Distribution of Np and Pu in Swedish lichen samples (Cladonia stellaris) contaminated by atmospheric fallout.

The activity concentrations of (237)Np and the two Pu isotopes, (239)Pu and (240)Pu, were determined in lichen samples (Cladonia stellaris) contaminated by fallout from atmospheric nuclear test explosions and the Chernobyl accident. The samples were collected at 18 locations in Sweden, from north to south, between 1986 and 1988 and analysed with high-resolution inductively coupled plasma mass spectrometry (HR-ICP-MS) and alpha spectrometry. Data on the activity ratios (238)Pu/(239+240)Pu and (134)Cs/(137)Cs measured previously were also included in this study for comparison. The (237)Np activity concentration ranged from 0.08 +/- 0.01 to 2.08 +/- 0.17 MBq kg(-1), depending on the location of the sampling site and time of collection. The (239+240)Pu activity concentration ranged from 0.09 +/- 0.01 to 4.09 +/- 0.15 Bq kg(-1), with the (240)Pu/(239)Pu atomic ratio ranging between 0.16 +/- 0.01 and 0.44 +/- 0.03, the higher ratios indicating a combination of weapons test fallout and Chernobyl fallout. The (237)Np/(239)Pu atomic ratios ranged between 0.06 +/- 0.01 and 0.42 +/- 0.04, the lower ratios indicating combination of weapons test fallout and Chernobyl fallout. At a well-defined sampling site at Lake Rogen (62.32 degrees N, 12.38 degrees E), additional lichen samples were collected between 1987 and 1998 to study the distribution of Np and Pu in different layers. The concentrations of the two elements follow each other quite well in the profile.

Computer modelling of the chemical speciation of caesium, uranium(VI) and neptunium(V) in human duodenal fluids under fasting conditions.

A model simulating the human duodenal contents under physiologically realistic, fasting conditions was developed using the joint expert speciation system (JESS) computer program and database and used to investigate the chemical speciation of caesium, uranium(VI) and neptunium(V). Over the pH range 5.0-9.0, and the concentration range 5 x 10(-15) x 10(-5) mol dm(-3), caesium was predicted to occur predominantly as the absorbable free monovalent cation Cs+ (approximately 95%) with species such as CsHPO4- and CsCl representing the remainder. The presence or absence of sulphate at 2.1 x 10(-3) mol dm(-3) did not influence the predicted speciation. Uranium was predicted to be present entirely as a soluble, highly charged species, both in the absence and in the presence of sulphate. Between pH 5.0 and approximately 6.5 the UO2H2(PO4)2(2-) predominated, above this pH carbonate species, either UO2(CO3)4(6-) or, possibly, UO2(CO3)5(8-). At pH 8.0, and in the presence of sulphate, neptunium(V) was predicted to exist solely as the tetrasulphate species, whilst in the absence of sulphate, an array of negatively charged soluble carbonate species predominated. Studies over the pH range 5.0-9.0 predicted the formation of a spectrum of negatively charged carbonate and phosphate species, approximately 40% of the total neptunium was predicted to be present as the electrically net-neutral species NpO2HCO3 at pH6.0, approximately 20% at pH 7.0, approximately 10% at pH 7.5 and approximately 1% at pH 8.0. The observed speciation patterns of uranium and neptunium did not change over the concentration range 5 x 10(-15) - 5 x 10(-5) mol dm(-3) and no solid species were predicted to occur under the conditions simulated. Whether the predicted electrically net-neutral neptunium species or the uranium pentacarbonate species do actually occur under true physiological conditions remains to be established. The observed speciation patterns for caesium and uranium are consistent with the observed absorption of these elements by humans; however, the observations for neptunium appear to be equivocal.

Survival, lung clearance, dosimetry and gross pathology of rats exposed to either NpO2 or PuO2 aerosols.

