Globally, the use of BPA has progressively increased, reaching more than 10 million tonnes per year [7,10]. BPA is present in 95% of products requiring epoxy resins and polycarbonates, such as food containers, bottles, toys, dental products, CDs, DVDs, and water pipes [14]. The use of BPA in consumables and medical products makes its exposure continuous, having been detected, for example, in urine in over 90% of the United States (US) population [15]. In addition, BPA has also been identified in other biological samples, such as maternal blood (0.3 to 18.9 ng/mL) [16,17,18,19], maternal urine (31.9 μg/L) [19], amniotic liquid (median = 0.26 ng/mL) [17], placental tissue (median = 12.7 ng/g) [16], umbilical cord blood (0.2 to 9.2 ng/mL) [16,18,20], breast milk (0.61 to 0.7 μg/L) [19,21], and human colostrum (3.41 ng/mL) [22]. However, in biomonitoring studies, urinary samples of BPA are often used. The reason is that BPA is a non-persistent chemical, so its chemical concentration is higher in these samples, compared to human plasma or serum [6,23]. Nevertheless, the degree of exposure to BPA is quite variable depending on socioeconomic factors, lifestyle, medical status, and exposure pathways [6]. With regard to this, oral exposure is considered the most prevalent, with BPA levels associated with dietary choices [6,24]. On the other hand, cutaneous absorption and/or inhalation may also be associated with a higher level of exposure to unconjugated or biologically active BPA, which may persist for longer periods (~5.4 h) compared to ingested, subject to first-pass metabolism [23].

BPA, similarly to other EDCs, interacts with receptors activated by estrogens, androgens, thyroid hormones, and peroxisome proliferator, and acts as an agonist or antagonist via a receptor-dependent signaling pathway; this is attributed to its chemical structure. However, its chemical structure may be an advantage, as demonstrated for binding to ER, in which BPA does not achieve proper accommodation in the confines of the hormone-binding site (it only induces a displacement of α-helices forming the ligand-binding domain (LBD)) [11]. Moreover, Tan et al. demonstrated that EDCs share three levels of key fragments: primary and secondary fragments (responsible for the receptors binding, which discriminate active and inactive compounds), and tertiary fragments that determine their activity type (agonist, antagonist, or agonist–antagonist (A-Anta)). This determination is achieved via the interaction of EDCs with the functional lobes, directly affecting the AF-2 surface, which is responsible for coregulator recruitment. In the case of BPA, this EDC contained primary fragments of oxygen-containing aromatics and secondary ones (bisphenol group) [25]. The coexistence of primary and secondary fragments is responsible for activating BPA (active compound). Activation of the estrogen receptor (ER) and androgen receptor (AR) is achieved via interactions of the secondary fragment of stabilized BPA conformations in the LBD by forming hydrogen bonds with R394 amino acid and via van der Waals interactions with N705 amino acid, respectively. The comprehension of secondary fragments forming interacting networks with LBD amino acids is the basis for the activity of BPA. Ligand fragments of BPA interact with LBD and cause changes in the conformation of the AF-2 surface, recruiting two cofactors and, thus, determining its tertiary fragment (A-Anta activity).

Similar to natural hormones, some of the experimental studies with BPA suggest a non-monotonic response, highlighting that risk assessment is required with exposures from ‘lower’ to ‘higher’ doses, given the characteristic U-shaped response also observed by other EDCs [26]. Not surprisingly, this property can complicate BPA toxicity risk assessment, as this EDC can interact with hormone receptors in specific cell types and/or have multiple biological endpoints with linear dose–response that collectively produce a non-monotonic dose–response relationship [27].

Over the past few years, there has been growing concern regarding the adverse effects of BPA exposure on human health. These adverse effects have led countries such as Denmark and Belgium to restrict the use of BPA in food packaging for children between the ages of 0 and 3. Sweden has also limited the use of BPA in varnishes and food packaging coatings for children in the same age group. In addition, Austria has restricted the use of BPA in pacifiers and bottles since October 2010 [28].