Comparative toxicokinetics of environmental hormones and phytohormones in humans and rats
Project management at the University of Würzburg:
Humans may be exposed to chemicals with estrogenic activity from different sources. In human diet, plant constituents with estrogenic activity (phytoestrogens) are present in high concentrations and are consumed in large amounts. In addition to phytoestrogens, industrial chemicals with estrogenic acitivity may be present as residues in low concentrations in diet. In this project, comparative toxicokinetics in rats and humans of an industrial chemical with estrogenic activity (bisphenol A) and a phytoestrogen (daidzein) were investigated for inclusion into the risk assessment process. Bisphenol A is widely used with many potential sources of human exposures and daidzein is a major plant phytoestrogen. To study kinetics of excretion and biotransformation in rats, bisphenol A and daidzein were orally administered. Bisphenol A, daidzein and formed metabolites were quantified. In urine of bisphenol A treated rats, app. 30 % of the administered dose were recovered, mainly in the form of conjugates. Bisphenol A and its conjugates were slowly excreted, major pathway of excretion was with feces. Total urinary excretion of daidzein (mainly in the form of conjugates) accounted for < 10 % of dose and the major pathway of elimination was excretion of unchanged daidzein with feces. Excretion of daidzein and conjugates with urine and feces was rapid with elimination half-lives < 12 h. To study human disposition of bisphenol A and daidzein, human volunteers (three males and three females) were administered d16-bisphenol A or daidzein. Blood and urine samples were taken in intervals and d16-bisphenol A or daidzein content was determined. d16-Bisphenol A was cleared from human blood and urine with half-lives of less than 6 hours; the applied dose was completely recovered in urine as d16-bisphenol A glucuronide. Maximum blood levels of bisphenol A glucuronide (800 pmol/ml) were observed in blood samples taken after 80 minutes; free bisphenol A could not be detected. Excretion of daidzein with urine, also mainly in the form of conjugates, was also rapid (elimination half-life of 8 h), recovery of daidzein in urine accounted for app. 40 % of applied dose. The obtained data indicate major species differences in the disposition of bisphenol A and daidzein.
Projekt period: from 08.1997 to 07.2000