Genotoxicity evaluation of the flavonoid, myricitrin, and its aglycone, myricetin

• Published in: Food and chemical toxicology Vol. 83; pp. 283 - 292
• Main Authors: Hobbs, Cheryl A., Swartz, Carol, Maronpot, Robert, Davis, Jeffrey, Recio, Leslie, Koyanagi, Mihoko, Hayashi, Shim-mo
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-09-2015
• Subjects: Animals; DNA Damage; Female; Flavonoid; Flavonoids - administration & dosage; Flavonoids - adverse effects; Flavonoids - metabolism; Flavoring agent; Food Additives - administration & dosage; Food Additives - adverse effects; Food Additives - metabolism; Fruit - chemistry; Genotoxicity; Glycosides - administration & dosage; Glycosides - adverse effects; Glycosides - metabolism; Humans; Japan; Male; Mice; Mutagenicity Tests; Myrica; Myrica - chemistry; Myricetin; Myricitrin; Plant Bark - chemistry; Plant Leaves - chemistry; Rats; Toxicity Tests, Acute; Japan; RET; MN; FDA; Flavoring agent; DNA damage; Genotoxicity; GLP; Myricetin; Flavonoid; EFSA; JECFA; MN-RET; OECD; FAO; Myricitrin; WHO
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2015.06.016

Myricitrin, a flavonoid extracted from the fruit, leaves, and bark of Chinese bayberry (Myrica rubra SIEBOLD), is currently used as a flavor modifier in snack foods, dairy products, and beverages in Japan. Myricitrin is converted to myricetin by intestinal microflora; myricetin also occurs ubiquitously in plants and is consumed in fruits, vegetables, and beverages. The genotoxic potential of myricitrin and myricetin was evaluated in anticipation of worldwide marketing of food products containing myricitrin. In a bacterial reverse mutation assay, myricetin tested positive for frameshift mutations under metabolic activation conditions whereas myricitrin tested negative for mutagenic potential. Both myricitrin and myricetin induced micronuclei formation in human TK6 lymphoblastoid cells under conditions lacking metabolic activation; however, the negative response observed in the presence of metabolic activation suggests that rat liver S9 homogenate may detoxify reactive metabolites of these chemicals in mammalian cells. In 3-day combined micronucleus/Comet assays using male and female B6C3F1 mice, no induction of micronuclei was observed in peripheral blood, or conclusive evidence of damage detected in the liver, glandular stomach, or duodenum following exposure to myricitrin or myricetin. Our studies did not reveal evidence of genotoxic potential of myricitrin in vivo, supporting its safe use in food and beverages.
•Myricetin induced mutations in bacteria only under metabolic activation conditions.•Myricitrin tested negative for mutagenic potential in bacteria.•Both chemicals induced micronuclei in human TK6 cells −S9, but not +S9, homogenate.•Myricitrin did not induce genotoxicity in mice; equivocal result for myricetin.•Results support the safe use of myricitrin in food and beverages.