SUMMARY
Thousands of man-made chemicals have been released into the environment
in vast quantities since the chemical industry began to boom in the 1950s.
This has brought many, often unforeseeable, problems for the environment.
Only very recently evidence of a potentially huge threat has been unfolding
- that of endocrine disruption – the disruption of hormone systems in wildlife
and humans by man-made chemicals.
In 1991, scientists hypothesised that endocrine-disruption could be
the cause of declines in the populations of many wildlife species which
have occurred over the past 50 years. Effects in wildlife which are suspected
to result from exposure to endocrine-disrupting chemicals, include adverse
effects on the development of young, reproductive problems and weakened
immune systems. Human health could also be affected. The ability of these
chemicals to interfere with hormone systems has potentially implicated
them in decreasing sperm counts, increases in reproductive problems, reduced
intellectual capacity and behavioural problems. Many of the effects appear
to be caused by disturbing development of the embryo or foetus, either
in the womb of mammals and humans or in the eggs of egg-laying animals.
This can occur because the chemicals are passed on from a mother’s body
to the next generation.
It is imperative that precautionary action on endocrine-disrupting chemicals
is taken now to safeguard the future. These chemicals could already pose
a long-term threat to world biodiversity and to human society. Many scientists
have expressed great concern about endocrine-disruption. At a meeting in
Erice, Sicily, in 1995, scientists were certain that:
"A trivial amount of government resources is devoted to monitoring
environmental chemicals and health effects. The public is unaware of this
and believes that they are adequately protected. The message that endocrine
disrupters are present in the environment and have the potential to affect
many people over a lifespan has not effectively reached the general public,
the scientific community, regulators or policy makers. Although this message
is difficult to reduce to simple statements without over- or understating
the problem, the potential risks to human health are so widespread and
far-reaching that any policy based on continued ignorance of the facts
would be unconscionable".
Endocrine-Disrupting Chemicals - A Global Problem
Over 50 chemicals, most of which are still in commercial use, have been
identified as endocrine disrupters. However, those identified to date may
only represent the tip of the iceberg. Of the thousands of synthetic chemicals
which are currently produced, only a tiny fraction have been tested for
their ability to disrupt hormones, since current regulation does not require
such testing.
Chemicals which vary widely in their structure and which have numerous
different uses have been identified as endocrine disrupters. They include
chemicals in the following categories:
-
plastics: Chemicals used in PVC and in the production of other plastics
including certain phthalate plasticisers.
-
organohalogen chemicals: Particularly those containing chlorine
(organochlorines), including PCBs, dioxins and many pesticides.
-
pesticides: a variety of different pesticides used in agriculture.
-
industrial chemicals: various industrial chemicals, including alkylphenols
which are derived from chemicals used in detergents and other products.
Many endocrine disrupting chemicals have become widespread contaminants
across the globe. This is not only due to their vast usage on a
world-wide scale, but also because some can be transported for thousands
of kilometres on air currents. Many are persistent in the environment,
taking years to degrade. Some persistent chemicals now pollute polar regions
where they have never even been used.
Even low environmental levels of many endocrine-disrupting chemicals
can lead to high levels in the body tissues of animals and humans.
This is because many endocrine disrupters, most notably more persistent
chemicals, become stored in fatty tissues. They build up to higher levels
in fat as more of a chemical is taken in. For many, the levels in fat increase
as one animal eats another, so that the highest levels are found in predator
animals at the top of food webs.
Exposure to Endocrine Disrupters is Unavoidable
For the general population, the greatest exposure to endocrine-disrupting
chemicals is from food intake. Since many are fat soluble, the highest
levels are present in meat, fish and dairy products. Exposure may also
come from pesticide residues remaining in fruit and vegetables, and from
low levels in drinking water. Food packaging has been reported to contaminate
food with endocrine-disrupters. Bisphenol-A is used in the lining of some
food cans, and phthalates have been found in some food wrappers. Recent
concern has also focused on PVC toys which could potentially expose children
to certain hazardous chemicals including some endocrine-disrupters.
The developing young are directly exposed to endocrine-disrupting
chemicals. Chemicals which are circulating in the maternal body may
be passed directly to the eggs of egg laying animals, or through the placenta
to the developing foetus in the womb in mammals, and through breastmilk
to the nursing young. It is almost certain that every pregnant woman has
endocrine-disrupting chemicals in her body that are transferred to the
foetus in the womb, and are present in her breastmilk. It is thought that
body fat is mobilised before pregnancy and lactation, releasing persistent
chemicals stored in the fat. This means that a proportion of the chemicals
which have accumulated in a woman’s body during her whole lifetime may
be passed to her child.
Endocrine Disruption
There are profound interconnections between many body systems and
the hormone (endocrine) system, including the nervous, reproductive and
immune system. Hormones act like chemical messengers, providing communication
between different parts of the body and regulating many body functions.
For their messages to be interpreted, hormones bind to specific sites in
cells called receptors, following which a particular biological effect
will be triggered.
Endocrine-disrupting chemicals may upset the balance of hormones
in the body and thereby disturb the regulation of body functions. Chemicals
may interfere with the balance of hormones in a number of ways. They may
bind to hormone receptors and consequently mimic or block the actions of
hormones, alter the natural production and breakdown of hormones, or interfere
with hormonal control by the brain.
It is particularly thyroid hormones and steroid hormones which are affected
by endocrine disrupters. Steroid hormones include the male sex hormone
testosterone, the female sex hormone estrogen, and other hormones which
are produced by the brain and adrenal glands. To date, most research has
focused on "estrogenic" chemicals which mimic an estrogen hormone. Less
is known about effects on other hormones.
The developing young are the most vulnerable. Steroid and thyroid
hormones play a major role in regulating the development of organs and
tissues in the foetus and developing young. For instance, sex hormones
are involved in controlling the development of the reproductive system,
and thyroid hormones are important in regulating development of the nervous
system. The foetus is exquisitely sensitive to changes in hormone levels.
Even a single disturbance at a critical time when a body system is developing
can cause irreversible changes, which in turn, can lead to permanent health
effects in the young or later in life. Exposure to endocrine-disrupting
chemicals during development may therefore lead to permanent effects on
health. Since hormones which are affected by endocrine disrupters, and
the processes of development which they regulate, are very similar in all
vertebrates, these chemicals may cause effects in animals and humans alike.
The greatest effects of endocrine-disrupters can occur at the lowest
doses. For many chemicals, increasing the dose will increase the toxic
effect it causes. However, for endocrine-disrupters, lower rather than
higher doses can have the most effect.
Health Effects of Endocrine Disrupters
Health effects which have been associated with exposure to endocrine-disrupting
chemicals in the egg or in the womb, often represent diminished potential
- a loss of health or competency. Such effects, including reduced fertility,
reduced intellectual capacity or weakened immune systems, may only be subtle.
They may not directly threaten the existence of an individual. However,
considered at a population level, these sorts of effects could destabilise
wildlife populations and change the whole character of human society.
Many different adverse effects in numerous wildlife species have
been associated with exposure to endocrine-disrupting chemicals. The
mechanism by which these effects have occurred is suspected to be endocrine-disruption,
although this is not certain in most cases. The effects in wildlife have
been recorded over the past 50 years, with many still becoming evident
today. They include decreased hatching success of eggs in fish, birds and
turtles, feminisation of male fish, embryo death and deformities in birds,
reproductive problems in reptiles, birds, and mammals, and altered immune
systems in marine mammals. In many cases these effects have lead to population
declines.
Exposure to endocrine-disrupting chemicals may be linked to increases
in reproductive disorders in humans. It is known that exposure in the
womb to a man-made synthetic estrogen drug causes a range of reproductive
problems in humans and in laboratory animals. Studies on animals also show
that exposure to estrogenic chemicals and other endocrine disrupting chemicals
cause very similar effects. From such evidence it has been suggested that
exposure to endocrine-disrupting chemicals could be partly or wholly responsible
for increases in the incidence of male reproductive disorders which have
been recorded in many countries over the past 20-50 years. These effects
include, reduced sperm count, an increased incidence of testicular maldescent,
urethral abnormalities, testicular cancer and prostate cancer.
Exposure to estrogenic chemicals in the womb may also be causing earlier
puberty in girls. Research indicates that exposure to some endocrine disrupters
throughout life could be associated with increases in the incidence of
breast cancer and endometriosis, and a shorter duration of lactation in
women.
Studies on the general population suggest that exposure in the womb
to PCBs and /or dioxins can reduce intellectual capacity and alter immune
systems. Studies indicate that the levels of PCBs and dioxins present
in body tissues in some women of the general population are sufficient
to cause subtle effects on the nervous and immune systems of their children.
Effects on the nervous system include slightly reduced IQ, attention deficits,
poorer memory and slight adverse effects on psychomotor and neurological
function. Whether such effects on the nervous and immune systems are caused
by endocrine-disrupting mechanisms is uncertain.
Prospects for the Future
The fact that many of the effects of endocrine-disrupting chemicals
impact on the next generation means that we may only see the consequences
many years after exposure. It is not possible to predict what the consequences
for our children and grandchildren will be if the production of endocrine-disrupting
chemicals continues. Nevertheless, there is a potential for severe widespread
impacts on wildlife, human health and human society. Global action of a
precautionary nature is needed now to safeguard the future. These chemicals
should be phased out and safer alternatives implemented where available.
Industry must pursue clean production technologies with the aim of preventing
further releases of these chemicals into the environment. This is not an
extreme viewpoint or an impossible task. The goal to phase out toxic, persistent
and bioaccumulative chemicals, some of which are endocrine disrupters,
has already been embraced at several international government conventions.
What is needed is implementation of these agreements and their extension
to include endocrine disruption as a recognised hazard in its own right.
1. INTRODUCTION
Since the late 1950s to the present day, many dramatic declines in wildlife
populations, caused by reproductive failure and problems with the development
of young, have been associated with exposure to man-made chemicals. Yet
it was not until 1991, that scientists realised that a common thread could
link these problems in wildlife. Many of the observed effects were synonymous
with what would be expected from disruption of the body’s hormones. At
that time, a meeting of expert scientists proposed a hypothesis that exposure
to chemicals which disrupt hormones, endocrine-disrupting chemicals, could
be to blame for the detrimental effects on health and declines of numerous
wildlife species (Wingspread 1991).
The adverse effects in wildlife included decreased hatching success
in fish, birds and turtles, reproductive abnormalities and decreased fertility
in fish, birds, reptiles and mammals, behavioural abnormalities in birds,
and compromised immune systems in birds and mammals. Such problems were
not only recorded in species inhabiting heavily polluted areas, such as
in the area of the US and Canadian Great Lakes, but were also evident in
wildlife in many other regions of the world (Wingspread 1991, Colborn et
al. 1993).
A high proportion of the adverse effects in wildlife, suspected to be
caused by endocrine-disrupting chemicals, result not from their impact
on adult animals but on the developing young. These chemicals are transferred
from the mother’s body to the egg, or to the developing foetus in the womb,
and via mothers’ milk to new-borns. Research has shown that hormones are
crucial for regulating the development of all animals which have backbones.
By disturbing the delicate balance of hormones during development, endocrine-disrupting
chemicals may permanently change the course of development, leading to
a wide range of adverse effects. The reproductive, nervous and immune systems
appear to be particularly vulnerable to these effects on the next generation.
In 1962, Rachel Carson warned of the dangers of man-made chemicals to
the environment and to humans in her book, Silent Spring, concluding, "Our
fate is connected with the animals". In 1993, after reviewing both human
and wildlife data on endocrine-disrupters, scientists similarly proposed
that wildlife could be acting like "sentinels", or mirrors to health effects
which could also occur in humans (Wingspread 1993). Presently, it is only
hypothesis rather than fact that endocrine-disrupting chemicals are affecting
human health, but evidence is mounting. Research suggests that the chemicals
may be implicated in the rise of several reproductive disorders in humans
over the past few decades, including reduced sperm counts and increased
breast cancer. They may also be associated with reduced intellectual capacity
and behavioural problems. Like the effects in wildlife, many effects in
humans appear to be on the next generation, although adults may be also
be affected (Colborn et al. 1993, US EPA 1997).
There is already evidence which suggests that some endocrine-disrupting
chemicals have reached levels in the environment where they could cause
adverse effects on development in humans and wildlife. Effects on development
are often not gross, but instead represent diminished potential - a loss
of health and competency, such as reduced fertility, reduced intellectual
capacity and weakened immune systems. These sorts of effects may not obviously
threaten the existence of an individual but, considered at a population
level, they could change the whole character of human society or destabilise
wildlife populations. There is now great concern among many scientists
that endocrine-disrupting chemicals could pose a long-term threat to world
biodiversity and to human society (Alleva et al. 1995).
2. IDENTIFICATION OF ENDOCRINE-DISRUPTING CHEMICALS
2.1 The Chemicals
Chemicals that have very different structures and all kinds of different
uses have been identified as being able to disrupt hormones. They include
(1) chemicals used in PVC and other plastics production, including certain
phthalate plasticisers (2) a variety of pesticides; (3) organohalogen chemicals,
particularly those containing chlorine (organochlorines), such as PCBs,
dioxins and many pesticides, and (4) various industrial chemicals including
alkylphenols which are derived from chemicals used in detergents and other
products, and bisphenol A for which the main uses are epoxy resins and
polycarbonate plastics.
A list of known and suspected endocrine-disrupting chemicals is given
in Table 1. Over 50 endocrine-disrupting chemicals have been identified
but there could be many more. Conservative estimates suggest there are
about 63,000 man-made chemicals in common use world-wide, and that 200
to 1000 new chemicals enter the market each year (Shane 1994). Presently
only a tiny fraction have been tested for their ability to disrupt hormones.
