

Since iodine readily passes through the placental barrier and the foetal thyroid progressively starts to function from the second trimester of pregnancy onwards, particular attention is also required for protecting pregnant women and their unborn babies. Breastfeeding women are also considered at risk because radioactive iodine is secreted into the mother's milk and may therefore be passed to the breastfed child (WHO, 2017). Children and adolescents are at higher risk of developing radiation-induced thyroid cancer compared to adults, due to a range of physiological and behavioural factors. In addition, populations living in areas with an alimentary iodine deficiency have been shown to be more vulnerable to radioactive iodine exposure and they may also demonstrate more undesirable effects when acutely exposed to relatively high doses of stable iodine (Cardis et al., 2005; WHO, 2017). Individuals over 40 years of age are less likely to benefit from ITB because their risk of developing thyroid cancer as a result of internal exposure to radioiodine is very limited compared to that for children or younger adults and older adults may also be at higher risk of developing side-effects from potassium iodide (KI) (Jang et al., 2008; WHO, 2017).

In order to prevent damage to the thyroid occurring as a consequence of internal contamination with radioactive iodine, non-radioactive, so-called ‘stable’ iodine can be used. If administered in sufficiently high doses at the right time, preferably prior to exposure, this stable iodine will saturate the thyroid gland almost completely and thereby prevent the subsequent uptake of radioactive iodine for a certain period of time. This approach is referred to as ‘iodine thyroid blocking’ (ITB) (WHO, 2017). ITB is often combined with other protective measures because ITB only provides protection against exposure to radioiodine and it does not offer protection against irradiation or exposure to any other radioactive isotopes. In adults with normal thyroid function, ingestion of 100 mg and 200 mg of iodide just before exposure to radioactive iodine blocks at least 95% of the thyroid dose (Verger et al., 2001).

In the aftermath of the Chernobyl accident, WHO published the first guidelines on the use of stable iodine as a protective action in nuclear accidents in 1989 (WHO, 1989). These guidelines were revised in 1999 (WHO, 1999 update), drawing on the experience gained since the accident. The International Atomic Energy Agency's (IAEA) General Safety Requirements Part 7, co-sponsored by the World Health Organization (WHO) and a number of other international organizations, provided updated guidance for the use of ITB in 2015 (IAEA, 2015). Later, in 2017 WHO published revised guidelines for ITB. The purpose of these guidelines is to support decision-makers in developing plans for responding to radiological and nuclear emergencies including public health aspects of planning and implementation of ITB. The evidence-based WHO (2017) guidelines elaborate on the practical aspects of ITB implementation and emphasise the greater risks from radioiodine incurred by those exposed at a younger age (WHO, 2017).

Material and methods

Objective of the survey

It is important for WHO to assess the impact its guidelines and activities have on policies in Member States. In the context of new guidelines, their impact can be assessed by comparing the situation before and after the release of new guidance. The purpose of the 2017 survey was to establish a baseline of how ITB is implemented, or not, worldwide, before the new WHO Guidelines were published.

The questionnaire

The questionnaire used for this purpose, was developed on the basis of an earlier survey performed by the Riskaudit consortium (a collaboration between French (IRSN) and German (GRS) research institutes), the results of which have been published as a report of the European Commission (EC, 2010). The reason for doing this was to facilitate a comparison of the results from both surveys in the future, if required. The WHO survey questionnaire consisted of six sections: (1) Pharmaceutical product(s) used for ITB (chemical formulation, iodine content, recommended dose, pharmaceutical status of the product and its shelf life); (2) Emergency planning (distribution methods and/or stockpiling); (3) Intervention levels for use; (4) Decision-making processes during an emergency (combination of ITB with other protective measures); (5) Time for intake and effectiveness; and (6) Public awareness and communication issues. The survey was conducted online using DataForm software and the data was analysed using MS Excel.

Distribution of the questionnaire

The WHO Secretariat distributed the online survey link through its global expert network – Radiation Emergency Medical Preparedness and Assistance Network (REMPAN). In addition, the members of the following international bodies in which WHO participates, were approached: IAEA's Emergency Preparedness and Response Standards Committee (EPReSC); OECD/NEA's Working Party on Nuclear Emergency Matters (WPNEM) and the Heads of European Radiological Protection Competent Authorities (HERCA) Working Group on Emergencies (WGE).

