Internal doses in experimental mice and rats following exposure to neutron-activated 56MnO2 powder: results of an international, multicenter study.

The experiment was performed in support of a Japanese initiative to investigate the biological effects of irradiation from residual neutron-activated radioactivity that resulted from the A-bombing. Radionuclide 56Mn (T1/2 = 2.58 h) is one of the main neutron-activated emitters during the first hours after neutron activation of soil dust particles. In our previous studies (2016-2017) related to irradiation of male Wistar rats after dispersion of 56MnO2 powder, the internal doses in rats were found to be very inhomogeneous: distribution of doses among different organs ranged from 1.3 Gy in small intestine to less than 0.0015 Gy in some of the other organs. Internal doses in the lungs ranged from 0.03 to 0.1 Gy. The essential pathological changes were found in lung tissue of rats despite a low level of irradiation. In the present study, the dosimetry investigations were extended: internal doses in experimental mice and rats were estimated for various activity levels of dispersed neutron-activated 56MnO2 powder. The following findings were noted: (a) internal radiation doses in mice were several times higher in comparison with rats under similar conditions of exposure to 56MnO2 powder. (b) When 2.74 × 108 Bq of 56MnO2 powder was dispersed over mice, doses of internal irradiation ranged from 0.81 to 4.5 Gy in the gastrointestinal tract (small intestine, stomach, large intestine), from 0.096 to 0.14 Gy in lungs, and doses in skin and eyes ranged from 0.29 to 0.42 Gy and from 0.12 to 0.16 Gy, respectively. Internal radiation doses in other organs of mice were much lower. (c) Internal radiation doses were significantly lower in organs of rats with the same activity of exposure to 56MnO2 powder (2.74 × 108 Bq): 0.09, 0.17, 0.29, and 0.025 Gy in stomach, small intestine, large intestine, and lungs, respectively. (d) Doses of internal irradiation in organs of rats and mice were two to four times higher when they were exposed to 8.0 × 108 Bq of 56MnO2 (in comparison with exposure to 2.74 × 108 Bq of 56MnO2). (e) Internal radiation doses in organs of mice were 7-14 times lower with the lowest 56MnO2 amount (8.0 × 107 Bq) in comparison with the highest amount, 8.0 × 108 Bq, of dispersed 56MnO2 powder. The data obtained will be used for interpretation of biological effects in experimental mice and rats that result from dispersion of various levels of neutron-activated 56MnO2 powder, which is the subject of separate studies.

Internal exposure to neutron-activated 56Mn dioxide powder in Wistar rats: part 1: dosimetry.

There were two sources of ionizing irradiation after the atomic bombings of Hiroshima and Nagasaki: (1) initial gamma-neutron irradiation at the moment of detonation and (2) residual radioactivity. Residual radioactivity consisted of two components: radioactive fallout containing fission products, including radioactive fissile materials from nuclear device, and neutron-activated radioisotopes from materials on the ground. The dosimetry systems DS86 and DS02 were mainly devoted to the assessment of initial radiation exposure to neutrons and gamma rays, while only brief considerations were given for the estimation of doses caused by residual radiation exposure. Currently, estimation of internal exposure of atomic bomb survivors due to dispersed radioactivity and neutron-activated radioisotopes from materials on the ground is a matter of some interest, in Japan. The main neutron-activated radionuclides in soil dust were 24Na, 28Al, 31Si, 32P, 38Cl, 42K, 45Ca, 46Sc, 56Mn, 59Fe, 60Co, and 134Cs. The radionuclide 56Mn (T 1/2 = 2.58 h) is known as one of the dominant beta- and gamma emitters during the first few hours after neutron irradiation of soil and other materials on ground, dispersed in the form of dust after a nuclear explosion in the atmosphere. To investigate the peculiarities of biological effects of internal exposure to 56Mn in comparison with external gamma irradiation, a dedicated experiment with Wistar rats exposed to neutron-activated 56Mn dioxide powder was performed recently by Shichijo and coworkers. The dosimetry required for this experiment is described here. Assessment of internal radiation doses was performed on the basis of measured 56Mn activity in the organs and tissues of the rats and of absorbed fractions of internal exposure to photons and electrons calculated with the MCNP-4C Monte Carlo using a mathematical rat phantom. The first results of this international multicenter study show that the internal irradiation due to incorporated 56Mn powder is highly inhomogeneous, and that the most irradiated organs of the experimental animals are: large intestine, small intestine, stomach, and lungs. Accumulated absorbed organ doses were 1.65, 1.33, 0.24, 0.10 Gy for large intestine, small intestine, stomach, and lungs, respectively. Other organs were irradiated at lower dose levels. These results will be useful for interpretation of the biological effects of internal exposure of experimental rats to powdered 56Mn as observed by Shichijo and coworkers.