2.2 Identification
Endocrine-disrupting chemicals vary widely in their chemical structure.
It is unlikely that the ability of a chemical to disrupt hormones will
ever be predictable from structure alone (McLaclan 1993, Katzenellenbogen
1995). Scientific studies which have identified these chemicals have relied
on using "in vitro" tests (cell culture) and "in vivo" (laboratory animals)
tests. Current regulatory systems do not require chemicals to be screened
for their ability to disrupt hormones, or tested for health effects resulting
from endocrine disruption, although this is now under discussion (see section
15.1).
To date, most testing for endocrine disrupters has focused on "estrogenic"
chemicals which mimic an estrogen hormone. Many chemicals have been
designated as being estrogenic based on laboratory tests which use animal
or human cells grown in culture. Cell culture tests are now available which
can identify whether a chemical is likely to be estrogenic in different
kinds of animals. For example, a test has been developed which uses fish
cells to find out whether chemicals which pollute the aquatic environment
would be estrogenic to fish (Sumpter and Jobling 1995). A test using human
cells has also been developed to predict whether a chemical would be likely
to be estrogenic in humans (Soto et al. 1992, 1995). Over 30 chemicals
have now been identified as being estrogenic using cell culture tests (eg.
Soto et al. 1995). In addition, several chemicals have also been
identified which interfere with male sex hormones known as anti-androgenic
chemicals (Kelce et al. 1995, Danzo 1997). Some endocrine-disrupting
chemicals, such as DDT, have also been identified by the sorts of adverse
health effects they cause when tested in laboratory animals (Bustos et
al. 1988).
Note that estrogenic and anti-androgenic effects represent only a subset
of the potential effects of known or suspected endocrine disrupters, as
sex hormones are only one component of the endocrine system. Testing for
other effects has been extremely limited to date.
3. ENDOCRINE-DISRUPTING CHEMICALS IN THE ENVIRONMENT
Once discharged into the environment, endocrine-disrupting chemicals
do not always remain close to where they are released, but instead may
be transported over long distances in air currents or by water. Coupled
with their immense usage on a world-wide scale, this means that, in many
cases, endocrine-disrupting chemicals now present a global problem rather
than just one of localised contamination. Furthermore, some of the endocrine-disrupting
chemicals, in particular the organochlorine pesticides, PCBs and dioxins,
are persistent in the environment, taking years or even decades to degrade.
3.1 Transport and Distribution of Endocrine-Disrupting
Chemicals in the Environment
Chemicals can become airborne either by their direct emission to air,
such as from factory or incinerator stacks, or by evaporation from the
ground, water, or the leaves of sprayed crops. Once airborne, they may
be transported for thousands of kilometres in the atmosphere before condensing
and falling once more to the earth’s surface.
Research has shown that many persistent organochlorines, appear to be
carried on air currents from warmer regions of the globe towards polar
regions where they are subsequently deposited. This "global fractionation"
process is thought to have led to the high concentrations of these chemicals
which are now found in Arctic and Antarctic regions, where they have never
even been used (Iwata et al. 1993, Wania and Mackay 1996).
Some endocrine disrupters are now very widespread across the globe.
These include several persistent organochlorine pesticides, PCBs, dioxins
and phthalates (Loganthan and Kannan 1994, Jobling et al. 1995).
In addition, levels of lead, mercury and cadmium have become elevated,
even in remote areas, as a result of man’s activities (Pacyna 1997). Although
many of the persistent organochlorine pesticides are now banned in Europe,
their input into the environment continues in some developing countries
where they remain in use, often in a widespread and poorly unregulated
fashion (Iwata 1994, Wania and Mackay 1996). PCBs are no longer manufactured
intentionally but, due to their persistent nature and continued input into
the environment from wastedumps, there is not a global downward trend in
their levels. It is estimated that about 31% of the PCBs which were manufactured
have entered the environment, but more than double this amount still remain
in use in older electrical equipment or is present in dumps and landfill
sites or in storage (Tanabe 1988). This means that PCBs could continue
to enter the environment in large quantities in the future if measures
are not taken to prevent this. In addition, PCBs and dioxins continue to
be generated as by-products of some chemical and combustion processes.
Other known or suspected endocrine disrupters, including many modern pesticides,
industrial chemicals and additives in consumer products, remain in widespread
use globally.
3.2 Endocrine-Disrupting Chemicals in the Food
Web
Most endocrine-disrupting chemicals which are persistent, such as the
dioxins, PCBs, organochlorine pesticides and alkylphenols, are also soluble
in fats. As a consequence of this, and because of the way that animals
and humans deal with these toxic substances once they enter the body, they
can become stored in fatty tissues. The levels of chemicals build up or
"bioaccumulate", in the animal’s fat as more of the chemical is taken in
(Hall 1992, Warhurst 1995). For many of these chemicals, the levels in
fat increase as one animal eats another, so that the highest levels are
found in predator animals at the top of food webs, for example, humans,
seals, dolphins and fish-eating birds.
Even low environmental levels of chemicals which bioaccumulate can lead
to very high levels in the body tissues of animals. For example, in a food
web in Lake Ontario, small aquatic organisms such as algae, accumulate
PCBs at concentrations hundreds of times higher than levels in the surrounding
water. Fish which eat the algae accumulate still higher levels, and predatory
birds like herring gulls at the top of the food web which eat fish accrue
the highest levels. The levels in their eggs can be 25 million times greater
than the original level in the water (Colborn et al. 1990).
When persistent chemicals are stored in fatty tissue they are only very
gradually released and excreted from the body. For example, it is estimated
that the half life for residence of PCBs in the human body is 12 years,
which means that after one single exposure to PCBs it would take 12 years
for just half of it to be excreted from the body. However, as we are normally
exposed to these chemicals at each meal , body levels inevitably build
up (Hall 1992).
4. HUMAN EXPOSURE TO ENDOCRINE-DISRUPTING CHEMICALS
Exposure to man-made endocrine-disrupting chemicals is presently unavoidable
because of their widespread presence in the environment. For the general
population, by far the largest exposure comes from foods that are contaminated
with these chemicals. As a result of the widespread occurrence of many
endocrine-disrupting chemicals in the environment, most foodstuffs are
contaminated by some of them. Since many of the chemicals are soluble in
fat and/or bioaccumulate, the highest levels are found in meat, fish and
dairy products. It has been estimated for the persistent organochlorine
chemicals for example, that about 80% of our intake of these chemicals
come from these foodstuffs (Hall 1992). Some individuals may also be exposed
to endocrine disrupters as a result of handling chemicals at work.
4.1 Pesticide Residues in Food and Drinking Water
Aside from chemicals that have accumulated in foods, other dietary exposure
may come from pesticide residues which remain on sprayed crops and contaminate
drinking water. Spraying pesticides on crops means that a proportion of
them may remain on the crops by the time they are harvested. A review of
pesticides in the US reported that fruit and vegetable crops receive most
of the pesticides applied to agricultural crops, and the contamination
rate with pesticides is higher for fruits than for any other commodities
(Culliney et al. 1992).
In The Netherlands, residues of several endocrine-disrupting pesticides
were found to be present in foods that were tested, including carbaryl,
dicofol, endosulfan, lindane and vinclozolin (Health Inspector for Public
Health, The Netherlands, 1995). Another study revealed that 33.2% of fruit
and vegetables produced in the Netherlands, and 59.4% of imported foods,
contained detectable levels of pesticide residues (van Klaveren 1997).
Pesticides can leach from sprayed land into watercourses which are used
for drinking water supplies. Monitoring in The Netherlands has shown that
the most commonly detected pesticides in surface waters include several
endocrine disrupters, namely organochlorine insecticides lindane, endosulfan
and dieldrin, and the fungicide vinclozolin. In the Netherlands and most
European countries, the safety limit for the total amount of pesticides
in drinking water is sometimes exceeded (HMSO 1995).
4.2 Food Packaging and Processing
Some endocrine-disrupting chemicals are used in the production of food
packaging materials. Several studies have shown that these chemicals can
leach out of packaging into food they are in contact with.
Bisphenol-A, an estrogenic chemical, is present in lacquer coatings
which are used to line the inside of some food cans. Tests on tins of peas,
artichokes, green beans, mixed vegetables, corn and mushrooms found the
liquid surrounding vegetables in food cans had estrogenic properties due
to bisphenol-A. (Brotons et al. 1995). The amount of this chemical
found in liquid from cans (highest level 80ug/kg) was well within the EC
safety limit (3 mg/kg). However, this was set before it was known that
bisphenol-A was estrogenic and, as such, cannot be regarded as protecting
the health of the public. Bisphenol-A is also present in polycarbonate
plastic which is widely used for packaging of food and drinks. Whether
it leaches from this plastic into foodstuffs is yet to be tested (Feldman
and Krishnan 1995).
Research indicates that some phthalates, including DBP and BBP which
are estrogenic, are present in foods from general environmental contamination
(MAFF 1995, MAFF 1996). However, DBP has also been found in printing inks
used in plastic food packaging and on paper and board packaging (Nerin
1993, MAFF 1995). Studies show that DBP can migrate from the packaging
into a wide variety of foods it is in contact with (Nerin 1993, MAFF 1995).
4.3 PVC Toys
Some children’s toys are made from soft PVC plastic which contain phthalate
plasticisers (Meek and Chan 1994, Vinkelsoe et al. 1997). A recent
study conducted by the Danish Environment Protection Agency, found that
a number of phthalates could leach from three brands of teethers, which
could potentially expose infants to these chemicals. The phthalates included
BBP and DBP which are estrogenic. In addition, another estrogenic chemical,
nonylphenol, was found to leach from the teethers (Vinkelsoe et al.
1997). As a result of the study, the manufacturer of the teethers withdrew
these products from sale in Denmark, Spain, Greece and Italy.
Two major retailers in Denmark and Sweden reacted by withdrawing soft
PVC toys from their shelves (ENDS 1997a). In The Netherlands, one of the
main suppliers and importers of PVC toys with almost 50% of the market,
has decided to stop selling PVC toys to children under 3, and has requested
suppliers not to use PVC toys for children older than 3 years.
Recent research by Harris et al. (1997) has demonstrated that
the isomeric phthalate DINP (diisononyl phthalate), commonly used at high
concentrations in consumer products such as PVC toys, can also show weak
estrogenic activity in vitro with human breast cancer cell lines.
DEP (diethyl phthalate) also showed some activity, although this phthalate
appears to be less widely used. In addition the authors note that there
was little, if any, relationship between molecular structure and estrogenic
activity, even within the phthalates as a chemical class.
5. EXPOSURE OF THE DEVELOPING YOUNG TO ENDOCRINE-DISRUPTING
CHEMICALS
Prior to egg laying in fish, amphibians, reptiles and birds, and during
pregnancy and lactation in mammals and humans, body fat is mobilised. This
may release persistent chemicals present in the fat. Such chemicals, as
well as others circulating in the maternal body, may be passed directly
to the egg in egg-laying animals, or passed through the placenta to the
developing foetus in the womb in mammals, and through breastmilk to the
nursing young. The developing stages of life may, therefore, be directly
exposed to endocrine-disrupting chemicals (Colborn et al. 1993).
Scientific experts at a meeting in Erice, Sicily (Alleva 1995), were
certain that:
"Gestational exposure to persistent man-made chemicals reflects the
lifetime of exposure of females before they become pregnant. Hence, the
transfer of contaminants to the developing embryo and foetus during pregnancy
and to the new-born during lactation is not simply a function of recent
maternal exposure".
5.1 Exposure in the Womb
The placenta, which connects the developing foetus in the womb to its
mother, does not act like a barrier and will not protect the foetus from
toxic substances circulating in the mother’s body. (Hall 1992). For instance,
it is common knowledge that smoking cigarettes during pregnancy can cause
detrimental effects to the unborn child, such as retarding growth. Another
example is the tragic effects which occurred on the development of limbs
following the administration of the pharmaceutical drug thalidomide to
pregnant women (Michal et al. 1993).
It is now known that many chemicals and pharmaceutical drugs can pass
directly across the placenta to the developing foetus (Sullivan 1993).
Endocrine-disrupting chemicals are no exception to the rule and many could
be passed to the foetus in this way. Those known to cross the placenta
include DDT, DDE, hexachlorobenzene, lead, methylmercury, PCBs and dioxins,
and phthalates (Ando et al. 1986, Kanja et al. 1992, Koopman-Esseboom
et al. 1994, Rice 1995, Howard et al. 1997 in prep).
Scientific experts at a meeting in Erice, Sicily (Alleva et. al. 1995),
estimated with confidence that: "Every pregnant woman in the world has
endocrine disrupters in her body that are transferred to the foetus. She
also has measurable concentrations of endocrine disrupters in her milk
that are transferred to the infant".
5.2 Exposure of the Nursing Young
Chemicals in a pregnant woman’s body which circulate in her blood may
contaminate her breast milk and pass to her nursing infant. Endocrine-disrupting
chemicals which are often found in human breast milk (in parts per million
or trillion levels) include PCBs, dioxins and the organochlorine pesticides
DDT, DDE, dieldrin, hexachlorobenzene, hexachlorocyclohexane and chlordane
(Galentin-Smith et al. 1990, Skaare and Polder 1990, Thomas and
Colborn 1992, Stevens et al. 1993, Furst et al. 1994).
Persistent chemicals which have accumulated in a woman’s body during
her lifetime decrease in the mother’s body as they pass to her breastmilk,
and hence to her nursing infant. It has been estimated that if a child
is breastfed for one year, it will accumulate 4-12% of the total amount
of dioxins which it would be expected to accumulate during its whole lifetime
in just its first year (US EPA 1994). Other estimates suggest that for
dioxins and PCBs which are known to bioaccumulate, a woman reduces her
body levels of these chemicals by over 50%, by breast feeding for 6 months.
