Modifying effects of health status, physiological, and dosimetric factors on extrapulmonary organ distribution and excretion of inhaled plutonium in workers at the Mayak Production Association.

This paper summarizes the systemic organ distribution of plutonium in workers exposed by chronic inhalation at the Mayak Production Association (MPA). Using results of radiochemical measurements in soft tissue and bone samples collected at autopsy of 853 autopsy cases, this paper provides data on the effects of various chronic diseases and malignant tumors as well as exposure time, age, sex, and body burden on systemic retention of plutonium in 22 extrapulmonary organs and on the urinary excretion rate of the nuclide. Some aspects of this work have been reported already. The results of present autopsy studies showed that liver pathology accompanied by strong fatty dystrophy of hepatocytes results in a significant relative decrease in the fraction of systemic plutonium in the liver and contravariant increase in the skeletal fraction. The average fractions of systemic plutonium in the liver and the skeleton of those MPA workers were 15% and 75%, respectively, in comparison with 47% and 45% in healthy individuals. Some of the plutonium also redistributed from the liver via blood to other systemic soft tissues. Plutonium not redistributed was excreted with urine. The results of multivariate regression analysis indicated some time-related and sex-related changes not connected with pathology for the liver and the skeleton retention fractions and excretion rate of plutonium. The current ICRP biokinetic models do not account for the influence of different pathological processes in the body on plutonium distribution in systemic organs and urinary excretion. This could have significant consequences for dosimetry calculations and risk estimations.

Plutonium microdistribution in the lungs of Mayak workers.

The degree of nonuniform distribution of plutonium in the human lung has not been determined; thus current dosimetric models do not account for nonuniform irradiation. A better scientific basis is needed for assessing the risk of developing radiation-induced disease from inhaled alpha-particle-emitting radionuclides. We measured the distribution of plutonium activity in the lung by autoradiography and related the activity to specific compartments of the lung. The study materials were lung specimens from deceased workers employed by the Mayak Production Association. The approach to analyzing these lung samples used contemporary stereological sampling and analysis techniques together with quantitative alpha-particle autoradiography. For the first time, plutonium distribution has been quantified in the human lung. The distribution of long-term retained plutonium is nonuniform, and a significant portion of plutonium was retained in pulmonary scars. In addition, a large fraction of plutonium was present in the parenchyma, where it was retained much longer than was estimated previously. The sequestration of plutonium particles in scars would greatly reduce the radiation exposure of the critical target cells and tissues for lung cancer. Thus the prolonged retention of plutonium in lung scars may not increase the dose or risk for lung cancer.

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.

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.

The effect of state of health on organ distribution and excretion of systemic plutonium in the Mayak workers.

The extrapulmonary distribution of plutonium in 20 organs (excluding the respiratory tract) was studied in workers who chronically inhaled plutonium at the radiochemical plants of the Mayak Production Association (Ozyorsk, Russia). The data were obtained by radiochemical analysis of soft tissue and bones samples collected at autopsy of 591 workers. The systemic plutonium distribution was determined in healthy individuals as well as in those with health impairment, specifically for those with liver diseases. Twenty-five years after the beginning of inhalation, systemic fractions in the liver and skeleton of individuals who were healthy at the time of death approximate the ratio 45%:45% proposed in the International Commission on Radiological Protection (ICRP) Publication 30. Pathological processes in the liver, accompanied by fatty dystrophy of hepatocytes, increased plutonium clearance from the liver. There was a considerable shift of the plutonium from the liver to the skeleton in individuals who died from liver disease. The average fractions of systemic plutonium in the liver and skeleton of those individuals were 14% and 78% respectively, which did not correspond to ICRP models, indicating a significant effect of disease conditions. Plutonium that was not redistributed was excreted. The urinary excretion rate of plutonium also correlated with state of health. The observed excretion as a fraction of systemic content was 1.64 x 10(-5) d(-1) for individuals in good health and 2.34 x 10(-5) d(-1) for individuals with various chronic diseases. The current models do not account for the influence of different pathological processes in the body on plutonium distribution and retention in systemic organs. This could have significant consequences for dosimetry calculations and risk estimations.

Assessing the uniformity of plutonium alpha radiation dose in human lung: the Mayak experience.

Radiation-induced lung cancer risk is currently estimated based on epidemiological data from populations exposed either to relatively uniform, low-LET radiation, or from uranium miners who inhaled radon and its progeny. Inhaled alpha-emitting radionuclides (e.g. Pu and Am) produce distinctive dose patterns that may not be adequately modelled at present. Thus the distribution of Pu is being measured in formalin-fixed autopsy lung tissue from former workers at the Mayak Production Association, and which is maintained in a tissue archive at SUBI. Lungs are sampled using contemporary stereological techniques and Pu particle activities and locations are determined using quantitative autoradiography and morphological identification of lung structures. To date, > 80% of Pu particles have been observed in parenchymal lung tissues with higher concentrations being found in scar tissue. Concentrations of Pu particles in conducting airways are uniformly low, thus indicating that long-term-retained Pu particles are non-uniformly distributed in human lung, mostly in the parenchyma.

