Six months chronic toxicological evaluation of naringin in Sprague–Dawley rats

Naringin is a flavonoid showing variable pharmacological properties and is distributed ubiquitously in plant foods. There is a paucity of reported data regarding its safety profile. In the present study, chronic toxicity studies of naringin was designed and conducted by oral gavage at doses of 0, 50, 250 and 1250 mg/kg in Sprague–Dawley (SD) rats for six months followed by 1-month recovery period. During the 6-month treatment period and one month recovery period, no mortality and toxicologically significant changes in clinical signs, opthalmoscopic examination, hematology, clinical biochemistry, serum sex hormone, macroscopic findings, organ weights and histopathological examination were noted and attributed to naringin administration. Although consecutive and/or isolated periods of significant body weights and food consumption decreases were relevant to naringin administration, they were not considered toxicologically significant. In addition, slight, non-pathological and reversible hair loss was noted during the 6-month treatment period and considered as a kind of change possibly relevant to naringin administration; however, it was not considered adverse change and to be of toxicological significance. Based on the results of this study, the no-observed-adverse-effect-level (NOAEL) of naringin in rats is greater than 1250 mg/kg/day when administered orally for 6 consecutive months.