Acute pulmonary dose-responses to inhaled multi-walled carbon nanotubes.
Porter-DW; Hubbs-AF; Chen-T-HB; McKinney-W; Mercer-RR; Wolfarth-MG; Battelli-L; Wu-N; Sriram-K; Leonard-S; Andrew-ME; Willard-P; Tsuruoka-S; Morinobu-E; Tsukada-T; Munekane-F; Frazier-DG; Castranova-V
Nanotoxicology 2013 Nov; 7(7):1179-1194
This study investigated the in vivopulmonary toxicity of inhaled multi-walled carbon nanotubes (MWCNT). Mice inhaled aerosolized MWCNT (10 mg/m(3), 5 hours/day) for 2, 4, 8 or 12 days. MWCNT lung burden was linearly related to exposure duration. MWCNT-induced pulmonary inflammation was assessed by determining whole lung lavage (WLL) polymorphonuclear leukocytes (PMN). Lung cytotoxicity was assessed by WLL fluid LDH activities. WLL fluid albumin concentrations were determined as a marker of alveolar air-blood barrier integrity. These parameters significantly increased in MWCNT-exposed mice versus controlsand were dose-dependent. Histopathologic alterations identified in the lung included 1) bronciolocentricinflammation, 2) bronchiolar epithelial hyperplasia and hypertrophy, 3) fibrosis, 4) vascular changes and 5) rare pleural penetration. MWCNT translocated to the lymph node where the deep paracortex was expanded after 8 or 12 days. Acute inhalation of MWCNT induced dosedependent pulmonary inflammation and damage with rapid development of pulmonary fibrosis, and also demonstrated that MWCNT can reach the pleura after inhalation exposure.
Nanotechnology; Respiratory-system-disorders; Pulmonary-system-disorders; Lung-disorders; Lung-fibrosis; Exposure-assessment; Dose-response; In-vivo-study; Immune-reaction; Toxic-dose; Toxic-effects; Toxic-materials; Laboratory-animals; Inhalation-studies; Lung-burden; Acute-exposure; Lung-cells; Cytotoxicity; Fibrosis; Pleural-cavity; Lymph-nodes;
Author Keywords: characterization; lung burden; inflammation; fibrosis; pleural penetration
Dale W. Porter, Ph.D., Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, M/S 2015, Morgantown, WV, 26505, USA