Characterizations and in vitro toxicity screening were performed on metal oxide engineered nanomaterials (ENMs) independently comprising ZnO, CuO, CeO2, Fe2O3, WO3, V2O5, TiO2, Al2O3 and MgO. Nanomaterials that exhibited the highest toxicity responses in the in vitro screening assays (ZnO, CuO, and V2O5) and the lesser explored material WO3 were tested for acute pulmonary toxicity in vivo. Female and male mice (C57Bl/6J) were exposed to aerosolized metal oxide ENMs in a nose-only exposure system and toxicity outcomes (biomarkers of cytotoxicity, immunotoxicity, inflammation, and lung histopathology) at 4 and 24 h after the start of exposure were assessed. The studies were performed as part of the NIEHS Nanomaterials Health Implications Research consortium with the purpose of investigating the effects of ENMs on various biological systems. ENMs were supplied by the Engineered Nanomaterials Resource and Coordination Core. Among the ENMs studied, the highest toxicity was observed for CuO and ZnO NPs in both in vitro and in vivo acute models. Compared to sham-exposed controls, there was a significant increase in bronchoalveolar lavage neutrophils and proinflammatory cytokines and a loss of macrophage viability at both 4 h and 24 h for ZnO and CuO but not seen for V2O5 or WO3. These effects were observed in both female and male mice. The cell viability performed after in vitro exposure to ENMs and assessment of lung inflammation after acute inhalation exposure in vivo were shown to be sensitive endpoints to predict ENM acute toxicity.
|State||Published - Apr 2020|
Bibliographical noteFunding Information:
The engineered nanomaterials used in the research presented in this publication have been procured/developed, characterized, and provided by the Engineered Nanomaterials Resource and Coordination Core established at Harvard T. H. Chan School of Public Health (NIH grant # U24ES026946) as part of the NHIR Consortium.
Research reported in this publication was supported by the National Institute of Environmental Health Sciences of the National Institutes of Health under Award Number [NIH grant # U01ES027252 ] as part of the Nanotechnology Health Implications Research (NHIR) Consortium which focuses on comprehensive evaluation of interactions between ENMs and biological systems. The research was conducted in laboratory facilities supported by the Environmental Health Sciences Research Center funded by NIH P30 ES005605. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
The research was conducted in laboratory facilities supported by the Environmental Health Sciences Research Center funded by NIH P30 ES005605. B.E.G. was supported by the Alfred P. Sloan Foundation Minority PhD Scholarship, National GEM Consortium Associate Fellowship , The University of Iowa Graduate College Dean's Fellowship. A.K.S. was supported by the Lyle & Sharon Bighley Endowed Professorship . We thank Dr. Xuefang Jing for her help with necropsies.
- In vitro toxicity
- Inhalation toxicity
- Metal oxides
ASJC Scopus subject areas
- Materials Science (miscellaneous)
- Safety, Risk, Reliability and Quality
- Safety Research
- Public Health, Environmental and Occupational Health