Extrapulmonary organ distribution of plutonium in healthy workers exposed by chronic inhalation at the Mayak production association.

The systemic distribution of plutonium was determined for "healthy" workers who chronically inhaled plutonium at the radiochemical plants of the Mayak Production Association. The data were obtained by radiochemical analysis of soft tissues and bones samples collected upon autopsy of 120 workers who died from acute coronary diseases and accidents. The soft tissue samples were wet-ashed using nitric acid and hydrogen peroxide. Bone samples were ashed in a muffle furnace at 500 degrees C. Plutonium was extracted on anionite and coprecipitated with bismuth phosphate. The precipitation was blended with ZnS powder, and the alpha-activity was measured by ZnS solid scintillation counting in a low-background alpha radiometer. Twenty-five years after the beginning of inhalation exposures, the average percentage of plutonium in the skeleton and liver was 50% and 42% of systemic burden, respectively. A multivariate regression was used to quantify the effects of exposure time, "transportability" of the various compounds, plutonium body content, and age on systemic plutonium distribution. The early retention of plutonium in the liver is assumed to be greater than that in the skeleton. The initial distribution of plutonium between the liver and the skeleton, immediately after entering the circulatory system, was 50:38%, respectively. With time, the fraction of plutonium found in the liver decreased, while the fraction in the skeleton increased at a rate of 0.5% y(-1) of systemic deposition. Exposure time had a greater effect on the relative retention of plutonium in the main organs when compared to age. The statistical estimates that characterized the relative plutonium distribution were less stable for the liver than for the skeleton, likely due to the slower turnover of skeletal tissues and the retention of plutonium in bone.

Mortality from external causes among the personnel of Mayak's radiochemical plant.

The mortality rate from accidents, poisoning, and traumas was analyzed in 12,806 persons who started work at the radiochemical plant from 1948 to 1972. 559 persons died from these causes, which corresponds to 21.1% of the total number of deaths. The global and age-specific mortality rates appeared to be lower than those for the general population. The structure of mortality from external causes differed in some way from that of the general population: the percentage of accidents connected with transport and of murders was lower, whereas it was higher for suicides. The mortality rate from specific causes including suicides, however, was lower than in the general population. The level of radiation exposure did not influence the mortality rates from the studied causes.

[The significance of immunity disorders in the development of tumorous effects during the long-term action of tritium in mice]. / Znachenie narushenii immuniteta v razvitii opukholevykh éffektov pri dlitel'nom deistvii tritiia u myshei.

In experiments with CBA mice it was shown that the long-term influence of tritium oxide administered with drinking water daily during 180 days (370 kBq.g-1 of body mass, cumulative dose 8.7 Gy, dose rate 4.5 cGy.day-1) causes the development of immunity deficiency 90 days after the onset of the administration that persists for up to 270 days. There is a 34% decrease in the average life of irradiated animals and an increase in the number of malignant neoplasms (postmortem examination was performed after natural death or killing on days 250, 350 and 450). There is a direct relationship between the occurrence of malignant neoplasms and the immunity deficiency.

[Modifying effect of the chemical components of dust on the induction of lung tumors by physical and chemical carcinogens (experimental study]. / O modifitsiruiushchem vliianii khimicheskikh komponentov pyli na induktsiiu opukholei legkogo fizicheskim i khimicheskim kantserogenom (éksperimenta'lnoe issledovanie).

Chronic inhalation intake of benzo(a)pyrene (BP) and polonium-210 (210Po) together with aluminum oxide caused increase of tumor formation in the lungs of mice. Synergy of BP and 210Po carcinogenic effect was pointed out, it was characterized by summation and possible effect involution by tumor development rates and the duration of the latent period. BP and 210Po carcinogenic effectiveness depended on the type of dust carrier and probably on the presence of silicon dioxide and also carcinogenic metals. It was pointed out that further studies were necessary to determine an etiologic role of mineral dust chemical components in carcinogenic activity of the above substances and also carcinogenic effectiveness of dusts as carriers of chemical carcinogens and alpha-active radionuclides.

[Quantitative assessment of inhalation exposure to various transuranium radionuclide compounds by integral nonstochastic criteria]. / Kolichestvennaia otsenka ingaliatsionnogo vozdeistviia raznymi soedineniiami transuranovykh radionuklidov po integral'nym nestokhasticheskim kriteriiam.

The comparison of the danger from inhalation of radionuclide transuranium compounds differently transferred within the body was made by the results of an examination of 169 mongrel dogs and 2000 Wistar rats. Effective and ineffective levels of the radionuclide inhaled were determined by integral nonstochastic criteria, that is, 50 per cent death rate, shortening and increase of the average life and reduction of body mass.