PURPOSE: To compare survival, lung dosimetry and gross pathology after inhalation exposure of rats to either NpO2 or industrial PuO2 aerosols with similar granulometric parameters. Because the specific alpha activity ratio Pu/Np is about 600, a much more homogeneous lung irradiation was expected for NpO2. MATERIALS AND METHODS: Male Sprague Dawley rats were exposed once and their lung burdens were measured by X-ray spectrometry at different times post-exposure up to death. The time-course of doses delivered to the lungs were estimated, taking into account individual lung clearance parameters and body and lung weights. Gross lung pathologies were scored at autopsy. RESULTS: In the range of initial lung deposits (ILD) studied (0.1-4 kBq), lung clearance impairment and reduced lifespan were only observed after exposure to NpO2. For similar ILD or doses, the highest incidences of lung lesions assumed to be tumours were observed for NpO2 with a saturation of lung tumour induction for doses larger than 8 Gy (ILD: 1.5kBq). Up to 22Gy (ILD: 3.5kBq), such saturation was not observed for PuO2. CONCLUSIONS: NpO2 appears much more toxic than PuO2. Before saturation, lung tumour incidence increased nearly linearly with dose, the slope of the curve for NpO2 being about twice as steep as that for PuO2.

Effect of pH and temperature on the sorption of Np and Pa to mixed anaerobic bacteria.

While considering the geological disposal of radioactive wastes, the behaviour of the radionuclide Np and its daughter element Pa was investigated in the presence of a mixture of anaerobic bacteria (MAB). Originally, MAB were used for the treatment of pulp and paper wastewater. The interaction between radionuclides and bacteria was evaluated by determining distribution coefficients (Kd) over 10 days and at 5 degrees C and 35 degrees C. Kd for Np at 35 degrees C after 5 days had a low value around 10(-2) After 10 days, however, Kd was > 100-fold higher. On the other hand, Kd at 5 degrees C was low (10(-2)) throughout, without any significant increase over time. The interaction between Pa and MAB was found to be stronger than that for Np, with Kd for Pa about 100 times higher. The Kd was controlled by some basic factors, the activity of MAB, the complexing capacity of MAB, and the chemical conditions in the solution such as pH and Eh.

Effect of external irradiation on the gastrointestinal absorption of uranium and neptunium in rats.

PURPOSE: The gastrointestinal absorption and systemic distribution of uranium and neptunium were determined after external gamma irradiation. MATERIALS AND METHODS: Rats were exposed to a single whole-body dose of gamma radiation (6Gy; 0.75Gy.min(-1)). Three days after irradiation they were orally and/or intravenously contaminated with 100 microg.kg(-1) uranium or 3kBq.kg(-1) neptunium. The gastrointestinal absorption and organ distribution of both radionuclides were measured 6 days after irradiation. RESULTS: External irradiation increased the intestinal transit time of uranium and neptunium but had no effect on their gastrointestinal absorption. The average fractional absorption was determined to be 0.93 and 0.98% (uranium) and 4.7 and 4.8% (neptunium) for the irradiated and non-irradiated rats respectively. The excretion of uranium and neptunium was not affected by the irradiation. CONCLUSION: A 6 Gy whole-body irradiation (gamma; 0.75Gy.min(-1)) did not affect the absorption of uranium and neptunium after oral intake.

237Np: oxidation state in vivo and chelation by multidentate catecholate and hydroxypyridinonate ligands.

Chemically, 237Np(V) is as toxic as U(VI), and radiologically, about as toxic as 239Pu. Depending on redox conditions in vivo, 237Np exists as weakly complexing Np(V) (NpO2+) or as Np(IV), which forms complexes as stable as those of Pu(IV). Ten multidentate catecholate (CAM) and hydroxypyridinonate (HOPO) ligands with great affinity for Pu(IV) were compared with CaNa3-DTPA for in vivo chelation of 237Np. Mice were injected intravenously with 237NpO2Cl: those in a kinetic study were killed 1 to 2880 min; in ligand studies, fed mice were injected intraperitoneally with a ligand 5, 60, or 1440 min after 237Np(V) (molar ratio 5.6 to 73), mice fasted for 16 h were gastrically intubated with a ligand 3 min after 237Np(V) (molar ratio 5.6 to 274), and all were killed 24 h after ligand administration; tissues and excreta were radioanalyzed. Rapid plasma clearance and urinary excretion of 237Np(V) resemble U(VI); deposition and early retention in skeleton and liver resemble Pu(IV). The x-ray absorption near edge structure spectroscopy (XANES) spectra of femora of 237Np(V)-injected mice, compared with spectra of Np(V) and Np(IV) from reference solids, showed predominantly Np(IV). Significant in vivo 237Np chelation was obtained with all of the HOPO and CAM ligands injected at molar ratio 22; the HOPO ligands reduced 237Np in skeleton, liver, and other soft tissue, on average, to 72, 25, and 25% of control, respectively, while CaNa3-DTPA was ineffective. Two HOPO ligands injected 60 min after 237Np (molar ratio 5.6) significantly reduced body and liver 237Np, and three HOPO ligands given orally (molar ratio > or = 73) significantly reduced body and liver 237Np, compared with controls. Combined with earlier work, these results indicate that: the dominant neptunium species circulating and excreted in urine is Np(V), while that in bone and liver deposits is Np(IV); Np(V) must be reduced to Np(IV) before it can be stably chelated; efficient decorporation of neptunium requires multidentate ligands that form exceptionally stable actinide(IV) chelates and facilitate Np(V) reduction.

