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Extrapulmonary transport of MWCNT following inhalation exposure.

Authors
Mercer-RR; Scabilloni-JF; Hubbs-AF; Wang-L; Battelli-LA; McKinney-W; Castranova-V; Porter-DW
Source
Part Fibre Toxicol 2013 Aug; 10:38
NIOSHTIC No.
20043086
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.
Keywords
Nanotechnology; Respiratory-system-disorders; Pulmonary-system-disorders; Lung-disorders; Laboratory-animals; Laboratory-testing; Exposure-assessment; Exposure-levels; Inhalation-studies; Lung-burden; Aerosol-particles; Aerosols; Lung-cells; Lung-tissue; Lymph-nodes; Microscopic-analysis; Cellular-reactions; Pleural-cavity
Contact
Robert R Mercer, Pathology and Physiology Research Branch, HELD, NIOSH, Morgantown, WV, USA
CAS No.
7440-44-0
Publication Date
20130809
Document Type
Journal Article
Email Address
rmercer@cdc.gov
Fiscal Year
2013
NTIS Accession No.
NTIS Price
Identifying No.
M082013
ISSN
1743-8977
NIOSH Division
HELD
Priority Area
Manufacturing
Source Name
Particle and Fibre Toxicology
State
WV
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