Chapters authored
The Role of Metabolism in the Estrogenic Activity of Endocrine-Disrupting Chemicals
Exposure to several natural and synthetic chemicals can disrupt the endocrine system and thus present a threat to human health. In vivo, such chemicals can be metabolized, which can change the endocrine activity of the parent chemical. Metabolism is usually considered to be a detoxification process, as it generally appears to reduce the estrogenic activity of a chemical and accelerate its elimination from the body. This is seen for bisphenol A (BPA), a known agonist of the estrogen receptor, whereby BPA glucuronide has no effects on this receptor. In contrast, numerous metabolites that show significantly greater estrogenic activities from their parent chemicals have been described in the literature. An example is the ipso metabolite of BPA, 4-methyl-2,4-bis(p-hydroxyphenyl)pent-1-ene, which shows >100-fold estrogenic activity compared to BPA. Consideration of metabolic pathways in in vitro models is therefore of great importance for reliable analysis and correct in vitro to in vivo correlations. The inclusion of metabolic aspects in these assays will reduce false-positive data for chemicals that are detoxified in vivo and false-negative data for proestrogens. Different approaches for this incorporation of metabolic systems for determination of estrogenic activities are already in use and are described in the present chapter.
Part of the book: Estrogen