239PuO2 Particles Research Articles

Диоксид плутония-239 в легких. Сообщение 1: Метаболизм 239PuO2 при внутритрахеальном введении

Purpose: Investigation of macro and micro distribution of 239PuO2 in the lungs of rats and metabolic parameters taking into account the variability of initial bronchoalveolar deposits. Materials and methods: Plutonium dioxide was single introduced intracheal into nonlinear male rats in the amount of 100 kBq / kg of body weight. The experimental animals were observed during their life. Lifetime measurement of radioactivity of the body and excreta and posthumous radiometry of organs were made. Auto and histoautoradiografic study of lungs and lymph nodes were performed. Results: 239PuO2 particles are removed from the respiratory organs most intensively during the first 7 days. Slowing of metabolic processes is observed in the period from 7 to 200 days. The data on post-mortem 239PuO2 content in the lungs and regional lymph nodes of rats indicate a decrease of the content of plutonium dioxide in the lungs and no reduction in the lymph nodes with time. Three periods of effective half-life of plutonium dioxide from the lungs were experimentally identified and calculated. These values indicate that the parameters of the respiratory clearance depend on the value of the initial radionuclide bronchoalveolar deposits. Conclusions: Сonsiderable variability of plutonium dioxide content in the lungs and regional lymph nodes of rats following intratracheal administration has been shown. Neven distribution of 239PuO2 with the expressed α-particle aggregation assumes a significant difference in the local fabric of absorbed radiation doses in the lungs, but does not exclude the possibility of their calculation on the respiratory system as a whole. Options clearance from the respiratory 239PuO2 correspond to the values of the initial bronchoalveolar deposits. The cleansing light of plutonium dioxide, in contrast to its soluble compounds, the role of radionuclide transport blood to other organs and tissues is not of great impotance . The results presented plutonium dioxide metabolism studies administered intratracheally, testifies to the fact that the implementation of the biological effects of the compounds can be expected mainly in the lungs. Evidence about the profile respiratory disease will be presented in a subsequent communication.

Rapid Estimation of Inhaled Particle Size for Internal Dose During Nuclear Emergency Medicine

Information on particle size is one of the important factors for internal dose estimation at accidents with airborne radioactive materials. An autoradiography method has been investigated as a technique for the sizing of alpha-emitting particles. Concerning nuclear emergency medicine, the waiting time for dose estimation is limited. For determining the shortest estimation time, the exposure time of autoradiography was examined using 239PuO2 particles captured on HEPA filters. In this study, the effective counting efficiency of tracks produced by alpha particles was evaluated to be 0.31 by a numerical simulation. The minimum exposure time for 239PuO2 with aerodynamic diameter of 5 μm was found to be only 10 min. When any star-like alpha particle track was not detected after 6 h of exposure, even if the sample had significant radioactivity, the aerodynamic diameter was assumed to be less than 1 μm. When the radioactivity of 239PuO2 particles detected by autoradiography within 1 h was dominant of total activity, the aerodynamic diameter would be estimated to be over 5 μm. These results indicate that the precise dose estimation is useful for the decision of medical treatment.

Retention, excretion and translocation of 239Pu in rats following inhalation of 239PuO2 calcined at 1150 and 400 degrees C.

Wistar rats inhaled 239PuO2 particles prepared by the calcination of 239Pu hydroxide at 1150 and 400 degrees C. Lung retention, fecal and urinary excretion, and translocation of 239Pu were compared between the two calcination temperatures. The clearance of 239Pu from the lungs was significantly faster in the rats exposed to 239PuO2 calcined at 400 degrees C (low-temperature group) than those exposed to 239PuO2 calcined at 1150 degrees C (high-temperature group). Both the fecal excretion of 239Pu and the ratio of fecal excretion to urinary excretion was greater in the low-temperature group than in high-temperature group. The amounts of 239Pu translocated from the lungs to the other organs were very small. Even in the liver, which accumulated the largest amount of 239Pu except for the lungs, only 0.13-0.20% of the initial lung burden was retained 1 year after inhalation. The amount of 239Pu deposited in the liver was greater in the high-temperature group than in the low-temperature group both at 1 month and 1 year after the inhalation. These findings clearly suggest that the lung retention of 239Pu in rats is significantly affected by the calcination temperature of 239PuO2.

