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Other factors affecting the activity of endocrine disrupters

There are many variables which affect whether a hormone disrupting chemical has a biological effect, including uptake, distribution, nature of action and time of action. These points are discussed in more detail here. For more detail and references, see Toppari et al. (1996) and Kavlock et al. (1996).

Uptake and distribution

First the chemical must enter the body, through ingesting food or drink, being absorbed from cosmetics or inhaled. The chemical will then be distributed through the body, usually by the blood. Several systems exist in the body to detoxify chemicals, notably the liver enzyme systems. These systems remove chemicals by a combination of breaking them down and attaching them to other chemicals, which promotes their excretion, usually through the kidneys and into the urine.

Some chemicals are not removed effectively by these processes, so remain in the body. Those chemicals that are lipophilic (fat soluble) can accumulate and be stored in the fat, notably PCBs and DDT. The fat stores of the body can be mobilised during stressful periods, malnutrition, or in pregnancy, releasing the stored chemicals into the blood stream. WWF have recently published a disturbing review of all the chemicals that have been found in body fat and breast milk - see the issues page for more details.

Bioavailability

Natural hormones such as oestrogen have their concentration in the blood modified by sex hormone binding globulin and albumin, which bind the majority of the hormone in the blood, so reducing its availability to bind to receptors and initiate responses (Arnold et al., 1996). Sex hormone binding globulin binds very strongly and specifically to oestradiol, whilst albumin binding is weaker and less specific. Arnold et al. (1996) have tested how these two compounds affect the availability of 17beta-estradiol, diethylstilbestrol, octylphenol and o, p'-DDT, by seeing how their presence affects binding to the human oestrogen receptor (expressed by a yeast). They found that the xenoestrogens bound far less to the albumin and the sex hormone binding globulin, leaving more free chemical available to bind the receptor and initiate an oestrogenic response.

Bioavailability of chemicals to a foetus is affected by the placenta, which is able to prevent the crossing of some chemicals from the mother's blood into the developing child or animal (Manson and Wise, 1991). This only provides a partial barrier and many chemicals can transfer into the foetus, particularly those which are lipophilic (fat soluble).

Timing

The timing of exposure to an endocrine disrupter can be crucial, as some stages of development are far more sensitive. This is covered in more detail on the complexity page.


This page was last updated in October 1999
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References

Arnold, S. F., Robinson, M. K., Notides, A. C., Guillette Jr, L. J. and McLachlan, J. A. 1996. A yeast estrogen screen for examining the relative exposure of cells to natural and xenoestrogens. Environ. Health Persp. 104: 544-548.

Kavlock, R. J., Daston, G. P., DeRosa, C., Fenner-Crisp, P., Gray, L. E., Kaattari, S., Lucier, G., Luster, M., Mac, M. J., Maczka, C., Miller, R., Moore, J., Rolland, R., Scott, G., Sheehan, D. M., Sinks, T. and Tilson, H. A. 1996. Research needs for the risk assessment of health and environmental effects of endocrine disruptors: A report of the U.S. EPA-sponsored workshop. Environ. Health Persp. 104 Suppl. 4: 714-740.

Manson, J. M. and Wise, D. L. 1991. Teratogens. In: Casarett and Doull's Toxicology: The Basic Science of Poisons. pp. 226-254. Amdur, M. O., Doull, J. and Klaassen, C. D. Eds., Pergamon Press, New York.

Toppari, J., Larsen, J. C., Christiansen, P., Giwercman, A., Grandjean, P., Guillette, L. J., Jégou, B., Jensen, T. K., Jouannet, P., Keiding, N., Leffers, H., McLachlan, J. A., Meyer, O., Müller, J., Rajpert-De Meyts, E., Scheike, T., Sharpe, R., Sumpter, J. and Skakkebaek, N. E. 1996. Male reproductive health and environmental xenoestrogens. Environ. Health Persp. 104 Suppl. 4: 741-803.


URL: http://website.lineone.net/~mwarhurst/factors.html