Limits...
Slow lung clearance and limited translocation of four sizes of inhaled iridium nanoparticles

View Article: PubMed Central - PubMed

ABSTRACT

Background: Concerns have been expressed that inhaled nanoparticles may behave differently to larger particles in terms of lung clearance and translocation, with potential implications for their toxicity. Studies undertaken to investigate this have typically involved limited post-exposure periods. There is a shortage of information on longer-term clearance and translocation patterns and their dependence on particle size, which this study aimed to address.

Methods: Rats were exposed (<3 h) nose-only to aerosols of spark-generated radioactive iridium-192 nanoparticles of four sizes: 10 nm, 15 nm, 35 nm and 75 nm (count median diameter) (aerosol mass concentrations 17, 140, 430, and 690 μg/m3, respectively). The content of iridium-192 in the whole animal, organs, tissues, and excreta was measured at various times post-exposure to ≥ 1 month. Limited toxicological investigations were undertaken for the 10 nm aerosol using bronchoalveolar lavage fluid. Elemental maps of tissue samples were produced using laser ablation inductively coupled plasma mass spectrometry and synchrotron micro-focus x-ray fluorescence. The chemical speciation of the iridium was explored using synchrotron micro focus x-ray near-edge absorption spectroscopy.

Results: Long-term lung retention half-times of several hundred days were found, which were not dependent on particle size. There was significant variation between individual animals. Analysis of bronchoalveolar lavage fluid for the 10 nm aerosol indicated a limited inflammatory response resolving within the first 7 days. Low levels of, particle size dependent, translocation to the kidney and liver were found (maximum 0.4% of the lung content). Any translocation to the brain was below the limits of detection (i.e. < 0.01% of the lung content). The kidney content increased to approximately 30 days and then remained broadly constant or decreased, whereas the content in the liver increased throughout the study. Laser ablation inductively coupled plasma mass spectrometry analysis indicated homogeneous iridium distribution in the liver and within the cortex in the kidney.

Conclusions: Slow lung clearance and a pattern of temporally increasing concentrations in key secondary target organs has been demonstrated for inhaled iridium aerosol particles < 100 nm, which may have implications for long-term toxicity, especially in the context of chronic exposures.

Electronic supplementary material: The online version of this article (doi:10.1186/s12989-017-0185-5) contains supplementary material, which is available to authorized users.

No MeSH data available.


Related in: MedlinePlus

Laser ablation inductively coupled plasma mass spectrometry (LA-ICM-PS) generated elemental maps of kidney samples at 30 days post-exposure from rats exposed to 10 nm (A) and 75 nm (B) iridium aerosols; showing light microscopy image of the kidney section analysed (a) and the distribution of copper (a), iridium (b) and an overlay of the two plots (c) (copper, magenta; iridium, green; both, white) Scales are in counts per second. The copper distribution map is included to enhance visualisation of the localisation of the iridium; results from control animals (not shown) indicate no iridium is present and the same overall pattern of copper distribution
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Fig6: Laser ablation inductively coupled plasma mass spectrometry (LA-ICM-PS) generated elemental maps of kidney samples at 30 days post-exposure from rats exposed to 10 nm (A) and 75 nm (B) iridium aerosols; showing light microscopy image of the kidney section analysed (a) and the distribution of copper (a), iridium (b) and an overlay of the two plots (c) (copper, magenta; iridium, green; both, white) Scales are in counts per second. The copper distribution map is included to enhance visualisation of the localisation of the iridium; results from control animals (not shown) indicate no iridium is present and the same overall pattern of copper distribution

Mentions: Elemental maps of iridium (and other elements for comparison purposes) were produced for sections of lung, liver, kidney, and brain, and BALF cells. Iridium is clearly seen in the lung at 1, 5 and 30 days post-exposure for both the 10 nm and 75 nm aerosol (Additional file 1: Figures S9, S10). Elemental maps of BALF cells samples for the 10 nm aerosol at 3 days post-exposure and 35 nm aerosol at 589 days post-exposure show similar patterns of iridium association with BALF cells (Fig. 5). At 30 days post-exposure iridium is clearly seen in the kidney (Fig. 6) and liver (Additional file 1: Figure S11) for both the 10 nm and 75 nm aerosols. The iridium is concentrated in the kidney cortex. Further investigation of a small area of cortex using a reduced spot size failed to establish whether the iridium was associated with particular structures. The results for the liver indicate a homogenous spread, however, at this resolution it is not possible to identify whether the iridium is associated with specific organ structures.Fig. 5


