A comparison of the chemo- and radiotoxicity of thorium and uranium at different enrichment grades.

Uranium and thorium are heavy metals, and all of their isotopes are radioactive, so it is impossible to study chemical effects entirely independent of the radiation effects. In the present study, we tried to compare the chemo- and radiotoxicity of both metals, taking into account deterministic radiation damages reflected by acute radiation sickness and stochastic radiation damages leading to long-term health impairments (e.g., tumor induction). We made at first a literature search on acute median lethal doses that may be expected to be caused by chemical effects, as even acute radiation sickness as a manifestation of acute radiotoxicity occurs with latency. By simulations based on the biokinetic models of the International Commission on Radiological Protection and using the Integrated Modules for Bioassay Analysis software, we determined the amounts of uranium at different enrichment grades and thorium-232 leading to a short-term red bone marrow equivalent dose of 3.5 Sv considered to cause 50% lethality in humans. Different intake pathways for incorporation were considered, and values were compared to the mean lethal doses by chemotoxicity. To assess stochastic radiotoxicity, we calculated the uranium and thorium amounts leading to a committed effective dose of 200 mSv that is often considered critical. Mean lethal values for uranium and thorium are in the same order of magnitude so that the data do not give evidence for substantial differences in acute chemical toxicity. When comparing radiotoxicity, the reference units (activity in Bq or weight in g) must always be taken into account. The mean lethal equivalent dose to the red bone marrow of 3.5 Sv is reached by lower activities of thorium compared to uranium in soluble compounds. However, for uranium as well as thorium-232, acute radiation sickness is expected only after incorporation of amounts exceeding the mean lethal doses by chemotoxicity. Thus, acute radiation sickness is not a relevant clinical issue for either metal. Concerning stochastic radiation damages, thorium-232 is more radiotoxic than uranium if incorporating the same activities. Using weight units for comparison show that for soluble compounds, thorium-232 is more radiotoxic than low-enriched uranium in the case of ingestion but even more toxic than high-enriched uranium after inhalation or intravenous administration. For insoluble compounds, the situation differs as the stochastic radiotoxicity of thorium-232 ranges between depleted and natural uranium. For acute effects, the chemotoxicity of uranium, even at high enrichment grades, as well as thorium-232 exceeds deterministic radiotoxicity. Simulations show that thorium-232 is more radiotoxic than uranium expressed in activity units. If the comparison is based on weight units, the rankings depend on the uranium enrichment grades and the route of intake.

Simulations of radioiodine exposure and protective thyroid blocking in a new biokinetic model of the mother-fetus unit at different pregnancy ages.

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.

A comparison of thyroidal protection by iodine and perchlorate against radioiodine exposure in Caucasians and Japanese.

Radioactive iodine released in nuclear accidents may accumulate in the thyroid and by irradiation enhances the risk of cancer. Radioiodine uptake into the gland can be inhibited by large doses of stable iodine or perchlorate. Nutritional iodine daily intake may impact thyroid physiology, so that radiological doses absorbed by the thyroid as well as thyroid blocking efficacy may differ in Japanese with a very rich iodine diet compared to Caucasians. Based on established biokinetic-dosimetric models for the thyroid, we derived the parameters for Caucasians and Japanese to quantitatively compare the effects of radioiodine exposure and the protective efficacy of thyroid blocking by stable iodine at the officially recommended dosages (100 mg in Germany, 76 mg in Japan) or perchlorate. The maximum transport capacity for iodine uptake into the thyroid is lower in Japanese compared to Caucasians. For the same radioiodine exposure pattern, the radiological equivalent thyroid dose is substantially lower in Japanese in the absence of thyroid blocking treatments. In the case of acute radioiodine exposure, stable iodine is less potent in Japanese (ED50 = 41.6 mg) than in Caucasians (ED50 = 2.7 mg) and confers less thyroid protection at the recommended dosages because of a delayed responsiveness to iodine saturation of the gland (Wolff-Chaikoff effect). Perchlorate (ED50 = 10 mg in Caucasians) at a dose of 1000 mg has roughly the same thyroid blocking effect as 100 mg iodine in Caucasians, whereas it confers a much better protection than 76 mg iodine in Japanese. For prolonged exposures, a single dose of iodine offer substantially lower protection than after acute radioiodine exposure in both groups. Repetitive daily iodine administrations improve efficacy without reaching levels after acute radioiodine exposure and achieve only slightly better protection in Japanese than in Caucasians. However, in the case of continuous radioiodine exposure, daily doses of 1000 mg perchlorate achieve a high protective efficacy in Caucasians as well as Japanese (> 0.98). In Caucasians, iodine (100 mg) and perchlorate (1000 mg) at the recommended dosages seem alternatives in case of acute radioiodine exposure, whereas perchlorate has a higher protective efficacy in the case of longer lasting radioiodine exposures. In Japanese, considering protective efficacy, preference should be given to perchlorate in acute as well as prolonged radioiodine exposure scenarios.

A quantitative comparison of the chemo- and radiotoxicity of uranium at different enrichment grades.

OBJECTIVE: The radiotoxic effects of uranium are often in the focus of the public fears but the chemical toxic effects of uranium are reported to surpass radiation effects. As there is no uranium isotope that is not radioactive, it is not possible to study chemical effects fully independently from radiation effects. In order to quantitate and compare radio- and chemotoxicity, we determined the median lethal doses of uranium due to its chemical toxicity and calculated the absorbed radiological doses resulting from the ingestion or inhalation of corresponding amounts depending on the isotopic enrichment grade. Committed effective doses over 50 years are related to the stochastic health effects like cancer occurrence and can be converted to a loss of statistical life time (mean loss 0.4 day / mSv). The equivalent doses absorbed within a short time frame permits conclusion on the induction of deterministic effects (e.g. acute radiation sickness). METHOD: Simulations were based on the biokinetic models of the International Commission for Radioprotection and performed using Integrated Modules for Bioassay Analysis software. Results were compared with the doses given by the calculator of the WISE uranium project. The fractions of the total doses absorbed within different time periods were derived from the respective areas under the activity-time curves in the whole body. RESULTS: The distribution of the total dose on the organs and tissues depends on the invasion pathway and the solubility of the compound. In the case of inhalation, the absorption of the total dose is more protracted than after ingestion. The incorporation of depleted or natural uranium in lethal amounts due to nephrotoxicity does not lead to deterministic radiation effects and is associated with committed effective doses reaching at most about 200 mSv (proposed possible threshold for therapeutic interventions after accidental radionuclide incorporation). The inhalation of low enriched uranium leads to higher effective doses up to 690 mSv, but they are still insufficient to cause acute deterministic effects. Even highly enriched uranium seems not to induce radiation nephropathy, but deterministic effects on the hematopoetic system cannot be excluded in particularly sensitive patients. But the equivalent doses to the lungs associated with the inhalation of poorly soluble compounds of highly enriched uranium are in a range that may induce radiation pneumonitis. CONCLUSION: Our findings give clear evidence that for depleted and natural uranium chemical toxicity is much more marked than radiotoxicity. However, this conclusion must not be drawn for enriched and in particular highly enriched compounds that besides stochastic effects may even cause deterministic radiation effects.