researchers bring experimental evidence on human tissue, a toxic effect increased in mixture of se substances.We live in a world overrun with chemical compounds. Some of m, grouped under term " endocrine disruptor ", have ability to interfere with our hormonal system. This results in alterations of biological mechanisms that regulate in particular functioning of reproductive system and developing brain.
The suspicion of a deleterious effect tenfold of this mixture of molecules called "effect-cocktail" – was previously based on studies in animals and in cells grown in laboratory. A new study carried out on human tissue – testis of fetal – shows that in humans, this cocktail of molecules is explosive.
This work, led by Bernard Jégou and colleagues of research Institute in health, environment and labour (Irset, Inserm) and university hospital of Rennes, in collaboration with Andreas Kortenkamp and Martin Scholze of university of Brunel in London (United Kingdom), were published on 13 September in journal Environmental Health Perspectives.
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researchers tested twenty-seven molecules for which pregnant women are likely to be exposed : eight pesticides (propiconazole, and glyphosate imazalil, etc), six industrial compounds (including bisphenol A and bisphenol S), seven drugs (including ibuprofen, ketoconazole, and valproic acid), and six molecules absorbed in consumption of alcohol and coffee. Among se compounds, eleven have induced a decrease in production of testosterone – a so-called anti-androgen by testicular tissue of fetus. It was, for example, bisphenol A – whose presence in baby bottles is banned in France since 2010 – and anti-fungal prochloraze and ketoconazole.One effect is multiplied by 10, or even 10 000
Worse, anti-androgen effect of each of molecules tested individually was amplified by mixing with or compounds. The toxicity of departure could as well be multiplied by 10, or 10 000, depending on substances involved.
" Our work represents a first : it is "proof of concept" that effects cocktail can operate on a human tissue in all its complexity, points out Bernard Jégou, a researcher at Inserm and research director at Ecole des hautes études en santé publique (EHESP). For example, one can strongly amplify anti-androgen effect of bisphenol A by addition of molecules with properties pertubatrices of same nature. And this, even when bisphenol A is found at a concentration causing little or no effect, in and of itself. "
However, exposure to endocrine disruptors during pregnancy can have serious consequences for genitals of baby, such as non-descending testes (cryptorchidism) or malformation of canal of urethra (hypospadias) – risk factors for cancer of testicles.
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" Our results open way to furr studies : it is now necessary to extend analysis to or molecules – including those that act on or hormones, such as estrogen and thyroid hormones – and combine experimental approaches of epidemiology, animal experiments and tissue culture systems in humans ", adds scientist.
In this context, researchers are currently testing cocktail effects of endocrine disruptors on testis tissue of adult. If results are not yet published, Bernard Jégou instills idea that " effect of mixing is not confined to foetal period ", but it could also be deleterious in course of puberty and adulthood. "Too often we forget that re are multiple windows of vulnerability throughout life, even after a fetal life normal. "prediction Model
in addition, researchers have developed a mamatical model allowing m to model effect of anti-androgen molecules and to predict ir toxicity, wher y are alone or in combination with ors.
The goal is to be able, in future, " to sift activities of many of chemicals present in environment ", because "currently, when one works experimentally on a mixture of molecules, selection of m is always arbitrary compared to real life," says Bernard Jégou. The world chemical is infinitely more complex than what one knows. "
The advantage of mamatical model - that accuracy of prediction has been experimentally verified on testicular tissue fetal - is also to be able to eliminate use of this " rare equipment ".