Carcinoma of the Upper Respiratory Tract in Rats Following Nose-Only Inhalation of 239PuO2

A total of 3157 female Wistar, 198 male Wistar, 200 female F344 and 192 female Long-Evans sham-exposed and exposed young adult rats were examined for distribution of plutonium and tumors in the upper respiratory tract following inhalation of high-fired 239puO2. A small number of inhaled 239puO2 particles were retained for long periods in subepithelial regions of the larynx and nasal cavity. These particles contributed a small fraction of the total dose to airway epithelium. No tumors were found originating from the trachea or larynx. One nasal cavity tumor was found in a control female Wistar rat (0.095%) while five tumors were found in exposed female Wistar rats (0.24%). Two nasal cavity tumors were found in exposed female Long-Evans rats (1.5%), while no nasal cavity tumors were found in control Long-Evans rats or in control or exposed female F344 or male Wistar rats. Nine oral squamous cell carcinomas were distributed among control and exposed Wistar rats of both genders; these tumors all appeared to be associated with malocclusion of incisor teeth. No oral carcinomas were found in F344 or Long-Evans rats. Only in the nasal cavity was a possible association found between inhaled 239puO2 and tumor formation in the upper respiratory tract.

Pleural mesothelioma in the rat following exposure to 239PuO2.

Pleural mesothelioma was an infrequent observation following deposition of 239PuO2 in the lung or pleural cavity. Only five tumors were found in 2,105 rats exposed to 239PuO2 aerosols in the present study, while four tumors were found in 527 rats that inhaled 239PuO2 in previously published lifespan studies. Risk of pleural mesothelioma was not significantly increased by intrapleural injection of 30 kBq 239PuO2. In contrast, a much higher incidence of peritoneal mesothelioma was seen following intraperitoneal injection of 239PuO2 due to aggregation of 239PuO2 particles on mesothelial surfaces. It was concluded that the lack of 239PuO2 aggregation on pleural surfaces is responsible for small numbers of pleural mesothelioma observed following deposition of 239PuO2.

A Method for Studying the Effect of the Distribution of Inhaled 239PuO2 Particles on Dose Rate Distribution in the Beagle Dog Lung

A Method for Studying the Effect of the Distribution of Inhaled 239PuO2 Particles on Dose Rate Distribution in the Beagle Dog Lung

A Method for Studying the Effect of the Distribution of Inhaled 239PuO2 Particles on Dose Rate Distribution in the Beagle Dog Lung

A Method for Studying the Effect of the Distribution of Inhaled 239PuO2 Particles on Dose Rate Distribution in the Beagle Dog Lung

Regional Human Lung Dose Following Inhalation of Radioactive Particles at Ages One Month to Adulthood

Abstract A model was developed to relate respiratory tract deposition of inhaled aerosol particles to age at exposure, beginning at 1 month old. The model was expanded to include calculation of radiation dose to the lung when the exposure was continuous through 70 years of life. An aerosol simulating 239PuO2 particles of 0.3μm aerodynamic diameter and in an air concentration of 1 Bq m–3 was used to establish the cumulative radiation doses over the lifetime exposure, using retention half-lives of 1, 10, 100, and 1000 days in the pulmonary region. A computer program was written to use the model in deposition calculations. The program is sufficiently flexible to accept all variables pertinent to lung deposition and dose calculations as a function of age at exposure.

SEM autoradiography: aggregation of inhaled 239PuO2.

Aggregation of inhaled 239PuO2 particles in the pulmonary region of the lung may be required for promotion of pulmonary carcinogenesis in rats. Female Wistar rats were exposed to an aerosol of 239PuO2 and their lungs examined by scanning electron microscopic (SEM) autoradiography. SEM autoradiography provides a rapid and inexpensive method for viewing a large lung tissue volume for alpha tracks. Evidence of particle aggregation was seen by 28 days postinhalation and was marked by 90 to 150 days post-inhalation. Subpleural plutonium particles resulted in exposure into the pleural cavity. Peribronchiolar, alveolar plutonium particles and particle aggregates gave the greatest radiation dose to the bronchiolar epithelium. High-dose, overlapping, alpha-track, radiation zones in bronchiolar epithelium may be required for maximum development of lung tumors.