Most of this will pass to her baby via breastmilk (Lindstrom et al.
1994).
There has been concern among some scientists regarding the levels of
certain persistent hormone-disrupting chemicals in breast milk, in particular
PCBs and dioxins. However, breast-feeding is known to convey very important
benefits to the overall health and development of infants. Consequently,
despite the presence of these chemicals in breastmilk, health authorities
still encourage and recommend breastfeeding (eg. WHO 1996, MAFF 1997).
6. LEVELS OF ENDOCRINE-DISRUPTING CHEMICALS IN
THE GENERAL POPULATION
Persistent endocrine-disrupting chemicals which bioaccumulate in body
fat are only excreted from the body at a very slow rate, and with continued
exposure, their levels progressively build up over a lifetime. Mobilisation
of stored contaminants from fat tissue only appears to take place during
lactation and starvation, and as a result of disease (Thomas and Colborn
1992).
Some endocrine disrupters, such as phthalates, do not become stored
in fat because they are more readily broken down and excreted from the
body. However, people are continually exposed to these chemicals because
they are ubiquitous in the environment. In addition, research by Dirven
et al. (1993) indicated that, following occupational exposure, phthalates
may persist in the human body for longer than previously assumed.
Levels of endocrine-disrupting chemicals in people’s bodies do vary
geographically. For instance, the general population of industrialised
nations have higher body levels of industry-related chemicals, like PCBs
and dioxins, than people in non-industrialised countries (Schecter 1996).
Some populations have particularly high body levels of endocrine-disrupters
due to a subsistence diet of fish and/or sea mammals. For example, in many
parts of the Arctic, a reliance on marine food which contains high levels
of PCBs, dioxins, methylmercury and organochlorine pesticides, has led
to elevated exposure in indigenous communities (Kuhnlein et al.
1995, Gilman et al. 1997). For example, levels of organochlorines
in women’s breastmilk in Inuit communities of Arctic Quebec, Canada, were
3 to 7 times higher than in other parts of the province (Dewailly et
al. 1994).
Localised chemical use can also be problematic. For instance DDT is
still used in sanitation campaigns against malaria in Mexico. Levels of
DDT in the general population and in workers are high, and it has been
suggested that infants could be exposed to potentially deleterious levels
through breastmilk. This research has generated much concern and calls
for alternative measures to be taken (Lopez-Carrillio et al. 1996,
Rivero-Rodriguez et al. 1997, Marien 1997).
Banning the use of persistent chemicals, such as DDT, has led to a gradual
reduction in levels present in breastmilk in some European countries (Thomas
and Colborn 1992). However, a study in Germany reported that following
bans, DDE and PCBs levels had initially decreased but levels have since
become more stable (Furst et al. 1994). With better technology and
tighter restrictions on the release of dioxins into the environment, a
recent European survey showed that levels in breastmilk were no longer
increasing and had decreased in some countries (WHO 1996).
7. HOW ENDOCRINE-DISRUPTING CHEMICALS CAUSE HEALTH
EFFECTS
7.1 Hormones in the Body - The Endocrine System
Hormones are natural chemicals which are produced by the body and are
normally effective at very low concentrations. They act as chemical messengers,
travelling in the blood and sending signals to cells to provide a means
of communication between different parts of the body. The hormone system
is known as the endocrine system, because it is the endocrine glands which
produce hormones.
Hormones are essential for maintaining the proper functioning of the
body, being involved, for instance, in regulating reproductive functions,
general body growth and metabolism, muscle and nervous system functions.
During the early stages of life, in the embryo/foetus and developing young,
hormones play a major role in the controlling the development of many tissues
and organs, including the reproductive, immune and nervous systems.
There are several endocrine glands in the body which produce hormones.
These include the gonads - testicles in men and ovaries in women, the thyroid
gland in the throat, the pituitary gland in the brain, the pancreas in
the abdomen and the adrenal glands. Each gland makes specific hormones
and releases them into the blood. For example, the sex organs produce the
female sex hormone estrogen and the male sex hormone testosterone, which
control reproductive function, whilst the thyroid gland makes thyroid hormones,
which regulates the use of food and body growth (Colborn et al.
1993, Colborn 1996, EPA 1997).
Hormones travel from their point of release in the bloodstream to particular
tissues where they convey their messages. For the messages to be interpreted,
hormones bind to special sites in cells called receptors. A hormone and
receptor have a precise fit, like a lock and key, so that only a specific
type of hormone can bind to a specific sort of receptor. For instance,
estrogen can only bind to estrogen receptors to convey its messages. Once
a certain number of connections between the hormones and their receptors
have been formed, a particular biological effect in cells will be triggered
(EPA 1997). Therefore, by binding to receptors, hormones cause biological
effects which can lead to changes in the functioning of cells, tissues
and organs. Although hormones are generally effective at low concentrations,
they can affect major changes in organ or body function.
7.2 Hormones Which Are Affected by Endocrine Disrupters
Steroid hormones include the male sex hormone testosterone, female sex
hormones, estrogen and progesterone, and various hormones produced by the
pituitary and adrenal glands. These hormones, together with thyroid hormones,
are not only found in humans but are produced by all animals which have
a backbone - fish, amphibians, reptiles, birds and mammals. In all of these
animals and in humans, the structure of these hormones is almost identical
and they have very similar functions. It appears that, throughout evolution,
these hormones have remained the same, being a successful way of regulating
bodily processes in animals and humans alike. It is these steroid hormones
and thyroid hormones in particular with which synthetic endocrine-disrupting
chemicals are able to interfere (Colborn et al. 1993).
7.3 How Endocrine Disrupters Work
Endocrine-disrupting chemicals can interfere with the way in which steroid
hormones and thyroid hormones normally work. As a consequence they may
upset the delicate balance of hormones in the body, which, in turn, may
lead to adverse effects on health.
A definition of an endocrine disrupter proposed by the US Environmental
Protection Agency, is "an exogenous agent that interferes with the synthesis,
secretion, transport, binding, action, or elimination of natural hormones
in the body that are responsible for the maintenance of homeostasis, reproduction,
development, and/or behaviour (US EPA 1997). Some of the mechanisms
by which man-made endocrine-disrupters can interfere with hormones are
outlined below:
-
Hormone Mimicry: Some chemicals mimic hormones by binding to hormone
receptors in cells, and thereby triggering the same biological effect as
the hormone (McLachlan 1993). For example, many chemicals are now known
which can mimic an estrogen hormone by binding to estrogen receptors in
cells. These are the so-called "estrogenic chemicals" because they act
like the an estrogen hormone (Soto et al. 1995).
-
Blocking Hormone Receptors: Some chemicals bind to hormone receptors
and block them. This prevents hormones from binding to the receptors and
exerting their normal biological effects (McLachlan 1993). A few chemicals
are known which can block the male sex hormone, the "androgen", receptor.
These include the pesticides vinclozolin and DDE, which is the breakdown
product of DDT (Kelce et al. 1994 and 1995, Gray et al. 1994).
These chemicals are known as "anti-androgenic chemicals".
-
Altering Hormone Metabolism: Some chemicals do not directly interfere
with hormones or their receptors, but upset the balance of hormones by
interfering with their metabolism, i.e., their synthesis or natural breakdown
and elimination from the body. For instance, the organochlorine pesticides
DDE, atrazine and kepone have been found to alter the metabolism of estrogen
(Bradlow et al. 1995). Another example of altered hormone metabolism
comes from a recent study of flounder fishes in Rotterdam harbour in the
Netherlands. Female fish had raised estrogen levels, most likely due to
the mixture of chemicals present in the harbour. The chemicals had the
effect of impeding the normal processes in the liver which are responsible
for the breakdown of estrogen (Janssen et al. 1997).
-
Affects on Hormonal Control: The brain and the endocrine system
are profoundly interconnected with each other. While the brain regulates
hormonal activity, hormones themselves influence brain function, including
behaviour, in adults and affect brain development during early life. The
main control centre for the hormone system is the pituitary gland in the
brain - which itself produces hormones that tell other endocrine glands
whether to increase or decrease their production of hormones. The pituitary
receives signals on how to act from another part of the brain, the hypothalamus,
which constantly monitors the levels of hormones in the blood. Some hormone-disrupting
chemicals appear to affect the brain’s control of the hormone system, either
by their direct impact on steroid hormone levels, or indirectly by affecting
the activities of the brain in other ways (Colborn et al. 1996,
EPA 1997).
-
Ah Receptor: The Ah receptor is not a hormone receptor but another
sort of receptor in cells. Some chemicals, notably the dioxins and certain
PCBs, can bind to these receptors and in so doing trigger many different
biological effects, among which can be the disruption of hormones. It is
thought that this is how these chemicals can cause anti-estrogenic effects
and alter levels of thyroid hormones (Safe and Krishnan 1995). Besides
the dioxins and PCBs, there are other chlorinated and non-chlorinated chemicals
which are suspected of being able to bind to the Ah receptor (see table
2), (Giesy et al. 1994). These chemicals may therefore also be endocrine-disrupters.
Indeed, there is experimental evidence for some, including certain PAHs,
that they might be (Santodonato 1997).
Research has shown that while some chemicals may disrupt hormones by one
of the above mechanisms, others may cause their effects in a multitude
of different ways. Experiments with DDT for instance have clearly shown
that it is estrogenic - it can bind to the estrogen receptor and causes
adverse effects on health that would be expected for an estrogenic chemical.
However, a recent study has shown that it can also bind to the androgen
receptor, and so it is possible that it could cause adverse effects from
this action too (Danzo 1997). Similarly, the organochlorine pesticides
endosulfan and alachlor have been found to bind not only to the estrogen
receptor but also to the progesterone receptor (Vonier et al. 1996).
Steroid hormones and their receptors are very similar in structure in
all animals which have backbones (vertebrates), which would suggest that
if a chemical was estrogenic in one species it could also be in another.
It is not yet possible to generalise and say that this is the case, but
most evidence supports the idea that if a chemical is estrogenic in one
species it will be in others (Sumpter and Jobling 1995). Endocrine-disrupting
chemicals could therefore have impacts on wildlife and humans alike on
a global scale. Creatures without backbones (invertebrates), and plants
have different hormones to vertebrates, but they too may be influenced
by chemicals which disrupt hormones (US EPA 1997).
7.4 Is endocrine-disruption feasible at current
environmental levels of chemicals?
It is accepted that endocrine-disrupting chemicals are generally very
weak in comparison to real hormones. When estrogenic chemicals have been
tested in cell culture for their ability to bind to hormone receptors,
they are 1000 to 1,000,000 times less potent than the hormone estrogen
(Soto et al. 1995, Harris et al. 1997). This implies that
it would take 1000 to over 1,000,000 times more of the chemical than estrogen
to achieve the same amount of binding to receptors.
Because of the apparent weak potency of the endocrine-disrupting chemicals,
it is difficult to see how they could overcome the normal functioning of
hormones in the body and cause adverse effects. There are however several
reasons which may explain how endocrine-disrupting chemicals could have
biological effects:
-
Persistence and Bioaccumulation. Many endocrine-disrupting chemicals
build up (bioaccumulate) in the fatty tissues of animals and humans reaching
levels which can be much higher than levels in the environment. Many are
also persistent, taking a long time to degrade and remain in the body for
years. As a result of these properties, some of the chemicals have now
reached levels in the bodies of animals and humans which are millions of
times higher than the levels of natural hormones in the body (Alleva et
al. 1995).
-
Chemical Mixtures. In the real world, humans and animals are exposed,
not to individual endocrine-disrupting chemicals, but to complex mixtures
of many different ones. Consequently, it is possible that the actions of
these chemicals may add up together and cause cumulative effects. By mixing
endocrine-disrupting chemicals together and testing them on human cells
in culture, studies have revealed that the effects of the chemicals can
indeed be additive (Soto et al. 1994, Soto et al. 1995).
One study has found that mixtures of estrogenic chemicals caused effects
that were even greater than additive, or i.e. synergistic. In this study
mixtures of estrogenic chemicals which are known to contaminate alligator
eggs in Lake Apopka, Florida, were found to produce synergistic effects
when tested on alligator estrogen receptors (Vonier et al. 1997).
-
Binding Proteins. Over 90% of natural estrogen circulating in the
body becomes bound to special binding proteins in the blood. Only the remaining
"free" estrogen is able to diffuse into cells and exert biological effects.
However, many endocrine-disrupting chemicals do not bind significantly
to the binding proteins, potentially leaving up to 100% of these chemicals
circulating in blood free to enter cells and exert effects (vom Saal et
al. 1995).
-
Multiple Pathways of Action. Some endocrine-disrupting chemicals
may not just exert their effects by one mechanism, such as mimicking estrogen,
but may be capable of causing effects through two or more endocrine-disrupting
mechanisms. This amplifies their potential for causing hormone-disrupting
effects (Danzo 1997).
When the above points are considered, it becomes clear that, even though
they are far less potent than normal hormones and are present at low concentrations
in the environment, endocrine disrupters could pose a threat to the health
of wildlife and humans.
8. HEALTH EFFECTS OF ENDOCRINE-DISRUPTING CHEMICALS
It has been hypothesised that endocrine-disrupting chemicals may be
causing adverse effects to wildlife and humans alike. In some cases it
is almost certain that detrimental effects in wildlife populations are
caused through endocrine disruption. There is also growing evidence that
endocrine disrupters could be implicated in human health effects, at levels
currently found in the environment.
A critical piece of evidence which showed that the human body could
mistake a man-made chemical for a hormone, arises from an unfortunate incident
between 1945 and 1971, in which about 5 million women were given a synthetic
drug during pregnancy. The drug, diethylstilbestrol (DES), is a man-made
estrogen. It caused a range of reproductive and immune system abnormalities
in sons and daughters born to these women (Blair 1992, Blair et al.