Evaluation of the efficiency of DTPA and other new chelating agents for removing neptunium from target organs.

Diethylenetriamine pentaacetic acid (DTPA) has been tested with 8 other new chelators for neptunium decorporation after systemic contamination in the rat. The ligands were injected intravenously at a dosage of 30 mumol kg-1 and the animals killed 24 h later. The results show that none of the chelators tested was efficient in removing significant amounts of the radionuclide from the body. In order to understand why these chelators were ineffective, in vitro approaches have since been developed in which high concentrations of DTPA were added to Np-bearing ligands in the blood, liver and skeleton. The main conclusions were that under our experimental conditions neptunium was not chelatable after its organ deposition.

Dosimetry and pathology of 237Np in female rats.

Female Sprague-Dawley rats, 10-12-week old and weighing about 240 g, were injected intravenously with 237Np-nitrate. In the toxicological study 77 rats served as controls and 28 rats per group received single doses of 5.2 and 26 kBq, respectively, per kg body weight. In addition, 12 rats of each injection level, sacrificed at defined points in time, were used for dosimetric studies. During the whole life-span the body weight and 237Np whole body-content of each animal were recorded. After death a detailed pathological examination was made of each animal in the cronical study. One day after injection 48% of the injected activity was in the skeleton, 9.3% in the liver, 3% in the kidneys and 4.4% in the rest of the organs. Whereas in all organs the activity decreased very fast, the half-life in the skeleton was about 1400 days. The bodyweights were comparable in the three groups, but the life span decreased from 800 days (control group) to 644 days after injection (26 kBq kg-1 body weight group). The main lesions in the female rats were mammary tumors (73%) and pituitary gland tumors (52%). With increasing activity the incidence of pituary gland tumors decreased and that of osteosarcomas increased from 1.3% (control group) to 32% (26 kBq kg-1 body weight group), whereas the remaining lesions showed no influence on the activity.

Subcellular localization of neptunium-237 in lung and kidney after intratracheal administration in the rat: an ultrastructural and microanalytical study.

Chronic intratracheal administration of 237Np to rate was performed during 6 weeks. The total dose administered was 45.8 kBq. Two methods, electron microscopy and electron probe X-ray microanalysis, were used to determine the intracellular sites of localization of 237Np. Clusters of dense granules were observed in nuclei of pneumocytes and proximal tubular cells of the kidneys. These clusters have been shown to contain neptunium associated with phosphorus, sulfur and calcium. Alterations of nuclei and ultrastructural cytoplasmic lesions were observed. The absorbed doses in lungs and kidneys were very low. These results suggest that the chemical toxicity of 237Np is more important than its radiological toxicity.

The effect of the mass and initial chemical form of neptunium on its molecular associations in blood and liver.

The present investigation was aimed at establishing the distribution of neptunium in blood and liver cells as a function of the mass and chemical form of the radionuclide injected. Four groups of rats received intravenous injections of 237Np(V), 237Np(IV), 239Np(V) or 239Np(IV). Twenty-four hours after injection of the radionuclide, subcellular structures of the liver were separated by ultracentrifugation and serum and liver cytosol were subjected to gel permeation chromatography. The intracellular distribution of neptunium in liver depends on the mass of the radionuclide injected; the relative specific activity for 237Np compared to 239Np was 2 in nuclei and 0.5-0.9 in cytosol. By contrast, the initial chemical form of the radionuclide has no significant effect on its intracellular distribution. In cytosol, neptunium was bound mainly by two proteins of molecular weight 450 and 200 kDa, respectively. The former was identified as ferritin, but the latter remains unidentified. In this compartment, no effect of mass or chemical form was seen. In blood, the bulk of the radionuclide was bound to transferrin whatever the mass and initial chemical form injected.

