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1.
Radiat Res ; 145(3): 361-81, 1996 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8927705

RESUMO

This study was conducted to determine the biological effects of inhaled 238PuO2 over the life spans of 144 beagle dogs. The dogs inhaled one of two sizes of monodisperse aerosols of 238PuO2 to achieve graded levels of initial lung burden (ILB). The aerosols also contained 169Yb to provide a gamma-ray-emitting label for the 238Pu inhaled by each dog. Excreta were collected periodically over each dog's life span to estimate plutonium excretion; at death, the tissues were analyzed radiochemically for plutonium activity. The tissue content and the amount of plutonium excreted were used to estimate the ILB. These data for each dog were used in a dosimetry model to estimate tissue doses. The lung, skeleton and liver received the highest alpha-particle doses, ranging from 0.16-68 Gy for the lung, 0.08-8.7 Gy for the skeleton and 0.18-19 for the liver. At death all dogs were necropsied, and all organs and lesions were sampled and examined by histopathology. Findings of non-neoplastic changes included neutropenia and lymphopenia that developed in a dose-related fashion soon after inhalation exposure. These effects persisted for up to 5 years in some animals, but no other health effects could be related to the blood changes observed. Radiation pneumonitis was observed among the dogs with the highest ILBs. Deaths from radiation pneumonitis occurred from 1.5 to 5.4 years after exposure. Tumors of the lung, skeleton and liver occurred beginning at about 3 years after exposure. Bone tumors found in 93 dogs were the most common cause of death. Lung tumors found in 46 dogs were the second most common cause of death. Liver tumors, which were found in 20 dogs but were the cause of death in only two dogs, occurred later than the tumors in bone and lung. Tumors in these three organs often occurred in the same animal and were competing causes of death. These findings in dogs suggest that similar dose-related biological effects could be expected in humans accidentally exposed to 238PuO2.


Assuntos
Neoplasias Ósseas/patologia , Longevidade/efeitos da radiação , Neoplasias Pulmonares/patologia , Neoplasias Induzidas por Radiação/patologia , Osteossarcoma/patologia , Plutônio/farmacocinética , Plutônio/toxicidade , Administração por Inalação , Partículas alfa , Animais , Carga Corporal (Radioterapia) , Neoplasias Ósseas/etiologia , Cães , Relação Dose-Resposta à Radiação , Feminino , Raios gama , Neoplasias Pulmonares/classificação , Neoplasias Pulmonares/etiologia , Masculino , Osteossarcoma/etiologia , Plutônio/administração & dosagem , Modelos de Riscos Proporcionais , Lesões Experimentais por Radiação , Valores de Referência , Análise de Regressão , Respiração/efeitos da radiação , Caracteres Sexuais , Fatores de Tempo , Distribuição Tecidual
2.
Environ Res ; 59(2): 400-15, 1992 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-1464291

RESUMO

We have shown previously that dogs exposed once to aerosols of beryllium oxide (BeO) calcined at 500 or 1000 degrees C developed granulomatous lung lesions as well as Be-specific immune responses in the blood and lung. In this report, we investigate the immunopathologic consequences of exposing dogs twice to aerosols of BeO. Dogs previously exposed to aerosols of 500 or 1000 degrees C calcined BeO to achieve an initial lung burden (ILB) of either 50 or 17 micrograms/kg body wt were exposed a second time to BeO calcined at 500 degrees C, 2.5 years after the first exposure, to achieve an ILB of about 50 micrograms/kg body wt. Immune responses of peripheral blood and lung lymphocytes were measured at 0, 14, 30, 60, 90, 120, 150, 165, 180, and 210 days postexposure (dpe), and dogs were euthanized at 210 dpe. Be-specific immune responses occurred in blood at 30 dpe and again at 150 to 210 dpe. Only sporadic positive responses were seen among lung lymphocytes when cells were cultured in 10% fetal bovine serum. In contrast, samples collected at 165, 180, and 210 dpe and incubated with 10% dog serum showed a large number of positive responses in both blood and lung. Histologic lesions were characterized by perivascular and interstitial infiltrates of lymphocytes and macrophages with progression to patchy granulomatous pneumonia accompanied by focal septal fibrosis. We conclude that Be-induced granulomatous and fibrotic lung lesions are accompanied by Be-specific immune responses within the lung but these changes do not appear to be cumulative if enough time has elapsed between exposures.


