%0 Journal Article
%T Factoring-in agglomeration of carbon nanotubes and nanofibers for better prediction of their toxicity versus asbestos
%A Ashley R Murray
%A Elena R Kisin
%A Alexey V Tkach
%A Naveena Yanamala
%A Robert Mercer
%A Shih-Houng Young
%A Bengt Fadeel
%A Valerian E Kagan
%A Anna A Shvedova
%J Particle and Fibre Toxicology
%D 2012
%I BioMed Central
%R 10.1186/1743-8977-9-10
%X 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.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.Carbon nanotubes (CNT), including single-walled (SWCNT), double-, and multi-walled (MWCNT), and carbon nanofibers (CNF) are allotropes of carbon featuring fibrous morphology. SWCNT (typically 0.4 - 3 nm in diameter) are composed of a single cylindrical sheet of graphene, MWCNT (2-200 nm in diameter) consist of several concentric, coaxial rolled up graphene sheets [1,2]. In contrast to CNT, CNF represent a less perfect
%U http://www.particleandfibretoxicology.com/content/9/1/10