Subcellular and intranuclear localization of neptunium-237 (V) in rat liver.

The present investigation was aimed at establishing the distribution of 237Np within the different structures of hepatocytes. Rats were contaminated experimentally by intravenous injection of 237Np (V) and the subcellular structures of the liver were separated by ultracentrifugation. Twenty-four hours after contamination, the nuclear and cytosolic fractions bound 54 and 32%, respectively, of the total radionuclide. Purification of the nuclei followed by dissociation of the protein components in medium of increasing ionic strength showed a specific binding of neptunium to the structural proteins of the nuclear matrix.

Intranuclear sites of Np 237 in mammalian cells: a study using electron microscopy and electron probe microanalysis.

Two methods, electron microscopy and wavelength dispersive electron probe microanalysis, were used to determine the intracellular sites and chemical form of concentrations of neptunium nitrate 237 after chronic intoxication by the intraperitoneal route in two organs in the rat known to concentrate this element (kidney, liver). Abnormal intranuclear formations in the form of clusters of dense granules containing neptunium, phosphorus, sulphur, and calcium were found in the nuclei of kidney proximal tubule cells and hepatocytes. These formations had a maximum diameter of the order of 2 microns and were located in the central part of the nucleus, away from the nucleolus and peripheral chromatin. Serious nuclear and cytoplasmic ultrastructural lesions are often associated in cells containing neptunium inclusions. The absorbed doses in the kidney and the liver were very low. A relationship between these abnormal intranuclear structures and the carcinogenic effect of neptunium remains to be clarified. This effect is related more probably to the chemical toxicity of Np 237.

The gastrointestinal absorption of neptunium, plutonium and americium in a primate (C. jacchus).

Mixtures of Np, Pu and Am were administered to primates (C. jacchus) by gastric intubation to measure their fractional gastrointestinal absorption (f1 values). The values obtained were about 2 x 10(-3) and 1 x 10(-3), respectively, for Np and Pu administered as the citrate, and 2 x 10(-3) and 6 x 10(-4), respectively, for Pu and Am in potato. The significance of these values in terms of absorption in humans is discussed.

Microdistribution of 237Np in the skeleton of female rats.

237Np nitrate was injected intravenously into 4-week-old (young) and 10-12-week-old (adult) female albino Sprague-Dawley rats. The amounts given were 52 (young), 5.2 (adult) and 26 kBq kg-1 body weight (adult). The microscopic distribution in the femur and the lumbar vertebrae was studied. Initially, neptunium was distributed uniformly on periosteal and endosteal bone surfaces, and additionally, activity was found in the vascular canals of hard tissue. Dose-rates and cumulative doses were found to increase from marrow to hard tissue, and periosteal and endosteal surfaces, the highest levels being found in the spongy bone of the distal femoral metaphysis. Initially, the highest dose rates were found in hard tissue of the distal femoral metaphysis (27 mGy per day per injected activity of 37 kBq kg-1), whereas periosteal bone surfaces showed levels of 65 mGy per day in all bone regions. One year later the normalized dose rates on the surfaces decreased to 10 or 15 mGy per day. After 1 year the cumulative doses in the 0-10 microns marrow layer on the endosteal bone surfaces were 8 (52 kBq kg-1, young), 2.1 (5.2 kBq kg-1, adult) and 8.7 Gy (26 kBq kg-1, adult). The microdosimetric findings were compared with the macroscopical doses of the whole skeleton.

Measurements of actinide gut-transfer factors in humans.

Measurements have been made of the gastrointestinal absorption in humans of 239Np and 242Cm administered together in citrate media. Using five volunteers, consistent results of (2.0 +/- 0.2) x 10(-4) and (1.7 +/- 0.3) x 10(-4) were obtained for Np and Cm respectively; the quoted uncertainties are the standard errors of the means. A progress report is given of work to measure the f1 value for Pu in humans. Early work suggests an f1 value of 2 x 10(-4).

Gastrointestinal absorption of neptunium and curium in humans.