Macrophage Depletion of Mouse Lung Following Inhalation of 239 PuO 2

Changes in the free-cell population of the lungs of two strains of mice (SAS/4 and CBA/H) were studied up to 4 months after inhalation exposure to a sized fraction of 239PuO2 particles (1.5 micron AMAD) to give initial alveolar depositions (IADs) ranging from 17 to 810 Bq. A sample of the free-cell population of the lung was recovered by bronchoalveolar lavage, and a radiometric method was used to estimate the total number of pulmonary alveolar macrophages (PAM) in the lung. The response of the lung to 239PuO2 was characterized by an initial, dose-dependent depression in the total number of PAM following an IAD as low as 50 Bq. At IADs greater than 150 Bq, the initial depression continued for longer, merging into a chronic phase in which the PAM were larger and were accompanied by a minor infiltration of leukocytes. These findings were confirmed by histology, which also revealed focal accumulations of Type II pneumocytes. The results indicate that inhaled alpha-emitting particles are effective at producing a depletion in the alveolar macrophage population at relatively low IADs and that chronic effects on the cells can be produced by higher concentrations.

Retention of 239 Pu in the Mouse Lung and Estimation of Consequent Dose Following Inhalation of Sized 239 PuO 2

The retention of 239Pu in the lungs of SAS/4 mice following inhalation exposure to sized 239PuO2 particles is described. When the initial alveolar deposition (IAD) was less than 200 Bq, retention of 239Pu could be described by a two-component exponential expression, about 90% being cleared with a half-time of about 40 days and the remainder with a half-time of about 150 days. Similar amounts of 239Pu were retained up to 3 months with IADs greater than 800 Bq, but clearance was impaired thereafter, the half-time of the second component increasing to about 720 days. The retention of 239Pu was independent of the particle size of the administered 239PuO2. Studies of the retention of 239Pu by individual lobes indicated that there were intrinsic interlobar differences which were enhanced at higher IADs. Lung clearance was also studied by the measurement of 239Pu in feces excreted by groups of mice in the period immediately prior to sacrifice. The estimation of radiation dose to lung is discussed.

The Induction of Liver Tumors by 239 Pu Citrate or 239 PuO 2 Particles in the Chinese Hamster

The influence of radiation dose distribution on the frequency of 239Pu-induced liver tumors was evaluated in the Chinese hamster. Different concentrations of 239Pu citrate 239PuO2 particles of known sizes were injected intravenously via the jugular vein. About 60% of the injected 239Pu citrate was deposited in the liver and 40% in the bone. The 239Pu citrate was rather uniformly distributed throughout the liver parenchyma. Injected plutonium oxide particles were taken up by the reticuloendothelial system with 90% of the body burden deposited in the liver. The 239PuO2 particles were localized in the Kupffer cells and produced nonuniform dose distributions that were dependent on particle size. There was an activity- and dose-dependent increase in the incidence of total liver parenchymal cell tumors following injection with either plutonium particles or citrate. For animals that received 14.0-, 2.7-, 0.3-, and 0.04-Gy dose to liver from 239Pu citrate the cumulative tumor incidence was 39, 32, 5, and 0%, respectively. Animals that were injected with the 0.24 micron 239PuO2 particles had doses of 42.0, 7.2, and 0.8 Gy to the liver and tumor incidences of 34, 26, and 5%, respectively. Plutonium citrate also produced hemangiosarcomas of the liver and tumors in bone and bone marrow. The latent period for liver tumor appearance in animals exposed to 239Pu citrate or 239PuO2 particles increased as the injected activity decreased. For animals injected with a similar total activity (7.4 Bq/g), the lifetime cumulative liver tumor incidence was similar for animals exposed to either 239Pu citrate (32%) or 239PuO2 (26%). There was little effect of particle size on liver tumor incidence. These data indicate that, in Chinese hamster liver, local radiation dose distribution is less important in altering tumor incidence than injected activity or average dose. However, the more uniform irradiation from 239Pu citrate administration was more effective in cancer production than the nonuniform irradiation from 239PuO2 particles.

Pulmonary tumours in Syrian hamsters following inhalation of 239PuO2.

