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Claude MONNERET: Emeritus Research Director, CNRS - Honorary President of the French National Academy of Pharmacy - Biological membrane chemistry and therapeutic targeting - Unité CNRS – INSERM 3666/U 1143, Institut Curie 26 rue d'Ulm, 75248 Paris Cedex 5, France - Editor's note: - This article is adapted from Annales des falsifications, de l'expertise chimique et toxicologique (n° 988) published by SECF (Société des experts chimistes de France).
INTRODUCTION
Exposure of the general population to endocrine disruptors and pesticides is characterized by low-dose, repeated exposure over time. As a result, risk assessment had to take into account the simultaneous effects of several compounds, known as "cocktail effects". This is all the more important as two epidemiological studies (NANHES and ELFE) have shown the presence of numerous endocrine disruptors and pesticides in the blood of pregnant women, who are the most vulnerable.
Pesticide mixtures have thus been assessed for cytotoxicity, either against liver and colon cell lines, the H2AX test, or the human nuclear receptor PXR. The latter test has been used to assess the toxicity of cocktails of endocrine disruptors, and more recently, assessments of mixtures of twenty-seven molecules, belonging or not to this class, and to which pregnant women are likely to be exposed, have been carried out on human tissue, testicular tissue of fetuses, by measuring their anti-androgenic effects via testosterone production.
These few examples illustrate the complexity of the problem, with effects that are either additive, synergistic or antagonistic, to which are added the notions of low exposure doses, diffuse presence in the environment, and the specificity of these exposure windows.
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Cocktail effects of pesticides and endocrine disruptors
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