Brain accumulation of inhaled uranium in the rat depends on aerosol concentration, exposure repetitions, particle size and solubility.

A rostro-caudal gradient of uranium (U) in the brain has been suggested after its inhalation. To study the factors influencing this mapping, we first used 30-min acute inhalation at 56 mg/m3 of the relatively soluble form UO4 in the rat. These exposure parameters were then used as a reference in comparison with the other experimental conditions. Other groups received acute inhalation at different concentrations, repeated low dose inhalation of UO4 (10 exposures) or acute low dose inhalation of the insoluble form UO2. At 24 h after the last exposure, all rats showed a brain U accumulation with a rostro-caudal gradient as compared to controls. However, the total concentration to the brain was greater after repeated exposure than acute exposure, demonstrating an accumulative effect. In comparison with the low dose soluble U exposure, a higher accumulation in the front of the brain was observed after exposure to higher dose, to insoluble particles and following repetition of exposures, thus demonstrating a dose effect and influences of solubility and repetition of exposures. In the last part, exposure to ultrafine U particles made it possible to show 24 h after exposure the presence of U in the brain according to a rostro-caudal gradient. Finally, the time-course after exposure to micronic or nanometric U particles has revealed greater residence times for nanoparticles.

A model study on the absorbed dose of radiation following respiratory intake of 238U3O8 aerosols.

Aerosols of depleted uranium oxides, formed upon high-energy impact of shells on hard targets during military operations, are able to disperse, reach the alveolar region of the lungs and be absorbed and distributed throughout various parts of the body. The absorbed particles are subjected to clearance in the upper respiratory tract, distribution to other body districts, dissolution and excretion. While the soluble forms of uranium are known to deliver a small dose of radiation to the body due to their homogeneous distribution and the low specific activity of (238)U, ceramic particles exhibit a low dissolution rate and irradiate a limited volume of tissue for a long time with alpha particles with an energy of 4.267 MeV. The extent of the irradiated tissues depends on the radius of the particles and the total intake of uranium oxides. For the measured intake of U3O8 of a war veteran (15.51 µg) the number of particles ranges from 5.56×10(4) to 6.95×10(6) for sizes of 0.4-2.0 µm. Modelling the distribution of the particles between two compartments of the body, the averaged dose absorbed in 20 y by tissues surrounding the particles and within the range of the alpha particles varies from 6.8 mGy to 0.85 Gy for lungs and 8.1 mGy to 1.0 Gy for the lymph nodes, respectively. Correspondingly, due to the clearance and redistribution, the mass irradiated by 2.0-µm particles falls in 20 y from 6.06 mg to 0.94 µg in the lungs and grows from 0 to 1.0 mg in the lymph nodes. The estimated rate of formation of hydroxyl radicals upon radiolysis of water in the lungs and lymph nodes is 5.17×10(4) d(-1) per cell after 1 y.

Late-occurring pulmonary pathologies following inhalation of mixed oxide (uranium + plutonium oxide) aerosol in the rat.

Accidental exposure by inhalation to alpha-emitting particles from mixed oxide (MOX: uranium and plutonium oxide) fuels is a potential long-term health risk to workers in nuclear fuel fabrication plants. For MOX fuels, the risk of lung cancer development may be different from that assigned to individual components (plutonium, uranium) given different physico-chemical characteristics. The objective of this study was to investigate late effects in rat lungs following inhalation of MOX aerosols of similar particle size containing 2.5 or 7.1% plutonium. Conscious rats were exposed to MOX aerosols and kept for their entire lifespan. Different initial lung burdens (ILBs) were obtained using different amounts of MOX. Lung total alpha activity was determined by external counting and at autopsy for total lung dose calculation. Fixed lung tissue was used for anatomopathological, autoradiographical, and immunohistochemical analyses. Inhalation of MOX at ILBs ranging from 1-20 kBq resulted in lung pathologies (90% of rats) including fibrosis (70%) and malignant lung tumors (45%). High ILBs (4-20 kBq) resulted in reduced survival time (N = 102; p < 0.05) frequently associated with lung fibrosis. Malignant tumor incidence increased linearly with dose (up to 60 Gy) with a risk of 1-1.6% Gy for MOX, similar to results for industrial plutonium oxide alone (1.9% Gy). Staining with antibodies against Surfactant Protein-C, Thyroid Transcription Factor-1, or Oct-4 showed differential labeling of tumor types. In conclusion, late effects following MOX inhalation result in similar risk for development of lung tumors as compared with industrial plutonium oxide.