[Frequency of structural chromosome aberrations in the hepatocytes of rats exposed to polymeric 239Pu]. / Chastota strukturnykh povrezhdenii khromosom gepatitsitov krys pri deistvii polimernogo 239Pu.

Intravenous injection of polymeric 239Pu(IV) nitrate (166.5, 55.5 and 18.5 kBq/kg body mass) to Wistar rats was shown to produce biphase changes in the frequency of hepatocyte chromosome aberrations. The increase in the structural damages to chromosomes at later times of observation was a pronounced function of radiation dose. The absence of such a dependence at early times was evidently due to the elimination of damaged liver parenchyma cells.

[Biological action of 239Pu during intake by inhalation and complexon therapy with Zn or Ca DTPA under experimental conditions]. / Biologicheskoe deistvie 239Pu pri ego ingaliatsionom postuplenii i kompleksonoterapii Zn-ili CaDTPA v éksperimente.

The authors described the effect of substantial amounts of plutonium nitrate administered to rats by inhalation in the presence of Zn- or CaDTPA-complexon therapy for 2 months. A 2-fold decrease of absorbed doses in the lung, a 3-fold decrease in the skeleton and a 4-fold decrease in the liver were shown. The mean life of the treated animals was considerably raised. A significant reduction of the frequency of development of severe pneumosclerosis and an increase in the frequency of lung tumor development were noted. In view of the above, complexon therapy should be necessarily recommended during inhalation of radionuclides in substantial amounts.

[Morphologic manifestations of early and late consequences of inhalation damage from 241Am to dogs]. / Morfologicheskie proiavleniia blizhaishikh i otdalennykh posledstvii ingaliatsionnogo porazheniia 241 Am u sobak.

In experiments on 56 mongrel dogs of both sexes it was shown that the severity of 241Am-induced injury to dogs was manifested by purulent and fibrous pneumonia combined with pneumosclerosis (acute damage), liver cirrhosis and pneumosclerosis (subacute damage), and malignant tumors in the skeleton, lungs, liver, and thyroid gland, and pneumosclerosis (chronic injury).

[Behavior and biological action of large amounts of 239Pu following intramuscular administration in rats undergoing long-term therapy with Zn- and Ca-DTPA]. / Povedenie i biologicheskoe deistvie bol'shikh kolichestv 239Pu posle vnutrimyshechnogo vvedeniia u krys v usloviiakh dlitel'noi terapii Zn- i Ca-DTPA.

The authors submit the results of the studies of the influence of large amounts of 239Pu, administered to rats via stab wounds, and subsequent treatment there of with clinical doses of Zn- and Ca-DTPA for two months. It is shown that the absorbed doses considerably decrease and the average life of treated rats increases; the incidence of malignant tumors does not change after the treatment with Ca-DTPA.

[Changes in the mucous membrane of the trachea and bronchi in dogs based on bronchoscopic data for the combined action of 239Pu and gamma-radiation as compared with the individual actions]. / Izmeneniia slizistoi obolochki trakhei i bronkhov u sobak po dannym bronkhoskopii pri sovmestnom vozdeistvii 239Pu i gamma-izlucheniia po sravneniiu s razlichnym vozdeistviem.

It was established that under conditions of combined exposure of dogs to external gamma- and internal alpha-radiation, a preirradiation with 51.6 mC/kg gamma-rays prevents the development of the signs of endobronchitis which are typical for endobronchitis induced by inhalation of submicron 239Pu dioxide and manifested by hyperemia of trachea and bronchus mucosa, edema, and the presence of mucopurulent exudate.

[Effect of Na3Zn- and Na3Ca-DTPA on the behavior and biological action of 239Pu on rats]. / Vliianie Na3Zn- i Na3Ca DTPA na povedenie i biologicheskoe deistvie 239Pu u krys.

The effect of a complexon therapy scheme including early (in 1 h) administration of Na3Ca DTPA and subsequent (in 1 day) administration of Na3Zn DTPA or Na3Ca DTPA at a dose of 25 mu Cimol/kg/day by three 2-week courses (5 times a week) with 2-week interruptions was studied in experiments on 541 male rats after intraperitoneal administration of 239Pu citrate complex (95 kBq/kg). The treatment resulted in a 3-fold lessening of the content of 239Pu and absorbed doses in the skeleton, a significant prolongation of the mean survival time (MST) from 452 to 593 days (Na3Zn DTPA) and 643 days (Na3Ca DTPA), and in a decrease of the osteosarcoma incidence from 76.4 to 32.6-41.2%. The ratio of osteosarcomas per 1 Gy retained in rats (0.076-0.083%) did not differ from that in untreated animals (0.067%) and varied within the ranges of established values (0.072-0.119%). The involvement of Na3Zn DTPA in the therapeutic scheme prolongs the MST of rats to a somewhat lesser degree than Na3Ca DTPA. No negative effects of Zn DTPA therapy were revealed.