1992, Gray 1992, Toppari et al. 1995).
Further evidence has come from direct study of the effects of exposure
to chemicals on human health. Most studies which are available on developmental
effects of chemicals which have endocrine disrupting properties have examined
effects of PCBs and dioxins. Scientific studies on laboratory animals have
also provided information. In the context of endocrine-disruption, animal
studies are useful as indicators of potential effects in humans because
steroid hormones, and the developmental processes they regulate, are extremely
similar in animals and humans.
Known and suspected effects of endocrine-disrupting chemicals on the
reproductive, nervous and immune systems of wildlife and humans are discussed
in the following sections. Many of the problems arise from effects during
development in the egg or in the womb.
8.1 The Vulnerable Foetus and Young
Steroid hormones and thyroid hormones play a major role in regulating
the development of tissues and organs in the foetus and young. Research
has shown that the foetus is exquisitely sensitive to changes in hormone
levels. A disturbance in hormone levels at a critical time when a body
system is developing can lead to irreversible changes, which, in turn,
can lead to permanent health effects in young or later in life (vom Saal
et al. 1992, Colborn et al. 1993).
Since endocrine-disrupting chemicals are present in the eggs of animals,
and can pass through the placenta to the developing foetus, or through
breastmilk to the young in mammals and humans, they have the potential
to disrupt hormones during development and cause permanent effects on health.
As a consequence of the extreme sensitivity of a developing foetus, levels
of endocrine-disrupting chemicals which cause little problem to the mother
may be harmful to the foetus.
Not only is the foetus the most sensitive lifestage to the potential
effects from endocrine-disrupting chemicals, it is also the most vulnerable.
This is because mechanisms which provide some protection against toxic
chemicals in the adult are not fully developed in the foetus.
9. MALE REPRODUCTION
9.1 Increasing Reproductive Disorders in Men
Over the last 50 years or so there has been a dramatic increase in the
incidence of several reproductive disorders in men. Studies show that :
-
Testicular cancer, a disease most common in men aged 20-45, has increased
world-wide, rising by as much as 4-fold in some areas. It is now the most
common form of cancer in men in some countries (Giwercman et al.
1993, Toppari et al. 1995).
-
The incidence of testicular maldescent (undecended testicles) appears to
have increased in several countries (Toppari et al. 1995).
-
The incidence of boy’s born with urethral abnormalities appears to have
increased in many countries (Toppari et al. 1995).
-
Prostate cancer is on the increase in a number of countries, particularly
northern Europe and North America (Santti et. al. 1994).
-
In 1992, a report suggested that sperm count had fallen by 50% in 50 years,
following an analysis of results from 61 previous studies which were undertaken
between 1938 and 1991 in several different countries (Carlsen et al.
1992). Subsequent studies carried out in Paris, Belgium and Scotland (UK)
have also indicated that sperm counts have declined (Auger et al.
1995, Van Waeleghem et al. 1996, Irvine et al. 1996). These
studies reported that sperm count has decreased over the past 20 years
at a rate of 2% per year. The year of a man’s birth was found to influence
sperm count, such that a 20 year old man’s sperm count today is lower than
at 20 year olds sperm count would have been 10-20 years ago. Furthermore,
the studies showed that it was not only sperm count, but other measures
of sperm quality which have declined. The percentage of motile sperm in
semen has decreased and the numbers of physically abnormal sperm has increased.
Preliminary findings of a study in Bangalore, India, also suggest sperm
count has decreased in the last 5 years (Mehta and Kumar 1997). Sperm count
does appear to vary geographically and may not be decreasing on a world-wide
basis. Two studies in the US, and one in Toulouse, France, found no evidence
that sperm count has fallen over the past 20-25 years (Fisch et al.
1996, Paulsen et al. 1996, Bujan et al. 1996).
9.2 Possible Causes of the Increasing Incidence of
Male Reproductive Disorders
All of the above disorders of the male reproductive system have increased
in many countries over a short time period. It is therefore most likely
that they are due to changes in environmental influences or "life-style",
rather than to genetic factors (Jensen et al. 1995). Based on the
evidence discussed below, this has led to the hypothesis that exposure
to endocrine-disrupting chemicals in the womb, and possibly during childhood,
could be partly or wholly to blame for the increased incidence of male
reproductive disorders:
It is thought that all of the disorders probably have their origins
during development in the womb and possibly also in childhood. A clue to
what could have caused the increase in these disorders in recent years
came from the exposure of pregnant mothers to DES. This synthetic estrogen
drug caused boys who were born to the women to have an increased incidence
of reproductive abnormalities similar to those listed above. There was
a greater incidence of urethral abnormalities and testicular maldescent
among the boys and, when they reached adulthood, many had reduced sperm
counts and sperm quality. Experiments with laboratory rodents showed that
comparable reproductive abnormalities occurred in the male offspring of
animals treated with DES during pregnancy (Gill et al. 1981, Sharpe
1993, Toppari et al. 1995). A recent follow-up study on over 200
men who were exposed to DES in the womb found that, although there was
no evidence of reduced fertility, the men were 3 times more likely to have
malformations of the genitalia than unexposed men (Wilcox et al.
1995).
Results of the tragic experience with DES clearly showed that the human
body could mistake a man-made estrogenic chemical for the real hormone
estrogen. It also showed that that inappropriate exposure to additional
estrogen during pregnancy can result in permanent effects in offspring,
including an increase in male reproductive disorders. Following this line
of thought, scientists have hypothesised that, if extra estrogen can cause
these effects, exposure to environmental estrogenic chemicals in the womb
may have the same effect (Sharpe and Skakkebaek 1993). Furthermore, it
is possible that other endocrine disrupters, including anti-androgenic
compounds and chemicals that exert effects through the Ah receptor such
as dioxin, could also cause similar effects. Considering this evidence,
it seems very reasonable to suggest that the increase in male reproductive
problems seen over the past few decades may be partly or wholly caused
by increased exposure to endocrine-disrupting chemicals which have been
introduced into the environment over the past 50 years (Jensen et al.
1995).
Presently, there is little direct evidence in humans of effects resulting
from exposure to endocrine-disrupting pollutants. Nevertheless, the hypothesis
is also supported by several laboratory animal studies described below.
One study of women who had accidentally been exposed to high levels of
PCB and dioxins whilst pregnant gave birth to boys who had slightly shorter
penises at age 11-14 (Guo et al. 1993).
It has been argued that other factors can reduce sperm count in adult
men, including drinking alcohol to excess, sexually transmitted diseases,
some commonly prescribed drugs, smoking cigarettes and wearing tight underwear
(Giwercman et al. 1993, Tiemessen et al. 1996, Vine 1996).
Exposure to certain pollutants like lead or ionising radiation may also
reduce sperm count. Such factors may have contributed to declining sperm
counts in men reported over the past 20-50 years. However, these factors
alone cannot account for increases in the other male reproductive problems
which have occurred concurrently with sperm count decrease. Exposure to
endocrine-disrupters during development maybe a more plausible explanation.
In addition, a recent study in Finland examined the reproductive tissues
from two groups of middle-aged men after their death, in 1981 and in 1991.
It found that the incidence of normal sperm production had deteriorated
over the ten year period, and testicular weight had decreased by 5.8%.
Sperm production was "normal" in 56% of the 1981 group, falling to only
27% in the 1991 group. The deterioration in sperm production could not
be explained by alcohol drinking, smoking or drug taking. In fact, the
results were more consistent with factors effecting the reproductive system
during development and/or before puberty, such as endocrine disrupters.
It was suggested that deteriorating sperm production may explain why sperm
counts are declining (Pajarinen et al. 1997).
9.3 Laboratory Studies
Several studies have shown that when male animals are exposed to endocrine
disrupters in the womb, they suffer from reproductive abnormalities. For
instance, when pregnant mice or rats are given high doses an estrogenic
chemical, such as DDT, methoxychlor, chlordecone, hexachlorocyclohexane,
PCBs, or di-n-butylphthalate (DBP), or given the anti-androgenic chemicals
DDE or vinclozolin, their male offspring have reduced testicular weight
and/or a lower sperm count (Toppari et al. 1995, Gray et al.
1992, Wine et al. 1997, Kelce et al. 1995, Gray et al.
1994).
Only a few studies have investigated the effects of endocrine-disrupters
on the male reproductive system at low doses which are more relevant to
current environmental levels of these chemicals. The studies looked at
the effect of exposing pregnant rodents to dioxin, an alkylphenol (octylphenol),
and the phthalate BBP, at levels close to, or within an order of magnitude
of, current exposure levels in humans. All 3 chemicals caused marked and
significant decreases in sperm count and other reproductive abnormalities
in the male offspring. For BBP, the level of exposure approached levels
to which humans are exposed in everyday life (Mably et al. 1992,
Gray et al. 1995a, Sharpe et al. 1995).
A recent study showed that exposing pregnant mice to synthetic estrogen,
or to the estrogenic chemical bisphenol-A, caused their male offspring
to have enlarged prostate glands. In humans, enlarged prostate glands may
predispose individuals to prostate cancer in later life. The effect in
mice occurred at doses close to those to which humans are exposed through
eating canned vegetables, which can be contaminated with bisphenol-A from
the lining of food cans (Nagel et al. 1997).
9.4 Wildlife Studies
Wildlife studies have revealed male reproductive problems in several
species that have been associated with exposure to endocrine-disrupting
chemicals.
Fish
Studies in the UK have found that sewage effluent may be disrupting
reproduction in wild fish populations in rivers and estuaries. Research
was initially prompted after fishermen found a high incidence of hermaphrodite
fish (which had both testis and ova), near to sewage treatment works. Scientific
investigations subsequently showed that when male fish were placed in cages
in rivers near to sewage discharges, they became "feminised". There was
an increased incidence of reduced testis size in the fish and they all
produced high levels of a protein called vitellogenin. This protein is
normally only made by female fish because it forms yolk in fish eggs. It
is only produced by male fish if they are exposed to estrogen. This indicated
that something in the sewage effluent had estrogen-like activity (Purdom
et al. 1994, Matthiessen 1996).
Subsequent studies showed that the estrogenic activity of domestic sewage
could be due to natural estrogens which are excreted by women and, to a
much lesser extent, to synthetic estrogen from the contraceptive pill.
However, this could not account for some of the effects being detected
in fish, especially from industrial sewage (Desbrow et al. 1996).
Estrogenic chemicals including alkylphenols and phthalates have been
detected in sewage (Jobling et al. 1995). Alkylphenols are now the
prime suspects for causing the feminisation of fish in some areas. These
chemicals are present in industrial sewage because of their formation as
persistent breakdown products of alkylphenol ethoxylates, which are used
in industrial detergents. The ethoxylates are also widely used as "inert"
additives in pesticides, although the potential for contamination of soils
and surface waters with alkylphenols from this source are not well studied.
Once discharged into the environment alkylphenols may bioaccumulate
in fish tissue (Warhurst 1995, Schwaiger et. al. 1997). The most
common ones are nonylphenol and octylphenol. Experiments found that these
chemicals caused yolk protein to be produced by male fish, and reduced
testes growth, at levels similar to those in some UK rivers (Jobling et
al. 1996). Scientists have concluded that, at least for the river Aire
in the UK where a wool scouring factory discharges these chemicals into
the river, alkylphenols could be solely responsible for causing feminisation
of male fish (Matthiessen 1996). Initial studies on wild fish in the Tyne
estuary have found feminisation in male fish which is associated with nonylphenol
levels, although it is not yet known whether other chemicals may be implicated
(Lye and Frid 1997).
Effluent discharges from pulp and paper mills have also been reported
to cause feminisation of male fish. These effects could relate to the presence
of organochlorines in the effluent and possibly also to natural chemicals
present in wood (Heuval et al. 1994, Landner et al. 1994).
Reptiles
Following an extensive spill of pesticides, dicofol and DDT, in Lake
Apopka, Florida, in 1980, the inhabiting population of alligators has continually
declined. The decline appears to be caused by a decrease in hatching success
of the alligator eggs, together with reproductive abnormalities in the
young alligators. The young males have abnormally small penises, half to
a quarter of the normal size, and abnormalities of the testes. Furthermore,
they have altered levels of sex hormones. The research indicates that the
gonads of the alligators are permanently changed during sexual development
whilst in the egg, leading to the reproductive abnormalities. This is almost
certainly because the eggs contain high amounts of estrogenic pesticides
from the chemical spill and DDE, the breakdown product of DDT. DDE has
two forms (isomers), one of which (o,p-DDE) is estrogenic and the other
(p,p’-DDE) has anti-androgenic properties (Guillette et al. 1994
and 1995, Kelce et al. 1995, Vonier et al. 1996, Crain et
al. 1997).
Birds
The Great Lakes, North America, were subjected to very high levels of
organochlorine chemical contamination in the 1960s and 1970s. Although
levels have now substantially decreased, residues remain significant. In
the 1970s, Herring Gull colonies around the Great Lakes regions suffered
from sharp population declines. Studies showed that this was probably due
to reduced numbers of male birds that were capable of breeding. The gonads
of male chicks were found to be feminised, ie. they had female (ovarian)
type structures. Subsequent experiments showed that the levels of chemicals
such as DDT and DDE found in the gulls eggs were sufficient to cause these
reproductive abnormalities in the male birds. Researchers suggested that
estrogenic properties of such chemicals could be the cause of the problem
(Fox et al. 1992, Fry 1995).
