title: Acute pulmonary dose-responses to inhaled multi-walled carbon nanotubes.
abstract: This study investigated the in vivo pulmonary toxicity of inhaled multi-walled carbon nanotubes (MWCNT). Mice-inhaled aerosolized MWCNT (10 mg/m³, 5 h/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 controls and were dose-dependent. Histopathologic alterations identified in the lung included (1) bronciolocentric inflammation, (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 dose-dependent pulmonary inflammation and damage with rapid development of pulmonary fibrosis, and also demonstrated that MWCNT can reach the pleura after inhalation exposure.
authors.affiliation: National Institute for Occupational Safety and Health , Morgantown, WV , USA.
authors.forename: Dale W
authors.initials: DW
authors.lastname: Porter
authors.forename: Ann F
authors.initials: AF
authors.lastname: Hubbs
authors.forename: Bean T
authors.initials: BT
authors.lastname: Chen
authors.forename: Walter
authors.initials: W
authors.lastname: McKinney
authors.forename: Robert R
authors.initials: RR
authors.lastname: Mercer
authors.forename: Michael G
authors.initials: MG
authors.lastname: Wolfarth
authors.forename: Lori
authors.initials: L
authors.lastname: Battelli
authors.forename: Nianqiang
authors.initials: N
authors.lastname: Wu
authors.forename: Krishnan
authors.initials: K
authors.lastname: Sriram
authors.forename: Stephen
authors.initials: S
authors.lastname: Leonard
authors.forename: Michael
authors.initials: M
authors.lastname: Andrew
authors.forename: Patsy
authors.initials: P
authors.lastname: Willard
authors.forename: Shuji
authors.initials: S
authors.lastname: Tsuruoka
authors.forename: Morinobu
authors.initials: M
authors.lastname: Endo
authors.forename: Takayuki
authors.initials: T
authors.lastname: Tsukada
authors.forename: Fuminori
authors.initials: F
authors.lastname: Munekane
authors.forename: David G
authors.initials: DG
authors.lastname: Frazer
authors.forename: Vincent
authors.initials: V
authors.lastname: Castranova
mesh_terms: D000336:Aerosols; D000418:Albumins / Q000032:analysis; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000032:analysis; D004578:Electron Spin Resonance Spectroscopy; D005355:Fibrosis; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000633:toxicity*; D009504:Neutrophils / Q000187:drug effects; D010316:Particle Size; D011014:Pneumonia / Q000139:chemically induced* / Q000473:pathology*; D013499:Surface Properties
chemical_list: D000336:Aerosols; D000418:Albumins; D016207:Cytokines; D037742:Nanotubes, Carbon