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Localization of plutonium-241 in the testis. An interspecies comparison using light and electron microscope autoradiography.

The distribution and localization of 241Pu in the testes of rats, guinea-pigs and a dog were determined using light and electron microscope autoradiography. These species were used because of the variation in the morphology and ultrastructure exhibited in their testicular tissues. In all animals the 241Pu was localized in testicular interstitial tissue and little was evident in the seminiferous tubules. There were marked species differences in the percentage of interstitial tissue cells labelled with 241Pu; 18 per cent of the cells labelled in rats, 9 per cent in guinea-pigs and 6 per cent in the dog. Electron microscope autoradiography demonstrates that 241Pu is localized in macrophages of the interstitial tissue in all species and appears to be concentrated in the lysosomal system of the cell. Based on differences in the histology and microstructure of testicular interstitial tissues and the patterns of 241Pu incorporation in these species, implications for predicting plutonium localization in human tissue are discussed.

Animals↗

Uptake and clearance of plutonium-238 from liver cells transplanted into fat pads of F344 rats.

This research is directed toward understanding the role of liver cells and the liver environment in plutonium biokinetics. Animals injected with liver cells and control animals received a single intraperitoneal injection of 37 kBq (1 microCi) 238Pu citrate and were serially sacrificed 1, 5, 10, 15, 30, 60 or 70 days later. Uptake, retention and distribution of Pu in intact liver and in liver cells growing in fat pads were determined. From these measurements, it was observed that the cells of the intact liver took up about twice as much 238Pu as liver cells transplanted into the fat pads of the same animal. The retention half-life was 8.3 days for the total activity in the liver, 20 days using tracks/cell measurements in the liver and 16 days for the tracks/cell measurements in the liver cells translocated to fat pads. When the data on tracks/cell were standardized relative to the amount of Pu present at 5 days after the injection, there was no significant difference between the retention of Pu in liver cells from intact animals and liver cells transplanted into the fat pads. About 20 per cent of the 5-day Pu liver burden in both liver cells and liver cells transplanted into fat pads was retained at 70 days. The smaller retention and clearance for liver cells in different environments indicate that uptake and clearance of Pu from the body is dependent, to a major extent, upon hepatocyte function.

Animals↗

Induction of sister chromatid exchanges (SCE) in G0 lymphocytes by plutonium-238 alpha-particles.

Irradiation of human G0 lymphocytes with plutonium-238 alpha-particles and X-rays was performed to investigate the production of sister chromatid exchanges (SCE). Alpha-particles produce a significant increase in SCE and this elevation is more significant when separated lymphocytes are irradiated. X-ray irradiation did not induce any significant increase in SCE. Therefore the relative biological effectiveness (RBE) for the induction of SCE by alpha-particles in this system is undefined and effectively infinite.

Alpha Particles↗

Long-term effects of plutonium-239 and radium-224 on the distribution and performance of pluripotent haemopoietic progenitor cells and their regulatory microenvironment.

Experiments are described which investigate the long-term damage to haemopoietic progenitor cells (CFU-S) and their microenvironment in mouse marrow resulting from the administration of leukaemogenic amounts of plutonium-239 and radium-224. 239Pu (35 Bq g-1 body weight) and 224Ra (555 Bg g-1 body weight) were injected into 10-12-week-old mice, and numbers, proliferative activity and self-renewal capacity of CFU-S were measured at different locations in femoral marrow at intervals over the following 2 years. Parallel measurements were also made of the quality of the haemopoietic microenvironment by ectopic transplantation of bone marrow cells. There was some recovery from the initial effects of 239Pu on CFU-S numbers after 3-6 months, although the recovery was not maintained in all marrow fractions. Following 224Ra administration there was an initial transient increase in CFU-S numbers in the fraction of marrow furthest from bone surfaces but a considerable depression in numbers in other regions of marrow; there was no recovery between 3 and 6 months and subsequent recovery was not complete in all regions of marrow. The differential responses of CFU-S and the haemopoietic microenvironment following 224Ra or 239Pu administration seemed in some ways related to the metabolism of the radionuclides. There was a profound reduction in the ability of marrow to generate ossicles when transplanted under the kidney capsule as a result of the administration of either 224Ra or 239Pu, with only transient recoveries from the effects of 239Pu at 4 days and at 3 months after injection.

Animals↗

Examination of testicular tumours in the beagle dog exposed to inhaled plutonium.

