A Dosimetry Model of Nickel Compounds in the Rat Lung

Hsieh, Tai Chiung; Yu, C.P.; Oberdörster, Günter

doi:10.1080/089583799197168

Cited by 24 publications

(14 citation statements)

References 18 publications

(19 reference statements)

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“…The modal diameter of the number size distribution was 14.6 ± 1.0 nm, median 17.1 ± 1.2 nm, and geometric standard deviation 1.38. The estimated total inhaled cumulative dose was 7.2 µg according to the formula of delivered dose (25,26). Four rats each were sacrificed on days 0, 1, 4, and 7 after the exposure for morphology and elemental analysis.…”

Section: Inhalation Exposurementioning

confidence: 99%

Pulmonary and systemic distribution of inhaled ultrafine silver particles in rats.

Takenaka¹,

Karg²,

Roth³

et al. 2001

Environ Health Perspect

520

382

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The cardiovascular system is currently considered a target for particulate matter, especially for ultrafine particles. In addition to autonomic or cytokine mediated effects, the direct interaction of inhaled materials with the target tissue must be examined to understand the underlying mechanisms. In the first approach, pulmonary and systemic distribution of inhaled ultrafine elemental silver (EAg) particles was investigated on the basis of morphology and inductively coupled plasma mass spectrometry (ICP-MS) analysis. Rats were exposed for 6 hr at a concentration of 133 microg EAg m(3) (3 x 10(6) cm(3), 15 nm modal diameter) and were sacrificed on days 0, 1, 4, and 7. ICP-MS analysis showed that 1.7 microg Ag was found in the lungs immediately after the end of exposure. Amounts of Ag in the lungs decreased rapidly with time, and by day 7 only 4% of the initial burden remained. In the blood, significant amounts of Ag were detected on day 0 and thereafter decreased rapidly. In the liver, kidney, spleen, brain, and heart, low concentrations of Ag were observed. Nasal cavities, especially the posterior portion, and lung-associated lymph nodes showed relatively high concentrations of Ag. For comparison, rats received by intratracheal instillation either 150 microL aqueous solution of 7 microg silver nitrate (AgNO(3) (4.4 microg Ag) or 150 microL aqueous suspension of 50 microg agglomerated ultrafine EAg particles. A portion of the agglomerates remained undissolved in the alveolar macrophages and in the septum for at least 7 days. In contrast, rapid clearance of instilled water-soluble AgNO(3) from the lung was observed. These findings show that although instilled agglomerates of ultrafine EAg particles were retained in the lung, Ag was rapidly cleared from the lung after inhalation of ultrafine EAg particles, as well as after instillation of AgNO(3), and entered systemic pathways.

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Section: Inhalation Exposurementioning

confidence: 99%

Pulmonary and systemic distribution of inhaled ultrafine silver particles in rats.

Takenaka¹,

Karg²,

Roth³

et al. 2001

Environ Health Perspect

520

382

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“…The calculated biological half-time of NiO nanoparticle from the lungs was 62 days (r 2 = .90). This biological half-time was similar to that of 3 mo for NiO particles in the micrometer range (Hsieh et al, 1999; 4 days 29 ± 3.7 1 month 16 ± 2.5 3 months 10 ± 1.1 Kodama et al, 1993) and to that of 1.5-2 mo for the other particulate matter (Morrow et al, 1991). As for the other nanoparticles, the retention half time of insoluble ultrafine iridium particles in the lung was 98 days (Semmler et al, 2004).…”

