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Endocrine disrupters are chemicals in
the environment that are similarin structure to natural sex
hormones and interfere with their normal functions, usually
by binding to the cell receptors and preventing the hormone
from binding to the receptor.
When hormones bind to their receptors,
this triggers their biological effects. Endocrine disrupters
are found in plastics and foods.
Infertility is an emotive issue, and having
children is a recognized "right," so any implication
that environmental pollution affects reproduction has to be
taken seriously.
When the causative agents might also be
responsible for various cancers and other diseases, then the
level of interest that the issue attracts is unsurprising
hence the calls in the early 1990s for action in line with
the "precautionary principle."1
In men hypospadias, cryptorchidism (undescended
testicles), cancer of the prostate, testicular cancer, and
semen quality and in women breast cancer, cystic ovaries,
and endometriosis have all been suggested as indicators of
adverse trends in reproductive health.2
The idea that these trends are real and
are connected with environmental pollution is gaining credence
internationally. The effect on human health of environmental
chemicals that are mediated through the endocrine system endocrine
disrupters has generated huge interest and investment.
Why Is This,
and What Is the Evidence for the Assumed Association?
Changes in the sexual morphology of fish
exposed to sewage effluent have led some scientists to conjecture
that humans also live in a "sea of estrogens" and
that the apparent increases in the incidence of certain reproductive
conditions may be due to exposure to chemicals in the environment.
The so called Sharpe-Skakkebaek hypothesis
offered a possible common cause and toxicological mechanism
for abnormalities in men and boys that is, increased exposure
to estrogen in utero may interfere with the multiplication
of fetal Sertoli cells, resulting in hormonally mediated developmental
effects and, after puberty, reduced quality of semen.3
It was postulated that synthetic chemicals
in the environment are the prime source of the excessive estrogenic
stimulation, with exposure through food and water being the
primary route.
Further research has extended the concern
to the role of antiandrogens and has led to the recognition
that a range of systems and processes may be susceptible to
hormonal modulation, including immune function, behavior,
and learning and memory, as well as reproduction.
The term environmental estrogen has given
way to the more encompassing term "environmental endocrine
disrupter," defined as "an exogenous substance that
causes adverse health effects in an intact organism, or its
progeny, subsequent to changes in endocrine function."4
Endocrine disrupters are potentially present
in food as natural "phytoestrogens" and chemical
contaminants, and there is a divide in the perception of natural
and synthetic substances.5
Hence the drive in some quarters to market
"healthy" bread that is rich in soy flour and linseed
at the same time that other people are warning against low
levels of weak estrogenic synthetic chemicals as contaminants
in food. Perhaps this reflects the common view of natural
things as good and synthetic things as necessarily bad.
Two Questions
Need To Be Addressed
- Do indicators of reproductive health
truly reveal a worsening situation?
- Can exposure to environmental chemical
contaminants conceivably be the cause of any such temporal
changes?
Baseline data on many of the implicated
conditions are so poor that it is not possible to say for
sure whether trends are occurring. There is also the issue
of geographical variability in the measured indices, which
can be related to genetic differences in the population or
to climatic differences or changes in lifestyle, for example.
None the less,
there is agreement that the incidence of testicular and prostate
cancer is increasing and that semen quality is probably worsening
in some regions of the world.
There is also some evidence for an increasing
incidence of cryptorchidism and hypospadias; and in women
endometriosis and polycystic ovaries may be more common.4-6
Perhaps the most controversial issues
in research on endocrine disrupters are the possible disproportionate
effects of low levels of exposure, as proposed by Vom Saal
et al and recently accepted by the US national toxicology
program.
At least for a limited number of chemicals7-9;
the question of synergism in mixtures, which has become something
of a no go area since the withdrawal of the much quoted paper
by Arnold et al10; and the development of appropriate test
methods.
Large amounts of resources have been invested
in this last activity, through the work of the endocrine disrupter
screening and testing advisory committee in the United States.
Yet according to Ashby the developmental effects of endocrine
disruptors that are seen in rodent studies cannot be extrapolated
to humans.
This is not only because of the uncertainty
of applying such results across species but also because of
the absence of an agreed control database in rodents and the
variability in test protocols and in the developmental effects
in test animals.11
Among specific
chemicals implicated as endocrine disrupters phthalates
may be of particular importance because of their ubiquity.
Similarly bisphenol
A has been shown in both in vitro and in vivo assays to
have high potential for endocrine disruption and potential
for exposure to humans for example, through its use in can
linings.
These are issues of major interest, not
least because of the possible exposure of infants to these
chemicals at critical stages of development. Sharpe has argued
that, until appropriate in vivo experiments are done, phthalates
and similar chemicals will continue to cause concern for testicular
development.12
British Medical
Journal December 8, 2001;323:1317-1318
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