Beyond iodine-131: protective effect of stable iodine for all iodine isotopes of radiological concern

The purpose of this study was to evaluate the influence of the intake of stable isotopes of carbon and iodine on the committed doses due to the ingestion of {sup 14}C and {sup 129}I. This was accomplished through the application of two different computational approaches. The first was based on the assumption that ground (drinking) water was the only source of intake of both {sup 14}C and {sup 129}I and stable carbon and stable iodine. For purposes of the second approach, the intake of {sup 14}C and {sup 129}I was still assumed to be only that in the ground (drinking) water, but the intake of stable carbon and stable iodine was assumed to be that in the drinking water plus other components of the diet. The doses were estimated using either a conversion formula or the applicable dose coefficients in Federal Guidance Reports No. 11 and No. 13. Serving as input for the analyses was the estimated maximum concentration of {sup 14}C or {sup 129}I that would be present in the ground water due to potential releases from the proposed Yucca Mountain high-level radioactive waste repository during the first 10,000 years after closure. The estimated concentrations of stable carbon and iodine were based on analyses of ground water samples collected in the Amargosa Valley, NV. Based on the accompanying analyses, three conclusions were reached. First, no dose estimate, using a conversion formula in which the ratios of the stable to radioactive isotopes of an element serve as input, should ever be made without including the stable element intake contributions from all components of the diet. Second, the study suggests that the dose coefficients for {sup 129}I in Federal Guidance Reports No. 11 and No. 12 which, in turn, are based on publications of the ICRP, may not be appropriate for application in developed nations of the world, especially those in which relatively large amounts of seafood are consumed and the use of iodized salt is common. The estimated average daily intake of stable iodine by the adult U.S. population, for example, is 400 pg. This is twice the value listed by the ICRP for Reference Man. This leads to a dose estimate that is too high by a factor of two. Although the ICRP accounts for stable isotope contributions through the selection of a corresponding biological half-time for iodine, the selection in this case may need reevaluation especially with respect to assessments of potential {sup 129}I releases from the proposed Yucca Mountain high-level radioactive waste repository. The third conclusion, which confirms earlier studies, is that an increase in the intake of either {sup 14}C or {sup 129}I will not lead to an increase in the dose if there is a corresponding increase in the intake of stable carbon or iodine such that the ratio of {sup 14}C or {sup 129}I to stable carbon or iodine does not change.

The purpose of this study was to evaluate and provide insights related to the influence of the intake of stable isotopes of carbon and iodine on the committed doses due to the ingestion of (14)C and (129)I. This was accomplished through the application of two different computational approaches. The first was based on the assumption that ground (drinking) water was the only source of intake of (14)C and (129)I, as well as stable carbon and stable iodine. In the second, the intake of (14)C and (129)I was still assumed to be restricted to that in the ground (drinking) water, but the intake of stable carbon and stable iodine was expanded to include that in other components of the diet. The doses were estimated using either a conversion formula or the applicable dose coefficients in Federal Guidance Reports No. 11 and No. 13. Serving as input for the analyses was the estimated maximum concentrations of (14)C or (129)I that would be present in the ground water due to potential releases from the proposed Yucca Mountain high-level radioactive waste repository during the first 10,000 y after closure. The estimated contributions of stable carbon and iodine through the consumption of ground water were based on analyses of samples collected in the Amargosa Valley, NV. The contributions through dietary intake were based on surveys conducted in the United States. Based on the accompanying analyses, it was noted that stable isotope intake has a significant effect on the estimated doses due to the intake of radioactive isotopes of the same element. While this is a well-known fact, this observation has international implications in terms of dose estimates for key radionuclides, such as (14)C and (129)I, a primary reason being the wide variations in the intakes of stable carbon and iodine in various countries. For this reason, analysts planning to apply the dose coefficients developed by the International Commission on Radiological Protection (ICRP) should either confirm that the average total intake in their country of stable isotope(s) of the radioactive isotope being evaluated is in reasonable agreement with the value assumed by the ICRP or suitably modify the ICRP dose coefficients to account for any differences. If such a procedure is to be implemented, there is a need for periodic updates of the dietary intakes of various stable elements in countries throughout the world. The importance of this is documented by recent surveys in Asia that revealed that their average total daily intake of stable iodine was less than half of the ICRP value for Reference Man. In this case, application of the ICRP dose coefficients, without modification, would underestimate the dose due to ingested (129)I by a factor of more than two. A related situation exists in the United States where the latest surveys indicate that the daily intake of stable iodine is 75% of the ICRP value.

