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PubMed1992

Decorporation of plutonium by oral administration of a partially lipophilic polyaminocarboxylic acid.

A new, orally administered, partially lipophilic polyaminocarboxylic acid chelator was tested for its ability to remove incorporated 239Pu deposits in rats. Animals were injected with 239Pu-citrate and 14 d later were treated for an additional 10 d with docosyl-triethylenetetraminepentaacetic acid (C22TT) added to the diet. There were significant reductions in the 239Pu content of selected organs in the chelated animals compared with controls. These results suggest that this class of chelators should be studied further for their ability to remove plutonium deposits from the body when given orally.

Acetates↗

PubMed1993

Metabolism of injected plutonium in two healthy men.

The metabolism of plutonium has been studied following intravenous injection of 237Pu as Pu (IV) citrate into two healthy male volunteers. Measurements of the tracer in samples of blood and excreta were made by gamma-ray spectrometry, and patterns of organ uptake were investigated through serial measurements with a scintillation counter viewing the liver and selected skeletal sites. Excretion in urine and feces measured during the first 3 wk accorded closely with the patterns deduced by Durbin from the report of Langham et al. on patients injected with 239Pu. However, concentrations in blood were roughly twice those suggested by Durbin during most of the 14 d covered by our measurements. In one subject, the liver deposit increased to a plateau after about 21 d, at roughly 55% of the injection; in the other, the increase was prolonged, reaching about 70% after several months.

Aged↗

PubMed1994

Design of an airborne plutonium survey program for personnel protection.

Various options were considered for surveying and real-time monitoring for airborne plutonium for optimum protection of personnel. Placement of samplers, dilution factors, and analysis time were considered in the strategy for achieving regulatory compliance and maintaining internal dose as low as reasonably achievable (ALARA). It was found that protection was relatively insensitive to placement as was sensitivity of detection. It was also found that maximum protection was obtained with few detectors and increasing the number of detectors above the optimum value did not appreciably increase the information about a release nor did it aid in locating the release. It was determined that the best protection was obtained with alarming monitors if the detection sensitivity was sufficiently low. Integrating samplers requiring laboratory analysis can be more sensitive than alarming monitors, but the lack of timeliness limits the amount of protection. The integrating samplers can be used effectively to monitor engineering controls. Personal air samplers also offer little protection but can be very effective in analyzing exposure by craft and job type.

Air Pollutants, Radioactive↗

PubMed1999

Plutonium excretion in urine of residents living near the Rocky Flats Environmental Technology Site.

An assessment of current levels of 239Pu in individuals living near the Rocky Flats Environmental Technology Site was conducted. Long-term residents of areas adjacent to the Site, as well as people living well beyond any expected influence of the site, provided urine samples, which were analyzed by fission track analysis for the levels of 239Pu. The Rocky Flats Environmental Technology Site vicinity participants were selected for maximum possible exposure to environmental plutonium by virtue of residence location, length of residence, age, and outdoor lifestyle. The mean 239Pu excretion rate in urine estimated for the entire Rocky Flats group was 1.1 microBq d(-1), in contrast to that estimated for the background group (0.85 microBq d(-1)). The estimated median 239Pu excretion rate for the Rocky Flats group was 1.1 microBq d(-1), compared to 0.54 microBq d(-1) for the background group. Both parametric and non-parametric tests indicated that these differences were not statistically significant (alpha = 0.05). Measured levels of 239Pu in urine from the Rocky Flats group were low and well within the range of reported "background" values, indicating small doses and low health risks. The fission track analysis technique may not be sufficiently accurate or precise to allow definitive comparisons between two groups of subjects with near-background levels of 239Pu in urine.

Adult↗

PubMed2000

Biokinetic and dosimetric model of plutonium in the dog.