Assuntos
Berílio/toxicidade , Granuloma/induzido quimicamente , Pneumopatias/induzido quimicamente , Pulmão/efeitos dos fármacos , Fibrose Pulmonar/induzido quimicamente , Aerossóis , Animais , Berílio/administração & dosagem , Líquido da Lavagem Broncoalveolar/citologia , Contagem de Células , Cães , Feminino , Imunidade Celular/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Linfócitos , Macrófagos , Masculino , Neutrófilos
3.
Int J Radiat Biol ; 62(1): 89-95, 1992 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-1353780

RESUMO

Because of the role that alveolar macrophages (PAM) play in the pulmonary clearance of inhaled particles via mechanical transport and dissolution, understanding the uptake and dissolution of particles by these cells might provide insight into the mechanisms of particle dissolution in lungs of various species and hence facilitate the extrapolation of animal data to humans. Therefore, experiments were conducted to study the phagocytosis and dissolution of 241AmO2 particles by rat, dog and monkey PAM in vitro. Rat, dog and monkey PAM were exposed for up to 72 h to 0.19, 0.93 or 4.6 kBq/ml 241Am, after which cell viability was determined. The 241Am concentration, 4.63 kBq/ml, was used for the phagocytosis and dissolution experiments. The phagocytosis and dissolution of 241AmO2 particles were followed up to 20 and 72 h, respectively. Dog and monkey PAM took up 241AmO2 particles at similar rates, whereas rat PAM phagocytosed only 60% of the amount phagocytosed by dog and monkey PAM at 20 h. The PAM of the three species dissolved 241AmO2 particles at similar rates; 8-10% was dissolved by 72 h. The results of the 241AmO2 uptake in vitro may reflect in vivo situations, where the differences in uptake seen in vitro would probably diminish at later times after exposure. The dissolution results imply that the dissolution of 241AmO2 particles by alveolar macrophages of the three species might be species-independent. This, at least, might be true for dog and monkey, where in vivo data have shown that 241AmO2 was translocated similarly in both species. Finally, the alveolar macrophage culture system provides a useful simulation to investigate uptake and dissolution of inhaled particles.


Assuntos
Amerício/metabolismo , Macrófagos Alveolares/fisiologia , Fagocitose/fisiologia , Animais , Cães , Feminino , Técnicas In Vitro , Macaca fascicularis , Ratos , Ratos Endogâmicos F344 , Solubilidade , Especificidade da Espécie , Fatores de Tempo
4.
Int J Radiat Biol ; 62(1): 81-8, 1992 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-1353779

RESUMO

Because alveolar macrophages play a role in the pulmonary clearance of inhaled particles, experiments were conducted to investigate the toxicity of 241AmO2 particles to alveolar macrophages and the role of these macrophages in the dissolution of 241AmO2 particles. Beagle dog pulmonary alveolar macrophages obtained by bronchopulmonary lavage were exposed in vitro to selected concentrations of 241AmO2. Macrophage viability determined by trypan-blue dye exclusion technique and the ability of the alveolar macrophages to phagocytose opsonized sheep red blood cells were the measures of 241AmO2 toxicity. The uptake of 241AmO2 particles was studied as a function of time. In addition, the dissolution of 241AmO2 by macrophages was determined for periods up to 72 h. After 20 h exposure to concentrations of 241Am higher than 4.63 kBq/ml, the phagocytic ability of macrophages was reduced, whereas no significant change in cell viability was observed at this concentration. Significant cell killing occurred at concentrations higher than 18.5 kBq/ml. After 72 h in the cultures, 10% of the 241AmO2 was dissolved by the alveolar macrophages. These findings imply that the inhalation of radioactive particles such as 241AmO2 particles might cause a reduction in the alveolar macrophage population in the lungs. In addition, the dissolution of 241AmO2 particles by alveolar macrophages might play a role in the short-term pulmonary clearance of inhaled 241AmO2 particles in the beagle dog.


Assuntos
Amerício/toxicidade , Macrófagos Alveolares/efeitos dos fármacos , Macrófagos Alveolares/efeitos da radiação , Amerício/farmacocinética , Animais , Cães , Feminino , Técnicas In Vitro , Macrófagos Alveolares/metabolismo , Masculino
5.
Radiat Res ; 130(1): 79-87, 1992 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-1561321

