Influence of Impurities from Manufacturing Process on the Toxicity Profile of Boron Nitride Nanotubes

Abstract

The toxicity of boron nitride nanotubes (BNNTs) has been the subject of conflicting reports, likely due to differences in the residuals and impurities that can make up to 30–60% of the material produced based on the manufacturing processes and purification employed. Four BNNTs manufactured by induction thermal plasma process with a gradient of BNNT purity levels achieved through sequential gas purification, water and solvent washing, allowed assessing the influence of these residuals/impurities on the toxicity profile of BNNTs. Extensive characterization including infrared and X‐ray spectroscopy, thermogravimetric analysis, size, charge, surface area, and density captured the alteration in physicochemical properties as the material went through sequential purification. The material from each step is screened using acellular and in vitro assays for evaluating general toxicity, mechanisms of toxicity, and macrophage function. As the material increased in purity, there are more high‐aspect‐ratio particulates and a corresponding distinct increase in cytotoxicity, nuclear factor‐κB transcription, and inflammasome activation. There is no alteration in macrophage function after BNNT exposure with all purity grades. The cytotoxicity and mechanism of screening clustered with the purity grade of BNNTs, illustrating that greater purity of BNNT corresponds to greater toxicity.

Pulmonary Toxicity of Boron Nitride Nanomaterials Is Aspect Ratio Dependent

“…Therefore, this study highlighted that the shape of 2D materials is an important physicochemical parameter influencing the biological interaction with cells . In another in vitro study using the macrophage-derived THP-1 human cell line, Kodali et al, have shown that both BNNTs and h -BN induced biological responses 24 h after exposure . They found that h -BN and BNNTs caused significant increases in the secretion of several pro-inflammatory cytokines, including IL-1β and GM-CSF with some of them secreted in response to BNNTs, but not to h -BN .…”

“…18 They also found less cytotoxicity for h-BN and impure BNNTs (low amount of nanotubes per mass) than for pure BNNTs (high amount of nanotubes per mass). 18 Observing less toxicity for low aspect ratio h-BN nanosheets in comparison to high aspect ratio BNNTs agrees with the fiber pathogenicity paradigm and definition of high aspect ratio nanomaterials. It is well accepted that high aspect ratio materials, with a length above 5 μm and a ratio "lengthdiameter/thickness" greater than 3, could cause chronic lung toxicity and permanent damage after lung administration if they reached the alveolar region and induced frustrated phagocytosis in alveolar macrophages.…”

“…18 They reported a significant activation of the NLRP3 inflammasome only after exposure to BNNTs and established the lowest observed adverse effects level (LOAEL) for cytokine secretion at 25 μg/mL for purified BNNTs and at 100 μg/mL for h-BN. 18 They also found less cytotoxicity for h-BN and impure BNNTs (low amount of nanotubes per mass) than for pure BNNTs (high amount of nanotubes per mass). 18 Observing less toxicity for low aspect ratio h-BN nanosheets in comparison to high aspect ratio BNNTs agrees with the fiber pathogenicity paradigm and definition of high aspect ratio nanomaterials.…”

“…In another in vitro study using the macrophage-derived THP-1 human cell line, Kodali et al, have shown that both BNNTs and h -BN induced biological responses 24 h after exposure . They found that h -BN and BNNTs caused significant increases in the secretion of several pro-inflammatory cytokines, including IL-1β and GM-CSF with some of them secreted in response to BNNTs, but not to h -BN . They reported a significant activation of the NLRP3 inflammasome only after exposure to BNNTs and established the lowest observed adverse effects level (LOAEL) for cytokine secretion at 25 μg/mL for purified BNNTs and at 100 μg/mL for h -BN .…”

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

“…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.…”