During a period of six months in 2017, a total of 36 countries replied to the survey (Table 1), the majority of which are located in the European region (26 countries), four countries are located in the Western Pacific region, three in the Americas region, two in the Eastern Mediterranean region and one in the South-East Asia region.

Table 1

The 36 countries participating in the survey.

European Region (26)
Armenia	Finland	Luxembourg	Spain
Austria	France	Netherlands	Sweden
Belarus	Germany	Norway	Switzerland
Belgium	Hungary	Poland	Ukraine
Bulgaria	Italy	Romania	United Kingdom
Croatia	Latvia	Russian Federation
Czech Republic	Lithuania	Slovakia
Americas Region (3)
Brazil	Canada	United States of America
Eastern Mediterranean Region (2)
Pakistan	United Arab Emirates
South-East Asia Region (1)
China
Western Pacific Region (4)
Australia	Indonesia	Japan	Republic of Korea

Results and discussion

Pharmaceutical product(s) used for ITB and recommended doses

All responding countries used potassium iodide (KI) as the active compound in their iodine tablets. The UK additionally used potassium iodate (KIO3) and Belarus also used the liquid ‘Solutio iodi spirituosa 5%’. A paediatric formulation (liquid solution or jelly) was used in 10 countries, while a majority (58% or 21 countries) chose not to use specific paediatric formulations.

Most countries used 65 mg KI tablets (58%) containing 50 mg of iodine. One hundred and thirty milligram KI tablets were also used, but only by about a quarter of all responding countries (28%). In a few countries, the iodine content reported was quite different: from 25 up to 200 mg of KI.

Iodine tablets were considered as pharmaceutical products in 50% of the responding countries. In 20 countries they were available to the public without prescription, free of charge. This is already in line with the WHO recommendation that voluntary purchase of iodine tablets by the general public should be allowed (WHO, 2017).

Shelf life differed considerably from one country to another, spanning from 1 year up to 10 years and with most countries assigning a shelf life of 5 years. Therefore, most countries were already aligned with the WHO (2017) recommendations stipulating that under adequate storage conditions, tablets packed in a hermetic packaging and kept in a dry and cool place fully preserve their iodine content for five years. After five years, the active iodine content may be checked and the shelf life extended, if needed (WHO, 2017).

The reported recommended doses corresponded well across the different age groups, with the exception of the Russian Federation recommendation for neonates (40 mg). Differences with respect to the 1999 WHO guidelines may be explained by a different assignment of children and adolescents of the same age to different age categories in different countries. Table 2 shows the recommended doses of stable iodine in the WHO (1999) guidelines and the number of countries using age-related dosages.

Table 2

The recommended doses of stable iodine in the WHO (1999) guidelines and the number of countries recommending age related dosages.

Equivalent mass of iodine	Neonates	Children aged 1 month to 3 years	Children aged 3 to 12 years	Children aged 13 to 18 years	Adults younger than 40 years	Pregnant women	Breastfeeding women	Adults older than 40
Recommended Doses (WHO 1999)	12.5 mg	25 mg	50 mg	100 mg	100 mg	100 mg	100 mg
0 mg								7
10 mg	32
25 mg	0	32
40 mg	1	1
50 mg		1	33	5		1	1
100 mg			1	29	35	28	28	23
No Answer	3	2	2	2	1	7	7	6

The majority of the responding countries did not use an age limit above which ITB is not recommended. Such an age limit was set in only 12 countries, eight countries use an age limit of 40 years, three countries use 45 years of age and 50 years is used in one country. Seven of these countries confirmed the use of a recommended dose of 0 mg of stable iodine to adults over the age limit of 40, 45 or 50 years in a specific question on the subject, while the other 5 countries left this question unanswered.

Recommendations for use

The optimal period of administration of stable iodine is less than 24 h prior to, and up to two hours after, the expected onset of exposure. Administration of ITB up to eight hours after the onset of exposure is still reasonable. However, starting ITB later than 24 h after the exposure will no longer provide a protective effect and may cause more harm than good by prolonging the retention time of radioactive iodine that has already accumulated in the thyroid, thereby enhancing the time of exposure and the dose to the thyroid and surrounding tissues (WHO, 2017; Hänscheid et al., 2011).

The recommended timing of intake in all responding countries corresponded to the WHO (2017) guidance of administration right before or shortly after onset of exposure. If administration of stable iodine before the exposure proved impossible, some countries had policies on how long after the onset of the exposure ITB is considered as effective. This period ranged from 2 h after onset of exposure up to 24 h (Fig. 1). Ten countries did not have a defined policy at the time of the 2017 survey and indicated that the decision would depend on the actual emergency conditions.