RESUMO

Twenty male cynomolgus monkeys were exposed by inhalation either to an aerosol of 239Pu(NO3)4 to produce projected initial lung burdens of either 40, 10, or 4 kBq or to a carrier aerosol as a control. Animals died or were sacrificed at 0.01, 1, 3, 6, 12, 24, 40, and 99 months after inhalation, and the distribution and biological effects of the 239Pu were determined. The 239Pu cleared efficiently from the lungs so that less than 0.05 kBq remained at 99 months after exposure to 40 kBq. Total skeletal 239Pu activity was nearly constant after the first year, but the fraction of the body burden in skeleton at sacrifice increased with time up to 99 months because of clearance from other organs. Plutonium in the liver increased to a peak at 1 year and then decreased to about 10% of the peak value at 99 months. Plutonium in the testes was localized in the interstitial tissue with only 0.01 to 0.002% of the projected lung burden remaining in testes at 99 months after inhalation. Three animals exposed to 40 kBq of 239Pu died of radiation-related pulmonary pneumonitis and fibrosis. A primary papillary adenocarcinoma of the lung was identified in one animal exposed to 40 kBq initial lung burden and sacrificed 99 months after inhalation. The frequency of chromosome aberrations in blood lymphocytes was significantly elevated only in monkeys with projected deposits of 40 kBq of 239Pu. There was no change in aberration frequency in other exposure groups as a function of inhaled activity, time after exposure, or calculated total dose to the lungs. Only in monkeys that had marked radiation-induced pathological changes in the lung did the frequency of chromosome-type aberrations increase significantly, to a value about twice the control level. In cynomolgus monkeys, chromosome aberration frequency in blood lymphocytes is not a good indicator of radiation dose or damage from inhaled soluble plutonium.


Assuntos
Nitratos , Plutônio , Administração por Inalação , Animais , Aberrações Cromossômicas , Pulmão/efeitos da radiação , Linfócitos/efeitos da radiação , Macaca fascicularis , Masculino , Plutônio/administração & dosagem , Plutônio/farmacocinética , Efeitos da Radiação , Distribuição Tecidual
6.
Fundam Appl Toxicol ; 15(2): 231-41, 1990 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-2227151

RESUMO

Beagle dogs inhaled radiolabeled beryllium oxide (7BeO) particles that were calcined at either 500 or 1000 degrees C, resulting in either high (mean of 50 micrograms/kg body wt) or low (mean of 17 micrograms/kg body wt) initial lung burdens (ILBs) of both preparations of BeO. Levels of beryllium in whole body, tissue, and excreta were measured by external gamma-ray counting. Dogs were euthanized in pairs at 8, 32, 64, and 180 days after exposure to determine beryllium distribution in tissues. Beryllium oxide calcined at 1000 degrees C was retained more tenaciously in the lungs (62% of the ILB retained at 180 days after exposure) than BeO calcined at 500 degrees C (14% of the ILB retained at 180 days after exposure). Most of the beryllium that was cleared from the lungs and not excreted was translocated to the tracheobronchial lymph nodes, skeleton, liver, and blood. More beryllium was translocated to the skeleton and liver at 180 days after inhalation of BeO prepared at 500 degrees C than at 1000 degrees C. The predominant mode of excretion at early times after exposure was through the feces, with urinary excretion assuming predominance at later times. These data are important for interpreting the toxic effects of beryllium in the exposed dogs. Furthermore, because little is known concerning the retention and clearance of inhaled beryllium in man, these results provide information that may be used to understand the disposition of beryllium in accidentally exposed humans.


Assuntos
Berílio/farmacocinética , Berílio/toxicidade , Administração por Inalação , Animais , Berílio/química , Carga Corporal (Radioterapia) , Cães , Feminino , Meia-Vida , Pulmão/metabolismo , Masculino , Tamanho da Partícula , Distribuição Tecidual
7.
Lab Invest ; 61(2): 219-27, 1989 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-2755079

RESUMO

Groups of beagle dogs were exposed by inhalation to attain either low or high initial lung burdens (ILB) of BeO calcined at 500 degrees or 1000 degrees C. Dogs were killed at 8, 32, 64, 180, and 365 days after exposure for evaluation of beryllium tissue burdens and histopathologic examination. Histologic lesions were characterized by perivascular and peribronchiolar infiltrates of lymphocytes and macrophages 8 days after exposure. These lesions progressed to distinct microgranulomas accompanied by patchy granulomatous pneumonia. Lesions were more severe in dogs exposed to 500 degrees C BeO. Additional dogs were sampled by bronchoalveolar lavage at 3, 6, 7, 11, 15, 18, and 22 months after exposure for characterization of lung cytology and lung immune responses. Lymphocyte percentages and numbers were increased in lavage samples 3 months after exposure in dogs with both the high and low ILB of 500 degrees C. Values for both parameters decreased rapidly thereafter. Dogs with either low or high ILB of 1000 degrees C-treated BeO displayed negligible to low and variable changes in both lymphocyte percentages and numbers. In vitro lymphocyte stimulation by beryllium was increased 180 and 210 days after exposure in dogs with the high ILB 500 degrees C BeO only. A marked degree of individual variation in both histologic lesions and lymphocyte responses among dogs was noted. Less soluble 1000 degrees C-treated BeO was retained in the lung longer than the more soluble 500 degrees C-treated material that was cleared almost entirely by 1 year after exposure. Because these changes are similar to those reported in humans with chronic beryllium disease, these data suggest that the beagle represents a good model to study histologic and immunologic aspects of this disease syndrome.


