Long‐term retention of pristine multi‐walled carbon nanotubes in rat lungs after intratracheal instillation

Abstract

As a result of the growing potential industrial and medical applications of multi‐walled carbon nanotubes (MWCNTs), people working in or residing near facilities that manufacture them may be exposed to airborne MWCNTs in the future. Because of concerns regarding their toxicity, quantitative data on the long‐term clearance of pristine MWCNTs from the lungs are required. We administered pristine MWCNTs well dispersed in 0.5 mg ml−1 Triton‐X solution to rats at doses of 0.20 or 0.55 mg via intratracheal instillation and investigated clearance over a 12‐month observation period. The pristine MWCNTs pulmonary burden was determined 1, 3, 7, 28, 91, 175 and 364 days after instillation using a method involving combustive oxidation and infrared analysis, combined with acid digestion and heat pretreatment. As 0.15‐ and 0.38‐mg MWCNTs were detected 1 day after administration of 0.20 and 0.55 mg MWCNTs, respectively, approximately 30% of administrated MWCNTs may have been cleared by bronchial ciliary motion within 24 h of administration. After that, the pulmonary MWCNT burden did not decrease significantly over time for up to 364 days after instillation, suggesting that MWCNTs were not readily cleared from the lung. Transmission electron microscopy (TEM) showed that alveolar macrophages internalized the MWCNTs and retained in the lung for at least 364 days after instillation. MWCNTs were not detected in the liver or brain within the 364‐day study period (<0.04 mg per liver, < 0.006 mg per brain). Copyright © 2015 The Authors Journal of Applied Toxicology Published by John Wiley & Sons Ltd.

Mechanisms of carbon nanotube‐induced pulmonary fibrosis: a physicochemical characteristic perspective

“…Methods for dispersing CNTs in an aqueous suspension using surfactant-containing media prior to instillation or aspiration in rats or mice have greatly improved, making this route of exposure generally acceptable 16 . Moreover, long term in vivo studies demonstrate that while CNTs clear from the lung to some extent via the mucociliary escalator or pulmonary lymphatics, longer nanotubes remain in the lung tissue of rodents over time due to their biopersistent nature 17–19 . Rodent exposure methods (e.g., inhalation vs aspiration) should be taken into consideration when comparing the relative fibrotic effects of CNTs.…”

Review of toxicity studies of carbon nanotubes

“…Although there are differences in the half-times, the authors considered that these delayed times were related to volumetric overload. A twelve-day inhalation study revealed that 65.1% of the total lung burden of MWCNTs at 5 mg/m 3 remained in the murine lungs 336 days after inhalation exposure 52) .Intratracheal instillation of MWCNTs at 0.2 mg and 0.55 mg revealed that the burden of MWCNTs in the lungs did not decrease significantly between 1 day and 364 days after exposure 53) .…”

Evaluating the mechanistic evidence and key data gaps in assessing the potential carcinogenicity of carbon nanotubes and nanofibers in humans

“…A study of well-dispersed MWCNT (geometric mean diameter and length: 48 nm and 2.5 μm, respectively; Nikkisco Co. Ltd., Tokyo, Japan) administered to rats by IT instillation (0.20 or 0.55 mg doses) showed significant pulmonary retention at 364 days post-instillation (Shinohara et al 2016). Approximately 30% of the MWCNT appeared to be cleared within 24 h of administration, while the lung burden of MWCNT did change significantly one year later.…”

“…Approximately 30% of the MWCNT appeared to be cleared within 24 h of administration, while the lung burden of MWCNT did change significantly one year later. MWCNT were observed inside alveolar macrophages, but were not detected by mass in the liver or brain at one year post-instillation (Shinohara et al 2016). …”