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.
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).
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
This page was last
updated in October 1999
to the hormone disrupting chemicals home page
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.