title: Factoring-in agglomeration of carbon nanotubes and nanofibers for better prediction of their toxicity versus asbestos.
abstract: BACKGROUND
  Carbon nanotubes (CNT) and carbon nanofibers (CNF) are allotropes of carbon featuring fibrous morphology. The dimensions and high aspect ratio of CNT and CNF have prompted the comparison with naturally occurring asbestos fibers which are known to be extremely pathogenic. While the toxicity and hazardous outcomes elicited by airborne exposure to single-walled CNT or asbestos have been widely reported, very limited data are currently available describing adverse effects of respirable CNF.
  
  
  RESULTS
  Here, we assessed pulmonary inflammation, fibrosis, oxidative stress markers and systemic immune responses to respirable CNF in comparison to single-walled CNT (SWCNT) and asbestos. Pulmonary inflammatory and fibrogenic responses to CNF, SWCNT and asbestos varied depending upon the agglomeration state of the particles/fibers. Foci of granulomatous lesions and collagen deposition were associated with dense particle-like SWCNT agglomerates, while no granuloma formation was found following exposure to fiber-like CNF or asbestos. The average thickness of the alveolar connective tissue--a marker of interstitial fibrosis--was increased 28 days post SWCNT, CNF or asbestos exposure. Exposure to SWCNT, CNF or asbestos resulted in oxidative stress evidenced by accumulations of 4-HNE and carbonylated proteins in the lung tissues. Additionally, local inflammatory and fibrogenic responses were accompanied by modified systemic immunity, as documented by decreased proliferation of splenic T cells ex vivo on day 28 post exposure. The accuracies of assessments of effective surface area for asbestos, SWCNT and CNF (based on geometrical analysis of their agglomeration) versus estimates of mass dose and number of particles were compared as predictors of toxicological outcomes.
  
  
  CONCLUSIONS
  We provide evidence that effective surface area along with mass dose rather than specific surface area or particle number are significantly correlated with toxicological responses to carbonaceous fibrous nanoparticles. Therefore, they could be useful dose metrics for risk assessment and management.
authors.affiliation: Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, USA.
authors.forename: Ashley R
authors.initials: AR
authors.lastname: Murray
authors.forename: Elena R
authors.initials: ER
authors.lastname: Kisin
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Tkach
authors.forename: Naveena
authors.initials: N
authors.lastname: Yanamala
authors.forename: Robert
authors.initials: R
authors.lastname: Mercer
authors.forename: Shih-Houng
authors.initials: SH
authors.lastname: Young
authors.forename: Bengt
authors.initials: B
authors.lastname: Fadeel
authors.forename: Valerian E
authors.initials: VE
authors.lastname: Kagan
authors.forename: Anna A
authors.initials: AA
authors.lastname: Shvedova
mesh_terms: D000818:Animals; D017638:Asbestos, Crocidolite / Q000737:chemistry / Q000633:toxicity*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005260:Female; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D019016:Mineral Fibers / Q000633:toxicity; D057139:Nanofibers / Q000737:chemistry / Q000633:toxicity*; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000633:toxicity*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018384:Oxidative Stress / Q000187:drug effects / Q000276:immunology; D010316:Particle Size; D011014:Pneumonia / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011237:Predictive Value of Tests; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D013499:Surface Properties; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013997:Time Factors
chemical_list: D016207:Cytokines; D019016:Mineral Fibers; D037742:Nanotubes, Carbon; D017638:Asbestos, Crocidolite; D003094:Collagen