Assessing Organomodified Nanoclay Pulmonary Toxicity Across Its Life Cycle Using Integrated Exposure and In Vitro/In Vivo Approaches
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2019/03/01
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Description:Organomodified nanoclay (ONC)-enabled composite technology continues to revolutionize commercial, industrial, and consumer materials, which entail unique coatings, thin film, and durable polymer applications. Pulmonary health risks to ONCs along their chemical life cycle, however, are not understood. This project aims to link physicochemical properties of ONCs in their as-produced, product breakdown, and incinerated byproduct forms to adverse pulmonary effects, with crystalline silica (CS) as a comparative benchmark particle. Low dose pre-incinerated ONC exposure (Clois30B, Clois25A, and to lesser extent, Clois93A) caused a mixed Th1/Th2/Th17 inflammation response while higher doses elicited a mixed apoptotic/necrotic effect in human macrophages. Uncoated CloisNa caused membrane damage, inflammasome activation, and apoptosis in epithelial and macrophage cells, with minimal response observed in incinerated ONC-exposed cells. High dose incinerated uncoated and ONC caused elevated IL-8 and MCP-1 release in both in vitro and in vivo models, and were greater than CS. Both CloisNa and Clois30B stimulated in vitro fibroblast proliferation and collagen production. Similar doses of pre- and post-incinerated Clois30B in a C57BL/6 mouse model caused a delayed, low-grade inflammatory response followed by an increased pro-fibrotic and inflammatory cytokine profile. Finally, dust release was compared across scenarios using different base sandpaper material and grits on breakdown of synthesized nanoclay-enabled polypropylene composite (NPC). Coarse grit sandpaper on 4% Clois93A NPC, a composite with well-dispersed nanoclay, caused the largest release of respirable particles compared to 4% Clois25A NPC, virgin polypropylene, all 1% NPCs, and all composites sanded with fine grit sandpaper. These findings suggest 1) coating presence, type, and incineration status determine pulmonary inflammation and fibrotic signaling, and 2) sandpaper characteristics, different ONC coatings, and percent ONC inclusion affected NPC breakdown and airborne particle mass and size distributions. Evaluation of ONCs along their life cycle, by incorporating exposure estimates into current in vitro/in vivo comparative toxicological tiered frameworks, provides key information for prevention-by-design and material user approaches. [Description provided by NIOSH]
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ISSN:1096-6080
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Volume:168
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Issue:1
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NIOSHTIC Number:nn:20054981
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Citation:Toxicologist 2019 Mar; 168(1):282
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Federal Fiscal Year:2019
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Peer Reviewed:False
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Source Full Name:The Toxicologist. Society of Toxicology 58th Annual Meeting and ToxExpo, March 10-14, 2019, Baltimore, Maryland
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Main Document Checksum:urn:sha-512:c0402b357217ea2c715d047d6fc2e9ab37cf82f9d3b716467d5c213a97ba3dcc67fd656dbab96c348a2db41ca98cb7141411cda93681f14cf6322556ba2bd19d
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