A biokinetic model of the systemic distribution and dosimetry of 239Pu in the beagle dog is presented. To achieve maximum consistency with experimental data, known histomorphometric parameters and results of autoradiographic studies were adopted directly. The remaining parameters were determined from retention and excretion measurements by optimization procedures. The beagle model attempts to parallel the human model as much as possible, but only one liver compartment and one compartment representing other soft tissues were needed to describe the data adequately. The salient features and differences of the biokinetic behavior of 239Pu beagles and humans are compared. Generally the organ retention of the beagle in relation to the lifetime is longer than in humans. This is particularly pronounced in the skeleton. Trabecular deposits of plutonium are gradually shifted to cortical sites. For the dosimetric model some additional features disregarded in the human model were employed. These relate to bone volume labels, a gradation of concentrations in marrow, the energy-dependence of absorbed fractions, and the self-absorption in marrow. The model predicts that the contribution of surface deposits to the endosteal dose still exceeds the contributions from bone volume and marrow labels. The average endosteal dose is about eight times and the marrow dose about two times larger than the average skeletal dose. The model provides the basis for the analysis of survival and relative risks.

Animals↗

PubMed2002

Summary of stationary and personal air sampling measurements made during a plutonium glovebox decommissioning project.

Workplace air sampling was performed during the decommissioning of a previously active plutonium glovebox facility located at Argonne National Laboratory. Personal air samplers (PAS) were used to measure breathing zone activity concentrations of workers engaged in size-reducing contaminated gloveboxes. Stationary air samplers (SAS) were used to measure the work area activity concentrations and test their application in providing representative sampling of breathing zone activity concentrations. The relative response of these samplers (PAS:SAS) was tracked during the course of the decommissioning work, with results yielding favorable agreement to within a factor of +/-5. A cascade impactor was used to determine the particle size distribution of workplace aerosols. The average activity median aerodynamic diameter (AMAD) was estimated to be 3.0 microm, with a corresponding geometric standard deviation of 2.4. A gas-flow proportional counter was utilized to measure the gross alpha activity collected on both the SAS glass fiber and the PAS cellulose fiber filters. A subset of this filter group was subsequently analyzed using an alpha spectrometer post radiochemical processing and isotopic separation. The quantity of alpha activity measured on the SAS filters was generally within +/-30% of the alpha spectrometry measurements. However, measurements made of the activity present on the PAS cellulose fiber filters were consistently underestimated using a gas-flow proportional counter, suggesting a small correction factor of 15-20% to account for the absorption of alpha particle emissions.

Air Pollutants, Occupational↗

PubMed2002

The historical and current application of the FIB-1 model to assess organ dose from plutonium intakes in Mayak workers.

One of the objectives of the Joint Coordinating Committee for Radiation Effects Research Project 2.4 is to document the methodology used to determine the radiation doses in workers from the Mayak Production Association who were exposed to plutonium. The doses have been employed in numerous dose response studies measuring both stochastic and deterministic effects. This article documents both the historical (pre-1999) and current ("Doses 1999") methods used by the FIB-1 scientists to determine the doses. Both methods are based on a three-chamber lung model developed by the FIB-1 scientists. This method was developed in partial isolation from the West and has unique characteristics from the more familiar ICRP biokinetic models. Some of these characteristics are the use of empirically based transportability classifications and the parameter modification for chelation-therapy-enhanced excretion data. An example dose calculation is provided and compared to the dose that would be obtained if the ICRP models were used. The comparison demonstrates that the models are not interchangeable and produce different results.

Humans↗

PubMed2003

Risk estimates for deterministic health effects of inhaled weapons grade plutonium.

