What are endocrine disruptors?

"An endocrine disruptor is an exogenous substance or mixture that alters function(s) of the endocrine system and consequently causes adverse health effects in an intact organism, or its progeny, or (sub)populations" 'Community strategy for endocrine disruptors'

Mechanisms of disruption

Some chemicals can act on the endocrine system to disturb the homeostatic mechanisms of the body or to initiate processes at abnormal times in the life cycle. The chemicals can exert their effects through a number of different mechanisms:

• They may mimic the biological activity of a hormone by binding to a cellular receptor, leading to an unwarranted response by initiating the cell's normal response to the naturally occurring hormone at the wrong time or to an excessive extent (agonistic effect).
• They may bind to the receptor but not activate it. Instead the presence of the chemical on the receptor will prevent binding of the natural hormone (antagonistic effect).
• They may bind to transport proteins in the blood, thus altering the amounts of natural hormones that are present in the circulation.
• They may interfere with the metabolic processes in the body, affecting the synthesis or breakdown rates of the natural hormones.

Up to now, because of a series of observations in both humans and wildlife the spotlight has focused on disruption to those hormones that play a major part in the control of reproduction and development. The main area of concern has been the steroid hormones produced by the gonads which, in conjunction with some other hormones (particularly those produced by the pituitary), control processes such as reproduction and sexual behaviour, fetal differentiation and development, and maturation. They also influence the immune system and general metabolism. The main sex steroids are:

More recently, research has indicated that some chemicals may disrupt thyroid function, with concerns focusing particularly on the role of the thyroid in the developmental process.

There is some evidence that known endocrine disruptors may affect the immune system and may also have some neurotoxicity although the mechanisms by which these effects may occur have not been elucidated.

What do we know about endocrine disruptors ?

The main evidence suggesting that exposure to environmental chemicals can lead to disruption of endocrine function comes from changes seen in a number of wildlife species. Effects suggested as being related to endocrine disruption have been reported in molluscs, crustacea, fish, reptiles, birds and mammals in various parts of the world.

There is also some limited evidence in humans that adverse endocrine-mediated effects have followed either intentional or accidental exposure to high levels of particular chemicals. The clearest example of an endocrine disruptor in humans is diethylstilbestrol (DES), a synthetic oestrogen prescribed in the 1950s and 1960s to five million pregnant women for the prevention of spontaneous abortion. It was found that some of the children who had been exposed in the uterus had developmental abnormalities, and that some of the girls developed an unusual form of vaginal cancer when they reached puberty. As a consequence, DES was banned in the 1970s. In addition, a number of adverse changes have been suggested to have occurred in a population living near a chemical plant in Seveso, Italy as a result of the accidental release of the chemical dioxin, a suspected endocrine disruptor.

Chemicals with hormonal activity, i.e. potential endocrine disruptors, include :

• Natural hormones from any animal, released into the environment, and chemicals produced by one species that exert hormonal actions on other animals, e.g. human hormones unintentionally reactivated during the processing of human waste in sewage effluent, may result in changes to fish
• Natural chemicals including toxins produced by components of plants (the so-called phytoestrogens, such as genistein or coumestrol) and certain fungi
• Synthetically produced pharmaceuticals that are intended to be highly hormonally active, e.g. the contraceptive pill and treatments for hormone-responsive cancers may also be detected in sewage effluent
• Man-made chemicals and by-products released into the environment. Laboratory experiments have suggested that some man-made chemicals might be able to cause endocrine changes. These include some pesticides (e.g. DDT and other chlorinated compounds), chemicals in some consumer and medical products (e.g. some plastic additives), and a number of industrial chemicals (e.g. polychlorinated biphenols (PCBs), dioxins). The hormonal activity of these chemicals, is many times weaker than the body's own naturally present hormones, e.g. nonyl phenol (a breakdown product of alkylphenol ethoxylate surfactants), found as a low level contaminant in some rivers in Europe, has an oestrogenic activity only about one-ten thousandth that of the natural hormone, oestrogen.