Preclinical Toxicity Assessment of Polyphenols-Based Standardized Extract of Cinnamomum zeylanicum Bark

Background: Cinnamon (Cinnamomum zeylanicum) bark is used as a spice in culinary practices and has been documented for health and medicinal benefits. Polyphenol (PP) is the major bioactive constituent of cinnamon bark. However, acceptable and safe dose levels and toxicity information of oral exposure to PP-based standardized cinnamon bark extract (PP-CZ) are crucial for safe human consumption. Objective: To evaluate PP-CZ for acute oral, subchronic oral toxicities in vivo, mutagenicity in vitro and genotoxic potential in vitro. Method:. The effects of oral treatment with single- and 90-days repeated dose were evaluated in rates as per OECD Test 423 and 408, respectively. Effects on body weight, food and water intake, organ weight, hematology, biochemistry, and histology were recorded . Mutagenicity and genotoxicity were evaluated using Ames (OECD No. 471) and chromosomal aberrations (OECD Test. 473) tests. Results: A single oral dose of PP-CZ did not cause death or treatment-related toxic effects, indicating a “median lethal dose” > 2,000 mg/kg. In addition, a subchronic dosage (500 mg/kg/day, 90 days) was found safe in rats, suggesting “no observed adverse effect level” (NOAEL) of 500 mg/kg and “Human Equivalent Dose” (HED) of 4.8 g/day. Furthermore, the absence of mutagenicity or genotoxicity of PP-CZ was observed during in vitro tests. PP-CZ showed a robust safety profile without mutagenicity or genotoxicity in rats.