Risk estimates for deterministic effects of inhaled weapons-grade plutonium (WG Pu) are needed to evaluate potential serious harm to (1) U.S. Department of Energy nuclear workers from accidental or other work-place releases of WG Pu; and (2) the public from terrorist actions resulting in the release of WG Pu to the environment. Deterministic health effects (the most serious radiobiological consequences to humans) can arise when large amounts of WG Pu are taken into the body. Inhalation is considered the most likely route of intake during work-place accidents or during a nuclear terrorism incident releasing WG Pu to the environment. Our current knowledge about radiation-related harm is insufficient for generating precise estimates of risk for a given WG Pu exposure scenario. This relates largely to uncertainties associated with currently available risk and dosimetry models. Thus, rather than generating point estimates of risk, distributions that account for variability/uncertainty are needed to properly characterize potential harm to humans from a given WG Pu exposure scenario. In this manuscript, we generate and summarize risk distributions for deterministic radiation effects in the lungs of nuclear workers from inhaled WG Pu particles (standard isotopic mix). These distributions were developed using NUREG/CR-4214 risk models and time-dependent, dose conversion factor data based on Publication 30 of the International Commission on Radiological Protection. Dose conversion factors based on ICRP Publication 30 are more relevant to deterministic effects than are the dose conversion factors based on ICRP Publication 66, which relate to targets for stochastic effects. Risk distributions that account for NUREG/CR-4214 parameter and model uncertainties were generated using the Monte Carlo method. Risks were evaluated for both lethality (from radiation pneumonitis) and morbidity (due to radiation-induced respiratory dysfunction) and were found to depend strongly on absorbed-dose-rate history (which depends on WG Pu solubility). The results obtained were compared to new data from animal and epidemiological studies. Our findings suggest that NUREG/CR-4214 models for assessing lethality risk from inhaled radionuclides may need some modest revision in light the new data. However, for assessing morbidity risks, major revisions may be needed.

Administration, Inhalation↗

PubMed1994

Enzymically accelerated biomineralization of heavy metals: application to the removal of americium and plutonium from aqueous flows.

A biological process for the removal of heavy metals from the aqueous flows is described. Metals are precipitated on the surface of immobilized cells of a Citrobacter sp. as cell-bound metal phosphates. This uses phosphate liberated by the activity of a cell-bound phosphatase. Some radionuclides (e.g. 241americium) form metal phosphates readily; efficient removal of 241Am on a continuous basis is demonstrated. At low phosphatase activities, the efficiency of uranium removal correlates with enzyme activity. High phosphatase activities are not realised as an increase in metal removal, suggesting that chemical events become rate-limiting. Studies have suggested that maximal metal uptake occurs only after nucleation and the formation of precipitation foci. A model is presented to illustrate how nucleation and crystallization processes could enhance the removal of plutonium and neptunium from dilute solutions.

Acrylic Resins↗

PubMed1992

Expression of epidermal growth factor receptor in plutonium-239-induced lung neoplasms in dogs.

The expression of epidermal growth factor receptor (EGF-R) was examined in canine lung tumors and in proliferative epithelial foci induced by plutonium-239 to determine if EGF-R was associated with specific neoplastic phenotypes or putative preneoplastic lesions. Seventeen (47%) of 36 canine lung tumors expressed EGF-R. Of these 17 tumors, three tumors hybridized with an erb-B RNA probe, which identified activated cell oncogenes. The expression of EGF-R was not correlated with tumor etiology, e.g., spontaneous versus radiation induced, but did correlate with specific histologic phenotypes. Nineteen (15%) of 127 proliferative epithelial foci in the canine lungs also expressed EGF-R. The phenotypic specificity demonstrated for EGF-R in canine lung tumors parallels that previously shown in human lung tumors. This finding, in addition to the identification of EGF-R in nonneoplastic proliferative lung lesions, indicates that radiation-induced lung tumors in the dog may be a useful animal model to investigate the role of EGF-R in lung carcinogenesis.

Adenocarcinoma↗

PubMed1985

Use of DTPA for increasing the rate of elimination of plutonium-238 and americium-241 from rodents after their inhalation as the nitrates.

This study has shown that: both inhaled (2 mumol/kg) and injected (30 mumol/kg) diethylenetriaminepenta-acetic acid (DTPA) can reduce the lung deposit of 238 Pu and 241 Am inhaled as nitrate to about 1% of that in untreated controls; injection of DTPA is more effective than aerosolized DTPA for reducing deposits of 238Pu and 241Am in the liver and skeleton; combined treatment involving early inhalation of DTPA followed by repeated intravenous injections is likely to be the most effective treatment for workers who have accidentally inhaled plutonium and americium nitrates.

Aerosols↗

PubMed1986

Efficacies of LICAM(C) and DTPA for the decorporation of inhaled transportable forms of plutonium and americium from the rat.