Activity determination of 56Mn using extended TDCR-Cerenkov method.

The accuracy of activity determination for activated nuclide 56Mn is the key to the manganese bath method applying to the characterization of radionuclide neutron source. As an alternative to the 4π(C)-γ method, TDCR-Cerenkov method could also be applied to the measurement of 56Mn in the manganese bath device, if the existing calculation model is extended. There are two difficulties when the existing TDCR-Cerenkov method is applied to the activity determination of 56Mn. One is that the efficiency computation of gamma transitions, and the other is the interference contributed by Cerenkov photons emitted in the photomultiplier windows induced by Compton scattering. In this study, the above two difficulties are solved by extending the calculation model. For efficiency computation, the decay scheme of 56Mn is taken into account in the calculation of efficiency. Among them, the efficiency of gamma transition is calculated from the simulated secondary electronic spectra. In addition, Cerenkov photons emitted in photomultiplier windows are corrected by additional light proof experiment and improved calculation model. The results derived from this extended method are in good agreement with other standardization technique.

Microdistribution of internal radiation dose in biological tissues exposed to 56Mn dioxide microparticles.

Manganese-56 (56Mn) was one of the dominant neutron-activated radionuclides during the first hours following the atomic-bombing of Hiroshima and Nagasaki. The radiation spectrum of 56Mn and the radiation emission from excited levels of 56Fe following 56Mn beta-decay include gamma-quanta, beta-particles, Auger electrons and X-rays. The dispersion of neutron activated 56Mn in the air can lead to entering of radioactive microparticles into the lungs. The investigation of spatial microdistribution of an internal dose in biological tissue exposed to 56Mn is an important matter with regards to the possible elevated irradiation of the lung alveoli and alveolar ducts. The Monte Carlo code (MCNP-4C) was used for the calculation of absorbed doses in biological tissue around 56Mn dioxide microparticles. The estimated absorbed dose has a very essential gradient in the epithelium cells of lung alveoli and alveolar duct: from 61 mGy/decay on the surface of simple squamous cells of epithelium to 0.15 mGy/decay at distance of 0.3 µm, which is maximal cell thickness. It has been concluded that epithelial cells of these pulmonary microstructures are selectively irradiated by low-energy electrons: short-range component of beta-particles spectrum and Auger electrons. The data obtained are important for the interpretation of biological experiments implementing dispersed neutron-activated 56Mn dioxide powder.

External dose estimates of laboratory rats and mice during exposure to dispersed neutron-activated 56Mn powder.

Estimates of external absorbed dose in experimental animals exposed to sprayed neutron-activated 56Mn powder are necessary for comparison with internal absorbed doses estimated under the same exposure conditions, which is required for a correct interpretation of the observed biological effects. It has been established that the measured dose of external absorbed dose as a result of gamma irradiation range 1-15 mGy, which is order of magnitude less than the maximal dose of internal gamma and beta irradiation of the whole body of the same experimental animals irradiated under the same conditions: according to the available literature data, the maximal values ​​of absorbed dose of internal gamma-beta irradiation of the whole body are in the range of 330 mGy-1200 mGy for mice and 100 mGy-150 mGy for rats. It is concluded that under the conditions of experiments with dispersed neutron-activated powder 56MnO2, internal gamma-beta irradiation of experimental animals is the main factor of radiation exposure compared to external gamma irradiation.

Overview and analysis of internal radiation dose estimates in experimental animals in a framework of international studies of the sprayed neutron-induced 56Mn radioactive microparticles effects.