Slow lung clearance and limited translocation of four sizes of inhaled iridium nanoparticles
Laser ablation inductively coupled plasma mass spectrometry (LA-ICM-PS) generated elemental maps of kidney samples at 30 days post-exposure from rats exposed to 10 nm (A) and 75 nm (B) iridium aerosols; showing light microscopy image of the kidney section analysed (a) and the distribution of copper (a), iridium (b) and an overlay of the two plots (c) (copper, magenta; iridium, green; both, white) Scales are in counts per second. The copper distribution map is included to enhance visualisation of the localisation of the iridium; results from control animals (not shown) indicate no iridium is present and the same overall pattern of copper distribution
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5304551&req=5

Fig6: Laser ablation inductively coupled plasma mass spectrometry (LA-ICM-PS) generated elemental maps of kidney samples at 30 days post-exposure from rats exposed to 10 nm (A) and 75 nm (B) iridium aerosols; showing light microscopy image of the kidney section analysed (a) and the distribution of copper (a), iridium (b) and an overlay of the two plots (c) (copper, magenta; iridium, green; both, white) Scales are in counts per second. The copper distribution map is included to enhance visualisation of the localisation of the iridium; results from control animals (not shown) indicate no iridium is present and the same overall pattern of copper distribution
Mentions: Elemental maps of iridium (and other elements for comparison purposes) were produced for sections of lung, liver, kidney, and brain, and BALF cells. Iridium is clearly seen in the lung at 1, 5 and 30 days post-exposure for both the 10 nm and 75 nm aerosol (Additional file 1: Figures S9, S10). Elemental maps of BALF cells samples for the 10 nm aerosol at 3 days post-exposure and 35 nm aerosol at 589 days post-exposure show similar patterns of iridium association with BALF cells (Fig. 5). At 30 days post-exposure iridium is clearly seen in the kidney (Fig. 6) and liver (Additional file 1: Figure S11) for both the 10 nm and 75 nm aerosols. The iridium is concentrated in the kidney cortex. Further investigation of a small area of cortex using a reduced spot size failed to establish whether the iridium was associated with particular structures. The results for the liver indicate a homogenous spread, however, at this resolution it is not possible to identify whether the iridium is associated with specific organ structures.Fig. 5

View Article: PubMed Central - PubMed

ABSTRACT

Background: Concerns have been expressed that inhaled nanoparticles may behave differently to larger particles in terms of lung clearance and translocation, with potential implications for their toxicity. Studies undertaken to investigate this have typically involved limited post-exposure periods. There is a shortage of information on longer-term clearance and translocation patterns and their dependence on particle size, which this study aimed to address.

Methods: Rats were exposed (<3 h) nose-only to aerosols of spark-generated radioactive iridium-192 nanoparticles of four sizes: 10 nm, 15 nm, 35 nm and 75 nm (count median diameter) (aerosol mass concentrations 17, 140, 430, and 690 μg/m3, respectively). The content of iridium-192 in the whole animal, organs, tissues, and excreta was measured at various times post-exposure to ≥ 1 month. Limited toxicological investigations were undertaken for the 10 nm aerosol using bronchoalveolar lavage fluid. Elemental maps of tissue samples were produced using laser ablation inductively coupled plasma mass spectrometry and synchrotron micro-focus x-ray fluorescence. The chemical speciation of the iridium was explored using synchrotron micro focus x-ray near-edge absorption spectroscopy.

Results: Long-term lung retention half-times of several hundred days were found, which were not dependent on particle size. There was significant variation between individual animals. Analysis of bronchoalveolar lavage fluid for the 10 nm aerosol indicated a limited inflammatory response resolving within the first 7 days. Low levels of, particle size dependent, translocation to the kidney and liver were found (maximum 0.4% of the lung content). Any translocation to the brain was below the limits of detection (i.e. < 0.01% of the lung content). The kidney content increased to approximately 30 days and then remained broadly constant or decreased, whereas the content in the liver increased throughout the study. Laser ablation inductively coupled plasma mass spectrometry analysis indicated homogeneous iridium distribution in the liver and within the cortex in the kidney.

Conclusions: Slow lung clearance and a pattern of temporally increasing concentrations in key secondary target organs has been demonstrated for inhaled iridium aerosol particles < 100 nm, which may have implications for long-term toxicity, especially in the context of chronic exposures.

Electronic supplementary material: The online version of this article (doi:10.1186/s12989-017-0185-5) contains supplementary material, which is available to authorized users.

No MeSH data available.


Related in: MedlinePlus