La protection de la thyroïde de l'enfant et du fœtus en cas d'accident nucléaire

Thyroid 131I activities were determined for five human subjects from a disaster medical assistance team of Fukui Prefectural Hospital. The team was dispatched to the Tamura City Sports Park, 40 km from the Fukushima Daiichi nuclear power plant. They were exposed to a radioactive plume on 15 March 2011. In vivo measurements at Fukui Prefectural Hospital were conducted around 17 h after the team left the park. A thyroid counter equipped with a 51-mm-diameter × 51-mm-thick NaI(Tl) detector with a 20-mm-thick lead collimator was used. Mock iodine (133Ba and 137Cs) with a thyroid uptake neck phantom was used for calibration. On 16 March 2011, at 11:30, thyroid activity of a member of the team age 53 y, who was never administered stable iodine, was 268 ± 38 Bq. The remaining four men, aged 49, 35, 34, and 27 y, ingested two stable iodine pills (a total of 100 mg of potassium iodide) approximately 36 h before being exposed to the plume. Their thyroid activity values were 249 ± 86 Bq, 676 ± 107 Bq, 569 ± 96 Bq, and 1,082 ± 119 Bq, respectively. An inverse relationship between age and thyroid activity was observed among those who ingested potassium iodide before exposure, indicating that stable iodine administration may have a protective effect. Thyroid 131I activity was reduced by approximately 70% in the oldest person. This can be explained by the iodine metabolism in the thyroid of younger individuals being significantly faster than that of older individuals.

Application of the new ICRP iodine biokinetic model for internal dosimetry in case of thyroid blocking

In the case of nuclear incidents, radioiodine may be released. After incorporation, it accumulates in the thyroid and enhances the risk of thyroidal dysfunctions and cancer occurrence by internal irradiation. Pregnant women and children are particularly vulnerable. Therefore, thyroidal protection by administering a large dose of stable (non-radioactive) iodine, blocking radioiodide uptake into the gland, is essential in these subpopulations. However, a quantitative estimation of the protection conferred to the maternal and fetal thyroids in the different stages of pregnancy is difficult. We departed from an established biokinetic model for radioiodine in pregnancy using first-order kinetics. As the uptake of iodide into the thyroid and several other tissues is mediated by a saturable active transport, we integrated an uptake mechanism described by a Michaelis–Menten kinetic. This permits simulating the competition between stable and radioactive iodide at the membrane carrier site, one of the protective mechanisms. The Wollf–Chaikoff effect, as the other protective mechanism, was simulated by adding a total net uptake block for iodide into the thyroid, becoming active when the gland is saturated with iodine. The model’s validity was confirmed by comparing predicted values with results from other models and sparse empirical data. According to our model, in the case of radioiodine exposure without thyroid blocking, the thyroid equivalent dose in the maternal gland increases about 45% within the first weeks of pregnancy to remain in the same range until term. Beginning in the 12th pregnancy week, the equivalent dose in the fetal thyroid disproportionately increases over time and amounts to three times the dose of the maternal gland at term. The maternal and fetal glands’ protection increases concomitantly with the amount of stable iodine administered to the mother simultaneously with acute radioiodine exposure. The dose–effect curves reflecting the combined thyroidal protection by the competition at the membrane carrier site and the Wolff–Chaikoff effect in the mother are characterized by a mean effective dose (ED50) of roughly 1.5 mg all over pregnancy. In the case of the fetal thyroid, the mean effective doses for thyroid blocking, taking into account only the competition at the carrier site are numerically lower than in the mother. Taking into account additionally the Wolff–Chaikoff effect, the dose–effect curves for thyroidal protection in the fetus show a shift to the left over time, with a mean effective dose of 12.9 mg in the 12th week of pregnancy decreasing to 0.5 mg at term. In any case, according to our model, the usually recommended dose of 100 mg stable iodine given at the time of acute radioiodine exposure confers a very high level of thyroidal protection to the maternal and fetal glands over pregnancy. For ethical reasons, the possibilities of experimental studies on thyroid blocking in pregnant women are extremely limited. Furthermore, results from animal studies are associated with the uncertainties related to the translation of the data to humans. Thus model-based simulations may be a valuable tool for better insight into the efficacy of thyroidal protection and improve preparedness planning for uncommon nuclear or radiological emergencies.

