Concerns related to ED-mediated effects of Bisphenol A and their regulatory consideration.

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.