The olive fruit, its oil and the leaves of the olive tree have a rich history of nutritional, medicinal and ceremonial uses. Olive oil, table olives and olive products are an important part of the Mediterranean diet, the greatest value of which may be due to olive polyphenols that contribute to the modulation of the oxidative balance in vivo. The objective of this review is to examine the available safety/toxicity literature on olive polyphenols, particularly hydroxytyrosol, to determine the safety-in-use of a standardized aqueous olive pulp extract (HIDROX). Among the polyphenols found in the extract, the major constituent of biological significance is hydroxytyrosol (50-70%). In oral bioavailability studies, urinary excretion of hydroxytyrosol and its glucuronide was found to be associated with the intake of hydroxytyrosol. Oral bioavailability of hydroxytyrosol in olive oil and in an aqueous solution was reported as 99% and 75%, respectively. In comparative studies, urinary excretion of hydroxytyrosol was greater in humans than in rats. The LD(50) of the extract and hydroxytyrosol was reported to be greater than 2000 mg/kg. In a subchronic study, the no observed adverse effect level (NOAEL) of the extract in rats was found to be 2000 mg/kg/day. In developmental and reproductive toxicity studies, HIDROX did not cause toxicity at levels up to 2000 mg/kg/day. In an in vivo micronucleus assay, oral exposure of rats to HIDROX at dose levels up to 5000 mg/kg/day for 29 days did not induce increases in polychromatic erythrocytes in bone marrow. Based on the available studies of the extract and polyphenols, and a history of exposure and use of components of the extract through table olives, olive products and olive oil, the consumption of HIDROX is considered safe at levels up to 20 mg/kg/day.