The most effective countermeasure for radioiodine contamination of milk is to provide dairy animals with uncontaminated feed, with the added advantage that it will be effective for other radionuclides in the fallout. Another effective response is to process the milk into storable dairy products for an appropriate length of time to allow for physical decay. The use of additives given to ruminants to reduce radioiodine in milk is an alternative countermeasure which could be effective. Stable iodine administration is a practically feasible option which has the potential to reduce radioiodine levels in milk by at most a factor of three. Stable iodine supplementation should be at sufficiently high rates to be effective (and at least 1 g d-1 for dairy cows), particularly for ruminants already receiving high amounts of iodine in the diet. Currently available data are inadequate to recommend a suitable stable iodine administration rate for different species of ruminants. Other compounds, such as perchlorate and thiocyanate, also reduce the transfer to radioiodine to milk (and thyroid). Some of these compounds seem to be potentially equally as effective as stable iodine. However, currently there is inadequate information on their effectiveness and possible toxicity to both ruminants and humans for these compounds to be considered as suitable countermeasure additives.

Purpose In the case of a nuclear incident, the release of radioiodine must be expected. Radioiodine accumulates in the thyroid and by irradiation enhances the risk of cancer. Large doses of stable (non-radioactive) iodine may inhibit radioiodine accumulation and protect the thyroid (‘thyroid blocking’). Protection is based on a competition at the active carrier site in the cellular membrane and an additional temporary inhibition of the organification of iodide (Wolff-Chaikoff effect). Alternatively, other agents like e.g. perchlorate that compete with iodide for the uptake into the thyrocytes may also confer thyroidal protection against radioiodine exposure. Biokinetic models for radioiodine mostly describe exchanges between compartments by first order kinetics. This leads to correct predictions only for low (radio)iodide concentrations. These models are not suited to describe the kinetics of iodine if administered at the dosages recommended for thyroid blocking and moreover does not permit to simulate either the protective competition mechanism at the membrane or the Wolff-Chaikoff effect. Models adapted for this purpose must be used. Such models may use a mathematical relation between the serum iodide concentration and a relative uptake suppression or a dependent rate constant determining total thyroidal radioiodine accumulation. Alternatively, the thyroidal uptake rate constant may be modeled as a function of the total iodine content of the gland relative to a saturation amount. Newer models integrate a carrier-mechanism described by Michalis-Menten kinetics in the membrane and in analogy to enzyme kinetics apply the rate law for monomolecular irreversible enzyme reactions with competing substrates to model the competition mechanism. An additional total iodide uptake block, independent on competition but limited in time, is used to simulate the Wolff-Chaikoff effect. Conclusion The selection of the best model depends on the issue to be studied. Most models cannot quantify the relative contributions of the competition mechanism at the membrane and the Wolff-Chaikoff effect. This makes it impossible or exceedingly difficult to simulate prolonged radioiodine exposure and the effect of repetitive administrations of stable iodine. The newer thyroid blocking models with a separate modeling of competition and Wolff-Chaikoff effect allow better quantitative mechanistic insights and offer the possibility to simulate complex radioiodine exposure scenarios and various protective dosage schemes of stable iodine relatively easily. Moreover, they permit to study the protective effects of other competitors at the membrane carrier site, like e.g. perchlorate, and to draw conclusions on their protective efficacy in comparison to stable iodine.

