title: Genotoxicity evaluation of the flavonoid, myricitrin, and its aglycone, myricetin.
abstract: 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.
authors.affiliation: Toxicology Program, Integrated Laboratory Systems, Inc., PO Box 13501, Research Triangle Park, NC 27709, USA. Electronic address: chobbs@ils-inc.com.
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Hobbs
authors.affiliation: Toxicology Program, Integrated Laboratory Systems, Inc., PO Box 13501, Research Triangle Park, NC 27709, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Swartz
authors.affiliation: Maronpot Consulting LLC, 1612 Medfield Road, Raleigh, NC 27607, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Maronpot
authors.affiliation: Toxicology Program, Integrated Laboratory Systems, Inc., PO Box 13501, Research Triangle Park, NC 27709, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Davis
authors.affiliation: Toxicology Program, Integrated Laboratory Systems, Inc., PO Box 13501, Research Triangle Park, NC 27709, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Recio
authors.affiliation: Global Scientific and Regulatory Affairs, San-Ei Gen F.F.I., Inc., 1-1-11 Sanwa-cho, Toyonaka, Osaka 561-8588, Japan.
authors.forename: Mihoko
authors.initials: M
authors.lastname: Koyanagi
authors.affiliation: Global Scientific and Regulatory Affairs, San-Ei Gen F.F.I., Inc., 1-1-11 Sanwa-cho, Toyonaka, Osaka 561-8588, Japan.
authors.forename: Shim-mo
authors.initials: SM
authors.lastname: Hayashi
mesh_terms: D000818:Animals; D004249:DNA Damage; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism; D005503:Food Additives / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism; D005638:Fruit / Q000737:chemistry*; D006027:Glycosides / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism; D006801:Humans; D007564:Japan; D008297:Male; D051379:Mice; D009152:Mutagenicity Tests; D031641:Myrica / Q000737:chemistry*; D024301:Plant Bark / Q000737:chemistry*; D018515:Plant Leaves / Q000737:chemistry*; D051381:Rats; D023382:Toxicity Tests, Acute
chemical_list: D005419:Flavonoids; D005503:Food Additives; D006027:Glycosides; C008577:myricitrin; C040015:myricetin
keywords: DNA damage; Flavonoid; Flavoring agent; Genotoxicity; Myricetin; Myricitrin