The efficacies of N1, N5, N10, N14-tetrakis (2,3-dihydroxy-4-carboxybenzoyl)-tetra-azatetradecane [LICAM(C)] and diethylenetriaminepenta-acetic acid (DTPA) (30 mumol/kg body wt.) have been investigated for plutonium (Pu) decorporation after inhalation as the nitrate or tributyl phosphate (TBP) complexes and the data compared with those obtained after its intravenous injection as the citrate. The efficacy of removal of americium (Am) inhaled as the nitrate has also been examined. The results show that: whereas LICAM(C) and DTPA were similarly effective for removing Pu from the blood, LICAM(C) was considerably inferior to DTPA when transportable forms of Pu were inhaled; LICAM(C) is ineffective for the decorporation of Am; the optimum treatment regimen for both Pu and Am involved the prompt and repeated administration of DTPA.

Aerosols↗

PubMed1986

Multicompartment kinetic models for the metabolism of americium, plutonium and uranium in rats.

To examine the kinetic behaviour of americium, plutonium and uranium in the different organs of male and female rats an extended mammillary model has been developed; the model is composed of 10 compartments connected with 17 linear transfer coefficients. The 10 compartments describe the behaviour of the three nuclides in the blood, skeleton, liver and kidney, whereas the remaining activity is assigned to one residual organ. Each organ is divided into two compartments, a short- and long-term compartment. Morphologically, in the skeleton the short-term compartment has been assumed to be the bone surface and bone marrow and the long-term compartment to be the deep bone, whereas in the liver there is some evidence to suggest that the short-term compartment is physiologically associated with lysosomes and the long-term compartment is identical with telolysosomes. The influence of age, sex and different nuclides on the transfer coefficients and the absorbed radiation dose have been discussed. Additionally, by using the transfer coefficients calculated for intravenous injection, the behaviour of the nuclides in skeleton and liver during continuous intake has been calculated. As a second example of the application of the model the behaviour of the three nuclides in skeleton and liver after intravenous injection has been calculated with the additional assumption that from the fifth day on the animals were treated continuously with a chelating agent.

Americium↗

PubMed1992

Differences in the radiotoxicity of two plutonium isotopes in cells in vitro: can they be ascribed to different handling by the cells?

Exposure of Co631 cells to plutonium leads to increasing cell death depending on the dose and incubation time. The effects, however, are more pronounced with 239Pu, than with 238Pu. Uptake and binding of the two radionuclides during a 5-h incubation are about equal, but 238Pu is lost more rapidly from the cell. There are also differences in the subcellular distribution which lead to a pronounced difference in the distribution of radioactivity. The influence of these differences in the handling of 238Pu and 239Pu by the cell and of the mass difference on the radiotoxicity of the radionuclides is discussed.

Animals↗

PubMed1998

Differential dose responses of pulmonary tumor types in the rat after inhalation of plutonium dioxide aerosols.

Dose responses were compared among primary lung tumors and their histological types induced by a single inhalation exposure of female Wistar strain rats to submicron-size and polydispersed aerosols of plutonium dioxide (239PuO2). While the primary lung tumors were found only in 2.3% of the unexposed control animals, the frequency of all the primary lung tumors in the exposed animals was 44% at the mean lung dose of 0.71 Gy, and increased sharply at the doses of 1.5 Gy or more, reaching the maximum of 97% at 5.4 Gy, and the dose responses around at 1.0 Gy were different between benign and malignant lung tumors. Almost all the pulmonary tumors in the exposed animals were classified into epithelial types such as adenomas, adenocarcinomas, adenosquamous carcinomas, and squamous cell carcinomas. The dose responses were different between these tumor types as shown by the peak incidence of adenomas at 0.71 Gy, adenocarcinomas at 2.9 Gy, adenosquamous and squamous cell carcinomas at 5.4-8.5 Gy, respectively. As the magnitudes of neoplastic lesions in pulmonary carcinomas were expressed by histological scores, metaplasias and adenomatous lesions most frequently appeared at doses of 1.5 Gy, while the appearance and increase of carcinomatous lesions differed in the dose ranges as shown by the peak incidence of adenocarcinomatous lesions at 2.9 Gy, and adenosquamous or squamous lesions at 5.4-6.6 Gy. These results indicate a differential dose response of pulmonary carcinogenesis in which metaplasias and benign adenomas were induced at lower doses (< 1.0 Gy), whereas malignant carcinomas were induced at relatively higher doses (> 1.5 Gy). Together with the increase of carcinomatous lesions at higher doses, the intranuclear p53 protein accumulation was detectable, but only in a few percentages of malignant carcinomas.

