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Mol Cell Endocrinol. 2018 Nov 5;475:10-28. doi: 10.1016/j.mce.2018.02.007. Epub 2018 Mar 22.

Evidence-based adverse outcome pathway approach for the identification of BPA as en endocrine disruptor in relation to its effect on the estrous cycle.

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Toxalim (Research Centre in Food Toxicology), INRA, ENVT, INP-Purpan, UPS, Toulouse, France.
Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Neuroscience Paris Seine, Institut de Biologie Paris Seine, 75005 Paris, France.
Genetic Stability, Stem Cells and Radiations, CEA, INSERM U 967, University Paris-Diderot, CEA Research Center, Fontenay aux Roses, France.
INSERM, UMR1085, Researche Institute for Environmental and Occupational Health, Rennes, France.
ANSES, Risk Assessment Department, Maisons-Alfort, France.
ANSES, Risk Assessment Department, Maisons-Alfort, France. Electronic address:


Proper cyclicity is essential to reach successful optimal fertility. In rats and mice, BPA exposure is repeatedly and reliably reported to show an adverse effect on the estrous cycle after exposures at different life stages. In humans, a possible association between modifications of menstrual cycle characteristics (e.g. length of the cycle, duration of menstrual bleeding) and sub-fecundity or spontaneous abortion has been observed. Alterations of ovarian cyclicity can therefore be definitely considered as an adverse health outcome. As a prerequisite for the EU REACH regulation to identify a substance as an endocrine disruptor and a SVHC,1 the proof has to be established that the substance can have deleterious health effects resulting from an endocrine mode of action. This review provides an overview of the currently available data allowing to conclude that the adverse effects of BPA exposure on ovarian cyclicity is mediated by an endocrine mode of action.


Bisphenol A; Endocrine disruption; Estrogen; Female reproduction


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