Assuntos
Beriliose/patologia , Granuloma/patologia , Aerossóis , Animais , Beriliose/imunologia , Berílio/administração & dosagem , Berílio/farmacocinética , Carga Corporal (Radioterapia) , Líquido da Lavagem Broncoalveolar/citologia , Modelos Animais de Doenças , Cães , Feminino , Granuloma/imunologia , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Ativação Linfocitária/efeitos dos fármacos , Linfócitos/patologia , Masculino
8.
Health Phys ; 57 Suppl 1: 187-97; discussion 197-8, 1989.
Artigo em Inglês | MEDLINE | ID: mdl-2606681

RESUMO

Curium isotopes are major by-products in irradiated nuclear reactor fuel and comprise a significant fraction of the alpha-emitting radionuclide inventory. Although little use is currently being made of purified Cm sources, such usage is possible if reprocessing of spent fuel becomes feasible. Because little information is available on the biokinetics and dosimetry of inhaled Cm compounds, a study was conducted in which adult beagle dogs received a single inhalation exposure to either a monodisperse aerosol of 244Cm2O3 (1.4 micron activity median aerodynamic diameter [AMAD]; sigma g = 1.16) or a polydisperse aerosol of 244Cm (NO3)3 (1.1 micron AMAD; sigma g = 1.74). At times ranging from 4 h to 2 y after exposure, animals were sacrificed and their tissues analyzed for Cm content. The data describing the uptake and retention of 244Cm in the different organs and tissues and the measured rates of excretion of these dogs formed the basis on which a biokinetic model of Cm metabolism was constructed. This Cm model was based on a previously published model of the biokinetics of 241Am that was shown to be applicable to data from human cases of inhalation exposure to 241Am aerosols. This Cm model was found to be adequate to describe the biological distribution of Cm in dogs and was also applied to the sparse data from humans. Reasonable agreement was found between the model predictions for lung retention of Cm and for urinary excretion patterns in humans.


Assuntos
Cúrio/farmacocinética , Pulmão/metabolismo , Modelos Biológicos , Nitratos , Administração por Inalação , Aerossóis , Animais , Cúrio/administração & dosagem , Cães , Humanos , Especificidade da Espécie , Distribuição Tecidual
9.
Am J Pathol ; 133(2): 265-76, 1988 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-3142267

RESUMO

Primary liver tumors developed in Beagle dogs exposed by inhalation to aerosols of 238PuO2. Initial deposition of 238PuO2 in the respiratory tract was followed by translocation of a portion of the 238Pu to the liver and skeleton, which resulted in a large dose commitment and tumor risk to all three tissues. In a population of 144 dogs exposed to 238PuO2, 112 dogs died or were killed 4000 days after 238Pu exposure, 100 dogs had osteosarcoma, and 28 dogs had lung cancers. At increasing times after exposure, however, liver lesions have become more pronounced. Ten primary liver tumors in nine animals were diagnosed in the dogs dying before 4000 days after exposure. An additional five primary liver tumors in three dogs occurred in 9 animals killed after 4000 days after exposure. The majority of these tumors have been fibrosarcomas. The liver tumors were usually not the cause of death, and rarely metastasized. The occurrence of liver tumors in this study indicates that 238Pu is an effective hepatic carcinogen. Liver carcinogenesis is assuming an increasing importance in this study at late times after inhalation exposure. These results suggest that the liver may be an important organ at risk for the development of neoplasia in humans at time periods long after inhalation of 238Pu.


