Mutagenic, Acute, and Subchronic Toxicity Studies of the Hesperetin-7-Glucoside–β-Cyclodextrin Inclusion Complex

• Published in: International journal of toxicology 2023-01, Vol.42 (1), p.50-62
• Main Authors: Moriwaki, Masamitsu, Kito, Kento, Nakagawa, Ryo, Tominaga, Etsuko, Kapoor, Mahendra P., Matsumiya, Yoshiki, Fukuhara, Tomohisa, Yamagata, Hiroshi, Katsumata, Toyohisa, Minegawa, Kazuyuki
• Format: Article
• Language: English
• Subjects: Animals; Female; Hesperidin - toxicity; Male; Mutagenicity Tests - methods; Mutagens; Mutation; Original; Rats
• ISSN: 1091-5818; 1092-874X
• DOI: 10.1177/10915818221134022

Hesperetin glucosides such as hesperidin and hesperetin-7-glucoside are abundantly present in citrus fruits and have various pharmacological properties. However, the potential toxicity of hesperetin glucosides remains unclear. An initial assessment of the safety of hesperetin-7-glucoside–β-cyclodextrin inclusion complex (HPTGCD) as a functional food ingredient was undertaken to assess toxicity and mutagenic potential. A bacterial reverse mutation assay (Ames test) using Salmonella typhimurium (strains TA98, TA1535, TA100, and TA1537) and Escherichia coli (strain WP2 uvrA) with HPTGCD (up to 5000 µg/plate) in the absence and presence of metabolic activation was negative. In a single oral (gavage) toxicity study in male and female rats, HPTGCD at dose up to 2000 mg/kg did not produce mortality nor clinical signs of toxicity or change in body weight. In a subchronic oral (dietary admix) toxicity study in rats receiving 0, 1.5, 3, and 5% HPTGCD for 13 weeks, no adverse effects were noted and the no-observed-adverse-effect level (NOAEL) was 5% in the diet (equivalent to 3267.7 mg/kg/day for males and to 3652.4 mg/kg/day for females). These results provide initial evidence of the safety of HPTGCD.