Understanding toxicity associated with boron nitride nanotubes: Review of toxicity studies, exposure assessment at manufacturing facilities, and read-across

Kodali, Vamsi; Roberts, Jenny R.; Glassford, Eric; Gill, Ryan T.; Friend, Sherri; Dunn, Kevin L.; Erdely, Aaron

doi:10.1557/s43578-022-00796-8

Cited by 14 publications

(12 citation statements)

References 98 publications

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“…In the present study, it is assumed that a single dose of 30 μg per mouse was representative of a worst-case scenario such as accidental exposure at a production facility with no respiratory protection. , Despite this high dose, low aspect ratio h -BN nanosheets did not cause any lung inflammation or damage and were eliminated efficiently from the lungs, with only a few materials remaining after 28 days. The absence of acute immune response was somewhat surprising because most of the 2D materials tested so far by us and others induced at least an acute lung inflammation after administration to high doses in rodents. ,, …”

Section: Resultsmentioning

confidence: 99%

“…Overall, it remains unknown if BNNTs with a greater amount of nanotubes per mass could cause permanent lung damage at doses similar to those used in previous in vivo works 10,11 or at a lower doses representative of occupational exposure. 16 The safety profile of h-BN nanosheets remains also largely unknown due to the lack of in vivo studies. Recently, Lucherelli et al, investigated two types of h-BN nanosheets, one with a cornered/sharp structure and one with a round form, the latter similar to h-BN used in the present study.…”

Section: Introductionmentioning

confidence: 99%

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Pulmonary Toxicity of Boron Nitride Nanomaterials Is Aspect Ratio Dependent

Visani de Luna,

Loret,

et al. 2023

ACS Nano

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Boron nitride (BN) nanomaterials have drawn a lot of interest in the material science community. However, extensive research is still needed to thoroughly analyze their safety profiles. Herein, we investigated the pulmonary impact and clearance of two-dimensional hexagonal boron nitride ( h -BN) nanosheets and boron nitride nanotubes (BNNTs) in mice. Animals were exposed by single oropharyngeal aspiration to h -BN or BNNTs. On days 1, 7, and 28, bronchoalveolar lavage (BAL) fluids and lungs were collected. On one hand, adverse effects on lungs were evaluated using various approaches ( e.g ., immune response, histopathology, tissue remodeling, and genotoxicity). On the other hand, material deposition and clearance from the lungs were assessed. Two-dimensional h -BN did not cause any significant immune response or lung damage, although the presence of materials was confirmed by Raman spectroscopy. In addition, the low aspect ratio h -BN nanosheets were internalized rapidly by phagocytic cells present in alveoli, resulting in efficient clearance from the lungs. In contrast, high aspect ratio BNNTs caused a strong and long-lasting inflammatory response, characterized by sustained inflammation up to 28 days after exposure and the activation of both innate and adaptive immunity. Moreover, the presence of granulomatous structures and an indication of ongoing fibrosis as well as DNA damage in the lung parenchyma were evidenced with these materials. Concurrently, BNNTs were identified in lung sections for up to 28 days, suggesting long-term biopersistence, as previously demonstrated for other high aspect ratio nanomaterials with poor lung clearance such as multiwalled carbon nanotubes (MWCNTs). Overall, we reveal the safer toxicological profile of BN-based two-dimensional nanosheets in comparison to their nanotube counterparts. We also report strong similarities between BNNTs and MWCNTs in lung response, emphasizing their high aspect ratio as a major driver of their toxicity.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pulmonary Toxicity of Boron Nitride Nanomaterials Is Aspect Ratio Dependent

Visani de Luna,

Loret,

et al. 2023

ACS Nano

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“…Similarly, while boron nitride nanotubes exhibit enticing properties, the complexity of their synthesis and potential reactivity challenge their seamless incorporation into biomimetic environments. 20 Moreover, achieving biocompatibility for silica nanotubes through surface modification is feasible, but their nonbiodegradable characteristics pose safety concerns and act as a barrier to their advancement. 21 Cyclic peptide nanotubes (CPNTs) emerge as a recent addition to this discourse, bringing forth substantial promise.…”

