Do Impurities in Boron Nitride Nanotube Material Influence Toxicity?
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2020/03/01
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Personal Author:Barger M ; Bowers L ; Dénommée S ; Erdely A ; Eye T ; Frasier K ; Hubczak J ; Jakubinek M ; Kim K ; Kodali V ; Leonard, Stephanie ; Porter, Dale ; Roach K ; Roberts J ; Shoeb M ; Stefaniak, Aleksandr B. ; Wolfarth M ; Xin X ; Yanamala N
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Description:Boron nitride nanotubes (BNNTs) have applications in a wide array of industries. Prior BNNT toxicity findings vary and could be attributed to the many manufacturing processes by which BNNTs are produced. These manufacturing processes result in BNNTs with a divergent array of physicochemical characteristics, but commercial processes share a common challenge of having 30-60 % residuals and impurities. Here we evaluated the impact of these impurities on the toxicological profile of BNNT materials. Four BNNT samples made by induction thermal plasma process with a gradient of BNNT purity levels (approximately 50-approximately 90% pure) were used to assess toxicity. Hexagonal boron nitride (h-BN) (approximately 100 nm in diameter) was used as a reference material. Electron micrographs confirmed a decrease in impurities and an increase in tubular structures across the gradient. The BNNTs dispersed in dispersion media decreased in as-produced dimensions and had a length of approximately 0.5-1.5 microm, diameter of approximately 5-30 nm, hydrodynamic diameter of 284-396 nm, surface area of 23-150 m2/g and density of 0.01-0.27 g/cm3. Electron paramagnetic resonance showed no change in acellular oxidative stress potential among the BNNTs of various purities. Cytotoxicity, proliferation, cellular oxidative stress, NF-kappaB-based induction of inflammation, and inflammasome activation were assessed in differentiated human monocytes (THP-1) at a concentration range of 0-100 microg/mL. There was a small increase in cytotoxicity and membrane damage with the highly purified BNNT materials, which decreased as the purity of the mixtures decreased. Oxidative stress measured by 4-hydroxynonenal expression, NF-kappaB by NF-kappaB-SEAP-expressing THP-1 cells, inflammasome activation by cellular caspase-1 and supernatants for IL1beta and IL18 showed a dose-dependent increase with increasing BNNT purity. At all measured end points there was minimal effect with h-BN at the measured concentrations. Computational modeling was used to identify the physicochemical characteristics that altered biological response. This work shows that BNNT mixtures manufactured through the plasma process have low toxicity in general; the increase in toxicity with increasing purity shows that the impurities have minimal role towards the toxicity endpoints measured. [Description provided by NIOSH]
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ISSN:1096-6080
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Volume:174
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Issue:1
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NIOSHTIC Number:nn:20058972
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Citation:Toxicologist 2020 Mar; 174(1):278
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Federal Fiscal Year:2020
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Peer Reviewed:False
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Source Full Name:The Toxicologist. Society of Toxicology 59th Annual Meeting and ToxExpo, March 15-19, 2020, Anaheim, California
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Main Document Checksum:urn:sha-512:482c8a95e904343721457ff5b3b82ab54607c59a949fd5687453eda3596b2825467bc4669c352ab48e1917739657630f579a9f3daffd18f2ae78bc0933eadeee
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