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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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Enhanced darkfield images of MWCNT fibers in the diaphragm, kidney and brain at 1 day and 336 days after inhalation exposure. MWCNT fibers in these figures are bright white, cell nuclei are brownish red and other tissue elements are green. With rare exceptions, MWCNT fibers detected in extrapulmonary organs were singlets. Normal (transmitted) light was blended into the fields and contrast adjusted to make the tissue histology of the organs visible in these photographs.
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Figure 3: Enhanced darkfield images of MWCNT fibers in the diaphragm, kidney and brain at 1 day and 336 days after inhalation exposure. MWCNT fibers in these figures are bright white, cell nuclei are brownish red and other tissue elements are green. With rare exceptions, MWCNT fibers detected in extrapulmonary organs were singlets. Normal (transmitted) light was blended into the fields and contrast adjusted to make the tissue histology of the organs visible in these photographs.

Mentions: Examples of the enhanced darkfield images of MWCNT fibers in the diaphragm, kidney and brain at 1 day and 336 days after inhalation exposure are given in Figure 3. MWCNT fibers detected in the diaphragm, chest wall and extrapulmonary organs were with rare exceptions, singlets. In these tissues, approximately one in 200 MWCNT structures were doublets. The nearly exclusive observation of singlet MWCNT in diaphragm, chest wall and extrapulmonary organs was in contrast to the observations of dense, large MWCNT structures observed at 336 days post-exposure in the tracheobronchial lymph nodes (Figure 2). At 336 days post-exposure, the concentration of fibers in diaphragm and extrapulmonary organs (Table 1) was significantly higher than at one day post-exposure. At 336 days post-exposure, singlet MWCNT were detectable in nearly all 40x fields of view in sections of liver and kidney with multiple, but separated, fibers detected in the same field of view as shown in the figure for the kidney. Average fiber length was 8.4 ± 0.3 and 8.8 ± 0.3 um at 1 and 336 days post-exposure in extrapulmonary organs (Mean ± S.E., N = 100). In the lungs, average fiber length of singlets was 8.2 ± 0.3 and 7.5 ± 0.4 um at 1 and 336 days post-exposure (N = 100).


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)

Enhanced darkfield images of MWCNT fibers in the diaphragm, kidney and brain at 1 day and 336 days after inhalation exposure. MWCNT fibers in these figures are bright white, cell nuclei are brownish red and other tissue elements are green. With rare exceptions, MWCNT fibers detected in extrapulmonary organs were singlets. Normal (transmitted) light was blended into the fields and contrast adjusted to make the tissue histology of the organs visible in these photographs.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Enhanced darkfield images of MWCNT fibers in the diaphragm, kidney and brain at 1 day and 336 days after inhalation exposure. MWCNT fibers in these figures are bright white, cell nuclei are brownish red and other tissue elements are green. With rare exceptions, MWCNT fibers detected in extrapulmonary organs were singlets. Normal (transmitted) light was blended into the fields and contrast adjusted to make the tissue histology of the organs visible in these photographs.
Mentions: Examples of the enhanced darkfield images of MWCNT fibers in the diaphragm, kidney and brain at 1 day and 336 days after inhalation exposure are given in Figure 3. MWCNT fibers detected in the diaphragm, chest wall and extrapulmonary organs were with rare exceptions, singlets. In these tissues, approximately one in 200 MWCNT structures were doublets. The nearly exclusive observation of singlet MWCNT in diaphragm, chest wall and extrapulmonary organs was in contrast to the observations of dense, large MWCNT structures observed at 336 days post-exposure in the tracheobronchial lymph nodes (Figure 2). At 336 days post-exposure, the concentration of fibers in diaphragm and extrapulmonary organs (Table 1) was significantly higher than at one day post-exposure. At 336 days post-exposure, singlet MWCNT were detectable in nearly all 40x fields of view in sections of liver and kidney with multiple, but separated, fibers detected in the same field of view as shown in the figure for the kidney. Average fiber length was 8.4 ± 0.3 and 8.8 ± 0.3 um at 1 and 336 days post-exposure in extrapulmonary organs (Mean ± S.E., N = 100). In the lungs, average fiber length of singlets was 8.2 ± 0.3 and 7.5 ± 0.4 um at 1 and 336 days post-exposure (N = 100).

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