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20(s)-ginsenoside Rg3 is a red ginseng-derived compound with the formula C 42 H 72 O 13 that has been increasingly used by humans, leading to safety concerns regarding this use. In the current study, we conducted a 26-week study during which 20(S)-ginsenoside Rg3 (0, 7, 20, or 60 mg/kg) was continuously administered orally to Beagle dogs in order to explore its toxicity in these animals, with control dogs receiving a vehicle capsule. In total, 10 dogs received each dose of this compound (n = 5 male, n = 5 female per dose). Animals were continuously monitored for a 26-week administration period and a subsequent 4-week follow-up recovery period. At the end of study, we observed no evidence of 20(S)-ginsenoside Rg3 toxicity in clinical indications, body weight, food intake, ophthalmoscopy, electrocardiogram, urinalysis, hematology, serum biochemistry, gross and histopathology findings. However, the kidney relative weight of animals receiving 60 mg/kg of compound was significantly elevated relative to control animals (5.15 ± 0.88‰ vs. 4.11 ± 0.59‰. P < 0.05), and this effect was reversed after 4-week recovery period. Based on these results, the NOAEL value for orally administered 20(S)-ginsenoside Rg3 in dogs is 20 mg/kg. • In 26-week chronic toxicity, the NOAEL of Rg3 for dogs is 20 mg/kg. • In toxicity study, 60 mg/kg Rg3 induced increasing of the kidney relative weight. • Increasing of kidney weight maybe a result of the excretion of Rg3. [ABSTRACT FROM AUTHOR]