Specific pathogen-free Sprague-Dawley rats [Crl: CD (SD)] were purchased from Koatech Inc., Republic of Korea. The animals were acclimated for 7 days after arrival at the laboratory animal facility of the National Institute of Food and Drug Safety Evaluation of the Ministry of Food and Drug Safety (Osong, Korea). The studies were approved by the Institutional Animal Care and Use Committee (IACUC) (2019, approval no. MFDS-19-002). The animals were housed at a temperature of 22 ± 3°C and relative humidity of 50 ± 20%. The animal rooms were maintained under a 12-h light-dark cycle and 10–20 air changes per hour. The toxicity test was performed strictly using “Toxicity Test Standards for Drugs” from the Korean Ministry of Food and Drug Safety (MFDS (The Ministry of Food and Drug Safety), 2017b). It is also referred to as the OECD Guideline No. 407 (OECD, 2008).

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