A 13-week subchronic toxicity study of grape skin extract in F344 rats.

A 13-week repeated oral dose toxicity study of grape skin extract (GSE) was performed using F344 rats. Four groups of animals, each consisting of ten males and ten females, were fed a diet containing 0%, 0.2%, 1.0% or 5.0% GSE for 13 weeks. Throughout the experiment, there were no treatment-related changes in clinical signs, body weight or mean food intake in any of the treated groups of either gender. Hematological studies and serum biochemical analyses revealed no treatment-related changes in all groups in both genders. In the glandular epithelial cells of the parotid glands, diffuse hypertrophy and basophilia was observed in all animals in both 5.0% groups. Hypertrophy of the parotid glands was not detected in the 0.2% or the 1.0% dose groups. In female kidneys, slight calcification in the renal proximal tubules of the cortex and medulla was observed in all groups including controls. This is a common spontaneous change in female rats, and the incidence was comparable between controls and treated groups. However, the number of tubules with calcification was higher in the 5.0% group based on a semi-morphometric analysis. Based on the histopathology of the parotid glands and the minor change in the kidneys, the no observed adverse effect level (NOAEL) of GSE in the present study was a 1.0% treatment dose in both genders (males: 0.6 ± 0.2 g/kg body weight/day; females: 0.7 ± 0.1 g/kg body weight/day).