Administration, Inhalation↗

PubMed2006

Plutonium and uranium in human bones from areas surrounding the Semipalatinsk nuclear test site.

To evaluate the present levels of 239,240Pu and U in residents living near the Semipalatinsk nuclear test site, more than 70 bone samples were obtained at autopsy. The subjects ranged in age from 30 to 86 years (mean 59.3+/-12.9). Most of the samples consisted of victims who died of various diseases. Plutonium and U were radiochemically separated and determined by alpha-ray spectrometry. The mean concentrations of 239,240Pu and 238U observed were 0.050+/-0.041 mBq/g-ash (vertebrae 71, long-bones 18) and 0.28+/-0.13 mBq/g-ash (22.8+/-10.6 microg U/kg-ash) (vertebrae 58, long bones 16), respectively. The present 239,240Pu levels were within the range found for human bone samples from other countries due solely to global fallout in the early 1980s. The average U concentration was close to the estimate (mean 22.5 microg U/kg-ash) for the UK, and about 10 times higher than those estimated for residents in New York City and Japan. By assuming that the average concentration of 239,240Pu in bone samples is the value at 45 years after instantaneous inhalation in 1955, the initial total intake and the effective dose for 45 years were estimated as 10 Bq and 0.2 mSv, respectively. The annual intake of total U (234,235,238U) and its effective dose for 60 years were estimated as 30 Bq for adult and 0.1 mSv, respectively, for chronic ingestion.

Adult↗

PubMed2003

Cancers among residents downwind of the Hanford, Washington, plutonium production site.

A community-based health survey for the time period between 1944 and 1995 was collected from 801 individuals who had lived downwind of the U.S. plutonium production facility located in Hanford, Washington. The results of the survey revealed high incidences of all cancers, including thyroid cancer. There were greater than expected numbers of central nervous system tumors and cancers that invaded the female reproductive system (e.g., cancers of the uterus, ovary, cervix, and breast). The authors argue that the greater-than-expected numbers found cannot be accounted for by selection bias alone. Comparisons of crude incidence rates, as well as of occurrence ratios between pairs of cancer types among Downwinders and reasonably similar populations, suggested that the excess neoplasms may be associated with radioactive contamination of food, water, soil, and/or air. In addition, a synergistic effect may exist with agricultural toxins. Previously neglected biophysical and physiological properties of internally lodged, long-lived 129I may be a significant etiological factor in the development of thyroid diseases, including cancer, and other malignancies in exposed populations.

Adolescent↗

PubMed1999

Carcinogenesis in mice after injection of soluble plutonium citrate.

The carcinogenicity of injected soluble plutonium ((239)Pu) citrate was investigated in life-span animal experiments using mice of three strains, C3H, C57BL/6 and their hybrid BC3F(1), that have different spectra of spontaneous and radiation-induced tumors. Bone tumors, mostly osteosarcomas, were induced at skeletal doses of 0.6 to 0.7 Gy, and the incidence increased markedly at doses of 2 to 4 Gy in all strains, while lymphoid tumors appeared to decrease at higher doses; the incidences of bone tumors remained higher at higher doses, suggesting a differential and competitive dose response between bone and lymphoid tumors. Among the histological phenotypes of lymphoid tumors, nonthymic, pre-B-cell type leukemic lymphomas were induced preferentially and early, while thymic lymphomas and myeloid leukemias were rarely or never observed in any of the strains after injection of (239)Pu. These findings indicate a specificity of (239)Pu-induced carcinogenesis in mice that is different from that of external low-LET irradiations.

Animals↗