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Verification and modification of the ICRP-67 model for plutonium dose calculation.

On the basis of the available data and empirical expressions for the plutonium excretion after injection, an age-related compartmental model has been developed. It provides a better agreement with measured urinary excretion data than the current ICRP 67 model. Moreover, the revised model avoids unphysiological assumptions such as the transfer of activity from soft tissue to urinary bladder, that were part of the ICRP model. The new predictions of the activity in feces and in blood after an injection are closer to the available data than the ICRP 67 estimations and there is also a good agreement with the partitioning of plutonium between skeleton and liver obtained from different autopsy studies. Furthermore, the urinary excretion estimated by the improved model has been checked using some data from occupationally exposed individuals. As the plutonium uptake in these workers occurred by inhalation, the improved model and the ICRP 67 model were compared by connecting them to the ICRP 66 respiratory tract model. The improved model consistently yields a better agreement with the measured excretion and higher estimations of intake than the ICRP 67 model.

Body Burden↗

The concepts of critical organ and radiation dose as applied to plutonium.

The concepts of critical organ or tissue and the calculation of radiation dose have been and may well continue to be central to the development of standards for most radionuclides. In the case of plutonium the occupational standard was based on a modification of the direct calculations of maximum permissible annual dose (MPAD) or dose rate but critical organs must still be chosen for different routes of entry and different compounds and for all of the derived standards. Changes in such standards by likely variations in metabolic parameters and models are shown to be significant but not large. Application of the critical organ concept to population exposure standards poses some new problems because the basic MPAD does not distinguish among organs. A simple scaling factor from occupational exposure standards thus is not satisfactory. Use of the concept of dose commitment has many advantages but it is still necessary to select a critical organ and calculate dose. By-passing some of the problems in present practices by using risk-estimates seems unlikely for plutonium at the present time because of the paucity of human effects data and the fact that the animal experiments used quite different dosage regimens from the likely exposure situations to plutonium. A brief comparison is made of radiation and chemical hazard evaluation procedures.

Body Burden↗

Characterization of plutonium aerosol collected during an accident.

This study determined the plutonium particle size distribution and dissolution rate of PuO2 aerosol collected during the 16 March 2000 release of an undetermined amount of PuO2 in a room within a plutonium facility at Los Alamos National Laboratory. The facility has been in operation since 1978 to support the development, fabrication, and testing of Pu heat sources for the U.S. Department of Energy. Several workers were in the room at the time of the release and in vivo study of five of the workers began the day after the exposure event. Four of the subjects subsequently received chelation therapy. Over 30 fixed air filter samplers (FASs) and four continuous air monitors (CAMs) were operating in the room during the radiological release. One 47-mm-diameter glass fiber FAS filter and one 25-cm-diameter mixed cellulose ester CAM filter containing Pu aerosol from the incident were examined in the study described here. Total alpha radioactivity on the filters was determined by gross alpha counting. Isotopic identification of the Pu was made by alpha spectrometry. Film autoradiography was used to characterize the spatial distribution of alpha-emitting particles on the filters. Track-etch autoradiography was used to estimate the distribution of alpha radioactivity in individual plutonium particles on the filters for particle size measurement. The glass fiber filter was then cut into six sections. Particles from two sections were resuspended in alcohol, dispersed as an aerosol using a Lovelace nebulizer, and characterized by aerodynamic diameter using a Lovelace Multi-jet cascade impactor. The measured activity median aerodynamic diameter from the cascade impactor was 4.8 mum with a geometric standard deviation of 1.5. That agreed with the size distribution obtained from the alpha track detection technique. The remaining four filter sections were used in an in vitro dissolution study with synthetic serum ultrafiltrate. The retention of undissolved Pu was consistent with a biphasic exponential function. The majority of the Pu dissolved with a half-time of 900 d. The information on particle size distribution and solubility from this study was useful in assigning a radiation dose to the exposed workers, supporting the decision to administer chelation therapy, and providing a model for characterizing accident-associated aerosols in the future.

Aerosols↗

Uncertainties analysis of doses resulting from chronic inhalation of plutonium at the Mayak production association.