Gross and light microscopic features of testicular neoplasms were examined in the male beagle dog used in three studies to examine the life-span effects of inhaled plutonium (Pu). One hundred and sixty-six cases of testicular neoplasia (TN) occurred among 105 dogs that ranged in age from 7.5 to 17.7 years at the time of diagnosis. The 166 cases of TN comprised 113 interstitial cell tumours, 27 seminomas in situ, 19 seminomas, and seven Sertoli cell tumours. Serum testosterone and estradiol 17-beta concentrations, and the serum testosterone-to-oestradiol ratio were determined in 39 dogs with TN and in five clinically normal, sexually intact, age-matched cohorts. Serum hormone concentrations did not differ significantly among tumour types or between dogs with neoplasms and age-matched cohorts. There was a significant relationship between initial lung deposition (ILD) of Pu and activity in the testis (Bq/g testis). The slope of the relationship was 0.35, 0.89 and 0.91 for 239PuO2, 238PuO2 and 239Pu(NO3)4 respectively. Pu in the testis at long times (> 5 years) after inhalation was between 0.0001 and 0.03% ILD, depending on the physicochemical form of Pu. Although the mean activity of Pu in the testis of dogs was higher in those life-span studies employing 238PuO2 and 239Pu(NO3)4, the cumulative proportion of dogs with tumours, the distribution of tumour types, and mean time to first tumour was not significantly different among the three studies or dose groups, including controls, within a study.

Administration, Inhalation↗

The distribution of plutonium between the mineral and organic components of rat bone: a biochemical study after in vivo and in vitro contamination.

PURPOSE: To measure the distribution of plutonium between the mineral and organic components of rat bone after chemical extraction of powdered bones, 48 h after contamination of rats with 238Pu-citrate. MATERIALS AND METHODS: Chemical extractions were performed by EDTA treatment or by formic acid followed by guanidine treatments. The extracts were analysed for proteins and Pu content after chromatography experiments. Complementary experiments have been performed, mainly the addition of citrate and/or Pu to the formic acid medium during the extraction of contaminated or uncontaminated bones. RESULTS: EDTA extracted most of the Pu in an ultrafilterable form. By contrast, formic acid extracted only about 20% of Pu, whereas the remaining Pu was solubilized by guanidine. Gel permeation chromatography showed that it was mostly associated with 20-40 kD macromolecules. The high affinity of these macromolecules for Pu was confirmed after in vitro contamination of dialysed EDTA extracts. The complementary experiments suggested that deposition of the solubilized Pu on the residue during the formic acid treatment might occur, and showed that the amount of extracted Pu increased by adding citrate. CONCLUSION: The results show that the initially observed distribution of Pu in mineral (20%) and organic (80%) bone matrix may be in error due to Pu deposition on the organic residue during the extraction procedure.

Animals↗

Lung cancer and internal lung doses among plutonium workers at the Rocky Flats Plant: a case-control study.

The authors conducted a nested case-control study of the association between lung cancer mortality and cumulative internal lung doses among a cohort of workers employed at the Rocky Flats Plant in Colorado from 1951 to 1989. Cases (n = 180) were individually matched with controls (n = 720) on age, sex, and birth year. Annual doses to the lung from plutonium, americium, and uranium isotopes were calculated for each worker with an internal dosimetry model. Lung cancer risk was elevated among workers with cumulative internal lung doses of more than 400 mSv in several different analytical models. The dose-response relation was not consistent at high doses. Restricting analysis to those employed for 15-25 years produced a statistically significant linear trend with dose (chi-square = 67.2, p < 0.001), suggesting a strong healthy worker survivor effect. The association between age at first internal lung dose and lung cancer mortality was statistically significant (odds ratio = 1.05, 95% confidence interval: 1.01, 1.10). No associations were found between lung cancer mortality and cumulative external penetrating radiation dose or cumulative exposures to asbestos, beryllium, hexavalent chromium, or nickel.

Adult↗

Sizing alpha emitting particles of aged plutonium on personal air sampler filters using CR-39 autoradiography.

Methods have been developed to assess the size distribution of alpha emitting particles of reactor fuel of known composition captured on air sampler filters. The sizes of uranium oxide and plutonium oxide particles were determined using a system based on CR-39 solid-state nuclear track detectors. The CR-39 plastic was exposed to the deposited particles across a 400 microm airgap. The exposed CR-39 was chemically etched to reveal clusters of tracks radially dispersed from central points. The number and location of the tracks were determined using an optical microscope with an XY motorised table and image analysis software. The sample mounting arrangement allowed individual particles to be simultaneously viewed with their respective track cluster. The predicted diameters correlated with the actual particle diameters, as measured using the optical microscope. The efficacy of the technique was demonstrated with particles of natural uranium oxide (natUO2) of known size, ranging from 4 to 150 microm in diameter. Two personal air sampler (PAS) filters contaminated with actinide particles were placed against CR-39 and estimated to have size distributions of 0.8 and 1.0 microm activity median aerodynamic diameter (AMAD).

