Toxicity assessment of metal oxide nanomaterials using in vitro screening and murine acute inhalation studies

Sudartip Areecheewakul; Andrea Adamcakova-Dodd; Brittany E. Givens; Benjamin R. Steines; Yifang Wang; David K. Meyerholz; Nathanial J. Parizek; Ralph Altmaier; Ezazul Haque; Patrick T. O'Shaughnessy; Aliasger K. Salem; Peter S. Thorne

doi:10.1016/j.impact.2020.100214

Toxicity assessment of metal oxide nanomaterials using in vitro screening and murine acute inhalation studies

Sudartip Areecheewakul, Andrea Adamcakova-Dodd, Brittany E. Givens, Benjamin R. Steines, Yifang Wang, David K. Meyerholz, Nathanial J. Parizek, Ralph Altmaier, Ezazul Haque, Patrick T. O'Shaughnessy, Aliasger K. Salem, Peter S. Thorne

Chemical and Materials Engineering

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

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.

Original language	English
Article number	100214
Journal	NanoImpact
Volume	18
DOIs	https://doi.org/10.1016/j.impact.2020.100214
State	Published - Apr 2020

Bibliographical note

Funding 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.

Funding Information:
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.

Funding Information:
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.

Publisher Copyright:
© 2020

Keywords

In vitro toxicity
Inhalation toxicity
Metal oxides
Nanomaterials
Nanoparticles

ASJC Scopus subject areas

Materials Science (miscellaneous)
Safety, Risk, Reliability and Quality
Safety Research
Public Health, Environmental and Occupational Health

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.impact.2020.100214

Cite this

Areecheewakul, S., Adamcakova-Dodd, A., Givens, B. E., Steines, B. R., Wang, Y., Meyerholz, D. K., Parizek, N. J., Altmaier, R., Haque, E., O'Shaughnessy, P. T., Salem, A. K., & Thorne, P. S. (2020). Toxicity assessment of metal oxide nanomaterials using in vitro screening and murine acute inhalation studies. NanoImpact, 18, Article 100214. https://doi.org/10.1016/j.impact.2020.100214

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title = "Toxicity assessment of metal oxide nanomaterials using in vitro screening and murine acute inhalation studies",

abstract = "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.",

keywords = "In vitro toxicity, Inhalation toxicity, Metal oxides, Nanomaterials, Nanoparticles",

author = "Sudartip Areecheewakul and Andrea Adamcakova-Dodd and Givens, {Brittany E.} and Steines, {Benjamin R.} and Yifang Wang and Meyerholz, {David K.} and Parizek, {Nathanial J.} and Ralph Altmaier and Ezazul Haque and O'Shaughnessy, {Patrick T.} and Salem, {Aliasger K.} and Thorne, {Peter S.}",

note = "Funding 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. Funding Information: 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. Funding Information: 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. Publisher Copyright: {\textcopyright} 2020",

year = "2020",

month = apr,

doi = "10.1016/j.impact.2020.100214",

language = "English",

volume = "18",

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T1 - Toxicity assessment of metal oxide nanomaterials using in vitro screening and murine acute inhalation studies

AU - Areecheewakul, Sudartip

AU - Adamcakova-Dodd, Andrea

AU - Givens, Brittany E.

AU - Steines, Benjamin R.

AU - Wang, Yifang

AU - Meyerholz, David K.

AU - Parizek, Nathanial J.

AU - Altmaier, Ralph

AU - Haque, Ezazul

AU - O'Shaughnessy, Patrick T.

AU - Salem, Aliasger K.

AU - Thorne, Peter S.

N1 - Funding 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. Funding Information: 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. Funding Information: 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. Publisher Copyright: © 2020

PY - 2020/4

Y1 - 2020/4

N2 - 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.

AB - 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.

KW - In vitro toxicity

KW - Inhalation toxicity

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KW - Nanomaterials

KW - Nanoparticles

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Toxicity assessment of metal oxide nanomaterials using in vitro screening and murine acute inhalation studies

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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