Oestrogenic, chemicals

It is biologically plausible that exposure to a sufficient level of an oestrogenic chemical could cause harmful biological effects. However, it is far more difficult to establish that environmental oestrogens are responsible for adverse effects on... 

NAGEL s c, VOM SAAL F s, WELSHONS w V (1999) Developmental effects of oestrogenic chemicals are predicted by an in vitro assay incorporating modification of cell uptake by serum. J Steroid Biochem Mol Biol. 69 343-57. 

In the case of some oestrogenic chemicals (that mimic the effects of the female hormone oestrogen) it has been shown that what should be added to predict the combined effect of a mixture is not the effects of the individual chemicals but their concentrations (Silva et al, 2002). This means that a substance present at a concentration at which on its own it has no oestrogenic effect will contribute to the total oestrogenic effect of a mixture containing other oestrogenic chemicals. For such substances there is in practice no real threshold concentration below which they do not have an effect. Such no-effect levels are a crucial part of chemicals risk assessment, as I will explain in Chapter 7. 

A possible interaction of many oestrogenic chemicals in the environment with the human oestrogen receptor has received publicity. A warning was actually issued that the synergistic interaction of mixtures of several low-dose environmental chemicals with the hER may have negative consequences on fertility. However, these fears seem to be unfounded.21... 

P.W. Harvey, P. Darbre, Endocrine disrupters and human health conld oestrogenic chemicals in body care cosmetics adversely affect breast cancer incidence in women J. Appl. Toxicol. 24 (3) (2004) 167-176. 

More subtle modes of action are also possible since the response to hormone receptor binding is complex and could be affected by chemical interference with receptor-related proteins, DNA methylation or histone acetylation. Dioxin (TCDD), for example, reduces the ability of the oestrogen-receptor complex to bind to the oestrogen response element of DNA, reducing gene transcription. ... 

The responsiveness of a tissue to a hormone depends on the density of receptors within its component cells. The number of receptors is determined by their rate of synthesis and catabolism, which is itself controlled by complex feedback mechanisms involving hormone action. Some chemicals are known to interfere with this regulation. For example, TCDD can act to increase or decrease the expression of the oestrogen receptor. ... 

Those man-made chemicals which have been identified as being oestrogenic belong to several major groups of chemicals including organochlorine pesticides, polychlorinated biphenyls, alkylphenolic compounds, ... 

Panter, G.H., Hutchinson, T.H., and Hurd, K.S. et al. (2006). Development of chronic tests for endocrine active chemicals—Part 1. An extended fish early-life stage test for oestrogenic active chemicals in the fathead minnow (Pimephales promelas). Aquatic Toxicology 77, 279-290. 

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