Efficacy of 3,4,3-LI(1,2-HOPO) for decorporation of Pu, Am and U from rats injected intramuscularly with high-fired particles of MOX.

This study aimed to assess the efficacy of 3,4,3-LI(1,2-HOPO) for reducing uranium, plutonium and americium in rats after intramuscular injection of (U-Pu)O2 particles (MOX). Sixteen rats were contaminated by intramuscular injection of a 1 mg MOX suspension and then treated daily for 7 d with LIHOPO (30 or 200 micromol kg(-1)) or DTPA (30 micromol kg(-1)). LIHOPO was inefficient for removing Pu, Am and U from the wound site. However, it reduced Pu retention in carcass and liver by factors of 2 and 6 respectively, and Am retention in carcass and liver by factors of 10 and 30. In contrast, the effect of LIHOPO on U was to decrease the retention in kidneys by a factor of 75. These results confirm that LIHOPO is a good candidate for use after contamination with MOX, in combination with localised wound lavage or surgical treatment aimed at removing most of the contaminant at the wound site.

Comparison of absorption after inhalation and instillation of uranium octoxide.

Values for the absorption parameters were compared after inhalation or intratracheal instillation of 1.5 microm mass median aerodynamic diameter (MMAD) 233U3O8 particles into the lungs of HMT strain rats. The two sets of parameter values were similar, as were the calculated dose coefficients and predicted biokinetics for workers. Hence the inhalation and instillation techniques can probably both be used to generate values of the absorption parameters for U3O8.

Optimising monitoring regimens for inhaled uranium oxides.

This paper provides guidance on the most appropriate monitoring procedures and intervals, the likely uncertainties in the assessment of intake and recommendations on appropriate investigation levels for repeated exposures to uranium trioxide, octoxide and dioxide of natural composition.

Translocation of plutonium from rat and monkey lung after inhalation of industrial plutonium oxide and mixed uranium and plutonium oxide.

This study was designed to compare the translocation from lung of the Pu contained in the pure and mixed industrial oxides PuO2 and (U,Pu)O2. The latter had a Pu content of 20% w/w. For this purpose, young adult male rats and male and female baboons were exposed to a single inhalation of these oxides. Two baboons were exposed to the reference PuO2, i.e. 239PuO2. Rats were killed under anaesthesia 1, 15, 30, 90 and 180 days after exposure, and baboons, also under anaesthesia, 1 year thereafter. The results indicate that lung retention of Pu was independent of the oxide inhaled, but was smaller in rat (12-15% of the initial pulmonary burden, 6 months after exposure) than in baboon (56-80% of this burden, 1 year after exposure). In rat, Pu translocation kinetics were similar for the two industrial oxides, but as from day 15 after inhalation until 6 months thereafter, measurement of Pu deposits in the liver and skeleton showed that translocation of Pu from the mixed oxide was 2-3 times greater than that from the industrial Pu oxide. In baboon, the largest amounts of Pu were retained in the lung and thoracic lymph nodes for the three oxides inhaled. Pu translocation to the liver, skeleton and kidneys, and also urinary Pu excretion, were greater after inhalation of the mixed oxide than after inhalation of the industrial and reference Pu oxides. Nevertheless, the amount of mixed oxide Pu translocated to these sites and excreted in urine remained under 3% of the initial pulmonary burden.

Distribution and short-term effects of intratracheally instilled neutron-irradiated UO2 particles in the rat.

In the present study we investigated the radionuclide distribution and histopathological effects of neutron-irradiated UO2 particles in the rat after intratracheal instillation. The kinetics and short-term effects of uranium fission products (95Zr, 95Nb, 103Ru, and 141Ce) were examined during a 3-month follow-up period. A rapid clearance (about 21%) of particles occurred via the gastrointestinal tract within 24 hr after the instillation. Autoradiographic and histological examinations revealed that the retained particles were nonuniformly distributed in the lungs. Translocation of the fission products from the lung to various other tissues was slow; 3 months after the instillation, the activity of the total body burden was below 1% in the liver, kidney, and spleen, whereas in the lungs it was 83%. Clearance of particles appeared to be mainly due to tracheobronchial mucociliary mechanisms. Translocation of the fission products to the bone and liver was significantly less than that reported by the ICRP, indicating that the clearance of uranium-matrix-associated fission products is preferably dependent on the physical characteristics of the particulate material. The cumulative lung doses ranging from 170 to 550 mSv caused slight or moderate local inflammatory reactions in the lungs, but at smaller dose levels there were no histopathological changes observed.