Safety evaluation of Evesse EPC, an apple polyphenol extract rich in flavan-3-ols.

The safety of the apple polyphenol extract EvesseEPC, which is rich in flavan-3-ols, particularly epicatechin, was evaluated. Both in a bacterial reverse mutation test and a mouse lymphoma assay, EvesseEPC showed a positive response in vitro. In vivo studies (UDS test in hepatocytes, bone marrow micronucleus test and comet assay in intestinal cells) were all negative and hence Evesse EPC is considered not to have genotoxic properties in vivo. In a 90-day study in rats, EvesseEPC was administered at dietary levels of 0%, 1.25%, 2% and 3.25%. Body weights were decreased in the high-dose group in both sexes without effects on feed or water intake. In the high-dose group, thrombocytes (males) and creatinine (both sexes) were decreased, prothrombin time (males) was increased, and liver, kidneys and spleen weights were increased (males), without histological correlates. Diffuse acinar cell hypertrophy, observed in the parotid salivary glands in all treatment groups, was not considered as adverse and presumably reflected a local, reversible and adaptive response to direct contact with EvesseEPC. The NOAEL for EvesseEPC in rats was 2% in the diet, equivalent to an overall average intake of 1.3 and 1.5 g/kg body weight/day for males and females, respectively.