A method is presented to determine the uncertainties in the reported dose due to incorporated plutonium for the Mayak Worker Cohort. The methodology includes errors generated by both detection methods and modeling methods. To accomplish the task, the method includes classical statistics, Monte Carlo, perturbation, and reliability groupings. Uncertainties are reported in percent of reported dose as a function of total body burden. The cohort was initially sorted into six reliability groups, with "A" being the data set that the investigators are most confident is correct and "G" being the data set with the most ambiguous data. Categories were adjusted based on preliminary calculation of uncertainties using the sorting criteria. Specifically, the impact of transportability (the parameter used to describe the transport of plutonium from the lung to systemic organs) was underestimated, and the structure of the sort was reorganized to reflect the impact of transportability. The finalized categories are designated with Roman numerals I through V, with "I" being the most reliable. Excluding Category V (neither bioassay nor autopsy), the highest uncertainty in lung doses is for individuals from Category IV-which ranged from 90-375% for total body burdens greater than 10 Bq, along with work histories that indicated exposure to more than one transportability class. The smallest estimated uncertainties for lung doses were determined by autopsy. Category I has a 32-38% uncertainty in the lung dose for total body burdens greater than 1 Bq. First, these results provide a further definition and characterization of the cohort and, second, they provide uncertainty estimates for these plutonium exposure categories.

Administration, Inhalation↗

Plutonium in drinking water: effects of chlorination on its maximum permissible concentration.

Soluble plutonium is oxidized to the Pi(VI) oxidation state by chlorine during water treatment. Under certain conditions Pi(VI) is readily absorbed from the gastrointestinal tract. It appears that due consideration has not been given to the effect that the presence of plutonium in this oxidation state may have on the maximum permissible concentration of plutonium in drinking water.

Animals↗

Plutonium hazard in respirable dust on the surface of soil.

Plutonium-239 in the fine particulate soil fraction of surface dust is subject to suspension by air currents and is a potential health hazard to humans who may inhale it. This respirable particulate fraction is defined as particles less than or equal to 5 micrometers. The respirable fraction of surface dust was separated by ultrasonic dispersion and a standard water-sedimentation procedure. Plutonium concentration in this fraction of off-site soils located downwind from the Rocky Flats Nuclear Weapons Plant (Jefferson County, Colorado) were as much as 380 times the background concentration. It is prposed that this method of evaluation defines more precisely the potential health hazard from the respirable fraction of plutonium-contaminated soils.

Colorado↗

Immunohistochemical study on cellular origins of rat lung tumors induced by inhalation exposures to plutonium dioxide aerosols as compared to those by X-ray irradiation.

Immunohistochemical examinations were performed on rat pulmonary tumors induced by inhalation exposures to 239PuO2 aerosols, or by X-ray-irradiation to identify and compare cellular origins or, in turn, target cells at risk for radiation carcinogenesis. Both plutonium-induced and X-ray-induced pulmonary tumors appeared to occur from the lower respiratory tract epithelium through bronchioles into alveoli, and were histopathologically diagnosed as adenoma, adenocarcinoma, adenosquamous carcinoma, and squamous cell carcinoma. Immunohistochemical staining of neoplastic lesions using rabbit polyclonal antibodies to rat surfactant apoprotein A specific for alveolar type II pneumocytes, and Clara cell antigen specific for nonciliated bronchiolar Clara cells, showed that most of the adenomatous and adenocarcinomatous lesions from plutonium-exposed or X-irradiated rats were positive for either or both antigens, while, in contrast, adenosquamous and squamous lesions were mostly negative for both antigens. Even though there were some differences in the proportions and distributions of immunoreactive cells between plutonium- and X-ray-induced tumors and among neoplastic lesions, the results indicate that radiation-induced pulmonary adenomas and adenocarcinomas mostly originate from either alveolar type II pneumocytes or bronchiolar Clara cells, while adenosquamous and squamous carcinomas may be derived from the other epithelial cell components, or might have lost specific antigenicity during their transforming differentiation.

Administration, Inhalation↗

Two-mutation models for bone cancer due to radium, strontium and plutonium.

Data from beagle experiments and radium dial painters were used to derive two-mutation carcinogenesis models for bone cancer induced by the bone-seeking radionuclides radium, strontium and plutonium. For all data, the model fits indicate that at low doses both mutation rates depend linearly and equally strongly on dose rate. For the high-LET alpha-particle emitters, a cell killing term reduces the second mutation rate at high dose rates. In all cases, the combined effect of both mutation rates is a linear-quadratic dose-effect relationship for cancer at low doses. This behavior may lead to experimental data that could be mistaken as showing a threshold below which no cancers are induced. Derived parameters such as toxicity ratios and tumor growth times compare well with values reported in the literature. Furthermore, results for plutonium indicate that rapid burial of the nuclide in the growing bones of juvenile beagles leads to a significant reduction of its toxicity, as was suggested previously. The results for radium in beagles compare well with those for humans and suggest that the models derived for strontium and plutonium in beagles may be translated to humans. The significant model parameters for the accurate animal data could then also be used to fit human epidemiological data.