Prophylaxis by stable iodine “KI 65 mg, breakable tablet” is a pharmacological countermeasure of radiological protection adapted for the prevention of thyroid cancer after exposure to radioactive iodine. A first modification of the marketing authorization of “KI 65 mg, breakable tablet” for repeated prophylaxis for adults and children above 12 years old was obtained in France in 2020. At this point in time, the recommendation of a unique “KI” intake by pregnant and breastfeeding women and children below 12 years old remain valid.

Data on transfer of radioiodine into human milk are rare in the literature. Data from sixteen publications were reviewed and analyzed to estimate the transfer coefficient (f(hm)*, having units of d L(-1)). The data on the radioiodine concentration in breast milk were analyzed by two methods: direct numerical integration and integration of a fitted exponential model. In general, the integrated fitted functions were greater. The fitted functions likely better describe the transfer into milk since few data sets sampled mothers' milk near the time of maximum excretion. The derived transfer coefficient values seem to represent two populations. The first group was those individuals who had very low excretions, including those where thyroid and mammary uptake was impaired by the administration of stable iodine or iodinated compounds. The second group included those with much higher excretions. The second group, termed the "normal-excretion" group, had transfers of iodine to milk that were more than ten-fold higher than in the "low-excretion" group. The derived milk transfer coefficient data for the low- and normal-excretion groups fitted to lognormal distributions gave geometric means, (geometric standard deviations), of 0.043 d L(-1) (2.1, n = 14) and 0.37 d L(-1) (1.5, n = 12), respectively. Estimates of the effective half-time (time from maximum concentration to half the value) were determined for the low- and normal-excretion groups separately. There was evidence that the effective half-time was longer for the normal- than for the low-excretion group; the geometric mean (and geometric standard deviation) were 12 (1.7) and 8.5 (2.6) h, respectively, though the difference was not statistically significant. The geometric mean times to maximum milk concentration in the low- and normal-excretion groups were nearly identical, 9.4 (3.1) and 9.0 (1.6) h, respectively. The data show that administration of large doses of stable iodine (commonly used to block uptake of iodine into the thyroid) is also an effective means to block radioiodine transfer into milk. Thus, protecting the mother's thyroid also protects the nursing infant. Despite inadequacies of available data describing the transfer of radioiodine to human milk within a healthy population of women, the values of f(hm)* provided here are believed to be the best available for use in radiological assessments. These values are particularly applicable to lactating women having normal diets and availability to stable iodine, as in the United States.

Simulation study on iodine thyroid blocking in Koreans with high dietary iodine consumption.

Environmental 131I contamination from atmospheric nuclear bomb tests conducted at the NTS from 1951 to 1958 exposed Americans nationwide to a cumulative average dose of 1 to 4 rad to the thyroid gland. By comparison, 10 years of exposure to natural background sources of thyroid radiation results in a cumulative dose of 1 rad. Americans living in certain high-deposition areas received an average cumulative thyroid dose of as much as 16 rad. Individual dose rates vary considerably as a function of age at the time of exposure, site of residence, and dietary habits with respect to milk consumption. The individual cumulative thyroid dose for persons born between 1945 and 1958 may be significantly higher than the reported averages for their locale. The NCI report contains voluminous data tables permitting detailed calculations of individual dose. Additionally, color-coded dose maps allow one to approximate individual dose conveniently. Translation of cumulative thyroid dose attributable to 131I to predictions of increased rates of thyroid cancer appears problematic and is the subject of further study. In contrast to studies of patients receiving external thyroid irradiation, existing studies of patients treated with 131I for diagnostic and therapeutic medical purposes do not document increased rates of thyroid cancer. An Institute of Medicine task force is expected to issue a report on this subject in September 1998. This review also briefly summarizes the evaluation, diagnosis, and treatment of patients with papillary and follicular thyroid cancers. Data from 53,856 patients with thyroid cancer accessioned to the NCDB from 1985 to 1995 document extremely high survival rates for patients in the United States with papillary and follicular thyroid cancer.