Assuntos
Neoplasias Hepáticas Experimentais/induzido quimicamente , Plutônio/farmacologia , Administração por Inalação , Aerossóis , Animais , Neoplasias dos Ductos Biliares/induzido quimicamente , Neoplasias dos Ductos Biliares/patologia , Cistadenoma/induzido quimicamente , Cães , Resíduos de Drogas/metabolismo , Fibroma/induzido quimicamente , Fibroma/patologia , Fibrossarcoma/induzido quimicamente , Fibrossarcoma/patologia , Fígado/patologia , Neoplasias Hepáticas Experimentais/patologia , Pulmão/metabolismo , Sarcoma de Mastócitos/induzido quimicamente , Sarcoma de Mastócitos/patologia , Osteossarcoma/induzido quimicamente , Osteossarcoma/mortalidade , Osteossarcoma/patologia , Plutônio/farmacocinética
10.
Toxicol Lett ; 41(2): 97-105, 1988 May.
Artigo em Inglês | MEDLINE | ID: mdl-3368931

RESUMO

Pulmonary alveolar macrophage cells (PAM), obtained by bronchopulmonary lavage of Beagle dogs, were exposed in vitro to beryllium oxide (BeO) particles calcined at either 500 or 1000 degrees C or to beryllium sulfate (BeSO4). Cell viability was determined by trypan blue dye exclusion after 20 h in culture. The most toxic material tested was BeSO4, followed by BeO calcined at 500 degrees C, then BeO calcined at 1000 degrees C. An in vitro dissolution technique was used to measure the relative solubility of the BeO particles. The BeO prepared at 500 degrees C exhibited greater solubility compared with BeO prepared at 1000 degrees C. This study extends previous work by examining the effects of beryllium compounds on canine PAM, and by relating PAM cytotoxicity with measured values of beryllium compound solubility.


Assuntos
Berílio/toxicidade , Macrófagos/efeitos dos fármacos , Alvéolos Pulmonares/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cães , Relação Dose-Resposta a Droga , Solubilidade
11.
Radiat Res ; 112(2): 391-7, 1987 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-3685265

RESUMO

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.


Assuntos
Fibrossarcoma/veterinária , Neoplasias Pulmonares/veterinária , Neoplasias Induzidas por Radiação/veterinária , Plutônio/administração & dosagem , Administração por Inalação , Animais , Fibrossarcoma/etiologia , Neoplasias Pulmonares/etiologia , Macaca mulatta , Masculino , Neoplasias Induzidas por Radiação/etiologia
12.
Health Phys ; 53(4): 377-84, 1987 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-3654225

RESUMO

Dissolution of gross alpha emitter radioactivity from particles composed of mixed uranium and plutonium oxides or of plutonium dioxide continually immersed in solvent typically display at least a two-phase dissolution pattern. Rapid dissolution of a small fraction of the total particulate mass is followed by much slower dissolution for the majority of the particulate mass. In this study, respirable particles of (U, Pu)O2 and PuO2 were subjected to dissolution using an alternate wetting and drying cycle. Particles were continuously immersed in solvent for 4 d and then dried in air for 3 d. This cycle was repeated weekly for 7 wk. Four solvents were used to represent a range of potential environmental conditions and a fifth solvent was used for comparison to other continuous immersion studies. In contrast to dissolution studies involving continuous immersion over periods of two or more weeks that exhibit a three-phase dissolution process, the alternate wet-dry cycling resulted in repetition of the first two phases of the dissolution pattern for each cycle. This led to significantly enhanced dissolution of both particulate materials. The enhancement in total dissolution ranged from two to ten times larger during each wet-dry cycle compared to studies involving continuous immersion. The results indicate a potential need to re-evaluate environmental models of actinide element bioavailability for particulate materials released to environments where wet-dry cycling may be routine, i.e. intermittent rainfall in an otherwise arid climate or in stream beds with intermittent flow.


Assuntos
Plutônio , Compostos de Urânio , Urânio , Partículas alfa , Concentração de Íons de Hidrogênio , Chuva , Solubilidade , Água
13.
Radiat Res ; 110(2): 199-218, 1987 May.
Artigo em Inglês | MEDLINE | ID: mdl-3575651

RESUMO

Existing data from human exposure cases and experimental animal studies on the fate and dosimetry of inhaled insoluble Pu particles are inadequate to provide a comprehensive description and evaluation of the tissues at risk from the alpha radiations of Pu. To improve our knowledge of the dosimetry of inhaled insoluble 239PuO2, this paper describes the uptake and retention of 239Pu in the tissues of dogs that received single inhalation exposures to monodisperse aerosols of 239PuO2. These data include times through 3 years after exposure. Using analytical functions fitted to each tissue data set, 1100-day radiation doses were calculated for lung, liver, skeleton, kidney, spleen, and tracheobronchial, mediastinal, sternal, hepatic, mandibular, and retropharyngeal lymph nodes. The dosimetry results suggest that the lung and lymph nodes associated with lymphatic drainage of the respiratory tract are the principal sites of alpha irradiation. However, the doses for the different respiratory tract lymph nodes vary by a factor of 2000, suggesting that assuming equivalent doses to respiratory tract lymph nodes is not appropriate. Other tissues receive radiation doses also but at levels one to three orders of magnitude less than the lung. Particle size dependence on uptake and retention was noted for the skeleton, mediastinal lymph nodes, hepatic lymph nodes, retropharyngeal lymph nodes, and mandibular lymph nodes.


