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The Importance of Evaluating the Lot-to-Lot Batch Consistency of Commercial Multi-Walled Carbon Nanotube Products.

ABSTRACT: The biological response of multi-walled carbon nanotubes (MWNTs) is related to their physicochemical properties and a thorough MWNT characterization should accompany an assessment of their biological activity, including their potential toxicity. Beyond characterizing the physicochemical properties of MWNTs from different sources or manufacturers, it is also important to characterize different production lots of the same MWNT product from the same vendor (i.e., lot-to-lot batch consistency). Herein, we present a comprehensive physicochemical characterization of two lots of commercial pristine MWNTs (pMWNTs) and carboxylated MWNTs (cMWNTs) used to study the response of mammalian macrophages to MWNTs. There were many similarities between the physicochemical properties of the two lots of cMWNTs and neither significantly diminished the 24-h proliferation of RAW 264.7 macrophages up to the highest concentration tested (200 ?g cMWNTs/mL). Conversely, several physicochemical properties of the two lots of pMWNTs were different; notably, the newer lot of pMWNTs displayed less oxidative stability, a higher defect density, and a smaller amount of surface oxygen species relative to the original lot. Furthermore, a 72-h half maximal inhibitory concentration (IC-50) of ~90 µg pMWNTs/mL was determined for RAW 264.7 cells with the new lot of pMWNTs. These results demonstrate that subtle physicochemical differences can lead to significantly dissimilar cellular responses, and that production-lot consistency must be considered when assessing the toxicity of MWNTs.

SUBMITTER: Huynh MT

PROVIDER: S-EPMC7601794 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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The Importance of Evaluating the Lot-to-Lot Batch Consistency of Commercial Multi-Walled Carbon Nanotube Products.

Huynh Mai T MT Veyan Jean Francois JF Pham Hong H Rahman Raina R Yousuf Samad S Brown Alexander A Lin Jason J Balkus Kenneth J KJ Diwakara Shashini D SD Smaldone Ronald A RA LeGrand Bryanna B Mikoryak Carole C Draper Rockford R Pantano Paul P

Nanomaterials (Basel, Switzerland) 20200927 10

The biological response of multi-walled carbon nanotubes (MWNTs) is related to their physicochemical properties and a thorough MWNT characterization should accompany an assessment of their biological activity, including their potential toxicity. Beyond characterizing the physicochemical properties of MWNTs from different sources or manufacturers, it is also important to characterize different production lots of the same MWNT product from the same vendor (i.e., lot-to-lot batch consistency). Here ...[more]

PMID: 32992617

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Project description:Carbon nanotubes were among the earliest products of nanotechnology and have many potential applications in medicine, electronics, and manufacturing. The low density, small size, and biological persistence of carbon nanotubes create challenges for exposure control and monitoring and make respiratory exposures to workers likely. We have previously shown mitotic spindle aberrations in cultured primary and immortalized human airway epithelial cells exposed to 24, 48 and 96 ?g/cm(2) single-walled carbon nanotubes (SWCNT). To investigate mitotic spindle aberrations at concentrations anticipated in exposed workers, primary and immortalized human airway epithelial cells were exposed to SWCNT for 24-72 h at doses equivalent to 20 weeks of exposure at the Permissible Exposure Limit for particulates not otherwise regulated. We have now demonstrated fragmented centrosomes, disrupted mitotic spindles and aneuploid chromosome number at those doses. The data further demonstrated multipolar mitotic spindles comprised 95% of the disrupted mitoses. The increased multipolar mitotic spindles were associated with an increased number of cells in the G2 phase of mitosis, indicating a mitotic checkpoint response. Nanotubes were observed in association with mitotic spindle microtubules, the centrosomes and condensed chromatin in cells exposed to 0.024, 0.24, 2.4 and 24 ?g/cm(2) SWCNT. Three-dimensional reconstructions showed carbon nanotubes within the centrosome structure. The lower doses did not cause cytotoxicity or reduction in colony formation after 24h; however, after three days, significant cytotoxicity was observed in the SWCNT-exposed cells. Colony formation assays showed an increased proliferation seven days after exposure. Our results show significant disruption of the mitotic spindle by SWCNT at occupationally relevant doses. The increased proliferation that was observed in carbon nanotube-exposed cells indicates a greater potential to pass the genetic damage to daughter cells. Disruption of the centrosome is common in many solid tumors including lung cancer. The resulting aneuploidy is an early event in the progression of many cancers, suggesting that it may play a role in both tumorigenesis and tumor progression. These results suggest caution should be used in the handling and processing of carbon nanotubes.

Dataset Information

The Importance of Evaluating the Lot-to-Lot Batch Consistency of Commercial Multi-Walled Carbon Nanotube Products.

Publications

The Importance of Evaluating the Lot-to-Lot Batch Consistency of Commercial Multi-Walled Carbon Nanotube Products.

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