Chemicals with Estrogenic Activity Xenoestrogens

A major group of endocrine-disrupting chemicals in the aquatic environment mimic the effects of estrogens [121,122]. Therefore, this section deals especially with environmental estrogens or the so-called xenoestrogens. 

Over the last decades, large amounts of different man-made chemicals which can act as weak estrogens have been released into the terrestrial and aquatic environment and are distributed world-wide. Classical environmental estrogens are pesticides, such as o,p -DDT, and its metabohtes o,p -DDE and o,p -DDD, methoxychlor and its metabolites, chlordecone (Kepone ), dieldrin, Toxaphene, and endosulfan [126, 135, 136]. It is also known that many chemicals with very weak or no measurable estrogenic activity can be metabolized in organisms especially to hydroxylated compounds which may have much more estrogenic potency than the parent compound. Examples are methoxychlor and its mono- and di-demethylated derivatives [126,127] as well as the alkylphenol 

Some polychlorinated biphenyls, especially their non-planar para-hydroxylat-ed metabolites also possess estrogenic activity [126,135,140]. These metabolites have a higher estrogenic potency than their parent compounds. Some co-planar polychlorinated biphenyls (PCB 77 and PCB 126) have been shown in vivo to have estrogenic as well as antiestrogenic activities, probably solely through hydroxy metabolites (NIH shift to para). This reinforces the European view that EDCs can only be confirmed in intact animals. It is also known that some hydroxylated metabolites of polycyclic aromatic hydrocarbons (PAHs), e.g. 3,9-dihydroxybenzo[a]anthracene, show estrogenic activity [141 -143]. 

Environmental chemicals such as p-nonylphenol (NP), 4-ferf.-octylphenol (OP), 4-ferf.-pentylphenol (TPP), bisphenol-A (BPA), tetrabromobisphenol-A (TBBA), butylbenzylphthalate (BBP), di- -butylphthalate (DBP), butylated hydroxyanisole (BHA), p-chloro-ra-cresol, p-chloro-o-cresol, ds-nonachlor, frans-nonachlor, and the herbicide alachlor [2-chloro-iV-(2,6-diethylphenyl)-N-(methoxymethyl) acetamide] have been discovered to be weakly estrogenic [128,129,137,138]. 

The natural female steroid hormone with the greatest estrogenic activity is 17C-estradiol. It is important to note that some synthetic estrogens, such as diethylstilbestrol (DES), moxestrol, and ll)8-chloromethyl estradiol show 10 times more estrogenic activity than 17)8-estradiol in the E-SCREEN assay [136]. Ethinylestradiol has the same estrogenic activity as 17/1-estradiol, whereas the activity of the synthetic EDCs is by some orders of magnitude lower [136]. In this context it is important to note that most, if not all, efflu- 

---