Short-term repeated-dose oral toxicity and mutagenicity studies on rice-derived glucosylceramides

Food-derived glucosylceramides (GlcCer) have been used for functional foods; however, limited information is currently available on their safety. Therefore, we examined the toxicity of repeated oral dose and mutagenicity of rice-derived GlcCer (RGlcCer).

RGlcCer containing 3% GlcCer was administered to mice in a 28-d repeated-dose oral toxicity study. Ames test and in vitro micronucleus test was performed followed OECD guideline.

Spontaneous motor suppression, sedation, and convulsions were observed prior to mortality in all animals treated with 6,000 mg/kg/d body weight RGlcCer (equivalent to 180 mg/kg/d body weight of GlcCer). Mice administered 600 mg/kg/d RGlcCer exhibited the same clinical symptoms as the high dose group, although to a milder extent and only during the first half of the treatment period. While a decrease in body weight was noted in the 600 mg/kg/d group, it recovered with continued administration, and no abnormalities were observed in blood, pathological, and anatomical examinations following the treatment period. At a dose of 60 mg/kg/d, no abnormalities were detected in any parameters. No mutagenicity was observed in either in vitro test.

The repeated oral administration of 600 mg/kg/d RGlcCer to mice for 28 d was considered safe and the lowest observed adverse effect level was 600 mg/kg/d RGlcCer under our study conditions. The effects of concentrated RGlcCer (CRGlcCer) consisting of 10% rice GlcCer were examined in a mutagenicity study. The results of the Ames test and in vitro micronucleus test showed that CRGlcCer did not induce mutagenic changes. In conclusion, RGlcCer is safe, is not mutagenic, and did not cause chromosomal damage.