Concerns related to ED-mediated effects of Bisphenol A and their regulatory consideration. (5th November 2018)

• Record Type: Journal Article
• Authors: Pouzaud, François; Thierry-Mieg, Morgane; Burga, Karen; Vérines-Jouin, Lauranne; Fiore, Karine; Beausoleil, Claire; Michel, Cécile; Rousselle, Christophe; Pasquier, Elodie
• Is Part Of: Molecular and cellular endocrinology. Volume 475(2018)
• Page Start: 92
• Page End: 106
• Publication Date: 2018-11-05
• Subjects: Bisphenol A -- Endocrine disruption -- ED -- SVHC -- Substance of very high concern -- REACH; 3D Three-dimensional -- ADHD Attention Deficit Hyperactivity Disorder -- AhR Aromatic Hydrocarbon Receptor -- ANSES Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (french agency for food, Environmental and Occupational Health & Safety) -- AR Androgen receptor -- ART Assisted Reproductive Technology -- BMDL Benchmark dose modelling -- BPA Bisphenol A -- CAF: cancer-associated fibroblasts CLP -- Classification, Labelling and packaging CMR -- Carcinogen, Mutagen, Reprotoxic CYP450arom -- Cytochrome P450 aromatase (also named CYP19A1) DCIS -- Ductal Carcinoma in situ DES -- Diethylstilbestrol DNEL -- Derived no effect level DOHaD -- Developmental origin of health and disease E2 -- 17-β estradiol EC -- European Commission ECHA -- European Chemical agency ECM -- Extracellular matrix ED -- Endocrine disruptor EDC -- Endocrine disruptor chemical EE2 -- Ethinylestradiol EFSA -- European Food Safety agency ELoC -- Equivalent level of concern ER -- Estrogen receptor ERRγ -- Estrogen-related receptor gamma EU -- European Union EU28 -- European Union with its 28 member states (since 2013) EZH2 -- Enhancer of Zeste Homolog 2 GDM -- Gestational diabetes mellitus GHS -- Globally harmonised system of classification and labelling of chemicals GnRH -- Gonadotrophin-releasing hormone GPER or GPR30 -- G protein-coupled estrogen receptor or G protein-coupled receptor 30, the membranous form of estrogen receptor HEAL -- Health and Environment alliance (NGO) HOTAIR -- HOX transcript antisense RNA HOX genes -- A subset of homeotic genes that control the body plan of an embryo HPG -- Hypothalamic–pituitary–gonadal axis IARC -- International agency for research on cancer IC50 -- Concentration estimated to cause 50% of binding inhibition ICI 182, 780 -- Specific inhibitor of ERα/β IQ -- Intelligence quotient JRC -- Joint Research Center, the European Commission's in-house science service LOAEL -- Lowest observed adverse effect level MCF -- Human breast epithelial cell lines MoA -- Mode of action MSC -- Member state committee NMDA -- N-Methyl-D-aspartate NMDAR -- NMDA receptor NOAEL -- No observed adverse effect level PL -- Prolactin PPARγ -- Peroxisome proliferator activated Receptor gamma PR: progesterone receptor -- PrL Prolactin -- PXR Pregnane X receptor -- QoL Quality of life -- RAC Risk Assessment Committee -- REACH Registration, Evaluation, Authorisation and Restriction of Chemicals -- RXR Retinoid X Receptor -- SVHC Substance of very high concern -- TDLU Terminal Ductal Lobular Unit -- TEB Terminal End Bud -- WHO World Health Organization; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2018.02.002
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: The extensive database on BPA provides strong evidence of its adverse effects on reproductive, neurobehavioural, metabolic functions and mammary gland. Disruption of estrogenic pathway is central in the mediation of these effects although other modes of action may be involved. BPA has a weak affinity for ERα/β but interaction with extranuclearly located pathways activated by estrogens such as ERRγ and GPER reveals how BPA can act at low doses. The effects are observed later in life after developmental exposure and are associated with pathologies of major societal concern in terms of severity, incidence, impact on quality of life, burden on public health system. The complexity of the dose response raise uncertainties on the possibility to establish safe levels and the scope of ED-mediated effects of BPA may be wider. These concerns fulfill the requirements for ED identification under REACH regulation. Highlights: BPA may alter reproductive, neurobehavioural, metabolic functions and mammary gland. Disruption of estrogenic pathway is central in mediation of these effects. Involved pathologies are of major societal and public health concern. There are important uncertainties on dose-response and scope of BPA's ED effects. These concerns justify application of a stringent regulation.