Assuntos
Plutônio/análise , Administração por Inalação , Aerossóis , Poluentes Radioativos do Ar , Partículas alfa , Animais , Cães , Relação Dose-Resposta à Radiação , Meia-Vida , Pulmão/análise , Linfonodos/análise , Tamanho da Partícula , Plutônio/administração & dosagem , Radiometria , Distribuição Tecidual
14.
Fundam Appl Toxicol ; 8(3): 372-81, 1987 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-3569707

RESUMO

Azodicarbonamide (ADA) is widely used as a blowing agent in the manufacture of expanded foam plastics, as an aging and bleaching agent in flour, and as a bread dough conditioner. Human exposures have been reported during manufacture as well as during use. Groups of male F344/N rats were administered ADA by gavage, by intratracheal instillation, and by inhalation exposure to determine the disposition and modes of excretion of ADA and its metabolites. At 72 hr following gavage, 30% of the administered ADA was absorbed whereas following intratracheal instillation, absorption was 90%. Comparison between groups of rats exposed by inhalation to ADA to achieve body burdens of 24 or 1230 micrograms showed no significant differences in modes or rates of excretion of [14C]ADA equivalents. ADA was readily converted to biurea under physiological conditions and biurea was the only 14C-labeled compound present in excreta. [14C]ADA equivalents were present in all examined tissues immediately after inhalation exposure, and clearance half-times on the order of 1 day were evident for all tissues investigated. Storage depots for [14C]ADA equivalents were not observed. The rate of buildup of [14C]ADA equivalents in blood was linearly related to the lung content as measured from rats withdrawn at selected times during a 6-hr inhalation exposure at an aerosol concentration of 25 micrograms ADA/liter. In a study extending 102 days after exposure, retention of [14C]ADA equivalents in tissues was described by a two-component negative exponential function. The results from this study indicate that upon inhalation, ADA is rapidly converted to biurea and that biurea is then eliminated rapidly from all tissues with the majority of the elimination via the urine.


Assuntos
Compostos Azo/toxicidade , Administração por Inalação , Aerossóis/metabolismo , Aerossóis/toxicidade , Animais , Compostos Azo/administração & dosagem , Compostos Azo/metabolismo , Carga Corporal (Radioterapia) , Ratos , Ratos Endogâmicos F344 , Estômago , Distribuição Tecidual , Traqueia
15.
Radiat Res ; 104(1): 83-93, 1985 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-3863193

RESUMO

Young, mature Beagle dogs underwent single inhalation exposure to respirable aerosols of 241AmO2 to determine the radiation dose distribution to tissues. The dogs were serially sacrificed to assess the clearance of 241Am from the lung, the rate of translocation to internal organs, the pattern of retention in the organs, and the rates and modes of excretion. Americium dioxide was relatively soluble in the lung, leading to the translocation of significant quantities of 241Am to bone and liver, thus delivering radiation doses to these tissues nearly equal to that received by the lung. Osteoblastic osteosarcomas developed in four dogs surviving more than 1000 days after exposure. Histologically, all of the osteosarcomas were associated with areas of radiation osteodystrophy characterized by bone infarction, peritrabecular new bone formation, marrow fibrosis, and microresorptive cavities. The retention and translocation of inhaled 241Am in dogs is similar to that of man, indicating that 241Am inhaled by humans may potentially result in significant risk of bone tumor development.


Assuntos
Amerício/toxicidade , Neoplasias Induzidas por Radiação/etiologia , Osteossarcoma/etiologia , Amerício/metabolismo , Animais , Cães , Exposição Ambiental , Neoplasias Femorais/etiologia , Neoplasias Femorais/patologia , Osteossarcoma/patologia , Neoplasias da Coluna Vertebral/etiologia , Neoplasias da Coluna Vertebral/patologia , Fatores de Tempo
16.
Toxicol Appl Pharmacol ; 78(2): 215-25, 1985 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-4035677

