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Food Chem Toxicol. 2002 May;40(5):599-607.

Safety evaluation of proanthocyanidin-rich extract from grape seeds.

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Research and Development Division, Kikkoman Corporation, 399 Noda, Noda City, Chiba Pref. 278-0037, Japan.


Proanthocyanidins, extracted from grape seeds, are widely used mainly as nutritional supplements. However, there has not been a systematic report to investigate toxicological studies on proanthocyanidins, especially in oral administration. In our studies, proanthocyanidin-rich extract from grape seeds was subjected to a series of toxicological tests to document its safety for use in various foods. The grape seed extract (GSE) was examined for acute and subchronic oral toxicity using Fischer 344 rats and for mutagenic potential by the reverse mutation test using Salmonella typhimurium, the chromosomal aberration test using CHL cells, and the micronucleus test using ddY mice. No evidence of acute oral toxicity at dosages of 2 and 4 g/kg, and no evidence of mutagenicity in the above tests was found. Administration of GSE as a dietary admixture at levels of 0.02, 0.2 and 2% (w/w) to the rats for 90 days did not induce noticeable signs of toxicity. The no-observed-adverse-effect level (NOAEL) of GSE in the subchronic toxicity study was 2% in the diet (equal to 1410 mg/kg body weight/day in males and 1501 mg/kg body weight/day in females). The results of our studies indicate a lack of toxicity and support the use of proanthocyanidin-rich extract from grape seeds for various foods.

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