Mammals
The Florida Panther is an endangered species of wildcat with fewer than
50 remaining in their natural habitat. Many of the males suffer from health
problems and reproductive problems, including a reduced sperm count, and
an increased incidence of undescended testes in male cubs. The female panthers
have very high levels chemicals in their bodies many of which are endocrine
disrupters, including DDE, PCBs, mercury, methoxychlor, and transnonachlor.
It is thought that the reproductive impairment of the males could be largely,
if not entirely, a result of exposure to these chemicals from their mothers
during development, and may be caused by endocrine-disruption (Facemire
et al. 1995).
10. FEMALE REPRODUCTION
Human and animal studies indicate that some endocrine-disrupters can
adversely affect the female reproductive system, both during development
and during adulthood. However, it is not certain whether exposure to current
environmental levels of these chemicals is having such effects.
10.1 Developmental Effects
The exposure of over 5 million women between 1945 and 1971 not only
caused reproductive abnormalities in boys born to the women (see section
9.2), but also affected the girls. Many of the girls suffered from vaginal
cancer in their teens, had reduced fertility and a high incidence of structural
abnormalities of the reproductive system (Gray 1992).
When DES was given to pregnant laboratory rodents, it caused comparable
reproductive problems in female offspring. This indicated that evidence
from animal studies on endocrine disrupters and reproductive effects is
very relevant to humans. Laboratory studies have also shown that when pregnant
laboratory rodents are exposed to high levels of estrogenic pesticides,
such as DDT, methoxychlor and chlordecone, their female offspring suffer
from similar effects to those caused by DES. These include reduced fertility
and various structural abnormalities of their reproductive systems (Gray
1992). Exposure to low doses of dioxin, that are within an order of magnitude
of doses which may be expected from current environmental levels, also
causes similar effects (Gray et al. 1995b).
From the above studies in animals, and from the unfortunate experience
with DES in humans, it is plausible that exposure to estrogenic chemicals,
and possibly to other endocrine disrupters, during development, could lead
to reproductive abnormalities in female offspring. Presently, there is
some evidence that exposure to endocrine disrupters in the environment,
both during development and during adult life, may affect the female reproductive
system:
Onset of Puberty
Animal studies have shown that exposure to increased levels of estrogens
in the womb causes an earlier onset of puberty. Records show that women
of industrialised countries now reach puberty at an earlier age. It has
been suggested that this may be a result of exposure to estrogenic chemicals
during development in the womb (Whitten 1992).
Increased Risk of Miscarriage and Occupational Chemical Exposure
Perchloroethylene (PERC) is the main solvent used in dry-cleaning. Consequently
workers in the industry are exposed to this chemical (Aggazzoti et al.
1994). Studies have shown that women who work in the dry-cleaning establishments
may have a greater risk of having miscarriages as a result of exposure
to PERC (Olsen et al. 1990, Lindbolm et al. 1992, Kyyronen
et al. 1989). PERC is suspected to be an endocrine disrupter, because
it appears to affect pituitary function in the brain. It has been suggested
that endocrine disruption may be the mechanism accounting for the increased
risk of miscarriage following exposure (Zielhuis et al. 1989, Ferroni
et al. 1992).
10.2 Effects in Adult Women
Shortened Duration of Lactation
Declines in the duration of lactation have been reported throughout
the world. This represents a serious public health concern because of the
associated implications for increased infant illness and death, especially
in developing countries.
The impact of DDE (breakdown product of DDT) on women’s ability to lactate,
has been investigated in North Carolina, US, and also in northern Mexico
where DDE levels are very high due to continued use of DDT in the country.
Both studies found that women with higher levels of DDE in their breastmilk
lactated for shorter time periods than women with lower levels. The main
reason why women lactated for shorter times was because they produced insufficient
milk to continue breast feeding. Researchers think that DDE could be inhibiting
lactation because of its estrogen-like effects. The study concluded that
exposure to DDE, and possibly to other estrogenic pollutant chemicals,
may therefore be contributing to lactation failure throughout the world
(Gladen and Rogan 1995).
Breast Cancer
The incidence of breast cancer has steadily risen world-wide since 1940.
Known risk factors for the disease in women, such as family history of
breast cancer, or age at puberty and menopause, at best can only account
for a third of all cases, leaving the cause of the remaining cases uncertain
(Harris et al. 1992).
Interestingly, there is good evidence in humans that elevated levels
of the bodies own natural estrogen actually increases the risk of getting
breast cancer (Toniolo et al. 1995). It is therefore plausible that
exposure to estrogenic chemicals, which might amplify the effects of estrogen,
could also increase the risk of breast cancer (Davis et al. 1993,
Davis and Bradlow 1995).
Both animal and human studies indicate that estrogenic organochlorine
chemicals could be involved in increasing the risk of breast cancer. Animal
studies show that at high levels, PCBs and the pesticides DDT and atrazine
cause an increased incidence of breast cancer (Stevens et al. 1994,
Wetzel et al. 1994, see Davis et al. 1993). Not all research
on women is consistent, but recent studies show that women from the general
population who have higher body levels of DDE appear to have an increased
risk of breast cancer (Wolff et al. 1993, Dewailly et al.
1993, Savitz 1994).
Further evidence that estrogenic organochlorine chemicals increase the
risk of breast cancer, comes from looking at how they affect estrogen metabolism.
Estrogen is normally broken down in the body to either of two forms - a
"good" estrogen and a "bad" estrogen. The actions of the "bad" estrogen
are thought to increase the risk of breast cancer, by causing breast cells
to multiply. Studies in animals and women with breast cancer have found
that the ratio of the two forms of estrogen is altered, so that there is
too much "bad" estrogen. This implicates elevated levels of "bad" estrogen
as a potential cause of breast cancer. When scientists tested the effect
of several organochlorine pesticides on estrogen metabolism, they found
that these chemicals also altered the ratio of the two forms of estrogen,
such that levels of "bad" estrogen were significantly
elevated. This suggested that exposure to these pesticides, namely
atrazine, DDE, DDT, and kepone, may influence estrogen metabolism in a
way that could increase breast cancer risk (Bradlow et al. 1995).
As yet the hypothesis that estrogenic organochlorines may increase the
risk of breast cancer is not proven. However, research does suggests that
exposure to such chemicals could contribute to an increased risk and thereby
account for many of the unexplained cases of this disease (Davis and Bradlow
1995).
Endometriosis
Endometriosis is a disease associated with infertility and chronic pain.
The incidence of this disease is thought to have risen over the past few
decades, and it is now estimated to affect 10% of all women of reproductive
age in the US (Rier et al. 1995). Studies on monkeys have indicated
that exposure to PCBs or dioxin can increase both the prevalence and severity
of endometriosis (Rier et al. 1993). It is possible that dioxin
may affect endometriosis because of its hormone-disrupting effects which
could impact on the immune system (Rier et al. 1995).
It is of concern that exposure to dioxin was associated with an increased
prevalence and severity of endometriosis in monkeys, at levels which are
within an order of magnitude of current levels in people’s bodies (US EPA
1994). This research suggests that PCBs and dioxins could also increase
the threat of endometriosis in women, although direct human evidence is
currently very limited. It is known that endometriosis is more prevalent
in industrialised countries where the levels of these chemicals are the
highest (Koninckx et al. 1995). One study on women found higher
body levels of PCBs were linked with endometriosis, but another found no
association with levels of PCBs or dioxins (see US EPA 1997). Further investigation
is therefore needed to confirm whether or not PCBs and dioxins are linked
to endometriosis in women. In the meantime, an attitude towards dioxin
pollution in the environment which considers levels to be "too low to be
harmful" could be over-optimistic (Koninckx et al. 1994).
10.3 Wildlife Studies
Reptiles
Lake Apopka in Florida was heavily contaminated by a spill of dicofol
and DDT in 1980, and young male alligators have altered sex hormone levels
and suffer from reproductive abnormalities. The females too have been affected.
They also have altered levels of sex hormones and abnormalities in the
structure of their reproductive systems. Again, these abnormalities are
most likely caused by permanent modification during development in the
egg as a result of exposure to endocrine-disrupting chemicals (Guillette
et al. 1994).
Birds
Pollutants which have been found in bird’s eggs, including organochlorines,
pesticides and heavy metals, have been reported to cause reduced hatchability
of eggs, death and deformities in the embryo, and reduced survival of chicks
hatched from eggs. Some of the effects may be due to the endocrine-disrupting
properties of these chemicals (Fry 1995).
The most dramatic effect on the reproductive performance of wild birds
was eggshell thinning caused by DDE, the breakdown product of DDT. From
the 1950s to 1970s, this resulted in the population decline of many predatory
and fish-eating wild bird species (Fry 1995, Giesy et al. 1994).
Egg-shell thinning is now less common, although other breeding problems
persist. Organochlorine pollution in the Great Lakes regions has decreased
over the past two decades but still remains relatively high. Some bird
populations such as double-crested cormorants and herring gulls have made
dramatic recoveries since population crashes in the 1970s, but others,
such as common and Fosters terns, continue to decline. Problems in these
Great Lakes birds include death and deformities in embryos and chicks,
(e.g. crossed bill, lack of eyes, skeletal malformations), as well as other
problems, including edema and behavioural changes. There is evidence that
these effects, which result in reproductive failure of the birds, may result
from contamination with dioxins, PCBs and possibly other chemicals which
exert toxic effects through the Ah receptor (Giesy 1994).
Severely reduced breeding success in cormorants has been reported in
the area of the Rhine and Meuse delta in the south-western part of The
Netherlands. Egg shell-thinning and increased embryonic mortality is reported
to be responsible for reduced hatching success of the birds. Research has
shown that high levels of DDE are linked to the egg-shell thinning, whilst
levels of PCBs are related to reduced hatching and breeding success of
the birds (Dirksen et al. 1995).
Marine Mammals
Between 1950 and 1975, the population of common seals inhabiting the
Wadden Sea, The Netherlands, collapsed from 3000 to less than 500 animals.
In 1986, studies revealed that the female seals were experiencing reproductive
failure due to problems relating to the process of implantation. This was
found to be linked to high levels of PCBs in the seals. Female Baltic ringed
seals and grey seals have also suffered from reproductive problems. Research
suggests that this can been attributed to hormone-disrupting effects of
PCBs and possibly other organochlorine pollutants in the seals (Reijnders
1986, Reijnders and Brasseur 1992).
The St. Lawrence estuary in Quebec, Canada, is heavily contaminated
with organochlorines and other pollutants. The local population of Beluga
whales was drastically reduced in the first half of the century by over-hunting.
It has, however, failed to recover in the past 40 years, despite a reduction
in hunting. Researchers think that this could be due to high levels organochlorine
chemicals which contaminate the whales and a range of adverse health effects
which could result from this contamination. The female whales suffer from
reproductive problems. A very low proportion of the females are breeding.
In addition, lesions have been detected in the mammary glands of 36% of
the females which would seriously affect their ability to feed if any calves
were produced. It is possible that the reproductive effects are caused
by estrogenic activity of the organochlorine pollutants (de Guise et
al. 1995, US EPA 1997, see Johnston and McCrea 1992).
11. SEX RATIO
In humans and many other animals, sex ratio is determined in humans
by the sperm, which carry either an X or a Y chromosome. All eggs have
X chromosomes, so at fertilisation, either a female (XX) or a male (XY)
is produced. Traditionally, the number of X and Y sperm produced was thought
to be equal so that the number of males and females born should also be
equal, giving a sex ratio of 0.5. In reality, there is a slight excess
of males at birth, which may be accounted for by several different factors,
including age of parents and time of insemination within the cycle (Moller
1996).
It has been hypothesised that the steroid hormone concentrations of
both parents may influence sex determination, so that changes in levels
may result in a skewed sex ratio. If this hypothesis is correct, with an
increased exposure to man-made estrogenic chemicals in recent decades,
it may be expected that the sex ratio would be altered, such that fewer
males were born (Moller 1996).
There is some evidence to support this hypothesis. Following an accident
at a chemical plant in Seveso, Italy, the local population was exposed
to high levels of dioxin (TCDD). Research shows that exposure of both parents
was associated with an significant increase in the proportion of girls
born (Mocarelli et al. 1996). Another study showed that more females
than males were fathered by men who were exposed to an endocrine-disrupting
pesticide DBCP (see Moller 1996).
Recent studies have investigated trends in the sex ratio of the general
population in The Netherlands and Denmark over the past few decades. It
was found that the proportion of boys born over the past 50 years had slightly,
but statistically significantly, decreased (Pal-de Bruin et al.
1997, Moller 1996). From 1950 to the mid 1990s the ratio declined from
0.515 to 0.513 in Denmark and from 0.516 to 0.513 in The Netherlands. If
the hypothesis that hormone levels influence sex determination is correct,
this may reflect the increased exposure to endocrine disrupting chemicals
over the past 50 years. The Netherlands study concluded: "Our finding
of a decreasing ratio of male to female newborn babies in The Netherlands
can only add to concern about the potential hazards of environmental endocrine
disrupters" (Pal-de Bruin et al. 1997).
12. EFFECTS ON THE NERVOUS SYSTEM
There is evidence from human studies that exposure to PCBs and/or dioxins
during development can lead to adverse effects on the nervous system of
infants and children. These effects include reduced cognitive function,
such as lower IQ, poorer short and long term memory, attention deficits
and effects on psychomotor development. Although the effects which have
been recorded are subtle in nature, they do represent diminished potential
in children. Research suggests that some women of the general population
currently have body levels of PCBs and dioxins which may cause such effects
in their children.
With regard to wildlife , some behavioural changes in birds have been
associated with exposure to man-made chemicals. In the Great Lakes region
in the 1970s, impaired incubation and chick rearing behaviours in gulls
has been associated with exposure to organochlorines. Also, female-female
pairs of birds have been found tending abnormally large clutches of eggs.