Aerosols↗

Distribution of plutonium particles in the lungs of Mayak workers.

Lung tissues from workers at the Mayak Production Association were examined to determine the distribution of plutonium (Pu) activity in various lung compartments. Stereological sampling methods and autoradiography were used. Pu particles were identified by microscopic examination of autoradiographs and localised in one of six normal anatomic sites and two sites of fibrosis (parenchymal, non-parenchymal). Particle activity was determined by counting the number of tracks emanating from the particles. Over 50% of the Pu activity was localised in sites of fibrosis, which had significantly higher than average activity for the lung. Over 40% of the activity was in lung parenchyma. Activity in the bronchovascular interstitium was significantly lower than average. These results support the hypothesis that Pu activity is not uniformly distributed in the lung, with long-term retained particles concentrated in scars of the lung. The results may significantly affect estimates of dose from inhaled Pu.

Adult↗

Modifying the ICRP 66 dosimetry model based on results obtained from Mayak plutonium workers.

Results obtained in a study of the microscopic distribution of plutonium in the lungs of deceased Pu workers from the Mayak Production Association showed that the long-term retention of Pu was greater than predicted by the current ICRP 66 respiratory tract dosimetry model (HRTM). These data were therefore applied to the HRTM by modifying selected parameters, namely the transfer rate of Pu from the transformed state compartment and the fraction of Pu that transfers to the bound state compartment. Invoking the latter compartment into the modelling allowed a better representation of the long-term Pu retention as well as providing a convenient means of describing the workplace-specific characteristics of the different Pu aerosols found in the Mayak plant. In particular, the present model describes a significantly greater long-term retention of Pu nitrate aerosols in the lung compared with the Type M default.

Air Pollutants, Radioactive↗

Sensitivity analysis of the urinary excretion of plutonium.

The transfer parameters of a new age-related model for plutonium metabolism, which have the largest influence on urinary excretion, are determined by applying a sensitivity analysis and assuming a direct uptake into blood. Realistic cases of contamination via ingestion and inhalation were considered as well and sensitivity coefficients for non-systemic parameters were calculated. The most important parameters in relation to the path of intake are identified and the effects of the modifying factors proposed by the ICRP in the case of alteration of respiratory tract physiology are briefly examined.

Absorption↗

241Am as a metabolic tracer for inhaled plutonium nitrate in external chest counting.

The plutonium (Pu) treated in the nuclear fuel cycle is usually accompanied by 241Am produced from 241Pu by beta disintegration, which emits gamma rays of 60 keV with the emission rate of 0.36, being more penetrating than the L X rays from Pu. The 241Am could imprve the detection limit of chest counting of Pu, if it was being used as a metabolic tracer for Pu in lungs. Young adult male Wistar rats were exposed to polydisperse aerosols of Pu(NO3)4 with 0.6 microm in activity median aerodynamic diameter. They were periodically killed and the radioactivity of 241Am was cleared from the lungs at almost the same rate as the Pu at least for half a year post-inhalation, which proved the validity of 241Am as a metabolic tracer for inhaled Pu nitrate in external chest counting.

Aerosols↗

Developing instruments for measurement of plutonium activity in the environmental samples in the case of radiation accident.

According to the Russian norms, the permissible specific activity of 239Pu in the air and water are the lowest. Still the problem of low (compared to permissible) Pu activity measurement for environmental samples arises, for instance, in the case of radiation accident during transportation or storage of excess weapons-grade plutonium transferred to the civil sphere of utilisation. The base method of Pu activity measurement is alpha spectrometry by using silicon detector. A new model of alpha spectrometer, based on silicon surface-barrier detector with background level less than 1-3 pulses per day has been developed. A simple unfolding method for the determination of Pu activity of samples with various thickness based on alpha spectrum measurement has been also developed. L-X photon detection is also used for reducing the measurement threshold of Pu activity determination. A method based on detecting L-X photons of Pu, excited by X rays and beta particles, is applied for further reducing the threshold.

Alpha Particles↗

Mechanistic models of bone cancer induction by radium and plutonium in animals compared to humans.

