2. Action mechanisms of endocrine disruptors(1) Definition
There is continuing international scientific debate over the definition of endocrine
disruptors because the interactions of these chemicals with the endocrine system
are not well known. At the 50th World Health Assembly in 1997, resolution WHA
50.13*1 was adopted. This resolution stipulated that the Director-General of theWHO should take the necessary steps to reinforce WHO leadership in undertaking
risk assessment of endocrine disruptors, and in promoting research on the healtheffects of exposure to these chemicals.*1
The term “endocrine disruptor” refers to any kind of chemical which disrupts theaforementioned endocrine system. The term “disruption” refers to damaging
effects on the reproduction and development of humans and wildlife that may
ultimately threaten the “continuation of species.” In practice, it has not yet been
determined which substances should come under this category, and various
attempts at categorization are under way. At present, the working definition is the
one given below, focusing on the phenomena that bring about “ ~ changes in
endocrine environment which have damaging effects on reproduction anddevelopment at various organism levels.”lWhat is an “endocrine disruptor”?

“An endocrine disruptor is an exogenous substance or mixture that alters
function(s) of the endocrine system and causes adverse health effects in an intact
organism, or its progeny, or (sub)populations.” [The International Programme on
Chemical Safety (IPCS)/the World Health Organization (WHO)]*2
However, the Smithsonian Workshop of February 1997 defined an endocrine
disruptor as “ ~ an exogenous agent which interferes with the synthesis, secretion,transport, binding, action, or elimination of natural hormones in the body which
are responsible for the maintenance of homeostasis, reproduction, development orbehavior.” This definition emphasized the importance of considering the functional
characteristics of endocrine mechanisms in understanding these chemicals.

(2 ) Action mechanisms

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Generally, endocrine disruptors are natural products or synthesized chemicals
which mimic, reinforce, or inhibit the actions of hormones. There are various
assumptions about the action mechanisms of these chemicals in the body. Several
possibilities, given below, have been suggested regarding actions on hormone
receptors.
1.

Inhibition of the interaction between hormones and receptors
A chemical may modify the binding of a hormone with its receptor, thereby
affecting normal cellular functions involving the hormone.

2.

Function as false hormones
A chemical similar to a hormone in structure may interact directly with thehormone receptor, thereby causing unnecessary and abnormal cellularfunctions.

3.

Alteration of the development of receptors and their functions
A chemical may activate or suppress the development of a cell receptor andalter the normal hormonal activities.

4.

Alteration of functions by interactions with hormones
A chemical may interact with a hormone and alter the message issued by thehormone, thereby altering cellular functions.

5.

Abnormalities or deficiencies due to impairment of hormone production
A chemical may damage the production of a hormone, in particular one which
regulates steroid metabolism, thereby causing hormone abnormalities ordeficiencies.

The actions of endocrine disruptors are known to involve several possible factors,
including (a) the same chemical may have different effects on different organs, (b)the same chemical may have different effects at different stages in development,
including the fetal period, (c) chemicals may be affected by the individualorganism’s environment, nutrition, age, or other effects, (d) chemicals may
interact with other factors, such as other chemicals that may be present (e.g.,additive effects and synergistic effects), and (e) the same chemical may cause
different responses in different species.
In this way, these chemicals are assumed to affect various processes involving
endocrine functions and their mechanisms; in fact, such phenomena have beenreported. As the actions of hormones in the body are very diverse, endocrine
16disruptors may cause commensurately extensive disorders. Therefore, thedefinition given at the Smithsonian Workshop (mentioned above) should be also
considered. Based on our present understanding is the suggestion that thesechemicals may affect not only the endocrine system but also higher-order systems,
such as the nervous and immune systems.

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