The environmental abundances of 129 I and 127 I in Lower Saxony, Germany, and their pathways to animals and man were investigated. The iodine isotopes are in severe disequilibrium in the different environmental compartments. Today, the environmental isotope ratios range from 10 -6 to 10 -10 . The highest ratios were found in North Sea water, the lowest in deep soil samples and ground water. A differentiation by about a factor of ten between the iodine isotopes was observed for different air-borne iodine species. Time series for iodine in precipitation show a decade-long increase of 129 I fallout until the 1990ties and an ongoing constant input of 129 I with deposition densities of ~ 15 mBq m -2 per year. In surface waters, a dilution of the fall-out iodine takes place by stable iodine which is just weakly adsorbed in the soils. The isotope ratios in soils and ground waters demonstrate a high mobility and an accumulation of 129 I in the water unsaturated soil zones and an efficient migration into water saturated soil layers and ground water. The transfer into the food chain is ruled by the complex situation in the water-soil system. Given the environmental 129 I abundances, the relatively low 129 I/ 127 I ratios in human thyroid glands (2 ⋅ 10 -9 - 3 ⋅ 10 -8 ) can only be explained by additional iodine sources with low ratios in the diet.

I : Fundamental and Technical Aspects.- 1 Theoretical bases of XRF.- 2 Incident sources.- 3 Detection systems for XRF studies of the thyroid.- 4 A stationary X-ray fluorescent system for measuring thyroid iodine concentrations.- 5 Quantification problems in X-ray fluorescence determination of intrathyroidal iodine.- 6 Quality control procedures and evaluation of a fluorescent thyroid scanner.- II : Clinical Applications.- 7 Stable iodine and the thyroid function.- 8 Endemic non-toxic goiter.- 9 Feasibility of in vivo XRF dynamic study of the thyroid following stable iodine administration.- 10 Thyroid iodine content measurement helps for the diagnosis of hyperthyroidism with undetectable radionuclide uptake.- 11 Clinical usefulness of X-ray fluorescence thyroid iodine quatitation and scanning.- Author index.- Index of subjects.

In the case of a nuclear power plant accident, repetitive/prolonged radioiodine release may occur. Radioiodine accumulates in the thyroid and by irradiation enhances the risk of cancer. Large doses of non-radioactive iodine may protect the thyroid by inhibiting radioiodine uptake into the gland (iodine blockade). Protection is based on a competition at the active carrier site in the cellular membrane and the Wolff–Chaikoff effect, the latter being, however, only transient (24–48 h). Perchlorate may alternatively provide protection by a carrier competition mechanism only. Perchlorate has, however, a stronger affinity to the carrier than iodide. Based on an established biokinetic–dosimetric model developed to study iodine blockade, and after its extension to describe perchlorate pharmacokinetics and the inhibition of iodine transport through the carrier, we computed the protective efficacies that can be achieved by stable iodine or perchlorate in the case of an acute or prolonged radioiodine exposure. In the case of acute radioiodine exposure, perchlorate is less potent than stable iodine considering its ED50. A dose of 100 mg stable iodine has roughly the same protective efficacy as 1000 mg perchlorate. For prolonged exposures, single doses of protective agents, whether stable iodine or perchlorate, offer substantially lower protection than after acute radioiodine exposure, and thus repetitive administrations seem necessary. In case of prolonged exposure, the higher affinity of perchlorate for the carrier in combination with the fading Wolff–Chaikoff effect of iodine confers perchlorate a higher protective efficacy compared to stable iodine. Taking into account the frequency and seriousness of adverse effects, iodine and perchlorate at equieffective dosages seem to be alternatives in case of short-term acute radioiodine exposure, whereas preference should be given to perchlorate in view of its higher protective efficacy in the case of longer lasting radioiodine exposures.