This phenomenon has been recorded between the late 1960s and 1980s in Western
gulls in Southern California, and in populations of Herring Gulls and Caspian
Terns from the Great Lakes regions. It has been suggested that the altered
behaviour of these gulls could be due to a reduction in the number of males
in the colonies which are capable of breeding. This could be due to exposure
to organochlorine chemicals which may cause feminisation of male embryos
or a reduction in male chick survival (see also section 9.4), (Fox 1992,
Fry 1995).
12.1 Development of the Nervous System
Thyroid hormones and gonadal sex hormones play a role in controlling
development of the nervous system both in the womb and during childhood
(Porterfield 1994, Hines 1992). A disturbance in the levels of these hormones
at critical times when the nervous system is developing can cause changes
which may, in extreme cases, even result in permanent brain damage. For
instance, in a condition known as congenital hypothyroidism, a deficiency
in thyroid hormones during late foetal life and early infancy, causes permanent
mental retardation. Treatment with hormones after birth can prevent mental
retardation, but children may still suffer from various psychomotor problems,
memory problems and slightly reduced IQ (Porterfield 1994).
It is known that PCBs and dioxins cause damage to the developing nervous
system, but how they do this is not well understood. It is possible that
they cause this damage by disrupting thyroid hormones and sex hormones
during development.
Thyroid hormones
Animal studies show that PCBs and dioxins can alter the levels of thyroid
hormones during development. Certain PCBs can also alter the levels of
natural chemicals which are essential for the transmission of nerve signals
(neurotransmitters). Both of these effects may explain why these chemicals
cause adverse effects on the developing nervous system (Morse et al.
1992, Seo et al. 1995, Seegal and Shain 1992).
In humans, exposure to PCBs and dioxins in the womb has been associated
with changes in thyroid hormone levels. In The Netherlands, a study was
undertaken on healthy women and their babies from the general population
who lived in the Zaandam region, near Amsterdam. The study calculated a
baby’s exposure to PCBs and dioxins in the womb by measuring the level
of these chemicals in the mothers. It found that babies who had a higher
exposure to PCBs and dioxins in the womb had slightly altered thyroid hormone
levels (Pluim et al. 1992, Brouwer et al. 1995).
Sex hormones
In mammals and humans there are some differences between males and females
in the structure and functioning of the brain. This accounts for a number
of differences in behaviour and learning between the sexes. The sex hormones,
estrogen and androgens, partly control the development of such differences
in the brain, although exactly how they do this is not fully understood.
It is known that disturbances in the delicate balance of estrogen and
androgens during development can lead to permanent effects on behaviour
in laboratory rodents (Dohler and Jarzab 1992). Some endocrine-disrupting
chemicals have also been shown to alter behaviour in animals. For example,
one study showed that male mice which were exposed in the womb to the
synthetic estrogen DES, had altered urine-marking behaviour. This is a
behaviour which plays a major part in determining reproductive success
in male mice. Exposure to the estrogenic chemicals DDT and methoxychlor
also caused the same effects. There was evidence that the effects could
have been caused by the binding of these chemicals to estrogen receptors
in the developing brain (vom Saal et al. 1995). Other research on
behaviour in rodents found that exposure of females in the womb to estrogenic
pesticides, including DDT, methoxychlor and chlordecone, causes them to
have more masculine-like sex behaviour (Gray 1992).
12.2 Effects of PCBs and Dioxins on the Human
Nervous System
There are several studies involving groups of children whose development
has been followed from birth, to investigate whether exposure to PCBs and
dioxins in the womb, and through breastfeeding, has an impact on health.
All but one of these studies was carried out on women and their children
from the general population. The other study focused on pregnant women
who were exposed to high levels of PCBs/dioxins following an accident in
Taiwan.
The studies estimated a baby’s exposure to PCBs/dioxins in the womb
and through breastfeeding by measuring levels of the chemicals in their
mothers bodies and breastmilk. In general, they found that exposure to
higher levels of PCBs/dioxins in the womb is associated with a number of
subtle adverse effects on neurological and intellectual function:
* YuCheng "Oil Disease" Incident, Taiwan
In 1979, 2000 people in Taiwan were accidentally exposed to high levels
of PCBs and dioxins after eating contaminated rice oil. Women who were
pregnant at the time of the incident gave birth to children who, on average,
have slightly reduced cognitive function. The effects did not improve by
age 7 in the children, indicating they were probably permanent. Their IQ
was about 5 points lower than unexposed children and they suffered from
mildly disordered behaviour. Furthermore, due to the persistence of PCBs
and dioxins in the body, children born up to 12 years after the accident
suffered from the same problems. (Chen et al. 1992, Guo et al.
1994 and 1995, Yu et al. 1994).
* Lake Michigan Study, US
Studies were undertaken on women from the Lake Michigan area who had
eaten moderate amounts of fish from the lake over several years before
becoming pregnant. Lake Michigan fish are known to contain relatively high
amounts of PCBs and, consequently, the women had body levels of PCBs which
were slightly above those of the general population. The studies compared
development of their children with that of children whose mothers had not
eaten fish and who therefore had slightly lower body levels of PCBs.
It was found that infants and children who had been exposed to higher
levels of PCBs in the womb showed small, but significant, deficits in cognitive
function (Jacobson et al. 1985, Jacobson and Jacobson 1993). The
effects are long-term, still being apparent in the children at age 11.
Problems include deficits in general intellectual ability, especially with
respect to reading skills, poorer short and long-term memory, and deficits
in attention. The most highly exposed children had a 6.2 point decrease
in IQ. Even though scores on these tests for the children fell within the
normal range, they were at the lower end of the normal range, which means
the children would be expected to perform less well at school (Jacobson
and Jacobson 1996).
* North Carolina Study, US
This study investigated women and their children from the general population.
Children who were exposed to higher levels of PCBs in the womb had deficits
in their psychomotor development up to the age of 2. No effects on cognitive
development were found (Rogan and Gladen 1992).
* The Netherlands Study
The Netherlands study investigated healthy women and their babies from
the general population who lived in the Rotterdam or Groningen area. There
was a slight adverse effect on psychomotor development in infants who were
exposed to higher levels of PCBs and dioxins in the womb and during breastfeeding
(Koopman-Esseboom et al. 1995). There was also a slight adverse
effect on neurological development in the children detected at 18 months
of age. Tests on neurological development looked at movement co-ordination,
(e.g. sitting, crawling, standing and walking), and are a way of measuring
the quality and integrity of brain function (Huisman et al. 1995).
At the age of 2 years and 7 months, tests on a subgroup of infants found
slight changes in some measures of neurological development in the more
highly exposed individuals. These changes were regarded as "unwanted" by
researchers, and it was proposed that they could be due to the action of
dioxins on thyroid hormones during development (Ilsen et al. 1996).
12.3 Possible Consequences of Effects on the Nervous
System
Although effects which have been found on the nervous system are relatively
subtle in nature and may not greatly affect an individual, they do, nevertheless
represent diminished potential of individuals. When considered at a population
level, such effects could be far reaching. For example, a 5 point drop
in IQ across a population would, in effect, halve the number of people
with high powered minds who have the ability to become the most gifted
doctors, scientists, writers etc., and would greatly increase the number
of slow learners who require special remedial education. This could fundamentally
change the character of society (Colborn 1996).
Experts at a meeting in Erice, Sicily (Alleva et. al. 1995),
expressed concern about neurological effects resulting from exposure to
endocrine disrupters. They were certain that: "Endocrine-disrupting
chemicals can undermine neurological and behavioural development and subsequent
potential of individuals exposed in the womb or, in fish, amphibians, reptiles
and birds, the egg. This loss of potential in humans and wildlife is expressed
as behavioural and physical abnormalities. It may be expressed as reduced
intellectual capacity and social adaptability, as impaired responsiveness
to environmental demands, or in a variety of other functional guises. Widespread
loss of this in nature can change the character of human societies or destabilise
wildlife populations. Because profound economic and social consequences
emerge from small shifts in functional potential at the population level,
it is imperative to monitor levels of contaminants in humans, animals,
and the environment that are associated with disruption of nervous and
endocrine systems and reduce their production and release".
13. IMMUNE SYSTEM
The immune system consists of a network of various types of specialised
cells which circulate in the body and serve to prevent infection and disease.
Some toxic chemicals can alter the levels or functioning of immune system
cells. This can lead to a decrease in resistance to infection and tumours,
or an increase in auto-immune diseases (Thomas 1990).
Research has shown that the immune system and the endocrine system are
closely inter-connected. For instance, steroid hormones, including estrogen,
testosterone, and hormones produced by the pituitary and adrenal glands,
are all involved in the regulation of the immune system (Grossman 1984,
Berczi 1989).
13.1 Effect of Endocrine-Disrupters on Immune
System Development
Presently, little is known about the potential impact that endocrine-disrupting
chemicals could have on the immune system during development. There is
evidence that exposure to the synthetic estrogen drug DES during development
in the womb, leads to permanent changes in the immune system of both laboratory
rodents and humans. For example, women who were exposed to DES in the womb,
had changes in some immune system cells, and had an increased susceptibility
to auto-immune and other diseases associated with defects in immune system
regulation (Blair et al. 1992, Blair 1992).
Evidence from studies on DES raises the possibility that exposure to
estrogenic or other endocrine-disrupting chemicals during development,
could alter development of immunity and lead to permanent changes in immune
system function in later life. Animal studies do show that exposure to
some estrogenic chemicals during development, including DDT and chlordane,
cause suppression of the immune system (Rehana and Rao 1992, see Holladay
and Luster 1996). However, it is not known whether immune suppression in
these studies was caused by disruption of hormones or by other mechanisms.
13.2 Human Studies
Several studies have shown that some women of the general population
have body levels of chemicals with the ability to disrupt hormones, i.e.
PCBs and/or dioxins, which are within the range at which changes in the
immune systems of their babies may occur. However, such effects may be
caused by mechanisms other than endocrine disruption.
Increased Infections
Inuit women inhabiting Arctic Quebec have relatively high body levels
of persistent organochlorines because of their seafood-rich diet. Research
has shown that higher levels of PCBs and dioxins in their breastmilk were
linked with an increased incidence of ear infections in their babies (Dewailly
et al. 1993). Other studies on women who ate fish from the Great
Lakes before becoming pregnant, reported that higher body levels of PCBs
in the women were associated with an increased incidence of bacterial infections
in their babies (Bernier et al. 1995, see Tryphonas 1995).
Changes in Immune System Cells
In the 1970s, residents of Times Beach in Missouri, USA, were accidentally
exposed to high levels of dioxins because waste oil which was sprayed on
roads for dust control was contaminated. Children born to women who were
pregnant during the incident, were found to have changes in the number
of some immune system cells at the ages of 9-14. This indicated that effects
on their immune systems were long-term (Smoger et al. 1993).
A recent study in The Netherlands focused on healthy women and their
babies from the general population. Some of the women had higher levels
of PCBs and dioxins in their bodies and breastmilk than others. It was
found that infants who were exposed to higher levels of these chemicals
in the womb, and via breastfeeding, had changes in the number of certain
immune system cells. It is not known what effect such changes could have
on their health (Weisglas-Kuperus et al. 1995).
13.3 Wildlife Studies
Mass Mortalities in Marine Mammals
Several marine mammal populations around the world have suffered from
sudden dramatic losses in numbers since the mid-1980s, in what have become
known as "mass mortalities". In both dolphins and seals, there is evidence
which suggests that high body levels of persistent, bioaccumulative chemicals
like PCBs and organochlorine pesticides may be resulting in weakening of
the immune system, and leaving the animals more susceptible to infections.
In turn, the infections may lead to their death. It is not known whether
the mechanisms leading to suppression of the immune system in these cases
are connected with disruption of hormones.
In 1988, an estimated 20,000 harbour seals died in seas around Germany,
Sweden, The Netherlands and the UK. The cause was a virus (phocine distemper
virus), similar to that which causes distemper in dogs. Since then, experiments
with captive seals have shown that feeding fish which contains high levels
of organochlorines to seals, causes suppression of their immune system,
weakening their ability to cope with disease (Ross et al. 1995,
de Swart et al. 1996). It is thought that the mass mortality of
seals could be due to suppression of their immune systems by these chemicals.
Further evidence is provided by the fact that seals which died had higher
body levels of organochlorines than surviving seals, and those living in
more highly polluted waters had higher death rates than those in less polluted
regions (Simmonds et al. 1993).
Mass mortalities of dolphins have been occurring since the late 1980s.
Huge numbers of striped dolphins died between 1990 and 1992 around the
whole of the Mediterranean, possibly due to a virus named dolphin morbillivirus.
The dead animals were found to have higher body levels of PCBs than healthy
animals (Aguilar and Borrell 1994). Similarly, in the late 80s and early
90s, many bottlenose dolphins died along the eastern coast of the United
States. They were also contaminated with high levels of PCBs and other
organochlorines. In both mass mortalities, is possible that these contaminants
could have contributed to suppression of the immune systems, rendering
the dolphins more susceptible to infections which subsequently led to their
death. This is further supported by a study on bottlenose dolphins resident
in Florida. Blood samples taken
from the animals found that suppression of the immune system increased
with increasing levels of pollutants in the dolphins especially DDT, DDE
and PCBs. More research is necessary to confirm these findings (Lahvis
et al. 1995).
Increased infections in Marine Mammals
A small isolated population of beluga whales in the St. Lawrence estuary
has very high body levels of organochlorine pollutants. Studies show that
they suffer from a high incidence of infections from mildly pathogenic
bacteria. The data strongly suggest that immunosuppression in the animals
could be related to the high levels of contaminants in their body tissues.
In addition, immune system suppression leading to decreased resistance
to tumours may be a contributing factor in the high prevalence of tumours
found in the belugas over the past 15 years. (de Guise et al. 1995).