Fig. 1

Time period after exposure onset in which KI use is recommended by different national policies.

In case of a protracted exposure, a second intake would be advised by the majority of the countries (55%), which is again in line with the WHO (2017) recommendations (WHO, 2017). For those countries, the administration of stable iodine would generally be repeated after 24 h and exceptions made for neonates (maximum of 1 dose) and pregnant or breastfeeding women (maximum of 1 or 2 doses).

Decision making process and distribution policy

The dose assessment (most often based on inhalation only, n = 25) calculated by dispersion models and based on information concerning plant status, source term and current weather conditions was often a key element in the decision-making process, especially in European countries. If the estimated committed dose to the thyroid was expected to exceed the emergency intervention level (EIL), this was a strong stimulus for implementation of ITB. For most countries, the EILs apply to the early phase, but application in the intermediate phase is also considered in some countries (n = 4).

The EILs used differ quite extensively between countries. Eleven countries use a different EIL for sensitive populations and other adults, other countries use only one EIL (n = 17) that is most often applicable to the sensitive populations. Some countries left the question unanswered (n = 4), do not define EILs (n = 2) or use emergency operational levels only (n = 4). In 16 countries, emergency operational levels (EOLs) would also be a factor in the decision regarding whether ITB should be implemented, often as an addition to the EILs.

When using different EILs, the lower value is usually applicable to the sensitive population. The value of the lower EIL ranges mainly between 5 mSv (n = 1) and 50 mSv (n = 3) estimated committed thyroid dose (10 mSv: n = 4; 30 mSv: n = 2), while the upper value is usually between 50 mSv (n = 2) and 500 mSv (n = 1) estimated committed thyroid dose (100 mSv: n = 4; 200 mSv: n = 1; 250 mSv: n = 1; 300 mSv: n = 1). One respondent uses an EIL of 100 mSv thyroid dose for children up to an age of 18, and of 1000 mSv thyroid dose for adults between 18 and 40 years. They explained that these relatively high values were chosen at a time when the side effects of iodine intake was deemed to be high. Of the 17 countries using one EIL, eight countries use a thyroid dose of 50 mSv, another eight countries use a thyroid dose of 100 mSv and one country set the EIL at 500 mSv thyroid dose.

The results of the survey showed that ITB is generally combined with other protective measures (n = 31), especially with sheltering, but evacuation and measures for the protection of the food chain can also be combined with ITB. It is correct that ITB should not be seen as a stand-alone protective measure (WHO, 2017).

The distribution policy was very country-specific and in some cases differed between regions in one single country. Half of all the respondent countries pre-distributed the KI tablets to their residents in planning zones of different magnitude. Other countries had stockpiles that could be distributed fairly rapidly during an emergency. Thirteen countries combined both pre-distribution and stockpiling (Fig. 2). Some policies differentiated between sensitive populations, for example by pre-distributing stable iodine to day-care centres and schools only.

Fig. 2

Strategies used for the national distribution policy.

Pre-distribution zones varied in accordance with the type of installations considered. For nuclear power plants, this varied between 5 and 50 km for different countries. Larger planning zones may include the whole country, as was the case in Luxembourg. An increase of the emergency planning zones for implementation of ITB around large nuclear installations was also evident.

Different countries identified gaps in their national distribution policy. When stable iodine is pre-distributed, this presents practical challenges such as limited pick-up rates from pharmacies, problems with mail distribution, varying number of inhabitants, etc. However, practical arrangements for establishing and maintaining stockpiles also present specific challenges in addition to the problem of distribution to affected populations at the time of an emergency. Most countries applied the IAEA safety requirements (IAEA, 2015) and were familiar with the 1999 WHO guidelines (78%).

Public information

WHO recommends that emergency response plans should include arrangements for training health professionals and emergency workers on risk communication, to raise public awareness and to avoid unjustified use of ITB and giving false reassurance to the affected population (WHO, 2017).