RESUMO

Methyl bromide is a widely used soil fumigant and poses potential inhalation hazard to workers. Uptake of methyl bromide and pathways for excretion of 14C were investigated in male Fischer-344 rats after nose-only inhalation of 50, 300, 5700, or 10,400 nmol (1.6 to 310 ppm) of [14C]methyl bromide/liter of air for 6 hr. Fractional uptake of methyl bromide decreased at the highest concentrations, 5700 and 10400 nmol/liter, with 37 and 27% of the inhaled methyl bromide absorbed, respectively, compared to 48% at the lower levels. This resulted in the same total amount of methyl bromide being absorbed at the two higher exposure concentrations (650 mumol/kg body wt). Total methyl bromide adsorbed was 9 or 40 mumol/kg body wt after exposure to 50 or 300 nmol/liter, respectively. Elimination of 14C was linearly related to the amount of methyl bromide absorbed as determined from urine, feces, expired CO2, and parent compound collected for 66 hr after the end of exposure. Exhaled 14CO2 was the dominant route of excretion, with from 1.2 to 110 mumol (50% of amount absorbed) exhaled, and was described by a two-component negative exponential function; 85% was exhaled with a t 1/2 of 4 hr, and the remaining 15% was exhaled with a t 1/2 of 17 hr. The rate of exhalation of 14CO2 was not affected by the amount of [14C]methyl bromide absorbed. From 0.4 to 54 mumol was excreted in urine (20% of amount absorbed). The half-time for excretion of 14C in urine was approximately 10 hr, and the rate of excretion was not dependent on the amount of [14C]methyl bromide absorbed. Little 14C was exhaled as methyl bromide (less than 4% of the dose) or excreted in feces (less than 2%). At the end of 66 hr, 25% of the 14C absorbed remained in the rats. Liver, kidneys, adrenals, lungs, thymus, and turbinates (maxilloturbinates, ethmoturbinates, and nasal epithelial membrane) contained the highest concentrations of 14C. Results indicated that uptake of inhaled methyl bromide could be saturated. Any [14C]methyl bromide equivalents absorbed, however, would be excreted by concentration-independent mechanisms.


Assuntos
Poluentes Ocupacionais do Ar/toxicidade , Hidrocarbonetos Bromados/metabolismo , Animais , Relação Dose-Resposta a Droga , Meia-Vida , Hidrocarbonetos Bromados/toxicidade , Hidrocarbonetos Bromados/urina , Cinética , Masculino , Modelos Biológicos , Ratos , Ratos Endogâmicos F344 , Respiração/efeitos dos fármacos , Sistema Respiratório/metabolismo , Distribuição Tecidual
17.
Toxicol Appl Pharmacol ; 78(1): 47-54, 1985 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-4035672

RESUMO

2,3-Dichloropropene (2,3-DCP) is a constituent of some commercially available preplant soil fumigants for the control of plant parasitic nematodes. Human exposure potential exists during manufacture of the chemicals or during bulk handling activities. The purpose of this investigation was to determine the disposition and metabolism of 2,3-[14C]DCP in rats after inhalation. Male Fischer-344 rats were exposed nose-only to a vapor concentration of 250 nmol 2,3-[14C]DCP/liter air (7.5 ppm; 25 degrees C, 620 Torr) for 6 hr. Blood samples were taken during exposure, and urine, feces, expired air, and tissues were collected for up to 65 hr after exposure. Urinary excretion was the major route of elimination of 14C (55% of estimated absorbed 2,3-DCP). Half-time for elimination of 14C in urine was 9.8 +/- 0.05 hr (means +/- SE). Half-time for elimination of 14C feces (17% of absorbed 2,3-DCP) was 12.9 +/- 0.14 hr (means +/- SE). Approximately 1 and 3% of the estimated absorbed 2,3-[14C]DCP were exhaled as either 2,3-[14C]DCP or 14CO2, respectively. Concentrations of 14C in blood increased during 240 min of exposure, after which no further increases in blood concentration of 14C were seen. 14C was widely distributed in tissues analyzed after a 6-hr exposure of rats to 2,3-[14C]DCP. Urinary bladder (150 nmol/g), nasal turbinates (125 nmol/g), kidneys (84 nmol/g), small intestine (61 nmol/g), and liver (35 nmol/g) were tissues with the highest concentrations of 14C immediately after exposure. Over 90% of the 14C in tissues analyzed was 2,3-DCP metabolites. Half-times for elimination of 14C from tissues examined ranged from 3 to 11 hr. The data from this study indicate that after inhalation 2,3-DCP is metabolized in tissues and readily excreted.