14. PHYTOESTROGENS: NATURALLY OCCURRING CHEMICALS
IN PLANTS WHICH AFFECT HORMONE SYSTEMS
About 300 different plants are known to produce and contain a number
of natural chemicals called phytoestrogens. These are thought to serve
a variety of functions, acting as natural fungicides, regulating plant
hormones, deterring herbivores from eating them and as a protection against
ultraviolet radiation from the sun. Plants which contain phytoestrogens
include many in our diet, such as whole cereal grains, seeds, soy, cabbage,
beet, broccoli and peas (Barrett 1996).
When some phytoestrogens are eaten, they are broken down in the gut
to form estrogen-like compounds, which are able to bind to estrogen receptors.
Phytoestrogens spend relatively little time in the body before being excreted.
However, during this time they may affect sex hormones and their binding
proteins. Studies show they can result in lowering the biological activity
of sex hormones in the body. Some also have antioxidant properties.
Research suggests that phytoestrogens in the diet have many beneficial
effects, but harmful effects have also been found. For example, in Australia,
female sheep which grazed for prolonged periods on a species of clover
containing phytoestrogens suffered sharp declines in fertility. Phytoestrogens
may act as a defence mechanism, to deter herbivores from heavy predation
on a single plant species (Adlercreutz 1995, Barrett 1996).
If phytoestrogens can affect the fertility of sheep, they may be also
be able to affect human fertility. This is indeed the case for a few plants
which have been known to herbal medicine for centuries and used as contraceptives
(Colborn et al. 1996). However, eating a variety of plants in a
normal diet does not seem to affect human fertility. For example, Asians
consume very high levels of phytoestrogens in their diet without affecting
their fertility. The most likely explanation is that, as humans and animals
have evolved alongside plants, any harmful effects on fertility that a
normal diet may cause, may have been selectively bred out of the populations
long ago (Hughes 1988, Barrett 1996).
It has been suggested that phytoestrogens in soy-based infant milk formulas
may have adverse effects on sexual development. Presently there is no human
evidence to substantiate this, and the levels in soy infant milk are at
least 100 times lower than doses reported to affect sexual development
in rodents (Kardinaal 1997).
Beneficial health effects have been associated with eating a diet which
is rich in grains and vegetables, containing high quantities of phytoestrogens.
Studies on populations who consume such a diet suggest that it has a protective
effect against several hormone-related diseases. These include estrogen-related
cancers, such as breast cancer and prostate cancer, colon cancer, and possibly
osteoporosis and cardiovascular diseases. Whether the protective effect
against such diseases is a direct result of the phytoestrogens themselves,
or due to other factors, is uncertain. Preventative effects of phytoestrogens
on such diseases have been demonstrated in some laboratory studies (Adlercreutz
1995, Barrett 1996).
There are major differences between phytoestrogens and man-made endocrine-disrupting
chemicals. Phytoestrogens are readily broken down and excreted from the
body. Consequently they spend very little time inside the body. The situation
with man-made chemicals is different. Humans and animals have not evolved
alongside vast quantities of man-made endocrine-disrupting chemicals in
the environment. Unlike phytoestrogens, many are persistent and cannot
be broken down or detoxified. These may bioaccumulate in body fat, remaining
in the body for long periods of time (Barrett 1996).
15. PROSPECTS FOR THE FUTURE
15.1 Regulation
Presently, governments employ two basic strategies which attempt to
protect the environment and human health from harmful effects of chemicals.
These are prevention and regulation.
Prevention
To prevent harmful effects of chemicals on the environment necessitates
government authorities to take measures to ban the production and use of
chemicals in a country. For example, several persistent organochlorine
chemicals have been banned in the US and most European countries, including
PCBs, DDT and toxaphene.
Nevertheless, exposure to such chemicals continues because of their
persistence, recirculation in the environment, and passage from one generation
to the next. Furthermore, most bans are not implemented globally. For example,
DDT and other persistent organochlorine pesticides continue to be produced
and used in bulk in Asia, Africa and Latin America. Once released into
the environment, these chemicals add to the global burden of contamination.
A further problem is the export of chemicals (Bason and Colborn 1992),
or the technology to make chemicals, from a country where they are banned
to a country where bans are not in place.
Current Regulatory Strategies
Present regulations do not consider the potentially harmful effects
of endocrine disrupters to the environment or to human health. Consequently
no chemical has been banned or restricted solely because it is an endocrine
disrupter. Chemicals with a known ability to interfere with hormone systems,
including some industrial detergents, pesticides, mixing agents, softeners
in plastics, flame retardants and preservatives, are still being manufactured
and used in bulk quantities in Europe and the US. Others, such as dioxins,
are produced as unwanted by-products of existing industrial and waste management
processes. Exposure to these chemicals therefore continues.
The current regulatory system aims to set quantities or rates at which
chemicals can legally be released into the environment. In Europe, limits
are generally based on the process of hazard assessment. In recent years,
the process of risk assessment, has also been increasingly implemented.
Hazard assessment involves the use of toxicity testing to identify the
potential impact of a chemical on the environment. Chemicals are tested
either vitro and/or in laboratory animals. Information is generated on
the relationship between the dose of a chemical and the size of the particular
biological effect it causes - known as the dose-response relationship.
This information is interpreted in order to set an exposure level for the
environment and for humans which is thought to be "safe" (Johnston et
al. 1996 in press). This generally includes a safety factor
which is largely arbitrary in nature.
The process of risk assessment also uses data from toxicity testing.
In addition, it attempts to estimate exposure to that chemical from emissions,
and finally the probability of health effects from the exposure. It determines
what are deemed to be "acceptable risks" from the release of chemicals
into the environment. For instance, in the US, a risk of less than one
in a million individuals contracting cancer from exposure to a chemical
in the environment is generally considered to be an acceptable risk on
which to base legal limits for the release of many chemicals. Risk assessment
therefore attempts to provide a more accurate assessment of the dangers
presented by chemicals by linking known hazards with estimates of exposure
and by replacing safety factors with numerical estimates of risk. In practice,
the uncertainties which prevail in estimates of both hazard and exposure
often lead to risk assessments which are incomplete or yield information
which is of little greater utility than a hazard assessment.
In hazard and risk assessment, the toxicity tests are based upon the
ability of a chemical to produce an adverse effect on health such as causing
cancer. Testing of some chemicals also takes into account their effects
on development. For instance, after exposing animals to a chemical in the
womb, the effects on reproduction would be investigated by checking whether
the animals were fertile when they reached adulthood. However, with regard
to endocrine-disrupting chemicals, such endpoints would often not be sensitive
enough to detect adverse health effects caused by these chemicals. For
example, animals may still be fertile after being exposed to a chemical
in the womb, but their sperm count may have been substantially reduced
(Gray 1992). Therefore, the dose of an endocrine-disrupting chemicals that
are calculated by present methods to be "safe" may actually cause harmful
effects.
In summary, toxicity tests for the purposes of hazard and risk assessment
are not currently designed to look specifically for endocrine-disrupting
effects. Current endpoints which are used in toxicity tests would potentially
leave many health effects caused by endocrine-disrupting chemicals undetected.
Consequently, based on the current system, the legal limits which have
been set for the permitted release of endocrine-disrupting chemicals into
the environment, or for allowable levels in products, are unlikely to be
protective of human health.
Yet a further problem which questions current "safe" limits set for
endocrine-disrupters and other chemicals is the process of risk assessment
itself. This is because the calculations in the process of risk assessment
often depend on highly uncertain and subjective assumptions. This frequently
leads to a high degree of uncertainty and in risk assessment for legislative
purposes. Consequently, it is questionable whether this process can be
protective of public health. Furthermore, risk assessment generally only
considers the effects of single chemicals, whereas, in the real world,
humans are exposed to mixtures of numerous chemicals. Research has shown
that endocrine disrupters may have cumulative effects when mixed together.
This could further confound attempts to set safety limits for such chemicals
(Johnston et al. 1996a, Johnston et al. in press).
Proposed Future Screening and Testing Programs for Endocrine Disrupters
To date, the identification of endocrine-disrupting chemicals has been
largely based on specific scientific studies. No routine screening to identify
endocrine disrupters been undertaken by government authorities. However,
future programs to screen chemicals for their ability to interfere with
hormone systems are currently under discussion in the US.
In the US, the Environmental Protection Agency (US EPA), has been given
the task of developing a strategy to screen and test common chemicals for
endocrine disrupting effects within the next two years. With over 63,000
chemicals in commercial use, this prospect is daunting. The EPA have already
started to whittle down the vast numbers of chemicals in commercial use
to about 17,000 common chemicals which are presently produced in bulk quantities.
It is likely that this number will be further reduced by focusing on chemicals
found in drinking water, food, ambient air and household products. Current
legislation requires that all pesticides will have to be screened and endocrine-disrupting
chemicals in drinking water identified (Patlak 1997).
There are many problems which face the development of tests to screen
large numbers of chemicals for endocrine-disrupting effects. To minimise
costs and time, the use of in vitro testing using cell culture is
the method of choice. Presently, in vitro tests are available which
can detect estrogenic chemicals. However, there are problems with using
such tests. The effects of an estrogenic chemical can vary depending on
dose, timing, tissue type, organism, and interaction with other hormones
and metabolism. This means that a chemical which is estrogenic in one in
vitro test system, may be innocuous in a different test system. It
is therefore likely that the US EPA will develop a screening plan that
uses several different in vitro tests.
The use of in vitro tests rather than testing in laboratory animals
means that effects of a chemical on the developing foetus cannot be detected.
Also, some chemicals may not be estrogenic in an in vitro test,
but exert estrogenic effects in an animal. This is because the chemical
itself is not estrogenic, but when it is broken down in the body, the resulting
product is estrogenic. It is therefore argued by some that a testing program
should also include testing chemicals in laboratory animals. Again, this
is not without its problems, including ethical considerations. There is
one test which can detect whether a chemical is estrogenic to the developing
reproductive system in animals. However, this test can take up to 18 months
to complete. This would be too expensive financially and too time consuming
as a test for screening vast numbers of chemicals. According to toxicologist
Paul Foster, of the Chemical Industry Institute of Toxicology in Research
Triangle Park, US, "There would be enough work to keep labs going for
the next three to four hundred years" (Patlak 1997).
Given the problems of developing a screening strategy to detect endocrine
disrupters, it is probable that a group of in vitro tests will be
used. It is possible that following an initial screening to identify estrogenic
chemicals, there may be further testing for developmental effects in laboratory
animals (Patlak 1997).
Further Problems Facing Future Screening and Testing Programs for
Endocrine Disrupters.
* Endocrine disruption is a much wider problem than estrogenicity
alone:
Since most research to date has focused on estrogenic chemicals, future
plans for screening chemicals for risk assessment purposes are concentrating
on estrogenic effects. However, while attracting the greatest concern to
date, estrogenic effects represent only one aspect of a complex range of
potential interference’s with the hormone system. Effects of chemicals
on male sex hormones, androgens, on thyroid hormones, on hormones from
the adrenal glands and those produced by the brain are not being considered.
Thus, in the rush to develop methods to screen chemicals for estrogenicity,
other hormones affected by endocrine-disrupters and the resulting impacts
on health, could be increasingly overlooked.
* Classical Risk Assessment Ceases to be of Any Use for Endocrine
Disrupters:
In risk assessment, toxicity tests to determine the effects of endocrine
disrupters in laboratory animals, would not only be time consuming and
expensive, but are also plagued by several other problems. The effects
of endocrine disrupters can vary depending on which tissues are tested,
and the time during development when the chemical is given. The effects
are often subtle in nature and may not be detectable until adulthood. This
makes it both time consuming and very difficult to predict with certainty
the effects of endocrine disrupters (Howard 1997).
Furthermore, the greatest effects of endocrine disrupters often occur
at the lowest doses. In contrast, in classical toxicology, the dose-response
curve of many chemicals is usually linear, with small effects occurring
at low doses and more drastic effects occurring at the highest doses. However,
increasing the dose of endocrine disrupters may have less effect because
of receptor "down regulation", in which the body reacts to hormonal over-stimulation
by reducing the number of hormone receptors it produces. This results in
an upside down U-shaped dose-response curve. The shape of the dose-response
curve for endocrine-disrupters makes it very difficult to predict what
effects would be at different doses. It would be extremely difficult, if
indeed possible, to determine a minimum dose which caused adverse effects
(Patlak 1997, ENDS 1997b). Classical risk assessment may, therefore, be
of little use in assessing risks of endocrine disrupters.
This presents a massive dilemma for industry because of the reliance
on risk assessment for regulation of chemicals. Presently, the chemical
industry play down the concerns, arguing that as there is insufficient
information to assess risks at present, it is too early to take action.
However, in reality, risk assessment will never provide the protection
required. As noted by Professor vom Saal (University of Missouri), (ENDS
1997b), "There are no safe doses of endocrine disrupters, just as there
are no safe doses of carcinogens"
* Defining Endocrine disruption:
An endocrine disrupter has been defined as an exogenous agent that interferes
with the synthesis, secretion, transport, binding, action, or elimination
of natural hormones in the body that are responsible for the maintenance
of homeostasis, reproduction, development, and/or behaviour (US EPA 1997).
However, the effects of interference with hormones in themselves are not
considered to be "adverse" effects by regulators. An adverse effect would
only be considered as an effect which manifested in a physiological outcome
in an animal. For instance, the US EPA (1997) state that:
"Based on current science, the Agency does not consider endocrine
disruption to be an adverse effect per se, but rather to be a mode or mechanism
of action potentially leading to other outcomes, for example, carcinogenic,
reproductive of developmental effects, routinely considered in reaching
regulatory decisions".
