Acute and long-term safety evaluation of a novel IH636 grape seed proanthocyanidin extract

Grape seed proanthocyanidins are known to possess a broad spectrum of pharm acological, medicinal and therapeutic properties. Previous studies in our l aboratories have demonstrated the various protective abilities of a novel I H636 grape seed proanthocyanidin extract (GSPE) against various pathologic conditions. However no extensive safety studies have been conducted on grap e seed proanthocyanidins to date. This study demonstrates the acute and chr onic safety studies on GSPE. Acute oral toxicity, dermal toxicity, dermal i rritation and eye irritation studies have been conducted. The LD50 of GSPE was found to be greater than 5000 mg/kg when administered once orally via g astric intubation to fasted male and female albino rats. The LD50 of GSPE w as found to be greater than 2000 mg/kg when administered once for 24 hr to the clipped, intact skin of male and female albino rats. In addition, 2000 mg/kg was found to be the no-observed-effect level (NOEL) for systemic toxi city under the conditions of the study. In a dermal irritation study, GSPE received a descriptive rating classification of moderately irritating. Exte nsive chronic studies were also conducted. We have assessed the effects of chronic administration of 100 mg GSPE/kg/day for twelve months and its effe ct on seven vital target organs, namely, brain, heart, intestine, kidney, l iver, lung and spleen, and on serum chemistry changes in male B6C3F1 mice. Furthermore, the dose-dependent chronic effects of GSPE in female B6C3F1 mi ce were evaluated. Mice were fed 0, 100, 250 or 500 mg GSPE/kg/day for six months and the effects of GSPE exposure were examined on brain, duodenum, h eart, kidney, liver, lung, pancreas and spleen, and on serum chemistry chan ges in female mice. These acute studies demonstrated that GSPE is safe and did not cause any detrimental effects in vivo under the conditions investig ated in this study.