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Extrapulmonary transport of MWCNT following inhalation exposure.

Mercer RR, Scabilloni JF, Hubbs AF, Wang L, Battelli LA, McKinney W, Castranova V, Porter DW - Part Fibre Toxicol (2013)

Bottom Line: Tracheobronchial lymph nodes were found to contain 1.08 and 7.34 percent of the lung burden at 1 day and 336 days post-exposure, respectively.The burden of singlet MWCNT in the lymph nodes, diaphragm, chest wall and extrapulmonary organs at 336 days post-exposure was significantly higher than at 1 day post-exposure.The tracheobronchial lymph nodes contain high levels of MWCNT following exposure and further accumulate over nearly a year to levels that are a significant fraction of the lung burden 1 day post-exposure.

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ABSTRACT

Background: Inhalation exposure studies of mice were conducted to determine if multi-walled carbon nanotubes (MWCNT) distribute to the tracheobronchial lymphatics, parietal pleura, respiratory musculature and/or extrapulmonary organs. Male C57BL/6 J mice were exposed in a whole-body inhalation system to a 5 mg/m3 MWCNT aerosol for 5 hours/day for 12 days (4 times/week for 3 weeks, lung burden 28.1 ug/lung). At 1 day and 336 days after the 12 day exposure period, mice were anesthetized and lungs, lymph nodes and extrapulmonary tissues were preserved by whole body vascular perfusion of paraformaldehyde while the lungs were inflated with air. Separate, clean-air control groups were studied at 1 day and 336 days post-exposure. Sirius Red stained sections from lung, tracheobronchial lymph nodes, diaphragm, chest wall, heart, brain, kidney and liver were analyzed. Enhanced darkfield microscopy and morphometric methods were used to detect and count MWCNT in tissue sections. Counts in tissue sections were expressed as number of MWCNT per g of tissue and as a percentage of total lung burden (Mean ± S.E., N = 8 mice per group). MWCNT burden in tracheobronchial lymph nodes was determined separately based on the volume density in the lymph nodes relative to the volume density in the lungs. Field emission scanning electron microscopy (FESEM) was used to examine MWCNT structure in the various tissues.

Results: Tracheobronchial lymph nodes were found to contain 1.08 and 7.34 percent of the lung burden at 1 day and 336 days post-exposure, respectively. Although agglomerates account for approximately 54% of lung burden, only singlet MWCNT were observed in the diaphragm, chest wall, liver, kidney, heart and brain. At one day post exposure, the average length of singlet MWCNT in liver and kidney, was comparable to that of singlet MWCNT in the lungs 8.2 ± 0.3 versus 7.5 ± 0.4 um, respectively. On average, there were 15,371 and 109,885 fibers per gram in liver, kidney, heart and brain at 1 day and 336 days post-exposure, respectively. The burden of singlet MWCNT in the lymph nodes, diaphragm, chest wall and extrapulmonary organs at 336 days post-exposure was significantly higher than at 1 day post-exposure.

Conclusions: Inhaled MWCNT, which deposit in the lungs, are transported to the parietal pleura, the respiratory musculature, liver, kidney, heart and brain in a singlet form and accumulate with time following exposure. The tracheobronchial lymph nodes contain high levels of MWCNT following exposure and further accumulate over nearly a year to levels that are a significant fraction of the lung burden 1 day post-exposure.

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Percentage of 1 day post-exposure lung burden detected in tracheobronchial lymph nodes, extrapulmonary organs, diaphragm and chest wall. By 336 days post-exposure there was a 7-fold increase in MWCNT in extrapulmonary organs and diaphragm over that measured at 1 day post-exposure. Categories of extrapulmonary organs are ordered relative to MWCNT concentration in the respective tissue. Asterisks indicate significantly different between day 1 and 336 days post-exposure, p < 0.05.
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Figure 5: Percentage of 1 day post-exposure lung burden detected in tracheobronchial lymph nodes, extrapulmonary organs, diaphragm and chest wall. By 336 days post-exposure there was a 7-fold increase in MWCNT in extrapulmonary organs and diaphragm over that measured at 1 day post-exposure. Categories of extrapulmonary organs are ordered relative to MWCNT concentration in the respective tissue. Asterisks indicate significantly different between day 1 and 336 days post-exposure, p < 0.05.

Mentions: Results from morphometric analysis of MWCNT fibers in tracheobronchial lymph nodes, diaphragm, chest wall and extrapulmonary organs are shown in Figure 5. At 1 day post-exposure, the content of MWCNT fibers in the tracheobronchial lymph nodes was principally in the form of singlets or a few fibers per MWCNT structure and accounted for 1.08% of the lung burden 1 day post-exposure. MWCNT structures in tracheobronchial lymph nodes at 336 days included foci with dense accumulations with the content being substantially increased and equal to 7.34% of the lung burden 1 day post-exposure. MWCNT were only rarely observed in examination of the adventitia attached to the node capsules.