However, as previously discussed, there are many problems with testing
for the effects of endocrine disrupters in animals and to wait for scientific
proof from such studies before taking any action could take decades. Therefore,
once a chemical is identified as being able to interfere with hormones
by in vitro test systems alone, or by in vivo tests, this
should be sufficient information to warrant action. Such chemicals should
be targeted to be phased out of production and use.
15.2 The Way Forward
It is clear that more research is needed to understand fully the mechanisms,
the effects and the consequences of endocrine disruption. However, scientific
certainties about the effects and the risks posed by endocrine-disrupting
chemicals could be decades away. To wait for conclusive scientific proof
that these chemicals are adversely affecting human and wildlife populations
before taking action could have devastating consequences for future generations.
Action at a global level is needed now to deal with what has become a global
problem.
From the discussion above, it is evident that current methods of regulating
chemicals based on risk assessment and hazard assessment are wholly unsuitable
for assessing risks and effects of endocrine disrupters. There is only
one clear way forward which can avoid all these problems and safeguard
future generations - the adoption of the precautionary principle and the
implementation of zero discharge strategies. This means prevention of pollution
at source, and implementation of clean production in industry and agriculture.
Adoption of the Precautionary Principle
The precautionary principle acknowledges that, if further environmental
degradation is to be minimised and reversed, precaution and prevention
must be the overriding principles of policy. It requires that the burden
of proof should not be laid upon the protectors of the environment to demonstrate
conclusive harm, but rather on the prospective polluter to demonstrate
no likelihood of harm. The precautionary principle is now gaining acceptance
internationally as a foundation for strategies to protect the environment
and human health (Stairs and Johnston 1991).
It is already known that over 50 man-made chemicals, most of which are
still in use, can interfere with steroid or thyroid hormones. This should
be sufficient evidence to justify the phase out of these chemicals under
the precautionary principle. For some endocrine disrupters, including many
persistent, bioaccumaltive chemicals, safer alternatives are already available
which could be used. For instance, phthalate plasticisers are used in the
production of PVC, and in manufacturing this plastic, dioxins are produced
as unwanted by-products. However, there are already alternative materials
which can be used for many applications of PVC (Greenpeace 1996).
Phasing out chemicals requires careful planning to take into account
the many factors involved. For example, a proposed plan to phase out organochlorine
chemicals was made to the governments of Canada and the US by the International
Joint Commission for the Great Lakes. In essence, it requires orderly timetables
to be set for the elimination of chemicals, together with implementing
safer alternatives and looking after the interests of workers. For example,
it is necessary to: "Consult with industry and other interests to develop
timetables to sunset the use of chlorine and chlorine containing compounds
as industrial feedstocks, and examine the means of reducing and eliminating
other uses, recognising that socioeconomic considerations must be taken
into account in developing the strategies and timetables", and, essential
that: "Governments, industry and labour begin devising plans to cope
with economic and social dislocation that may occur as a result of sunsetting
persistent toxic substances" (IJC 1994).
Adoption of Zero Discharge
The aim of "zero discharge" is to halt environmental emissions of all
hazardous substances into the environment. Although it is sometimes discussed
as being simplistic or even impossible, it is a goal whereby regulation
can be seen as resting places on the way to achieving it (Sprague 1991).
Zero discharge necessitates the adoption of clean production techniques
both in industry and agriculture. It is essential that the change to clean
production and material use should be fully supported by fiscal incentives
and enforceable legislation.
The principle of clean production has already been endorsed by the Governing
Council of the UNEP and has received growing recognition at a wide range
of international fora. For example, the Fourth Ministerial Conference on
the Protection of the North Sea committed signatory states to the cessation
of all discharges, emissions and losses of hazardous substances within
25 years (MINDEC 1995). This essentially represents the adoption of a zero
discharge strategy (Johnston 1996b). The North Sea States agreed at the
conference: "to pursue the development and use of clean technology for
production processes", and, "to give priority to the development
of environmentally sound products, taking into account the whole life cycle
of substances or products".
The UK government was the only country at the North Sea Conference to
object to the target of cessation within 25 years, but recently, the new
UK government has agreed on a new approach to policy, including a commitment
to address discharges of hazardous substances.
Industry Must Take Responsibility
In the long-term, industry must adopt the principles of clean production.
In the interim and thereafter, the responsibility must rest with those
who manufacture and market chemicals to assure product safety beyond reasonable
doubt. In the judgement of experts taking part at the Erice meeting on
endocrine disrupters in 1995, "Manufacturers should be required to release
the names of all chemicals used in their products with the appropriate
evidence that the products pose no developmental health hazard". (Alleva
et al. 1995),
Presently, emphasis must be placed on the identification of safer substitute
processes and products, many of which already exist. Industry must urgently
prepare for this change in markets.
Politicians Must Take Responsibility
At a political level, several important statements have already been
made, and decisions taken on chemicals which are persistent organic pollutants.
These chemicals include some endocrine-disrupting chemicals:
* Paris Commission (PARCOM 1992) - Concerns over the toxicity and persistence
of nonylphenol, a breakdown product of nonylphenol ethoxylate (NPE) detergents,
led to a recommendation by the Paris Commission to phase out their household
use by 1995 and industrial use by the year 2000.
* Oslo and Paris Commissions (1992) – 13 nations on the North East Atlantic
and the Commission of European Communities agreed to eliminate discharges
of persistent, bioaccumulative toxic substances, particularly organohalogens.
While decisions taken at these conferences are extremely important,
ultimately to solve problems posed by persistent toxic chemicals, and other
endocrine disrupters, decisions need to be taken at a global level. For
successful implementation, these decisions need to be legally binding.
This was recognised by experts at a conference in Tromso, Norway, in June
1997, in relation to problems of persistent chemicals in the Arctic. The
Arctic Monitoring and Assessment Programme (AMAP 1997) reached the conclusion
that, "The long-term reduction of exposure to persistent organic pollutants
can only be accomplished through international conventions on bans and
restrictions in production and use of these substances".
Increasingly the issue of endocrine-disruption is also being recognised
by political bodies in its own right:
* The Declaration from the 4th North Sea Ministerial Conference, Esbjerg
(MINDEC 1995) recognised "adverse effects on the function of the endocrine
system" as a form of toxity.
* In a statement issued on 11th April 1997, the Health Council of the
Netherlands warned that the entire population may be exposed to endocrine-disrupting
chemicals and that some effects on human development and reproduction may
be predicted (Health Council of the Netherlands 1997).
* A draft strategy to address hazardous substances, including endocrine
disrupters, will be considered by the joint meeting of the Oslo and Paris
Commissions (OSPAR) in September 1997. Recently, the UK government noted
that they would work with other states to address the emerging issues such
as endocrine disrupters which could pose serious problems.
Although these are important steps forward, there is still a long way
to go. It is essential to ensure that decisions taken at political level
will lead to effective action. Endocrine-disrupting chemicals are a global
problem and require global responsibility.
The Public Needs Information
Existing information regarding the potential impacts of endocrine-disrupting
chemicals is not being communicated effectively to the public. There is
an urgent need to give the public information about chemicals used in the
products they buy, to enable people to make informed decisions.
15.3 Conclusions
There is increasing evidence of adverse changes in health and development
in humans and wildlife at a population level. In many cases these effects
are suspected to be caused by interferences with hormone systems, possibly
as a result of exposure to endocrine-disrupting chemicals. We may never
have scientific proof that a particular chemical or group of chemicals
is responsible. However, the potential impacts that endocrine-disrupting
chemicals may be having now, and on future generations, are so far reaching
that to not take action now is unthinkable.
Presently there is no consensus to take action to phase out all known
endocrine-disrupting chemicals and exposure to these chemicals therefore
continues. We must learn rapidly from the mistakes of the past. History
has shown us that we have been very bad at predicting risks of exposure
to chemicals. It is essential that products and processes are no longer
assumed to be safe until proven otherwise. If not, we will continue to
experiment with our lives and the lives of our children.
The contention from industry that there is still insufficient information
on which to act is untrue. Although the problem is complex, involving a
wide range of chemicals and effects, there is already enough evidence regarding
some chemicals for them to be banned. The fact that a chemical is able
to interfere with hormones in in vitro or in vivo tests should
be enough for it to be targeted for elimination.
The only way forward is to take action to phase out known endocrine-disrupting
chemicals, implement safer alternatives, and rapidly adopt clean production
technologies. Such action needs to be enforced by legally binding international
agreements.
Table 1. KNOWN AND SUSPECTED ENDOCRINE DISRUPTERS AND THEIR USES
| CHEMICAL |
USES/COMMENTS |
| |
|
| ORGANOHALOGENS |
|
| Dioxins |
Unintentionally produced by-products of processes
in which chlorine and chlorine derived chemicals are produced, used and
disposed of. Combustion processes such as waste incineration are a major
source. |
| Several Polychlorinated biphenyls (PCBs) |
Now banned world-wide, but still found in old
electrical equipment. Due to persistence they still ubiquitous in the environment.
Inputs into the environment continue from waste dump leakage. |
| |
|
| Perchloroethylene (PERC) |
The main solvent used in dry-cleaning. Water-based
alternatives to dry-cleaning are now available. |
| Halogenated phenols:
pentachlorophenol (PCP),
Polybrominated bisphenol-A,
4-Cl-3-methylphenol,
4-Cl-2-methylphenol |
Used as a wood preservative and in textiles. Now banned in some European
countries.
Widely used as a flame retardant in plastics.
Used in cosmetic products.
Used as an additive in pesticides. |
| |
|
|
PESTICIDES |
|
| amitrole, benomyl, carbaryl, carbofuran, several
conazole fungicides (eg. propiconazole), diazinon, linuron, mancozeb, maneb,
metiram, metribuzin, oxydemeton-methyl, parathion, phenylphenol, procymidone,
certain synthetic pyrethroids (eg. permethrin, phenothrin), thiram, tributyl
tin (TBT), vinclozolin, zineb, ziram |
Used in agriculture and aquaculture. Other applications
include, e.g. the use of TBT in anti-fouling paints on ships. |
| Organochlorine Pesticides:
alachlor, atrazine, chlordane, chlordecone (kepone), DDT, DDE, DBCP,
dicofol, dieldrin, endosulfan, hexachlorobenzene, beta-HCH, gamma-HCH (lindane),
methoxychlor, mirex, toxaphene, transnonachlor
|
|
| PLASTICS |
|
| Phthalate plasticisers: eg. benzylbutylphthalate
(BBP), di-n-butylphthalate (DBP) |
Used in PVC, polyvinyl acetate, poly-urethane
and some polystyrene plastics. About 90% used in the manufacture of PVC
to make numerous products e.g. flooring, water pipes, cables, furniture,
children’s toys, pharmaceutical packaging including blood bags. Phthalates
are also used in non-plastic applications e.g. Paints, pesticides, inks,
hairspray and insect repellents. |
| |
|
| INDUSTRIAL CHEMICALS |
|
| Alkylphenolic chemicals: several including 4-nonylphenol,
4-tert-octylphenol |
Breakdown products of industrial alkylphenol
ethoxylate detergents and pesticide additives. Also used in paint, textiles,
metal finishing, certain plastics and lubricating oils. |
| Bisphenol-A |
Main uses in polycarbonate plastics and epoxy
resins. Also for coating thermosensitive paper, stabiliser for PVC softeners,
tyre production. |
| t-Butylhydroxyanisole (BHA) |
Used as an antioxidant, especially in foods |
| Lead |
Main use is in batteries. Also used in the production
of chemicals, petrol additives, various metal products and ammunition. |
| Methylmercury (organic form of mercury) |
Mercury uses include electrical equipment, batteries,
production of chlorine gas. It is a by-product of gold mining. Several
uses eg. in fungicides have declined in past 20 years. |
| Cadmium |
Main uses for batteries and metal plating, also
for pigments, plastics and synthetics. |
| Styrenes |
Used to produce polystyrene; also released from
some polystyrene applications. |
| Certain polyaromatic hydrocarbons |
Formed in combustion processes eg. burning fossil
fuels. Ubiquitous in the environment and food. |
| Dimethyl formamide (DMFA) |
Common industrial and laboratory solvent. Used
in the production of synthetic leather products. |
| Ethylene glycol |
Common industrial and laboratory solvent. Used
in the production of polymers for fabrics, and even in food products. |
Source: Adapted from Colborn et al.1993,
Jobling and Sumpter 1993, White et al. 1994, Bradlow et al. 1995,
Jobling et al.1995 and 1996, Kime 1995, Soto et al. 1995,
Toppari et al. 1995, Lyons 1996, Ren et al. 1996, Korner
et al. 1997 and personal communication, Moore and Waring (1997),
Santodonato 1997.
Table 2: Compounds that may have the potential to cause adverse effects
through the Ah receptor mediated mechanism of action (depending on experimental
evidence or structure).
Polycyclic aromatic hydrocarbons (PAHs) Polychlorinated fluorenes
Polychlorinated biphenyls (PCBs) Polychlorinated dihydroanthracenes
Polychlorinated dibenzo-p-dioxins Polychlorinated diphenylmethanes
Polychlorinated dibenzofurans Polychlorinated phenylxylylethanes
Polychlorinated napthalenes Polychlorinated dibenzothiophenes
Polychlorinated diphenyltoluenes Polychlorinated quaterphenyls
Polychlorinated diphenyl ethers Polychlorinated quaterphenyl ethers
Polychlorinated anisole Polychlorinated biphenylenes
Polychlorinated phenoxy anisoles Polychlorinated thioanthrenes
Polychlorinated xanthenes Polybrominated diphenyl ethers
Polychlorinated xanthones Polychlorinated azoanthracenes
Polychlorinated anthracenes
Source: Giesy et al. (1994).
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