Syrian hamsters were exposed to various levels of aerosolized 239PuO2 particles to attain a range of initial lung burdens (medians ranged from 40 to 144 nCi). They were allowed to live without sacrifice and had gross and microscopic tissue examinations at death. Over a range of median lung doses from 4-12 000 rad there was an average 2 per cent incidence of malignant tumours (adenocarcinomas) and 9 per cent incidence of total tumours (primarily adenomas). Some of these results are consistent with those from other laboratories using plutonium oxide aerosols but they represent considerably lower lung tumour incidences than previously observed in this laboratory using aerosols of 238PuO2-ZrO2 particles.

Ultrafine 239PuO2 aerosol generation, characterization and short-term inhalation study in the rat.

Ultrafine aggregate 239PuO2 aerosols were produced by the vaporization of a new plutonium chelate at less than 200°C with the subsequent thermal degradation of the vapor at 1150°C. The vaporizable plutonium chelate was prepared with ligand 2,2,6,6 tetramethyl-3,5-heptane dione. The aerosol size was determined by electron microscopy and diffusion battery measurements. A short-term inhalation study extending to 16 days was conducted in rats using an aerosol consisting of primary particles of 9 ± 5 nm diameter and 21 ± 14 particles per aggregate. The whole body and lung deposition were comparatively higher than those seen with micrometer size 239PuO2 particles. Both in vivo and in vitro dissolution data indicated low rates of dissolution, k = 10−10 g cm −2 day−1. The distribution of inhaled 239PuO2 particles in the lung was evaluated using autoradiography. Although ultrafine 239PuO2 particles were deposited in all regions of the lungs, a nonuniform distribution was found at all times from 2 hr to 16 days after exposure.

Dose distribution and neoplasia in the lung following intratracheal instillation of 239PuO2 and asbestos.

Abstract The influence of dose distribution on pulmonary carcinogenesis was examined in four groups of rats given an intratracheal instillation of either saline, 0.9 mg asbestos, 30 nCi 239PuO2 or mixed 0.9 mg asbestos + 50 nCi 239PuO2 particles. The pulmonary retention half time for 239Pu was about 200 days in rats given PuO2 and 450 days in rats given PuO2 + asbestos; the cumulative radiation dose to lung at 2 yr after instillation being 400 and 1200 rads, respectively. PuO2 particles were concentrated with asbestos-induced scars in peribronchiolar regions of the lung as compared to a more homogeneous distribution when PuO2 was given alone. No differences in mortality were seen between any of the groups. At 2 yr after instillation, the incidences of pulmonary carcinoma were none in rats given saline, 4.5% in rats given asbestos, 32% in rats given PuO2 and 21% in rats given PuO2 + asbestos. It was concluded that immobilization and concentration of alpha emitters in the lung reduces their carcinogenic effects.

Effect of 239 PuO 2 Particle Number and Size on the Frequency and Distribution of Chromosome Aberrations in the Liver of the Chinese Hamster

BROOKS, A. L., RETHERFORD, J. C., AND MCCLELLAN, R. O. The Effect of 239Pu02 Particle Number and Size on the Frequency and Distribution of Chromosome Aberrations in the Liver of the Chinese Hamster. Radiat. Res. 59, 693-709 (1974). Chinese hamsters were injected intravenously with 239Pu citrate or 239Pu02 particles. There were four particle sizes injected: 0.17, 0.30, 0.44, and 0.84 /m which would vary the local radiation dose and dose rate to the surrounding cells. Additional hamsters were injected with graded levels of activity from 6 X 10-5 to 6 X 10-3 ,Ci/g using 0.30 Mm particles. This changes the particle number and the average dose rate. An experiment was also conducted to determine the retention and distribution of the particles using '1Cr to trace the 39Pu02 particles. The particles were concentrated in the reticuloendothelial system with 90% of the injected activity in the liver, 3% in the spleen, and the remainder in either the bone or bone marrow. Autoradiographic studies with 239Pu showed that there was particle clumping causing high local doses to the liver cells in all particle sizes studied. The 239Pu citrate produced a linear increase in the chromosome aberration frequency with a slope of 4.8 X 10-3 aberrations/cell/rad. The chromosome aberration frequency increased with increasing average dose following injection of the 239Pu2 particles. This increase in response plateaued at higher average doses. There was little evidence of an effect of particle size on the aberration frequency. When local dose was related to aberration frequency, the smaller the particles the greater the effectiveness in producing chromosome damage. Following injection of all particle sizes, the nonuniform distribution of dose was reflected in a nonuniform distribution of chromosome damage in the cell population with up to 13 aberrations in an individual cell. The number of cells at risk following particulate deposition is much less than from uniform distribution of the same total activity. This may indicate that long-term risks from 239PuO2 particles would be less than that from uniformly distributed 23Pu citrate.

