Models of Am Metabolism in Beagles and Humans

Ja, Mewhinney; Wc, Griffith

doi:10.1097/00004032-198205000-00006

Cited by 14 publications

(7 citation statements)

References 4 publications

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“…The particles, although appearing to be uniformly dense by transmission electron microscopy, were not as smooth nor as spherical as other actinide aerosols that have been produced using similar techniques (e.g., 238Pu (Mewhinney and Die1 1983) and 241Am (Mewhinney et al 1982)). However, the differences were not considered sufficient to have affected the results of this study.…”

Section: Resultsmentioning

confidence: 78%

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PLANT/SOIL CONCENTRATION RATIOS OF 226Ra FOR CONTRASTING SITES AROUND AN ACTIVE U MINE-MILL

Guilmette

Kanapilly

1988

Health Physics

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This study was designed to provide tissue distribution data of 244Cm that was inhaled by beagle dogs. Two chemical forms that were presumed to bracket the solubility of pure Cm compounds in vivo were used: 244Cm2O3 (oxide) and 244Cm(NO3)3 (nitrate). Adult dogs of both sexes received a single brief pernasal exposure to either a monodisperse aerosol of 244Cm2O3 (1.4 micron activity median aerodynamic diameter, AMAD, and 1.16 geometric standard deviation, sigma g) or a polydisperse aerosol of 244Cm(NO3)3 (1.1 micron AMAD, 1.74 sigma g). The resulting initial pulmonary burdens (IPB) were 1.5 and 1.7 kBq kg-1 body mass for the oxide and nitrate groups, respectively. The tissue distribution data obtained from the dogs that were serially sacrificed from 4 h to 2 y after exposure showed that both chemical forms were very soluble in vivo. For the oxide group, 78% IPB was cleared from the lung with a T 1/2 of 7.6 d, whereas for the nitrate group, 42% IPB cleared with a T 1/2 of 0.6 d. The lung retention for each group was described by three-component exponential functions. Most of the Cm that cleared the lung was redeposited in the liver (37% IPB) and skeleton (27% IPB), with lesser amounts in the muscle, fat and connective tissue (3.5% IPB) and kidney (approximately 2% IPB). The only significant difference noted in the biokinetics of Cm for the two exposure groups was a more rapid translocation of Cm from the lung to liver and bone during the first 10-20 d after exposure to the nitrate compared to the oxide chemical form. Extrapolation of these data to obtain estimates of committed dose equivalents for man indicate substantial agreement with the limits for occupational exposure specified by ICRP 30 (1979).

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Section: Resultsmentioning

confidence: 78%

“…The relative importance of particle solubility, particle size and polydispersity in affecting the fecal excretion patterns are not obvious. Their importance will most readily be inferred by utilizing biomathematical modeling approaches similar to those used by Mewhinney and Griffith (1982).…”

Section: Fig 4 Comparison Of the Retention Of CM In Lung As Measurementioning

confidence: 99%

PLANT/SOIL CONCENTRATION RATIOS OF 226Ra FOR CONTRASTING SITES AROUND AN ACTIVE U MINE-MILL

Guilmette

Kanapilly

1988

Health Physics

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“…In fact, a translocation rate constant k = 6.9 x 10-8 g/cm2/day was determined for all canine lung clearance studies using Co304 particles (32). Interestingly, this constant was in the same range as the translocation rate constants found for other metal oxides in dogs (21)(22)(23)(24)(25)(26)(27)(28) (33).…”

Section: Introductionmentioning

confidence: 73%

“…This approach has also been applied to less soluble particles. Reasonable agreement was obtained when translocation in vivo was compared to dissolution of insoluble particles in lung fluid simulants (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28). It has to be stated, however, that the particles used were not uniform and that their physical parameters, in particular their specific surface areas, were not known exactly, resulting in considerable uncertainty.…”

Section: Introductionmentioning

confidence: 99%

Intracellular Particle Dissolution in Alveolar Macrophages

Kreyling¹

1992

Environmental Health Perspectives

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Aerosol particles deposited in the lungs that are not reaolily soluble in the epithelial lining fluid will be phagocytized by alveolar macrophages (AM). Inside the phagolysomal vacuole, the constituents ofthe plam allow dissolution ofavaiety ofcompounds at a higher rate than dissolutionietracelular lung fluids. Cielator concentration and a pH value ofabout 5 were found to control intracellular partice dissolution (IPD). Hence, IPD is the initial step oftranslocation ofdissolved material to blood, which is an important lung clearance nism for particles retined long term. IPD rtes of uniform test particles determined in human, baboon, and canine AM cultures were imilar to initialtrnslocation rates determined in lung clearnce studies ofthe same species after inhalation ofthe same test particles. IPD rate in cultured AM proved to be a sensitive functional parameter ofAM, which was used to identify changes in the clearance mechanism oftrnslocation during different exposure conditions.

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“…The empirical simulation model used ( Fig. 1 ) has been described in detail by Mewhinney and Griffith ( 1982). Briefly, mass balance among all compartments is assumed.…”

Section: Methodsmentioning

confidence: 99%

A Model for Scaling the Results of U Excretion Rate Studies in Beagle Dogs to Man

Af¹,

Wc²,

Ff³

et al. 1989

Health Physics

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A biokinetic model was used to simulate retention and excretion of two forms of U: ammonium diuranate (ADU), a relatively soluble form, and U3O8, a relatively insoluble form. These two U forms represent those most likely to be encountered in the U milling industry. The simulation model was compared with results from a study of aerosols of commercial refined U ore inhaled by laboratory animals. Beagle dogs were exposed by inhalation to ADU aerosols to achieve a median initial body burden of 0.058 mg U kg-1 body weight (within a range of 0.016 to 0.64 mg U kg-1), or to U3O8 aerosols to achieve a median retained body burden of 0.28 mg U kg-1 (0.030-0.81 mg U kg-1). The simulation model accurately described the accumulation of nephrotoxic concentrations of U in kidneys of animals exposed to ADU. Very small fractions of the initial body burden of U3O8 were translocated to kidney, and these fractions were overestimated by the model. The model showed general agreement with results of other laboratory animal studies and with available information from human exposures to ADU, UF6, or U3O8.

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Models of Am Metabolism in Beagles and Humans

Cited by 14 publications

References 4 publications

PLANT/SOIL CONCENTRATION RATIOS OF 226Ra FOR CONTRASTING SITES AROUND AN ACTIVE U MINE-MILL

PLANT/SOIL CONCENTRATION RATIOS OF 226Ra FOR CONTRASTING SITES AROUND AN ACTIVE U MINE-MILL

Intracellular Particle Dissolution in Alveolar Macrophages

A Model for Scaling the Results of U Excretion Rate Studies in Beagle Dogs to Man

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