Toxicological assessment of tyrosol.

Tyrosol is a naturally occurring phenolic compound widely present in olive oil, wine, and other plant-derived foods and is increasingly used in food, nutraceutical, and cosmetic products. Despite its dietary occurrence, systematic safety evaluation under internationally accepted testing guidelines is necessary to support risk assessment. The present study evaluated the acute oral toxicity, genotoxicity, and subchronic toxicity profile of tyrosol. In an acute oral toxicity study in rats, a single oral dose of 2000 mg/kg body weight was well tolerated, with no mortality or treatment-related clinical or pathological findings. Tyrosol showed no mutagenic activity in the bacterial reverse mutation (Ames) assay up to 5000 μg/plate, with or without metabolic activation. In vitro chromosomal aberration testing in mammalian cells showed no clastogenic effects up to 2000 μg/mL. An in vivo micronucleus assay in mice at doses up to 2000 mg/kg body weight demonstrated no increase in micronucleated polychromatic erythrocytes or evidence of bone marrow cytotoxicity. In a 90-day repeated-dose oral toxicity study in rats, daily administration up to 1200 mg/kg body weight/day produced no treatment-related adverse effects. The no-observed-adverse-effect level (NOAEL) was established at 1200 mg/kg body weight/day.