Assuntos
Compostos Alílicos/metabolismo , Praguicidas/metabolismo , Animais , Câmaras de Exposição Atmosférica , Testes Respiratórios , Fezes/análise , Hidrocarbonetos Clorados , Cinética , Masculino , Modelos Biológicos , Praguicidas/urina , Ratos , Ratos Endogâmicos F344 , Distribuição Tecidual
18.
Artigo em Inglês | MEDLINE | ID: mdl-6610656

RESUMO

This study was designed to measure the effect of aerosol particle size on the deposition, retention, excretion and translocation of 239Pu inhaled as the dioxide by Beagle dogs. To address these questions, young adult male and female Beagle dogs received single brief inhalation exposures to one of three monodisperse aerosols of 239PuO2 having sizes of 0.72, 1.4 or 2.8 microns activity median aerodynamic diameter (AMAD). Periodic collections of urine and faeces were made for each dog until sacrifice at times ranging from 4 hours to 2 years after exposure. The results indicate long term retention of a substantial percentage of the initial pulmonary burden (IPB), and that the retention was affected by particle size. The percentage of the initial pulmonary lung burden retained in the long term component and its effective half time (TE) were 90 per cent with TE = 680 days for the 0.72 micron AMAD aerosol, 68 per cent with TE = 1400 days for the 1.4 microns AMAD aerosol and 82 per cent with TE = 1800 days for the 2.8 microns AMAD aerosol. The major route of elimination of 239Pu from lung was via the faeces, but significant amounts were also translocated to thoracic lymph nodes (approximately 15 per cent IPB by 2 years). Small amounts were translocated to liver (0.2 per cent IPB) and skeleton (0.1 per cent IPB) by 2 years after exposure. The average alpha-radiation dose to the lung was projected to be twice as large for the 2.8 microns AMAD group as for the 0.72 micron AMAD group at 10 years after exposure.


Assuntos
Plutônio/metabolismo , Aerossóis , Animais , Osso e Ossos/metabolismo , Cães , Fezes/análise , Feminino , Fígado/metabolismo , Pulmão/metabolismo , Linfonodos/metabolismo , Masculino , Papio , Tamanho da Partícula , Plutônio/administração & dosagem , Doses de Radiação , Respiração , Fatores de Tempo
19.
Radiat Environ Biophys ; 23(3): 171-7, 1984.
Artigo em Inglês | MEDLINE | ID: mdl-6473702

RESUMO

Syrian hamsters, Fischer rats and Beagle dogs inhaled monodisperse aerosols of PuO2 and were sacrificed during the first 16 days after exposure. The microscopic distribution of radiation dose and tissue-at-risk to alpha irradiation around individual particles in lung was studied using autoradiographs of lung tissue sections. The dose distributions in dogs and rats were more diffuse than in hamsters. A slightly greater tumor incidence was calculated for rats and dogs than for hamsters on the basis of dose distribution using the same dose-effect model for all three species. The small differences in tumor incidence predicted on this basis do not explain the extremely large differences in tumor incidences observed in these species after inhalation of PuO2.


Assuntos
Pulmão , Plutônio , Doses de Radiação , Aerossóis , Partículas alfa , Animais , Cricetinae , Cães , Neoplasias Pulmonares/etiologia , Masculino , Mesocricetus , Neoplasias Induzidas por Radiação/etiologia , Ratos , Ratos Endogâmicos F344 , Especificidade da Espécie
20.
Health Phys ; 45(6): 1023-37, 1983 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-6643070

RESUMO

Dissolution characteristics of mixed-oxide nuclear fuels are important considerations for prediction of biological behavior of inhaled particles. Four representative industrial mixed-oxide powders were obtained from fuel fabrication enclosures. Studies of the dissolution of Pu, Am and U from aerosol particles of these materials in a serum simulant solution and in 0.1M HCl showed: (1) dissolution occurred at a rapid rate initially and slowed at longer times, (2) greater percentages of U dissolved than Pu or Am: with the dissolution rates of U and Pu generally reflecting the physical nature of the UO2-PuO2 matrix, (3) the temperature history of industrial mixed-oxides could not be reliably related to Pu dissolution except for a 3-5% increase when incorporated into a solid solution by sintering at 1750 degrees C, and (4) dissolution in the serum simulant agreed with the in vivo UO2 dissolution rate and suggested the dominant role of mechanical processes in PuO2 clearance from the lung. The rapid initial dissolution rate was shown to be related, in part, to an altered surface layer. The advantages and uses of in vitro solubility data for estimation of biological behavior of inhaled industrial mixed oxides, such as assessing the use of chelation therapy and interpretation of urinary excretion data, are discussed. It was concluded that in vitro solubility tests were useful, simple and easily applied to individual materials potentially inhaled by humans.


Assuntos
Reatores Nucleares , Plutônio , Respiração , Compostos de Urânio , Urânio , Aerossóis , Solubilidade
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