At the time of the survey in 2017, about 64% of respondents had communication plans regarding ITB for use before or during an emergency. Thirty-nine per cent of the responding countries periodically organised information campaigns for the general public and/or for specific professions, while 36% did not (the remaining 25% did not respond to this question). Some countries concentrated on specific target groups with a particular role in emergency planning and ITB (Fig. 3). In the preparedness phase, information would generally be distributed through conventional media, leaflets, flyers, brochures and information on websites. In Japan, local governments provided consultation desks at health centres to give medical advice regarding stable iodine tablets such as where and how to receive iodine tablets and information on nearby medical institutions in the unlikely event of acute presentation of severe undesirable effects after iodine tablet intake. In Belarus health workers distributed the stable iodine, while also informing the public about risk, providing instructions and additional information. In France, besides having a leaflet explaining what to do in case of an emergency, the authorities also provided a free phone number where questions about iodine tablets could be dealt with.

Fig. 3

Are there national campaigns for informing on iodine thyroid blocking for general population and/or specialists?

During an emergency, information would be communicated using other, more direct communication channels. Conventional media (such as radio and TV) and public alarm systems (such as sirens or civil protection vehicles) would be used to inform the public during the emergency; but newer methods such as social media (Facebook, Twitter etc), and text messaging, were gaining in importance.

Conclusion

A comprehensive public protection strategy covering all urgent and early protective actions, as well as other response actions, including evacuation and sheltering, ITB, restriction on consuming contaminated food, milk and drinking water, should be developed in accordance with the IAEA's general safety requirements (IAEA, 2015) and its supporting safety guide (IAEA, 2011). These international safety standards and criteria for urgent protective actions and other response actions should be used as a basis for setting national criteria and developing a national protection strategy in which ITB plays its role as one of the possible protective measures (WHO, 2017). The WHO (2017) guidelines on ITB administration offer practical recommendations on planning and implementing ITB before and during nuclear emergencies - thus, contributing to countries efforts on strengthening national preparedness for radiation emergencies, as recommended by the 74th World Health Assembly Resolutions (WHO, World Health Assembly, 2021).

Since a uniform approach for dealing with serious radiological or nuclear emergency situations allows for the implementation of coherent and coordinated protective measures, countries sharing borders should aim at harmonizing national approaches to ITB (WHO, 2017). The WHO survey provides a baseline to enable the monitoring of the implementation by member states of the 2017 WHO recommendation on ITB.

It is reassuring that at the time of participation in the survey (2016-2017), the vast majority of the responding countries had arrangements for ITB already in place that were generally in line with the existing WHO Guidelines in terms of chemical form, packaging, dosage for different age groups and timing of administration. However, the use of EILs to aid the decision-making process and the procedures for distribution and stockpiling stable iodine still show a lot of variability. About half of the respondents indicated their intent to review their approach to ITB arrangements at the time that they filled out the questionnaire, indicating a very dynamic situation worldwide.

The Heads of the European Radiological Protection Competent Authorities (HERCA) Working Group on Emergencies (WGE) actively works to harmonize emergency preparedness and response arrangements between European countries for nuclear emergencies occurring both within Europe and elsewhere. Since there is a lot of variability in how countries distribute stable iodine for use in a nuclear or radiological emergency, the HERCA WGE is undertaking a survey among member countries on the practical arrangements for the pre-distribution and distribution during an emergency of stable iodine. This survey will focus on distribution policies regarding how stable iodine tablets are or will be distributed, who will receive them and whether stockpiles are maintained. This information will be used by the HERCA WGE to develop guidance on the most efficient and effective strategy for iodine tablet pre-distribution/distribution and to promote exchange of such information, particularly between neighbouring countries.

Limitations of the survey lie in the small number of respondents, which may be related to ITB being less relevant for countries not using nuclear reactors since the likelihood that ITB needs to be implemented decreases with distance from a reactor; as well as in the heterogeneity of responses which sometimes impeded clear interpretation. Future surveys should aim for higher response rate, an even more comprehensive overview of issues surrounding ITB, as well as for further improved clarity of survey questions.

Overall, the situation worldwide seems to indicate a moderate degree of alignment and harmonisation with respect to ITB policies, with room for further evidence-based policy development.

CRediT authorship contribution statement

Petra Willems: Writing – original draft, Methodology, Validation, Formal analysis, Visualization. Zhanat Carr: Conceptualization, Methodology, Validation, Writing – review & editing. Steffen Dreger: Methodology, Formal analysis. Hajo Zeeb: Methodology, Writing – review & editing. Nathalie Tchilian-Teng: Writing – review & editing. Veronica Smith: Writing – original draft, Writing – review & editing. Lodewijk Van Bladel: Conceptualization, Writing – original draft, Validation, Writing – review & editing.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.