Two-mutation carcinogenesis models of mice and rats injected with (239)Pu and (226)Ra have been derived extending previous modellings of beagle dogs injected with (239)Pu and (226)Ra and radium dial painters. In all cases statistically significant parameters could be derived fitting data from several research groups jointly. This also lead to similarly parametrised models for (239)Pu and (226)Ra for all species. For each data set not more than five free model parameters were needed to fit the data adequately. From the toxicity ratios of the animal models for (239)Pu and (226)Ra, together with the human model for (226)Ra, an approximate model for the exposure of humans to (239)Pu has been derived. Relative risk calculations with this approximate model are in good agreement with epidemiological findings for the plutonium-exposed Mayak workers. This promising result may indicate new possibilities for estimating risks for humans from animal experiments.

Animals↗

Further studies of plutonium and americium at Thule, Greenland.

Eleven years after the accidental loss of nuclear weapons in 1968, the fourth scientific expedition to Thule occurred. The estimated inventory of 1 TBq 239,240Pu in the marine sediments was unchanged when compared with the estimate based on the 1974 data. Plutonium from the accident had moved further away from the impact point and at some locations the vertical distribution indicated a downward displacement of Pu in the sediment column since 1974. Seawater and seaplants showed no evidence of the presence of Pu from sources other than fallout; but Pu in benthos varied nearly proportionally with the levels in sediments. From the measurements of 239,240Pu in the Macoma community since 1970, the transfer factor to this community was estimated at 0.01 Bq a per Bq released to the sediments. The inventory of 241Am was 0.1 TBq. The vertical distribution of Am in sediments did not differ from that of Pu, but in benthos 241Am/239,240Pu were two times higher than in sediments. Seaplants showed the same value of Am/Pu as seawater. There was no indication of any biomagnification of Pu or Am through the marine food chains at Thule.

Americium↗

Plutonium contents of broadleaf vegetable crops grown near a nuclear fuel chemical separations facility.

Among agricultural crops, broadleaf vegetables are particularly prone to intercept and retain aerially released contaminants. The plutonium concentration of four broadleaf crops (broccoli, cabbage, lettuce and turnip greens) was determined, when grown in close proximity to a nuclear-fuel chemical-separations facility. Concentrations varied among species, apparently influenced by the crop morphology, with Pu concentrations increasing in the sequence: cabbage less than broccoli less than turnip greens less than lettuce. Washing of the crops significantly reduced the Pu concentration of lettuce, but had no effect on Pu concentration of broccoli and cabbage. The vast majority of Pu found in the crops was due to direct deposition of recently released Pu and resuspension of Pu-bearing soil particles, and was not due to root uptake. Resultant doses from consumption are small relative to the annual background dose.

Food Contamination, Radioactive↗

Plutonium- or americium-induced liver tumors and lesions in beagles.

Plutonium-239 or 241Am administered intravenously in the monomeric citrate form was initially deposited in beagle livers principally in the hepatocytes and to a much lesser extent in the sinusoidal macrophages and connective tissues. The initial distribution was quite uniform throughout the hepatic parenchyma; however, at later postinjection intervals, depending on the amount of injected activity, the liver burden became increasingly more focal due to: (1) a progressive shift of the radionuclide from the hepatic epithelium to the macrophages; (2) the movement of such macrophages toward the portal or central regions of the lobule; and (3) the displacement of the older more radioactive tissue by regenerating hepatocytes, which generally have a much lower radionuclide content. The hepatic lesions produced by Pu or Am included: (1) necrosis and degenerative changes that were clinically serious or fatal in some of the animals injected with approximately 107 kBq kg-1; (2) marked structural and circulatory changes resulting from necrosis and focal hepatocyte hyperplasia; (3) a significant incidence of both benign and malignant primary liver tumors. In both Pu- and Am-treated dogs, the most frequently appearing neoplasm was the bile duct adenoma, followed by the cholangiocarcinoma. The most obvious difference between Pu- and Am-induced liver neoplasia was the greater frequency of fibrosarcomas and mast cell sarcomas in the Am-treated groups. Hepatomas were of relatively low frequency in animals with Pu or Am burdens. Although the incidence of bone neoplasia was high among the dogs in these studies, the risk of liver tumors, especially in the Am-treated animals, exceeded that of the skeleton in some of the lower dosage levels where the survival times were long. A risk coefficient of approximately 1200 fatal liver malignancies (10(4) beagle Gy)-1, derived from the dosage groups with long survival times, was calculated for combined Pu and Am animals. The prominence of the liver syndromes in beagles with burdens of Pu or Am indicates that humans with body burdens of 239Pu, 241Am, or other actinide elements may be at risk from radiation effects in the liver, including neoplasia development.

Adenoma↗