Metabolism and fate of xeno-oestrogens in man

A large variety of chemicals of either natural or synthetic origin possess oestrogen-like activity and are thus called xeno-oestrogens. Some of these chemicals such as the pesticide methoxychlor rc:quire metabolic activation for their oestrogenic activity, whereas other compounds may themselves be oestrogenic and may be deactivated by their metabolism. In this chapter, the metabolism of representative examples of environmental oestrogen-like chemicals has been discussed to illustrate common trends in the large structural variety of xeno-oestrogens. The compounds included are zearalenone, methoxychlor, bisphenol A, DDT, P-sitosterol, and genistein and have been selected based on availability of information, the potential of exposure of humans and wildlife to the compounds, their industrial or agricultural importance, and the importance of metabolism for their activation or deactivation. The oestrogenic activity of phenolic xeno-oestrogens, a large class of compounds of natural or synthetic origin or their metabolites, likely is based on the weak oestrogen receptor binding of phenol. These compounds are mainly metabolized by analogy to steroidal oestrogenic hormones, i.e., by aromatic ring hydroxylation (catechol formation), subsequent methylation of the catechol and further phase II metabolism by glucuronide and/or sulfate formation. In contrast, the chlorinated hydrocarbon pesticides, which are weakly oestrogenic, are mainly metabolized by dehalogenation at relatively low metabolic rates. Thus, these compounds may persist in the body, accumulate in fatty tissues and provide a chronic reservoir of oestrogenic chemicals.