Safety studies conducted on high-purity trans-resveratrol in experimental animals.

ABSTRACT

trans-Resveratrol is a naturally occurring polyphenolic compound found in a variety of foods, but predominantly in grapes. Safety studies were conducted on high-purity trans-resveratrol (Resvida), including skin and eye irritation, dermal sensitization, subchronic and reproductive toxicity, genotoxicity, and absorption, metabolism and excretion. Resvida was non-irritating to skin and eyes and non-sensitizing. It was non-mutagenic in a bacterial reverse mutation assay in Salmonella typhimurium and Escherichia coli, but exhibited clastogenic activity in a chromosomal aberration test in human lymphocytes. However, in an in vivo bone marrow micronucleus test in rats, Resvida was non-genotoxic. In a 28-day study, Resvida caused no adverse effects in rats at 50, 150 and 500 mg/kg bw/day. Similarly, in a 90-day study, Resvida did not cause any adverse effects in rats at up to 700 mg/kg bw/day; the highest dose tested. Resvida did not induce any adverse reproductive effects in an embryo-fetal toxicity study in rats at a dose of 750 mg/kg bw/day. Also, in vitro and in vivo absorption, metabolism, and excretion studies in Caco-2 cells, rat primary hepatocytes and male and female rats (in vivo) show that Resvida is readily absorbed, metabolized and excreted. These studies provide evidence that Resvida is well tolerated and non-toxic.