The aim of overview is to present the pooled data of published internal dose estimates and the results of corresponding analysis of internal irradiation features of experimental mice and rats after exposure to sprayed neutron activated radioactive 56MnO2. These dose estimates were conducted in a framework of multicenter international study to investigate biological effects as a result of exposure to sprayed radioactive 56MnO2 microparticles. Radionuclide 56Mn (T1/2 = 2.58 h) is one of the main gamma-beta emitters during the first hours after neutron activation of soil following nuclear explosion. It was concluded that there are three groups of organs of mice and rats, the radiation doses of which differ by approximately an order of magnitude: the group with the highest radiation doses (large and small intestine, stomach, skin and lungs), the group with lowered radiation doses (eyes, esophagus, trachea), the group with the lowest radiation doses (liver, heart, kidneys). The radiation doses to organs are proportional to the activity of the sprayed radioactive powder. The distribution of internal radiation doses among organs of experimental mice of different strains but of the same age was practically the same in case of exposure to the same activity of sprayed 56MnO2 powder. Doses of internal irradiation of experimental mice substantially exceed the doses of internal irradiation of experimental rats exposed to the same activities of the sprayed 56MnO2 powder. The data presented in the overview can be helpful for further investigation and for interpretation of the biological effects of this type of irradiation.

The overview of neutron-induced 56Mn radioactive microparticle effects in experimental animals and related studies.

Investigation into the risks associated with radiation exposure has been carried out on those exposed to radiation in Hiroshima and Nagasaki, Semipalatinsk and other parts of the world. These risks are used as a guidance standard for the protection for radiation workers and the general public when exposed to radiation, and it sets upper regulatory limits for the amount of radiation exposure. However, the effects of internal exposure to radioactive microparticles have not been considered in these studies. These effects cannot be ignored since the exposure dose increases are inversely proportional to the square of the distance to the vicinity of the particles and can exceed tens of thousands of mGy. So far, only retrospective studies of people who have been exposed to radiation have been conducted, therefore we hypothesized that animal experiments would be necessary to investigate these effects. As a result, we found specific effects of radioactive microparticles. One particularly noteworthy finding was that internal exposure to radioactive microparticles resulted in pathological changes that were more than 20 times greater than those caused by the same level of external exposure. In contrast, there were other results that showed no such effects, and the reasons for this discrepancy need to be clarified. We also conducted RNA expression experiments and found that there was a difference between external exposure to 60Co gamma rays and internal exposure to 56Mn microparticles. In the future, we will need to study the mechanisms behind these findings. If the mechanism can be confirmed, it is expected to lead to the development of protective and therapeutic methods.

A novel ß-cyclodextrin/alginate-combined-nickel oxide nanosorbent for adsorptive remediation of 51Cr and 56Mn radionuclides.

A Promising nanocomposite from ß-Cyclodextrin/Alginate (ß-CD/Alg) composite impregnated with nickel oxide nanoparticles (NiO) has been synthesized and characterized using diverse techniques like FT-IR, XRD, TGA, and SEM. The new nanocomposite has been investigated for the efficient remediation of 51Cr and 56Mn radionuclides from simulated contaminated radioactive water. All the controlling experimental parameters such as solution pH, contact time, initial radionuclides concentration and adsorbent mass have been investigated and optimized. The distribution coefficient values Kd (mL/g) for 51Cr and/or 56Mn radionuclides have been calculated for all factors it was found that the optimum pH values were at 5 and 6 with Kd 5300, and 4500, for 51Cr and/or 56Mn, respectively and the equilibrium was at 90 and 100 (min) with Kd values 5600 and 4800 for 51Cr and/or 56Mn, respectively.

Design and performance of an epithermal neutron flux detector using 55Mn(n,γ)56Mn reaction for BNCT.