Section: Resultsmentioning

confidence: 56%

Biopersistence of Inhaled Nickel Oxide Nanoparticles in Rat Lung

Oyabu

Ogami

Morimoto

et al. 2007

Inhalation Toxicology

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In order to investigate whether or not airborne nanoparticles with a minimum agglomeration could be used for exposure tests on animals, we developed a nanoparticle generation system and examined the biological effects of the particles in an inhalation study. The generation system was composed of an ultrasonic nebulizer and diffusion dryers, and 30 Wistar male rats were exposed to nickel oxide (NiO) nanoparticles for 4 wk (6 h/day). The geometric mean diameter of the particles and the daily average exposure concentration determined by a combination of a differential mobility analyzer and a condensation nucleus counter in the exposure chamber were 139 +/- 12 nm and 1.0 +/- 0.5 x 10(5) particles/cm3, respectively. At 4 days and 1 and 3 mo after the inhalation, each group of 10 rats were sacrificed and NiO nanoparticles deposited in the lung were determined by chemical analysis and the biopersistence (biological half time) was calculated. The deposited amount of NiO nanoparticles in the rat lungs at 4 days after the inhalation was 29 +/- 4 microg. The retained particle amount in the rat lungs after the inhalation exponentially decreased and the calculated biological half time was 62 days. The histopathological change was not severe just after the inhalation nor throughout the observation time. We concluded that nanoparticles with a minimum agglomeration were dispersed stably in the chamber and exposed to rats for 4 wk and that deposited amounts in the rat lungs and the biopersistence of the particles and the biological response in lung were detected.

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“…This process is dependent in part on the particle size, with larger particles deposited in the upper airways and smaller particles deposited in the smaller or terminal airways and alveoli. In the case of applying the cellular dosimetry model to in vivo exposures, the deposited dose (M D ) could be estimated using the PBPK models developed by Oberdorster (1989) and Hsieh et al (1999a). Once deposited, depending on the chemical and physical properties of the …”

Section: Deposition (M D ) and Mucociliary Clearance (Cl M )mentioning

confidence: 99%

“…Four models that address the pharmacokinetics of nickel after inhalation exposure have been published (Edelman & Roggli, 1989;Hsieh et al, 1999a;Menzel, 1988;Menzel et al, 1987;Oberdorster, 1989). However, these published pharmacokinetic models were developed to describe large-scale pharmacokinetics, such as lung deposition and clearance and systemic distribution, and do not describe intracellular events or quantify the dose of nickel ion to the nucleus.…”

mentioning

confidence: 99%

A Pharmacokinetic Model of the Intracellular Dosimetry of Inhaled Nickel

Hack

Covington

Lawrence

et al. 2007

Journal of Toxicology and Environmental Health, Part A

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The potential associations between exposure to nickel compounds and cancer have been evaluated in both animal and epidemiological studies of occupationally exposed workers. The results of the epidemiological studies suggest that not all nickel compounds are equally carcinogenic, an observation supported by the animal bioassay results. Given the complexity and the differences in the modes of uptake of different forms of nickel by cells and the subsequent delivery of nickel to the nucleus, it would be expected that some forms of nickel would be more potent than others. A physiologically based pharmacokinetic (PBPK) model would be useful in estimating the cellular exposure to nickel resulting from inhalation of the different forms of nickel. To this end, a preliminary model of a tracheobronchial epithelial cell was developed to describe the differences in the extracellular and intracellular kinetics of the different classes of nickel compounds. Data available in the published literature were used to define the initial model parameters. The resulting cellular dosimetry model was able to describe kinetic data on three forms of nickel (soluble chloride and insoluble sulfide and subsulfide). This preliminary model development effort has identified critical data gaps that could be filled by additional research. The ultimate goal will be to integrate a refined cellular dosimetry model with published lung deposition/clearance and systemic distribution/clearance models for nickel. The use of such an integrated PBPK model would allow for more biologically based risk estimates for the inhalation of the different nickel compounds, as well as mixtures of these compounds.

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A Dosimetry Model of Nickel Compounds in the Rat Lung

Cited by 24 publications

References 18 publications

Pulmonary and systemic distribution of inhaled ultrafine silver particles in rats.

Pulmonary and systemic distribution of inhaled ultrafine silver particles in rats.

Biopersistence of Inhaled Nickel Oxide Nanoparticles in Rat Lung

A Pharmacokinetic Model of the Intracellular Dosimetry of Inhaled Nickel

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