Relationships between nebulizer suspension concentration, concentration and size distribution of 239PuO2 aerosols generated for animal inhalation experiments.

In a study of low-level effects of inhaled 239PuO2 in beagle dogs, alveolar burdens over the 1500-fold range from 2 nCi to 3 μCi were deposited in unanesthetized dogs by aerosol inhalation. Aerosols were generated by nebulizing magnetically-stirred suspensions of 239PuO2 particles in water, the aerosol concentration (CONC) being varied, primarily, by changing the Pu concentration of the suspension (SSA). If the mass concentration of the suspension was kept below about 10 mg (540 μCi) PuO2/ml, a good correlation (R = 0.827 for n = 64) was observed between CONC and SSA with constant air flow through the exposure chamber. SSA values from 1 to 600 μCi/ml gave CONC values in the range 1.5 to about 3000 nCi/l. However, the aerodynamic equivalent size distribution of 239PuO2 in the exposure chamber was found to vary significantly with CONC. The aerosols were log-normally distributed and the activity median aerodynamic diameter (AMAD) increased from about 1.5 to 3 μm as CONC increased (R = 0.777 for n = 64), while the geometric standard deviation (GSD) decreased (R = −0.576 vs AMAD). An explanation of this unexpected phenomenon, based on aggregate formation due to the greater likelihood of there being more than one PuO2 particle per nebulizer droplet at the higher SSA values, is advanced. The effect is believed to contribute to the large variation observed in the percentage alveolar deposition of inhaled 239PuO2 aerosols from 1.4 to 31.3 in 52 dogs for which the thorax X-ray count was significantly different from zero at P < 0.05.

Induction of mesotheliomas and sarcomas from "hot spots" of 239 PuO 2 activity.

AbstractAlbino rats were given an intraperitoneal injection of approximately 2.8 μCi, submicron-sized 239PuO2 particles. From 30 to 35% of the initially injected dose was found in the omentum within fibrous adhesions by 6 months after plutonium injection. About 27% of the animals developed mesotheli

The distribution of inhaled plutonium-239 dioxide particles within pulmonary macrophages.

Pulmonary macrophages and radioactive plutonium dioxide particles were removed from the lungs of rats by lung washing following inhalation of 239PuO2 particles. Plutonium particles were rapidly phagocytized and retained within pulmonary macrophages for extended periods of time. Phagocytic indexes correlated well with the log 239pu content of the lung from one hour to 25 days after exposure. As much as half of lung- deposited plutonium could be removed from the lung by serial saline washing, the amount depending on the amount of plutonium inhaled and the time since inhalation. The greater the amount of plutonium in the lung, the earlier and more severe were the pathological alterations, resulting in less effective removal by lung washing. The removal of inhaled radioactive particles by lung washing is a useful experimental technique and may be of therapeutic value.

The Biological Behavior of 239 PuO 2 Particles: Role of the Peritoneal Mononuclear Phagocyte

SANDERS, CHARLES L. The biological Behavior of 239PuO2 particles: Role of the peritoneal Mononuclear Phagocyte. Radiation Res. 38,125-139 (1969). Plutonium-239 dioxide particles injected into the peritoneal cavity of rats were rapidly phagocytized by peritoneal mononuclear phagocytes. A marked accumulation of particles within phagocytes was demonstrated by electron microscopy. The average active phagocyte had engulfed the equivalent of approximately 500 particles, 0.12 micron in diameter, at 3 to 7 hours after administration. This represents an amount of 239Pu which would deliver an estimated alpha dose to the phagocyte of about 225 rads/hour. Early marked ultrastructural damage was observed in many phagocytes, engulfing large amounts of plutonium particles. The plutonium-ladened phagocytes traveled to the omentum and mesentery, where they accumulated within lymphatic nodules. A partial release of plutonium particles from the omentum and mesentery back into the peritoneal cavity was observed at 1 to 4 weeks. The phagocyte plays a very important role in determining the early behavior of plutonium particles in the peritoneal cavity.