Section: Introductionmentioning

confidence: 99%

“…Carbon nanotubes, celebrated for their unparalleled mechanical and electrical attributes, are hindered by biocompatibility concerns and potential toxicity limitations, − which curtail their widespread biological application. Similarly, while boron nitride nanotubes exhibit enticing properties, the complexity of their synthesis and potential reactivity challenge their seamless incorporation into biomimetic environments . Moreover, achieving biocompatibility for silica nanotubes through surface modification is feasible, but their nonbiodegradable characteristics pose safety concerns and act as a barrier to their advancement …”

Section: Introductionmentioning

confidence: 99%

Exploring Cyclic Peptide Nanotube Stability Across Diverse Lipid Bilayers and Unveiling Water Transport Dynamics

Moral,

Paul

2023

Langmuir

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Cyclic Peptide Nanotubes (CPNTs) have emerged as compelling candidates for various applications, particularly as nanochannels within lipid bilayers. In this study, the stability of two CPNTs, namely 8 × [(Cys-Gly-Met-Gly)2] and 8 × [(Gly-Leu)4], are comprehensively investigated across different lipid bilayers, including 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), a mixed model membrane (POPE/POPG), and a realistic yeast model membrane. The results demonstrate that both CPNTs maintain their tubular structures in all lipid bilayers, with [(Cys-Gly-Met-Gly)2] showing increased stability over an extended period in these lipid membranes. The insertion of CPNTs shows negligible impact on lipid bilayer properties, including area per lipid, volume per lipid, and bilayer thickness. The study demonstrates that the CPNT preserves its two-line water movement pattern within all the lipid membranes, reaffirming their potential as water channels. The MSD curves further reveal that the dynamics of water molecules inside the nanotube are similar for all the bilayer systems with minor differences that arise due to different lipid environments.

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“…BNNTs have potential for self-cleaning and anticorrosive surfaces . Owing to BNNTs biological compatibility and reduced toxicity to cells compared to carbon nanotubes, − there are many application arenas for BNNTs beyond the realm of industrial materials, including biological and clinical environments, such as in drug carrier design and cancer therapeutics . Despite the time since the first demonstration of BNNTs and their remarkable collection of properties, progress in their development has been slow.…”

Section: Introductionmentioning

confidence: 99%

Low-Temperature Triazine Functionalization of Boron Nitride Nanotubes for Applications from Drug Delivery to Advanced Composites

Homenick,

Bennett,

et al. 2023

ACS Appl. Nano Mater.

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Boron nitride nanotubes (BNNTs) are emerging nanomaterials with impressive mechanical properties and unique multifunctional properties including high thermal stability, electrical insulation, optical transparency, neutron absorption capability, and piezoelectricity. To harness the true potential of BNNTs for applications from drug delivery to advanced coatings and composites, functionalization is necessary to enhance their solubility and processability. Current functionalization approaches require aggressive reaction conditions such as long reaction times, high temperatures, high pressures, aggressive reagents, and an inert atmosphere. Herein, we present the development of a low temperature covalent functionalization method for enhanced solution processing of BNNTs utilizing a nitrene based (2 + 1) cycloaddition reaction that results in enhanced BNNT processability and solubility in N-methyl-2-pyrrolidone and N,N-dimethylformamide. Confirmation and degree of covalent functionalization are established using infrared (IR) spectroscopy, X-ray photoelectron spectroscopy (XPS), and thermal gravimetric analysis (TGA). Poly(3-hexylthiophene) (P3HT) is used to assess the quality of the BNNTs postfunctionalization to again confirm covalent functionalization. Finally, secondary functionalization of the functionalized BNNTs with propargyl chloride is achieved to demonstrate that this functionalization not only enhances the processability of the BNNTs but also results in a BNNT surface platform in which a plethora of molecules and nanomaterials can be grafted based on the application case. This nondestructive method preserves the extraordinary properties of BNNTs while opening their widespread use in many new and exciting opportunities in materials development.

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Understanding toxicity associated with boron nitride nanotubes: Review of toxicity studies, exposure assessment at manufacturing facilities, and read-across

Cited by 14 publications

References 98 publications

Pulmonary Toxicity of Boron Nitride Nanomaterials Is Aspect Ratio Dependent

Pulmonary Toxicity of Boron Nitride Nanomaterials Is Aspect Ratio Dependent

Exploring Cyclic Peptide Nanotube Stability Across Diverse Lipid Bilayers and Unveiling Water Transport Dynamics

Low-Temperature Triazine Functionalization of Boron Nitride Nanotubes for Applications from Drug Delivery to Advanced Composites

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