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Subchronic Toxicity Evaluation of Aluminum Oxide Nanoparticles in Rats Following 28-Day Repeated Oral Administration

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Abstract

Several studies on the potential adverse effects of aluminum oxide nanoparticles (Al2O3NPs) have reported conflicting results. The present study investigated the potential adverse effects of Al2O3NPs in Sprague–Dawley rats following 28-day repeated oral administration. In addition, we aimed to determine the target organ and no-observed-adverse-effect level (NOAEL) of Al2O3NPs. Al2O3NPs was administered once daily by gavage to male and female rats at dose levels of 0, 500, and 1000 mg/kg/day for 28 days. There were no treatment-related adverse effects as indicated by the clinical signs, body weight, food consumption, urinalysis, ophthalmology, hematology, serum biochemistry, gross pathology, organ weight, and histopathology at all the tested doses. Under the experimental conditions of the present study, 28-day repeated oral administration of Al2O3NPs at doses of up to 1000 mg/kg/day did not induce any treatment-related systemic toxicity in male and female rats. The NOAEL of Al2O3NPs was set at 1000 mg/kg/day in both male and female rats and no target organs were identified.

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Funding

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education [NRF-2016R1D1A2B04936124]. This work was also supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2020R1A4A1019395).

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Authors and Affiliations

  1. College of Veterinary Medicine, Chonnam National University, Gwangju, 61186, Republic of Korea

    Sung-Hyeuk Park, Je-Oh Lim, Woong-Il Kim, So-Won Park, Se-Jin Lee, In-Sik Shin, Changjong Moon & Jong-Choon Kim

  2. Bioenvironmental Science & Technology Division, Korea Institute of Toxicology, Gyeongnam, 52834, Republic of Korea

    Je-Hein Kim & Jeong-Doo Heo

Authors
  1. Sung-Hyeuk Park
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  2. Je-Oh Lim
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  3. Woong-Il Kim
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Contributions

SHP, JOL, WIK, SWP, SJL, and JHK designed and performed the animal experiments, analyzed the data, and interpreted the results of experiments. CM and ISS performed the physicochemical analyses of particle suspensions, histopathology, and statistical analysis. The manuscript was written by SHP and JOL, and revised critically by JDH and JCK. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Jong-Choon Kim.

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Ethics Approval

This study was conducted in facilities approved by the Association for Assessment and Accreditation of Laboratory Animal Care International. All the procedures were approved by our Institutional Animal Care and Use Committee (Approved number: 1701–0003).

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The authors declare no competing interests.

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Sung-Hyeuk Park and Je-Oh Lim contributed equally to this work as co-first authors

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Park, SH., Lim, JO., Kim, WI. et al. Subchronic Toxicity Evaluation of Aluminum Oxide Nanoparticles in Rats Following 28-Day Repeated Oral Administration. Biol Trace Elem Res 200, 3215–3226 (2022). https://doi.org/10.1007/s12011-021-02926-5

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  • DOI: https://doi.org/10.1007/s12011-021-02926-5

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