Risk assessment of the flavonoids, quercetin as an endocrine modifier

Flavonoids are constituents of a wide variety of plants and are consumed in vegetables, fruits and certain medicines. They display a dual character with respect to their pharmacological effects and potential toxicity. Recent studies have demonstrated that the flavonoid, quercetin promotes estradiol-induced tumorigenesis by elevating the level of its oestrogen metabolite. Flavonoids have been also characterized as a type of environmental oestrogen. In the present study, we evaluated whether quercetin is a potential carcinogen by consideration of its oestrogenic characteristics, as described in various reports. A complete database review of flavonoids including quercetin revealed that quercetin is only mutagenic in bacterial testing systems and is a weak carcinogenic in rodents, but there has been little evidence that quercetin is tumour-inducing in humans. National Toxicology Program (1992) showed that the nonobserved adverse effect level (NOAEL) is to be less than 416 mg kg-1 body weight day-1 for inducing renal tumours in rats. In a study of male hamsters, it has been found that when co-administrated with estradiol, quercetin had a NOAEL of 300 mg kg-1 day-1 corresponding to 0.3% of the diet and contributed to the development of estradiol-induced renal tumours in these animals. By employing a 200-fold safety factor to compensate for interspecies variation, intraspecies variation and pharmacokinetics/pharmacodynamics variation, the acceptable daily intake (ADI) was estimated to be 1.5 mg kg-1 day-1. It was concluded that the average daily intake of quercetin exceeds this ADI value, suggesting that the risk of developing cancer from this flavonoid is not negligible given the wide exposure to quercetin in our daily life.