NTP Technical Report on the Toxicity Studies of 1020 Long Multiwalled Carbon Nanotubes Administered by Inhalation to Sprague Dawley (Hsd:Sprague Dawley® SD®) Rats and B6C3F1/N Mice

The 2022 annual National Toxicology Program Satellite Symposium, entitled “Pathology Potpourri,” was held in Austin, Texas at the Society of Toxicologic Pathology’s 40th annual meeting during a half-day session on Sunday, June 19. The goal of this symposium was to present and discuss challenging diagnostic pathology and/or nomenclature issues. This article presents summaries of the speakers’ talks along with select images that were used by the audience for voting and discussion. Various lesions and topics covered during the symposium included induced and spontaneous neoplastic and nonneoplastic lesions in the mouse lung, spontaneous lesions in the reproductive tract of a female cynomolgus macaque, induced vascular lesions in a mouse asthma model and interesting case studies in a rhesus macaque, dog and genetically engineered mouse model.

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Respiratory and systemic impacts following MWCNT inhalation in B6C3F1/N mice

Migliaccio

Hamilton

Shaw

et al. 2021

Part Fibre Toxicol

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Background A very pure multi-walled carbon nanotube (MWCNT) that was shown to have very low toxicity in vitro, was evaluated for lung and systemic effects and distribution following inhalation exposure. Methods B6C3F1/N mice were exposed to varying doses (0, 0.06, 0.2, and 0.6 mg/m3) of the (99.1% carbon) MWCNT by inhalation for 30 days (excluding weekends). Ten days following the last exposure, the lungs and spleen were harvested and processed for histology and immune cell population assessment. In addition, lung lavage cells and fluid were analyzed. Stimulated Raman scattering (SRS) was used to identify particles in the lungs, spleen, kidneys, liver, mediastinal and brachial lymph nodes, and olfactory bulb. Splenic tissue sections were stained with hematoxylin and eosin (H&E) for light microscopic histopathology assessment. Blood plasma was analyzed for cytokines and cathepsins. A section of the spleen was processed for RNA isolation and relative gene expression for 84 inflammation-related cytokines/chemokines. Results Following MWCNT exposure, particles were clearly evident in the lungs, spleens, lymph nodes and olfactory bulbs, (but not livers or kidneys) of exposed mice in a dose-dependent manner. Examination of the lavaged lung cells was unremarkable with no significant inflammation indicated at all particle doses. In contrast, histological examination of the spleen indicated the presence of apoptotic bodies within T cells regions of the white pulp area. Isolated splenic leukocytes had significant changes in various cells including an increased number of proinflammatory CD11b+Ly6C+ splenic cells. The gene expression studies confirmed this observation as several inflammation-related genes were upregulated particularly in the high dose exposure (0.6 mg/m3). Blood plasma evaluations showed a systemic down-regulation of inflammatory cytokines and a dose-dependent up-regulation of lysosomal cathepsins. Conclusions The findings in the lungs were consistent with our hypothesis that this MWCNT exposure would result in minimal lung inflammation and injury. However, the low toxicity of the MWCNT to lung macrophages may have contributed to enhanced migration of the MWCNT to the spleen through the lymph nodes, resulting in splenic toxicity and systemic changes in inflammatory mediators.

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NTP Technical Report on the Toxicity Studies of 1020 Long Multiwalled Carbon Nanotubes Administered by Inhalation to Sprague Dawley (Hsd:Sprague Dawley® SD®) Rats and B6C3F1/N Mice

Cited by 4 publications

References 87 publications

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Physicochemical and biological characterization of oxidized multi-walled carbon nanotubes on HepG2 liver cells

Proceedings of the 2022 National Toxicology Program Satellite Symposium

Respiratory and systemic impacts following MWCNT inhalation in B6C3F1/N mice

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