Animals↗

Mayak worker study: an improved biokinetic model for reconstructing doses from internally deposited plutonium.

The plutonium production facility known as the Mayak Production Association was put into operation in June 1948. A high incidence of cancer in the Mayak workers has been related to the level of exposure to plutonium, but uncertainties in tissue doses have hampered development of dose-risk relationships. As part of an effort to improve dose estimates for these workers, the systemic biokinetic model for plutonium currently recommended by the International Commission on Radiological Protection (ICRP) has been modified to reflect recently developed data and facilitate interpretation of case-specific information. This paper describes the proposed model and discusses its implications for dose reconstruction for the Mayak workers.

Bone and Bones↗

Effect of occupational radiation exposures on chromosome aberration rates in former plutonium workers.

A fluorescence in situ hybridization (FISH) method was used to measure chromosome aberration rates in lymphocytes of 30 retired plutonium workers with combined internal and external radiation doses greater than 0.5 Sv along with 17 additional workers with predominantly external doses below 0.1 Sv. The former group was defined as high-dose and the latter as low-dose with respect to occupational radiation exposure. The two groups were compared to each other and also to 21 control subjects having no history of occupational radiation exposure. Radiation exposures to the high-dose group were primarily the result of internal depositions of plutonium and its radioactive decay products resulting from various work-related activities and accidents. The median external dose for the high-dose group was 280 mSv (range 10-730) compared to a median of 22 mSv (range 10-76) for the low-dose group. The median internal dose to the bone marrow for the high-dose group was 168 mSv (range 29-20,904) while that of the low-dose group was considered negligible. Over 200,000 metaphase cells were analyzed for chromosome aberrations by painting pairs 1, 4 and 12 in combination with a pancentromeric probe. Additionally, 136,000 binucleated lymphocytes were analyzed for micronuclei in parallel cultures to assess mitotic abnormalities arising from damaged chromosomes. The results showed that the frequency of structural aberrations affecting any of the painted chromosomes in the high-dose group correlated with the bone marrow dose but not with the external dose. In contrast, the frequency of micronuclei did not vary significantly between the study groups. The total translocation frequency per genome equivalent x 10(-3) +/- SE was 4.0 +/- 0.6, 9.0 +/- 1.1 and 17.0 +/- 2.1 for the control, low-dose and high-dose groups, respectively. Statistical analysis of the data showed that the frequency of total translocations and S-cells correlated with the bone marrow dose, with P values of 0.005 and 0.004, respectively. In contrast, these two end points did not correlate with the external dose, with P values of 0.45 and 0.39, respectively. In conclusion, elevated rates of stable chromosome aberrations were found in lymphocytes of former workers decades after plutonium intakes, providing evidence that chronic irradiation of hematopoietic precursor cells in the bone marrow induces cytogenetically altered cells that persist in peripheral blood.

Aged↗

Enhanced plutonium absorption in iron-deficient mice.

The total body burden of plutonium 24 or 96 hr following a single gastric intubation was approximately fourfold greater in iron-deficient than in iron-replete mice. There was also a more rapid translocation of plutonium from soft tissues to bone in the iron-deficient mice by 96 hr after gavage. In the iron-replete group only liver concentrations of plutonium increased during the corresponding time period.

Animals↗

Plutonium and uranium in Japanese human tissues.

Plutonium and uranium in human tissues obtained from residents of the Tokyo area were determined by a-spectrometry and the fission track method, respectively. The distribution pattern of each element was estimated on the basis of mean concentration obtained. Plutonium is concentrated in some special organs, while uranium is distributed rather generally throughout the whole body. This difference of distribution tendency is considered to be due to the characteristics of stable chemical states of the elements in body fluid; Pu4+ for plutonium and UO2(2+) for uranium.

Asian People↗

Accelerator mass spectrometry for the detection of ultra-low levels of plutonium in urine, including that excreted after the ingestion of Irish sea sediments.

