Article

Extrapulmonary translocation of ultrafine carbon particles following whole-body inhalation exposure of rats. J Toxicol Environ Health 65(20): 1531-1543

University of Rochester, Department of Environmental Medicine, Rochester, New York 14642, USA.
Journal of Toxicology and Environmental Health Part A (Impact Factor: 2.35). 11/2002; 65(20):1531-43. DOI: 10.1080/00984100290071658
Source: PubMed

ABSTRACT

Studies with intravenously injected ultrafine particles have shown that the liver is the major organ of their uptake from the blood circulation. Measuring translocation of inhaled ultrafine particles to extrapulmonary organs via the blood compartment is hampered by methodological difficulties (i.e., label may come off, partial solubilization) and analytical limitations (measurement of very small amounts). The objective of our pilot study was to determine whether ultrafine elemental carbon particles translocate to the liver and other extrapulmonary organs following inhalation as singlet particles by rats. We generated ultrafine (13)C particles as an aerosol with count median diameters (CMDs) of 20-29 nm (GSD 1.7) using electric spark discharge of (13)C graphite electrodes in argon. Nine Fischer 344 rats were exposed to these particles for 6 h. in whole-body inhalation chambers at concentrations of 180 and 80 microg/m(3); 3 animals each were killed at 0.5, 18, and 24 h postexposure. Six unexposed rats served as controls. Lung lobes, liver, heart, brain, olfactory bulb, and kidney were excised, homogenized, and freeze-dried for analysis of the added (13)C by isotope ratio mass spectrometry. Organic (13)C was not detected in the (13)C particles. The (13)C retained in the lung at 0.5 h postexposure was about 70% less than predicted by rat deposition models for ultrafine particles, and did not change significantly during the 24-h postexposure period. Normalized to exposure concentration, the added (13)C per gram of lung on average in the postexposure period was approximately 9 ng/g organ/microg/m(3). Significant amounts of (13)C had accumulated in the liver by 0.5 h postinhalation only at the high exposure concentration, whereas by 18 and 24 h postexposure the (13)C amount of the livers of all exposed rats was about fivefold greater than the (13)C burden retained in the lung. No significant increase in (13)C was detected in the other organs which were examined. These results demonstrate effective translocation of ultrafine elemental carbon particles to the liver by 1 d after inhalation exposure. Translocation pathways include direct input into the blood compartment from ultrafine carbon particles deposited throughout the respiratory tract. However, since predictive particle deposition models indicate that respiratory tract deposits alone may not fully account for the hepatic (13)C burden, input from ultrafine particles present in the GI tract needs to be considered as well. Such translocation to blood and extrapulmonary tissues may well be different between ultrafine carbon and other insoluble (metal) ultrafine particles.

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    • "Due to their very small density, SiNP can be readily evaporated into air, and can be inhaled. Following inhalation, nanoparticles have been reported to rapidly cross the alveolar capillary barrier and penetrate into to the systemic circulation and reach various organs [2] [3] [4] [5]. Furthermore, with their medical usage, after injection or skin application, nanoparticles can be distributed into the blood and affect the circulatory cells including platelets [1]. "

    Full-text · Dataset · Aug 2015
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    • "Due to their very small density, SiNP can be readily evaporated into air, and can be inhaled. Following inhalation, nanoparticles have been reported to rapidly cross the alveolar capillary barrier and penetrate into to the systemic circulation and reach various organs [2] [3] [4] [5]. Furthermore, with their medical usage, after injection or skin application, nanoparticles can be distributed into the blood and affect the circulatory cells including platelets [1]. "

    Full-text · Dataset · Jul 2015
    • "Target organ toxicity, especially pulmonary toxicity following exposure via inhalation, has been the focus of several studies in the last decade (Ferin et al., 1992; Grassian et al., 2007; Renwick et al., 2004; Warheit et al., 2007); however, very few in vivo studies have investigated the effects of translocation of particles to non-target tissues. In biodistribution studies using isotope-tagged or fluorescence labelled particles, a small fraction (less than 1%) of NPs [gold nanoparticles (2–40 nm), titanium dioxide nanoparticles (22 nm), ultrafine iridium particles (15 and 80 nm) radiolabeled with 192 iridium ( 192 Ir), carbon nanoparticles (25 nm) spiked with radio-labeled primary iridium ( 192 Ir) and isotopic ultrafine carbon particles ( 13 C; 20–29 nm)] deposited in lungs were shown to translocate to systemic circulation and reach extra-pulmonary organs including heart and liver (Geiser & Kreyling, 2010; Geiser et al., 2005; Kreyling et al., 2002; Muhlfeld et al., 2007; Nemmar et al., 2002a,b; Oberdorster et al., 2002; Sadauskas et al., 2007, 2009b). These studies did not elucidate the systemic effects of such particle translocation and the potential influence of doping the particles with isotope or fluorescent tags on translocation was not clear. "
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    ABSTRACT: An estimated 1% or less of nanoparticles (NPs) deposited in the lungs translocate to systemic circulation and enter other organs; however, this estimation may not be accurate given the low sensitivity of existing in vivo NP detection methods. Moreover, the biological effects of such low levels of translocation are unclear. We employed a nano-scale hyperspectral microscope to spatially observe and spectrally profile NPs in tissues and blood following pulmonary deposition in mice. In addition, we characterized effects occurring in blood, liver and heart at the mRNA and protein level following translocation from the lungs. Adult female C57BL/6 mice were exposed via intratracheal instillation to 18 or 162 µg of industrially relevant titanium dioxide nanoparticles (nano-TiO2) alongside vehicle controls. Using the nano-scale hyperspectral microscope, translocation to heart and liver was confirmed at both doses, and to blood at the highest dose, in mice analyzed 24 h post-exposure. Global gene expression profiling and ELISA analysis revealed activation of complement cascade and inflammatory processes in heart and specific activation of complement factor 3 in blood, suggesting activation of an early innate immune response essential for particle opsonisation and clearance. The liver showed a subtle response with changes in the expression of genes associated with acute phase response. This study characterizes the subtle systemic effects that occur in liver and heart tissues following pulmonary exposure and low levels of translocation of nano-TiO2 from lungs.
    No preview · Article · May 2015 · Nanotoxicology
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