Inhalation exposure studies of mice were conducted to determine if multi-walled carbon nanotubes (MWCNT) distribute to the parietal pleura, respiratory musculature and systemic organs. Male C57BL/6J 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). At 1 day and 48 weeks after the 12 day exposure period, mice were anesthetized and lungs and systemic tissues were preserved by whole body vascular perfusion of paraformaldehyde while inflated with air. A separate, clean-air control group was studied. Sirius Red stained sections from lung, diaphragm, chest wall, heart, 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 cm2 of tissue (mean±SE, N=8 mice per group). Although agglomerates account for approximately 60% of lung burden, only singlet MWCNT were observed in diaphragm, chest wall and systemic tissues. At one day post exposure, the average length of singlet MWCNT in diaphragm was comparable to that of singlet MWCNT in the lungs 5.6 ± 0.6 versus 5.1 ± 0.6 um, respectively. There were 26 ± 13 and 134 ± 25 per cm2 in tissue sections of diaphragm at 1 day and 48 weeks post exposure, respectively. On average, there were 18 ± 5 and 50 ± 20 per cm2 singlet MWCNT observed in systemic organ tissue sections at 1 day and 48 weeks, respectively. The burden of singlet MWCNT in parietal pleura, respiratory musculature and systemic organs at 48 weeks post exposure was significantly higher than at 1 day post exposure. Results demonstrate that inhaled MWCNT, which deposit in the lungs, are transported to the parietal pleura, the respiratory musculature and the systemic organs in a singlet form and accumulate with time following exposure.
Toxicology; Nanotechnology; Aerosols; Laboratory-animals; Laboratory-techniques; Exposure-assessment; Exposure-levels; Inhalation-studies; Pulmonary-system; Dose-response; Histopathology; Lung-burden; Fiber-deposition; Pleural-cavity; Lung-tissue; Tissue-culture; Heart; Kidneys; Liver-tissue; Liver; Particle-counters; Muscle-tissue
The Toxicologist. Society of Toxicology 52nd Annual Meeting and ToxExpo, San Antonio, Texas, March 10-14, 2013