Extrapulmonary transport of MWCNT following inhalation exposure.

Mercer RR, Scabilloni JF, Hubbs AF, Wang L, Battelli LA, McKinney W, Castranova V, Porter DW - Part Fibre Toxicol (2013)

Percentage of 1 day post-exposure lung burden detected in tracheobronchial lymph nodes, extrapulmonary organs, diaphragm and chest wall. By 336 days post-exposure there was a 7-fold increase in MWCNT in extrapulmonary organs and diaphragm over that measured at 1 day post-exposure. Categories of extrapulmonary organs are ordered relative to MWCNT concentration in the respective tissue. Asterisks indicate significantly different between day 1 and 336 days post-exposure, p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750633&req=5

Figure 5: Percentage of 1 day post-exposure lung burden detected in tracheobronchial lymph nodes, extrapulmonary organs, diaphragm and chest wall. By 336 days post-exposure there was a 7-fold increase in MWCNT in extrapulmonary organs and diaphragm over that measured at 1 day post-exposure. Categories of extrapulmonary organs are ordered relative to MWCNT concentration in the respective tissue. Asterisks indicate significantly different between day 1 and 336 days post-exposure, p < 0.05.
Mentions: Results from morphometric analysis of MWCNT fibers in tracheobronchial lymph nodes, diaphragm, chest wall and extrapulmonary organs are shown in Figure 5. At 1 day post-exposure, the content of MWCNT fibers in the tracheobronchial lymph nodes was principally in the form of singlets or a few fibers per MWCNT structure and accounted for 1.08% of the lung burden 1 day post-exposure. MWCNT structures in tracheobronchial lymph nodes at 336 days included foci with dense accumulations with the content being substantially increased and equal to 7.34% of the lung burden 1 day post-exposure. MWCNT were only rarely observed in examination of the adventitia attached to the node capsules.

Bottom Line: Tracheobronchial lymph nodes were found to contain 1.08 and 7.34 percent of the lung burden at 1 day and 336 days post-exposure, respectively.The burden of singlet MWCNT in the lymph nodes, diaphragm, chest wall and extrapulmonary organs at 336 days post-exposure was significantly higher than at 1 day post-exposure.The tracheobronchial lymph nodes contain high levels of MWCNT following exposure and further accumulate over nearly a year to levels that are a significant fraction of the lung burden 1 day post-exposure.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Background: Inhalation exposure studies of mice were conducted to determine if multi-walled carbon nanotubes (MWCNT) distribute to the tracheobronchial lymphatics, parietal pleura, respiratory musculature and/or extrapulmonary organs. Male C57BL/6 J mice were exposed in a whole-body inhalation system to a 5 mg/m3 MWCNT aerosol for 5 hours/day for 12 days (4 times/week for 3 weeks, lung burden 28.1 ug/lung). At 1 day and 336 days after the 12 day exposure period, mice were anesthetized and lungs, lymph nodes and extrapulmonary tissues were preserved by whole body vascular perfusion of paraformaldehyde while the lungs were inflated with air. Separate, clean-air control groups were studied at 1 day and 336 days post-exposure. Sirius Red stained sections from lung, tracheobronchial lymph nodes, diaphragm, chest wall, heart, brain, kidney and liver were analyzed. Enhanced darkfield microscopy and morphometric methods were used to detect and count MWCNT in tissue sections. Counts in tissue sections were expressed as number of MWCNT per g of tissue and as a percentage of total lung burden (Mean ± S.E., N = 8 mice per group). MWCNT burden in tracheobronchial lymph nodes was determined separately based on the volume density in the lymph nodes relative to the volume density in the lungs. Field emission scanning electron microscopy (FESEM) was used to examine MWCNT structure in the various tissues.

Results: Tracheobronchial lymph nodes were found to contain 1.08 and 7.34 percent of the lung burden at 1 day and 336 days post-exposure, respectively. Although agglomerates account for approximately 54% of lung burden, only singlet MWCNT were observed in the diaphragm, chest wall, liver, kidney, heart and brain. At one day post exposure, the average length of singlet MWCNT in liver and kidney, was comparable to that of singlet MWCNT in the lungs 8.2 ± 0.3 versus 7.5 ± 0.4 um, respectively. On average, there were 15,371 and 109,885 fibers per gram in liver, kidney, heart and brain at 1 day and 336 days post-exposure, respectively. The burden of singlet MWCNT in the lymph nodes, diaphragm, chest wall and extrapulmonary organs at 336 days post-exposure was significantly higher than at 1 day post-exposure.

Conclusions: Inhaled MWCNT, which deposit in the lungs, are transported to the parietal pleura, the respiratory musculature, liver, kidney, heart and brain in a singlet form and accumulate with time following exposure. The tracheobronchial lymph nodes contain high levels of MWCNT following exposure and further accumulate over nearly a year to levels that are a significant fraction of the lung burden 1 day post-exposure.

Show MeSH
Related in: MedlinePlus