Pulmonary toxicity of well-dispersed cerium oxide nanoparticles following intratracheal instillation and inhalation
Open accessAbstract
We performed inhalation and intratracheal instillation studies of cerium dioxide (CeO 2 ) nanoparticles in order to investigate their pulmonary toxicity, and observed pulmonary inflammation not only in the acute and but also in the chronic phases. In the intratracheal instillation study, F344 rats were exposed to 0.2 mg or 1 mg of CeO 2 nanoparticles. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed from 3 days to 6 months following the instillation. In the inhalation study, rats were exposed to the maximum concentration of inhaled CeO 2 nanoparticles (2, 10 mg/m 3 , respectively) for 4 weeks (6 h/day, 5 days/week). The same endpoints as in the intratracheal instillation study were examined from 3 days to 3 months after the end of the exposure. The intratracheal instillation of CeO 2 nanoparticles caused a persistent increase in the total and neutrophil number in BALF and in the concentration of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2, chemokine for neutrophil, and heme oxygenase-1 (HO-1), an oxidative stress marker, in BALF during the observation time. The inhalation of CeO 2 nanoparticles also induced a persistent influx of neutrophils and expression of CINC-1, CINC-2, and HO-1 in BALF. Pathological features revealed that inflammatory cells, including macrophages and neutrophils, invaded the alveolar space in both studies. Taken together, the CeO 2 nanoparticles induced not only acute but also chronic inflammation in the lung, suggesting that CeO 2 nanoparticles have a pulmonary toxicity that can lead to irreversible lesions.
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Morimoto et al. reported a PMN increase persisting over 90 days post-exposure after 28 day exposure to 3 mg/m3 nano-ceria.
“Morimoto et al. [23] stated as the result of a 28 day exposure of rats to 3 mg/m3 of nano-ceria (Wako Chemical, Ltd.) a PMN increase persisting over 90 days post-exposure.”
From Effects from a 90-day inhalation toxicity study with cerium oxide and barium sulfate nanoparticles in rats (2017) · cites this paper as [23]
The Results (Inhalation study; page unavailable) report persistently elevated BALF neutrophil counts during follow-up, and Materials and methods (Inhalation of nanomaterial; page unavailable) specify four weeks of exposure with recovery observations through three months. The measured aerosol concentrations were 2.09 ± 0.29 and 10.2 ± 1.38 mg/m³, not 3 mg/m³; the paper also does not report follow-up beyond three months. (LLM, conf=0.91)
Experimental — accuracy not yet measuredInhalation of CeO2 induced pulmonary inflammation in a concentration-dependent manner with post-exposure persistency.
“Inhalation of CeO2induced pulmonary inflammation in a concentration-dependent manner with post-exposure persistency [3, 17, 22, 23].”
From Effects from a 90-day inhalation toxicity study with cerium oxide and barium sulfate nanoparticles in rats (2017) · cites this paper as [23]
Available in vivo studies on CeO2 nanoparticles confirm the induction of inflammation after inhalation.
“Available in vivo studies on CeO2nanoparticles confirm the induction of inflammation after inhalation [3, 6, 17, 22–26].”
From Effects from a 90-day inhalation toxicity study with cerium oxide and barium sulfate nanoparticles in rats (2017) · cites this paper as [23]
Few in vivo studies on CeO2 nanoparticles handle concentrations at lower levels (< 3 mg/m3).
“However, few of them handle concentrations at lower levels (< 3 mg/m3) [17, 23, 34].”
From Effects from a 90-day inhalation toxicity study with cerium oxide and barium sulfate nanoparticles in rats (2017) · cites this paper as [23]
Morimoto et al. did not detect fibrosis or tumor development of lung tissue after single ceria intratracheal instillation or 28-day inhalation with up to 90 days recovery.
“In contrast, Morimoto et al. [23] did not detect fibrosis or tumor development of lung tissue after single ceria intratracheal instillation or 28-day inhalation with up to 90 days recovery.”
From Effects from a 90-day inhalation toxicity study with cerium oxide and barium sulfate nanoparticles in rats (2017) · cites this paper as [23]
In most of the in vivo studies mentioned earlier, histopathological investigations revealed comparable findings after CeO2 exposure, especially particle-laden macrophages and lung inflammation.
“In most of the in vivo studies mentioned earlier, histopathological investigations were performed, revealing comparable findings after CeO2 exposure, especially in terms of particle-laden macrophages and lung inflammation [3, 6, 17, 22, 23, 26].”
From Effects from a 90-day inhalation toxicity study with cerium oxide and barium sulfate nanoparticles in rats (2017) · cites this paper as [23]
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- Authors
- Morimoto, Y., Izumi, H., Yoshiura, Y., Tomonaga, T., Oyabu, T., Myojo, T., Kawai, K., Yatera, K., Shimada, M., Kubo, M., Yamamoto, K., Kitajima, S., Kuroda, E., Kawaguchi, K., & Sasaki, T.
- Affiliations
- University of Occupational and Environmental Health Japan (JP)
- Hiroshima University (JP)
- National Institute of Advanced Industrial Science and Technology (JP)
- National Sanatorium Hoshizuka Keiaien (JP)
- Immunology Frontier Research Center, The University of Osaka (JP)
- Corresponding author
- Morimoto, Yasuo
- ORCID
- Venue
- Journal of Nanoparticle Research
- Published
- 2015-11
- Volume
- 17
- Issue
- 11
- Pages
- 442-442
- ISSN
- 1388-0764 (ISSN-L)
- 1572-896X
- PMC
- PMC4644191
- OpenAlex
- W2178606820
- Cited by
- 83
- References
- 31
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 7 · 2023: 2 · 2022: 12 · 2021: 5 · 2020: 12 · 2019: 15 · 2018: 7 · 2017: 10 · 2016: 5
- FWCI
- 2.98
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Nanoparticle Research (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Ministry of Economy, Trade and Industry (JP)
- Topics
- Physical Sciences › Materials Science › Materials Chemistry › Nanoparticles: synthesis and applications
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Occupational and environmental lung diseases
- Keywords
- cerium oxide nanoparticles, pulmonary toxicity, intratracheal instillation, inhalation exposure, lung inflammation, neutrophil infiltration, chemokines, CINC-1, heme oxygenase-1, oxidative stress, bronchoalveolar lavage fluid, alveolar macrophages, chronic lung inflammation
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