Internal contamination by actinides after wounding: a robust rodent model for assessment of local and distant actinide retention.

Internal contamination by actinides following wounding may occur in nuclear fuel industry workers or subsequent to terrorist activities, causing dissemination of radioactive elements. Contamination by alpha particle emitting actinides can result in pathological effects, either local or distant from the site of entry. The objective of the present study was to develop a robust experimental approach in the rat for short- and long- term actinide contamination following wounding by incision of the skin and muscles of the hind limb. Anesthetized rats were contaminated with Mixed OXide (MOX, uranium, plutonium oxides containing 7.1% plutonium) or plutonium nitrate (Pu nitrate) following wounding by deep incision of the hind leg. Actinide excretion and tissue levels were measured as well as histological changes from 2 h to 3 mo. Humid swabs were used for rapid evaluation of contamination levels and proved to be an initial guide for contamination levels. Although the activity transferred from wound to blood is higher after contamination with a moderately soluble form of plutonium (nitrate), at 7 d most of the MOX (98%) or Pu nitrate (87%) was retained at the wound site. Rapid actinide retention in liver and bone was observed within 24 h, which increased up to 3 mo. After MOX contamination, a more rapid initial urinary excretion of americium was observed compared with plutonium. At 3 mo, around 95% of activity remained at the wound site, and excretion of Pu and Am was extremely low. This experimental approach could be applied to other situations involving contamination following wounding including rupture of the dermal, vascular, and muscle barriers.

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.

Simplified structure of a new model to describe urinary excretion of plutonium after systemic, liver or pulmonary contamination of rats associated with Ca-DTPA treatments.

This study validates, by targeted experiments, several modeling hypotheses for interpretation of urinary excretion of plutonium after Ca-DTPA treatments. Different formulations and doses of Ca-DTPA were administered to rats before or after systemic, liver or lung contamination with various chemical forms of plutonium. The biokinetics of plutonium was also characterized after i.v. injection of Pu-DTPA. Once formed, Pu-DTPA complexes are stable in most biological environments. Pu-DTPA present in circulating fluids is rapidly excreted in the urine, but 2-3% is retained, mainly in soft tissues, and is then excreted slowly in the urine after transfer to blood. Potentially, all intracellular monoatomic forms of plutonium could be decorporated after DTPA internalization involving slow urinary excretion of Pu-DTPA with half-lives varying from 2.5 to 6 days as a function of tissue retention. The ratio of fast to slow urinary excretion of Pu-DTPA depends on both plutonium contamination and Ca-DTPA treatment. Fast urinary excretion of Pu-DTPA corresponds to extracellular decorporation that occurs beyond a threshold of the free DTPA concentration in circulating fluids. Slow excretion corresponds mostly to intracellular decorporation and depends on the amount of intracellular DTPA. From these results, the structure of a simplified model is proposed for interpretation of data obtained with Ca-DTPA treatments after systemic, wound or pulmonary contamination by plutonium.

In vivo measurement of Pu dissolution parameters of MOX aerosols and related uncertainties in the values of the dose per unit intake.

The aim of this study was to compare dissolution parameter values for Pu from industrial MOX with different Pu contents. For this purpose, preliminary results obtained after inhalation exposure of rats to MOX containing 2.5% Pu are reported and compared to those obtained previously with MOX containing 5% Pu. Dissolution parameter values appear to increase when the amount of Pu decreases. Rapid fractions, f(r), of 4 x 10(-3) (s.d. = 2 x 10(-3)) and 1 x 10(-3) (s.d. = 6 x 10(-4)) and slow dissolution rates, s(s) of 2 x 10(-4) d(-1) (standard deviation, sigma = 5 x 10(-5)) and 5 x 10(-5) d(-1) (sigma = 1 x 10(-5)) were derived for MOX containing 2.5 and 5% of Pu, respectively. Simulations were performed to assess uncertainties on dose due to experimental errors. The relative standard deviations of the dose per unit intake (DPUI) due to f(r) (4-8%), are far less than those due to s(s) (about 20%), which is the main parameter altering the dose. Although quite different dissolution parameter values were derived, similar DPUIs were obtained for MOX aerosols containing 2.5 and 5% Pu which appear close to that for default Type S values.

[Specific parameters for the calculation of dose after aerosol inhalation of transuranium elements]. / Mesure de paramètres spécifiques pour le calcul de dose après inhalation d'aérosols renfermant des éléments transuraniens.

A review on specific parameter measurements to calculate doses per unit of incorporation according to recommendations of the International Commission of Radiological Protection has been performed for inhaled actinide oxides. Alpha activity distribution of the particles can be obtained by autoradiography analysis using aerosol sampling filters at the work places. This allows us to characterize granulometric parameters of "pure" actinide oxides, but complementary analysis by scanning electron microscopy is needed for complex aerosols. Dissolution parameters with their standard deviation are obtained after rat inhalation exposure, taking into account both mechanical lung clearance and actinide transfer to the blood estimated from bone retention. In vitro experiments suggest that the slow dissolution rate might decrease as a function of time following exposure. Dose calculation software packages have been developed to take into account granulometry and dissolution parameters as well as specific physiological parameters of exposed individuals. In the case of poorly soluble actinide oxides, granulometry and physiology appear as the main parameters controlling dose value, whereas dissolution only alters dose distribution. Validation of these software packages are in progress.

Comparative biokinetics of plutonium and americium after inhalation of PuO2 and mixed oxides (U, Pu)O2 in rat.

PURPOSE: To compare the biokinetics of Pu and Am in rat after inhalation of PuO2 and two (U, Pu) mixed oxides (MOX), referred to as MIMAS and SOLGEL. MATERIALS AND METHODS: Lung clearance was measured in vivo by X-and y-ray spectrometry. Retention of Pu and Am in femurs, liver and kidneys was measured by alpha-spectrometry. RESULTS: Observed lung clearance was in the same range for all three powders. Extra-pulmonary transfers were expressed as the percent of the initial deep lung deposit (IDLD) measured 7 days after inhalation. After PuO2 exposure, bone retention remained nearly constant throughout the 270-day experiment. It was approximately 0.7% of the IDLD for Pu and Am. By contrast, a gradual increase was observed for the two MOX. After 7 days, bone retention of Pu and Am was respectively 0.05 and 0.08% for MIMAS, and 0.2 and 0.6% for SOLGEL. The retention reached maximal values between 180 and 270 days post-exposure, which were 0.2 and 0.3% for MIMAS, and 1.2 and 2.8% for SOLGEL for Pu and Am respectively. CONCLUSIONS: Different transfer rates of Pu and Am from the lung were observed depending on the chemical composition of the oxides and/or the method of their preparation.

Use of a pneumatic tube system for delivery of blood bank products and specimens.

This study evaluated the effect of pneumatic tube transport on blood bank specimens and products. No important differences were found between aliquots transported in the tube system and those stored in the laboratory as controls. ABO, Rh, antibody detection or identification, direct antiglobulin testing, and elution were studied. Further, no differences in plasma hemoglobin and potassium concentration were found between units of whole blood and packed cells handled in either manner. Platelet counts in platelet concentrates were not decreased and coagulation factor levels in units of fresh-frozen plasma and cryoprecipitate did not decrease after pneumatic transport. The system tested is currently providing expeditious transport of specimens and blood between blood banks and patient care areas.