The measurement of the epithermal neutron (0.5 eV - 10 keV) flux of a boron neutron capture therapy (BNCT) treatment beam is a critical issue to its quality assessment and evaluation of the radiation dose to the treated patients. In this work, an activation detector using 55Mn(n,γ)56Mn reaction is designed by Monte Carlo simulations to measure the epithermal neutron flux of BNCT treatment beam. The detector is spherical and it has an absorber/moderator/absorber/manganese (Mn) foil arrangement from outside to inside. The activation material, i.e., Mn foil, is located at the geometrical center of the detector. After the design, the performance of the detector is evaluated by Monte Carlo simulations using the treatment neutron beams of operating reactor-based BNCT facilities. The results and related analysis indicate that the proposed detector will be efficiently applicable in the quality assessment of BNCT treatment beam and evaluation of the radiation dose to the treated patients.

Impact of Local High Doses of Radiation by Neutron Activated Mn Dioxide Powder in Rat Lungs: Protracted Pathologic Damage Initiated by Internal Exposure.

Internal radiation exposure from neutron-induced radioisotopes environmentally activated following atomic bombing or nuclear accidents should be considered for a complete picture of pathologic effects on survivors. Inhaled hot particles expose neighboring tissues to locally ultra-high doses of ß-rays and can cause pathologic damage. 55MnO2 powder was activated by a nuclear reactor to make 56MnO2 which emits ß-rays. Internal exposures were compared with external γ-rays. Male Wistar rats were administered activated powder by inhalation. Lung samples were observed by histological staining at six hours, three days, 14 days, two months, six months and eight months after the exposure. Synchrotron radiation - X-ray fluorescence - X-ray absorption near-edge structure (SR-XRF-XANES) was utilized for the chemical analysis of the activated 56Mn embedded in lung tissues. 56Mn beta energy spectrum around the particles was calculated to assess the local dose rate and accumulated dose. Hot particles located in the bronchiole and in damaged alveolar tissue were identified as accumulations of Mn and iron. Histological changes showed evidence of emphysema, hemorrhage and severe inflammation from six hours through eight months. Apoptosis was observed in the bronchiole epithelium. Our study shows early event damage from the locally ultra-high internal dose leads to pathogenesis. The trigger of emphysema and hemorrhage was likely early event damage to blood vessels integral to alveolar walls.

Production of a carrier-free standard 56Mn source for the NRC manganese salt bath.

The National Research Council (NRC) of Canada's primary method for emission rate for radionuclide neutron sources utilizes a manganese salt bath which was last calibrated in the 1960s. At that time, an NRC RaBe neutron source was used to irradiate a solution of calcium permanganate to take advantage of the Szilard-Chalmers effect in producing the bulk 56Mn material for standardization and calibration of the bath. When attempting to repeat this exercise, a small amount (~100 kBq) was produced. This amount was sufficient for the standardization process but did not yield enough material to calibrate the bath to a sufficient level of precision. Improvements upon the previous separation scheme adopted at NRC for the separation of the 56Mn from the bulk irradiated material included the rinsing of the 56Mn dioxide precipitate using a mixture of sulfuric acid and hydrogen peroxide. While these improvements made in the separation chemistry improved the yield of 56Mn extraction from 60% to above 95% the maximum amount of activity was still quite low. Hence in March of 2018, the SLOWPOKE-2 Facility at the Royal Military College in Kingston, ON, was used to irradiate three vials of KMnO4 in solution. An estimated 2 GBq was produced and sent to NRC, from which the extraction procedure recovered essentially all of the available 56Mn. The 56Mn was standardized using the 4πß-γ anti-coincidence counting system and confirmed using the CIEMAT/NIST primary method. The resulting bulk material was certified with an uncertainty of 0.8% (k = 2). Minor quantities of 65Zn, 69mZn and 42K were unexpectedly observed but were in minute quantities so as not to affect the results of the standardization or calibration. The standardized 56Mn artifact was used to calibrate the Secondary Standard Ionizing Radiation Chamber System (SSIRCS) for a more rapid deployment of the calibrant in the future.

"Hot background" of the mobile inelastic neutron scattering system for soil carbon analysis.

The problem of gamma spectrum peak identification arises when conducting soil carbon analysis using the inelastic neutron scattering (INS) system. Some spectral peaks could be associated with radioisotopes appearing due to neutron activation of both the measurement system and soil samples. The investigation of "hot background" gamma spectra from the construction materials, whole measurement system, and soil samples over time showed that activation of (28)Al isotope can contribute noticeable additions to the soil neutron stimulated gamma spectra.