The gastrointestinal absorption of Np and Cm has been determined in five male adult volunteers. The Np and Cm, which were in citrate solution, were taken with food. An initial experiment with each individual determined the fraction of each element excreted in the urine following intravenous administration. Subsequently, the results for urinary excretion for the two routes of administration were used to calculate the fractional absorption (f1) of ingested Np and Cm. The mean f1 values were: Np (2.0 +/- 0.2) X 10(-4), range (1.2-2.9) X 10(-4), and Cm (1.7 +/- 0.3) X 10(-4), range (0.95-3.0) X 10(-4), the quoted uncertainties being the standard error of the means. Currently, the International Commission on Radiological Protection recommends a value of 10(-3) for both elements. Cumulative urinary excretion over 1 wk after intravenous injection accounted for about 20%-40% of administered Np and 7%-10% of Cm. At the conclusion of the experiment, the total committed effective dose equivalent for each volunteer was calculated to be in the range 130-250 microSv, based on the individual f1 values, and, in some cases, a knowledge of the rate of clearance of 239Np through the gut as measured by whole-body counting.

Short-term bioconcentration studies of Np in freshwater biota.

Short-term laboratory exposures were conducted to determine the potential accumulation of Np in aquatic organisms. Concentration factors were highest in green algae. Daphnia magna, a filter-feeding crustacean, accumulated Np at levels one order of magnitude greater than the amphipod Gammarus sp., an omnivorous substrate feeder. Accumulation of Np in juvenile rainbow trout (Oncorhynchus mykiss) was highest in carcass (generally greater than 78% of the total body burden) and lowest in fillets. Recommended concentration factors for Np, based on fresh weight, were 300 for green algae, 100 for filter-feeding invertebrates, for nonfilter-feeding invertebrates, 10 for whole fish, and one for fish flesh.

Influence of nutritional factors on 239Np and 233Pa retention in weanling rats.

The estimated intestinal absorption after a single administration of 239Np-nitrate to fasted weanling rats (about 2% of the oral dose) was ten times higher than that of 233Pa administered as the chloride. Rats drinking tomato juice, apple juice or tea instead of water had a similar retention to the control group. However, when a small amount of tea was administered immediately before 239Np, the absorption and retention values were six times lower. When animals received only milk or glucose, the whole body retention of 239Np and 233Pa increased about 20 and 200-300 times, respectively, due mainly to a very high retention in the large intestine. When rats were fed milk plus rat chow, the whole body and gut retention of 233Pa was only two and three times higher, respectively; in the other organs less 233Pa was found than in control animals. This indicates that the extremely high retention of radionuclides in the gut contents of young rats fed only milk is temporary and disappears when solid food is available.

The biodistribution and toxicity of plutonium, americium and neptunium.

In the nuclear fuel cycle the transuranic radionuclides plutonium-239, americium-241 and neptunium-237 would probably present the most serious hazard to human health if released into the environment. Despite differences in their solution chemistry the three elements exhibit remarkable similarity in their biochemical behaviour, apparently sharing similar transport pathways in blood and cells. After entering the blood the elements deposit predominantly in liver and skeleton, where retention appears to be prolonged, with half-times of the order of years. The principal late effects of all three radionuclides are the induction of cancers of bone, lung or liver. For the latter tumours the induction risk per unit radiation dose appears similar for the three radionuclides. But in bone there are indications that, due to microscopic differences in the distribution of the alpha-particle radiation dose, the efficiency of bone cancer induction may increase in the order americium-241 less than plutonium-239 less than neptunium-237. No case of human cancer induced by these radionuclides is known.

Absorption of 233U, 237Np, 238Pu, 241Am and 244Cm from the gastrointestinal tracts of rats fed an iron-deficient diet.

Absorption of U, Np, Am and Cm was increased by factors of 3.4, 7.1, 2.7 and 1.7, respectively, when nitrate solutions of these actinides were gavaged to adult rats fed an iron-deficient diet. Retention increased proportionately in liver, kidney and carcass. The concentration of the actinides excreted also increased substantially (over that of controls) in the urine of iron-deficient rats gavaged with 233U and 237Np, but not in those with 241Am or 244Cm. Weanling rats on an iron-deficient diet, gavaged with ferric nitrate immediately before administration of 238Pu nitrate, retained between 4% and 12% of the 238Pu retained by litter mates that were not treated intragastrically with iron.