Rémy Slama is research director at Inserm and Chair of Scientific Council of National Endocrine disrupter Research program. He recalls that a good knowledge of effects of se substances on organism still requires a lot of research.
le FIGARO.-What exactly are we talking about when we talk about endocrine disruptors?
Remy Slama. -A endocrine disruptor (PE) is a substance-or a mixture of substances-outside body, which modifies functioning of endocrine system and causes a detrimental health effect. The latter can be expressed at level of body of person but also possibly in his offspring. There are currently several hundred substances that are “endocrine” active and refore likely to be PE. Several dozen have already been recognized as such. This is case with DDT-which increases risk of breast cancer-, mercury and its derivatives, bisphenol A, flame retardants, certain organophosphate pesticides …
How do endocrine disrupters act?
“A endocrine disrupter can block action of hormones”
We can describe three examples. A PE can block action of hormones by attaching to receptors with which y usually interact. It can also mimic action of hormone. So bisphenol A binds to estrogen receptors and it is recognized as estrogen-one could talk about a hormonal sham … The organism reacts as if re were hormones, while re are none … Anor mode of action, more upstream of receptors: a endocrine disruptor can act by blocking synsis of a hormone.
The TOS are now implicated in development of many developmental pathologies or anomalies. What exactly do we know?
Endocrine disruptors target Our hormonal system that is involved in many biological functions. The range of pathologies that can be induced is refore extremely varied. We need to see endocrine system as a kind of rmostat of our organism. It regulates certain balances such as body temperature, cardiac function, fertility, moods … Adipose tissue responds to hormonal messages, immune and nervous systems interact with it. .. A disturbance of this system can result in disorders of fertility, behavior, cardiac function, metabolism with a risk of obesity … PE may also be involved in occurrence of breast or prostate cancer. Bisphenol A, for example, is able to disrupt cardiac function, but also behavior, anxiety, fertility … Perfluorinated compounds appear to be implicated in an increase in risk of overweight in adolescence after intrauterine exposure …
The palette of pathologies that can be induced is refore extremely varied. “We need to see endocrine system as a kind of rmostat in our body.”
It is seen that endocrine disruption affects a very broad spectrum of chronic or developmental diseases, which are generally multifactorial diseases, for which or risk factors, environmental, genetic or Behaviors come into play.
What diseases can be attributed with certainty to TOS?
There is no pathology constituting a signature of exposure to PE. As mentioned, most chronic diseases, both individually and population-wide, have a set of multiple causes. With rare exceptions, such as pleura cancers that are very often due to asbestos, this is true for all environmental pollutants. Air pollution, one of biggest environmental killers, does not cause a specific disease. However, re are two exceptions of pathologies specifically caused by PE: Minamata disease and gynecological cancers due to diethylstilbestrol (or Distilbène).
“There is no pathology constituting a signature of exposure to PE.”
In 1950 years, mercury intoxication of inhabitants of Minamata Bay resulted in special neurological disorders in children born to contaminated mors. It is now known that se disorders are linked to blocking of an enzyme, responsible for activation of thyroid hormones that control development of fetal brain.
In case of diethylstilbestrol, this syntic estrogen administered to mors during pregnancy, link was made with vaginal cancers occurring at end of adolescence in descendants, while this pathology occurred until n Essentially after menopause.
in this case, how do we establish level of evidence between exposure and health risk?
It is by combining a set of scientific approaches that a causal link can be established between exposure to a given factor and occurrence of a multifactorial disease. We are relying on molecular biology, which will allow us to decipher mechanisms of disturbance and its interaction with endocrine system. We also use toxicological studies in animals: we observe consequences of exposure to a given substance in a controlled environment. And finally, in humans, we have observational studies, in which we statistically control or risk factors in order to quantify proper effect of exposure to some suspected endocrine disruptors. To establish a causal link, we will confront all se elements. This is work of interdisciplinary expertise. This is substance by substance and it is necessarily a long time.
We talk a lot about cocktail effect of PE. What does that mean?
The cocktail effect refers to power of several chemical substances, when associated, to induce a toxic effect to organism at doses to which each is usually considered harmless taken individually.
A CNRS-Inserm team in Montpellier has thus shown that two molecules which, separately, are unable to bind to a hormonal receptor, form, as soon as y are put into contact, a new molecule capable of embedding in receiver. Today we discover importance of cocktail effect.
