Physicochemical Drivers of Primary Toxicologic Outcomes Induced by Carbon Nanotubes and Nanofibers from U.S. Facilities
Public Domain
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2022/08/28
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English
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Personal Author:Fraser, Kelly ; Yanamala, Naveena ; Eye, Tracy ; Friend, Sherri A. ; Stefaniak, Aleksandr B.
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Dahm, Matthew M.
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Schubauer-Berigan, Mary K.
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Lersch, Traci L.
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Casuccio, Gary
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Bunker, Kristin
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Hubbs, Ann F.
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Kodali, Vamsi K.
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Erdely, Aaron
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Description:Pulmonary exposure to carbon nanotubes or nanofibers (CNT/F) is known to induce inflammation, cytotoxicity, or tumorigenesis, and is a concern in the occupational setting. We have established toxicity profiles from male C57BL6/J mice aged8-10 weeks exposed to either 4 or 40 µg of one of nine different CNT/F via oropharyngeal aspiration as well as human epithelial BEAS-2B cells (0-24 µg/ml), differentiated THP-1cells (0-120 µg/ml), and human fibroblasts (0-2 µg/ml)for four primary outcomes: genotoxicity, inflammation, histopathology, and translocation. An overarching goal of our expansive study was to determine the relationship between particle physicochemical characteristics and those four major outcomes. The nine materials had a wide range of characteristics including diameter (6-397 nm), length (0.1-50 µm), surface area (18-238 m2/g), aspect ratio (2-1396), residual metal catalyst (0.3-6.2 %), density (0.007-0.220 g/cm3). While all materials induced some extent of adverse outcomes, not all materials induced the same specific outcomes, or the same severity or persistence of quantified toxicity endpoints. The distinguishing physicochemical characteristics were noted as particle physical dimensions and agglomeration size and shape. As a general trend, materials of longer length and diameter, as well as particles with larger or less spherical agglomerations, were more likely to induce greater genotoxicity and more severe and persistent inflammation. Furthermore, the particle size and agglomeration characteristics were determinants of the severity and general location for histopathological changes, specifically the bronchial/bronchiolar or alveolar regions. Extrapulmonary translocation did not follow these same trends with a narrower range of peak liver accumulation at 84 days post-exposure which correlated with one day singlet lung burden. Importantly, physical dimension profiling indicated only a small population of individual CNT/F in the sample need to have the larger length and diameter to confer greater toxicity. The study identified physicochemical drivers of CNT/F toxicity, which was supported by an integrated approach, combining experimental evidence with computational modeling, and may have potential for broad application. Description provided by NIOSH
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Pages in Document:3 pdf pages
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NIOSHTIC Number:nn:20071762
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Citation:13th International Particle Toxicology Conference, August 28-31, 2022, Santa Fe, New Mexico. Albuquerque, NM: University of New Mexico, 2022 Aug; :47-48
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CAS Registry Number:
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Federal Fiscal Year:2022
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Peer Reviewed:False
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Main Document Checksum:urn:sha-512:91ecf130beef074fae90d919daf33115b6228f0973a5a1d140c0d16b2eca48ca7b86477bc77932aa9ceeaf0a050c1bed9d828989f7c6e1571186bfcd67474f64
File Language:
English
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