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). 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. 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. 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.

A wide spectrum of scenarios may lead to radiation incidents and the liberation of radioactive material. In the case of a terrorist attack by a “dirty bomb”, there is a risk of mechanical and thermal trauma, external irradiation, superficial contamination and incorporation of radioactive material. The first treatment priority must be given to the care of trauma patients with life-threatening injuries, as the health effects of radiation occur with latency. Radionuclide incorporation will lead to a longer-lasting irradiation from inside the body, associated with a higher risk of stochastic radiation effects (e.g., occurrence of tumors) in the long run. It must be expected that victims with potentially incorporated radionuclides will far outnumber trauma patients. The elimination of radionuclides can be enhanced by the administration of decorporation agents such as (Ca) Diethylenetriaminepentaacetic acid (DTPA) or Prussian blue, reducing the radiological burden of the body. There is still no consensus whether decorporation treatment should be started immediately based only on a suspicion of radionuclide incorporation (“urgent approach”) or if the results of internal dosimetry confirming the necessity of a treatment should be awaited, accepting the delay caused by the measurements and computations (“precautionary approach”). As the therapeutic effectiveness may be substantially decreased if treatment initiation is delayed only by several days, depending on the radionuclide, the physicochemical properties of the compounds involved and the route of absorption, we favor an “urgent approach” from a medical point of view. In doubt, it seems justified to treat victims by precaution, as the adverse effects of the medication seem minimal. However, in the case of a high number of victims, an “urgent treatment approach” may require a large number of daily doses of antidotes, and therefore, adequate investments in preparedness and antidote stockpiling are necessary.

In the case of a terrorist attack by a “dirty bomb”, blast injuries, external irradiation and the incorporation of radioactivity are to be expected. Departing from information about the radiological attack scenario with cesium-137 in the U.S. National Scenario Planning Guide, we estimated the radiological doses absorbed. Similar calculations were performed for a smaller plume size and a detonation in a subway. For conditions as described in the U.S. scenario, the committed effective dose amounted to a maximum of 848 mSv, even for very unfavorable conditions. Red bone marrow equivalent doses are insufficient to induce acute radiation sickness (ARS). In the case of a smaller plume size, the ARS threshold may be exceeded in some cases. In a subway bombing, doses are much higher and the occurrence of ARS should be expected. The health hazards from a dirty bomb attack will depend on the location and the explosive device. The derived Haddon matrix indicates that preparing for such an event includes education of all the medical staff about radiation effects, the time lines of radiation damages and the treatment priorities. Further determinants of the outcome include rapid evacuation even from difficult locations, the availability of a specific triage tool to rapidly identify victims at risk for ARS, the availability of an antidote stockpile and dedicated hospital beds to treat seriously irradiated victims.

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 ED_50. 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.

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.

Background: In radiological emergencies with radionuclide incorporation, decorporation treatment is particularly effective if started early. Treating all people potentially contaminated (“urgent treatment”) may require large antidote stockpiles. An efficacious way to reduce antidote requirements is by using radioactivity screening equipment. We analyzed the suitability of such equipment for triage purposes and determined the most efficient mix of screening units and antidote daily doses. Methods: The committed effective doses corresponding to activities within the detection limits of monitoring portals and mobile whole-body counters were used to assess their usefulness as triage tools. To determine the optimal resource mix, we departed from a large-scale scenario (60,000 victims) and based on purchase prices of antidotes and screening equipment in Germany, we calculated efficiencies of different combinations of medical countermeasure resources by data envelopment analysis. Cost-effectiveness was expressed as the costs per life year saved and compared to risk reduction opportunities in other sectors of society as well as the values of a statistical life. Results: Monitoring portals are adequate instruments for a sensitive triage after cesium-137 exposure with a high screening throughput. For the detection of americium-241 whole-body counters with a lower daily screening capacity per unit are needed. Assuming that 1% of the potentially contaminated patients actually need decorporation treatment, an efficient resource mix includes 6 monitoring portals and 25 mobile whole-body counters. The optimum mix depends on price discounts and in particular the fraction of victims actually needing treatment. The cost-effectiveness of preparedness for a “dirty bomb” attack is less than for common health care, but costs for a life year saved are less than for many risk-reduction interventions in the environmental sector. Conclusion: To achieve economic efficiency a high daily screening capacity is of major importance to substantially decrease the required amount of antidote doses. Among the determinants of the number of equipment units needed, the fraction of the potentially contaminated victims that actually needs treatment is the most difficult to assess. Judging cost-effectiveness of the preparedness for “dirty bomb” attacks is an issue of principle that must be dealt with by political leaders.