Abstract
Myricitrin, a flavonol rhamnoside of myricetin, extracted from the Chinese bayberry (Myrica rubra SIEBOLD) plant is used in Japan as a food flavoring in snack foods, dairy products and beverages. It is affirmed as GRAS by the U.S. FEMA and was recently considered safe by JECFA at current estimated dietary exposures. Its toxic potential was evaluated in anticipation of expanded worldwide marketing of myricitrin in food and beverage products. Following OECD guidelines, myricitrin was evaluated in standard in vitro and in vivo genotoxicity assays, in the comet assay in mouse liver, stomach and duodenum, in a 90-day repeated dose rat toxicity study at dietary concentrations up to 5%, and in a rat toxicokinetic study at single gavage doses of myricitrin up to 1000 mg/kg and a single 1.6 mg/kg dose of myricetin. Bacterial reverse mutation, in vivo micronucleus, and comet assays were negative. In vitro micronucleus in TK6 cells without S9 was positive but was negative with S9. There were no treatment-related adverse clinical or pathological findings in the rat toxicity study. Median myricitrin plasma Tmax was 3 hours at 250 mg/kg and 6 hours at 500 & 1000 mg/kg. Increases in mean Cmax and mean AUC values were both approximately dose proportional. Plasma levels of myricetin were present at 12 and 24 hours in some rats dosed with myricitrin, but not in rats dosed with myricetin. Using JECFA myricitrin intake estimates and assuming similar myricitrin metabolism in rats and humans, myricetin blood levels would be 30 (SPET) and 300 (MSDI) times lower in humans than in rats and would be below the level of detection in human blood. The genotoxicity assays and repeated dose toxicity study along with a favorable toxicokinetic profile support the safe use of myricitrin as a flavoring in food and beverages.