Currently, most methods for the quantitative assessment of (239)Pu have minimum detection levels (25 microBq for alpha-particle spectrometry) that are much higher than the levels of this isotope in many human bioassay and environmental samples. Accordingly, a priority has existed to develop methods that are more sensitive. Fission-track and ICP-MS methods have been used, but these can suffer either from an uncertain level of removal and/or recovery of uranium or from isobaric mass interferences. Accelerator mass spectrometry (AMS) has no such disadvantages, and its demonstrated detection limits for plutonium isotopes approach levels of attograms, equivalent to about 500 nBq for (239)Pu. This paper describes the application of AMS to the measurement of (239)Pu in urine produced by youths living in London (3.5 microBq day(-1)) and by adults (approximately 2-260 microBq day(-1)), some of whom were exposed occupationally. In addition, an experiment was undertaken to measure the fasted absorbed fraction of ingested plutonium after the ingestion of 15 g of Irish Sea sediment by a volunteer. The measured absorbed fraction was 4.5 x 10(-5). It is concluded that accelerator mass spectrometry is a suitable method for the ultra-trace detection of plutonium.

Adult↗

Mutations in Tp53 gene sequences from lung tumors in rats that inhaled plutonium dioxide.

We investigated mutations of the Tp53 tumor suppressor gene (formerly known as p53) in the lung tumors induced in rats after inhalation of plutonium dioxide ((239)PuO(2)) aerosols. Exons 5, 6, 7 and 8 of the Tp53 gene were examined for mutations by single-strand conformation polymorphism (SSCP) analysis of polymerase chain reaction (PCR)-amplified fragments and direct sequencing analysis. Almost all the mutations were guanine (G) to adenine (A) transitions and were distributed in exons 5 and 6. The Tp53 mutations occurred in lung tumors of various phenotypes and levels of immunohistochemical staining of Tp53 nuclear protein. These results indicate that the Tp53 mutations are not associated with tumor phenotype and nuclear accumulation of Tp53 protein, and that the G to A transition could be a common point mutation in the lung tumors seen after the inhalation of plutonium dioxide. The point mutations in the Tp53 gene seem to play a role in the development of lung tumors in rats after inhalation exposures to plutonium dioxide.

Animals↗

[Distribution of plutonium-239 in the body of dogs 7 days after the intravenous administration of a citrate complex of the metal].

In experiments with 12 dogs of both sexes it was found that 7 days after intravenous injection of the citrate (2%) complex the concentration of plutonium in the organs and tissues, which are considered noncritical, is lower than in the skeleton by one or two orders of magnitude. No substantial differences were found in plutonium levels in the endocrine glands, (0.7-4.2) X 10(-3%), different parts of the gastrointestinal tract, (0.9-1.7) X 10(-3%), different regional lymph nodes, (2.4-3.8) X 10(-3%), and in different parts of the central nervous system, (0.06-0.19) X 10(-3%) of the total amount of plutonium administered.

Animals↗

Plutonium in the tissues of foetal, neonatal and suckling mice after Pu-administration to their dams.

Twelve-week-old female (C3H x 101)F1 mice were injected intravenously with an ultrafiltered solution of 239Pu in per cent trisodium citrate, and mated to uninjected PCT males. The plutonium content was examined radiochemically and autoradiographically in placentae and foetuses on the 12th and 18th days of gestation, and in neonates during the 24 hours after birth and also at 18 days postnatally. Plutonium was distributed in most tissues of the late foetus and the suckling as it is in adult mice. However, on both the 12th and 18th days of gestation the concentration in the yolk-sac splanchnopleure was much higher than in any other foetal tissue. The amount of 239Pu in 18-day-old sucklings was between two and seven times as great as in 1-day-old neonates because of ingestion of milk from the lactating dams. In the first litter following administration of the radionuclide to the dam, about 0.02 per cent of the plutonium injected was transferred to an individual offspring by the time of birth, and a further 0.08 per cent by the time of weaning.

Animals↗

A primary pulmonary sarcoma in a rhesus monkey after inhalation of plutonium dioxide.

A pulmonary fibrosarcoma of bronchial origin was discovered in a Rhesus monkey that died of pulmonary fibrosis 9 years after inhalation of plutonium-239 dioxide and with a radiation dose to lung of 1400 rad (14 Gy). It grew around the major bronchus of the right cardiac lung lobe and extended into the bronchial lumen and into surrounding pulmonary parenchyma. It also readily invaded muscular pulmonary arteries, resulting in infarction and scarring in the right cardiac lobe. Despite this aggressive growth, the tumor did not metastasize. The primary cause of death was severe pulmonary fibrosis involving the alveolar septa and and perivascular and peribronchial interstitium. Bullous or pericitrical emphysema was prominent. The initial lung burden of plutonium in this monkey was 270 nCi (10 kBq) which is equivalent to approximately 500 times the maximum permissible lung burden for man on a radioactivity per unit body weight basis. The time-dose relationship for survival is consistent with that of dogs and baboons that inhaled plutonium dioxide and died with lung tumors.

Administration, Inhalation↗