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emerging pollutant (Liao et al., 2012a,b,c). BPS can be found in many commercial products labeled “BPA-free”. The chemical is now widely used in making polycarbonate plastics, epoxy resins as well as a variety of common consumer products, such as thermal receipt papers (Konkel, 2013). BPS can enter the human body by ingestion via food or drink (Liao and Kannan, 2013), inhalation from air or particle (Wang et al., 2015), and dermal Dorsomorphin (Compound C) from thermal papers or personal care products (Liao and Kannan, 2014). Espe-cially, handling thermal receipt paper represents a typical source of exposure to BPS occupationally (Ndaw et al., 2018).
Epidemiological data of the human burden of BPS is very limited, but recent studies have shown that BPS can be detected in human samples worldwide, including urine (Liao et al., 2012a,b,c; Lehmler et al., 2018; Machtinger et al., 2018) and blood (Wan et al., 2018b). The detection rate and concentration of BPS in human samples are almost comparable to BPA (Lehmler et al., 2018). BPS was reported to be as hormonally active as BPA, and it could also cause endocrine-disrupting effects (Rochester and Bolden, 2015). BPS exposure might lead to thyroid disruption via thyroid hormone receptor b in zebrafish embryos (Lu et al., 2018). A study on sheep
showed that gestational BPS exposure resulted in placental endo-crine dysfunction and pointed to a dysregulation in the fusogenic trophoblast signaling pathway (Gingrich et al., 2018). Low dose BPS exposure during the prenatal period altered female mouse mam-mary gland development (Kolla et al., 2018). Neonatal exposure to high concentrations of BPS was reported to induce BPA like endo-crine and structural alterations in female rats (Ahsan et al., 2018). In addition, data on human indicated that there was a significant relevance between maternal urinary BPS and increased gestational age as well as the increased odds of late term birth for girls, but not significantly for boys (Wan et al., 2018a). Except for the endocrine-disrupting effects, BPS was also suggested to alter cellular apoptotic and survival signaling pathway by inducing caspase 8 production (Vinas and Watson, 2013). Subchronic BPS exposure could induce oxidative damage to mice liver which affect liver function (Zhang et al., 2018). The above findings indicated that BPS might not be a safe alternative to BPA.
Epigenetics refers to changes in gene expression without alter-ations in DNA sequence (Holliday, 1987). It relies on histone modification, DNA methylation and noncoding RNAs to regulate gene expression before translation (Gasser et al., 1998; Gibney and Nolan, 2010). Epigenetic effects play vital roles in biological pro-cesses throughout the whole human life, including cell differenti-ation, development, aging and disease (Tycko and Ashkenas, 2000; Feinberg and Tycko, 2004; Kiefer, 2007; Esteller, 2008). In the last few years, many studies have examined the epigenetic effects of environmental chemicals and identified several toxicants including BPA that can change epigenetic marks (Alonso-Magdalena et al., 2016; Ideta-Otsuka et al., 2017). Previous studies indicated that short-term administration of BPA might increase the risk for carcinogenesis, which was associated with an increased risk of epigenetic modifications (Ferreira et al., 2015). BPA could influence murine adipocyte differentiation in vitro, which was accompanied by global genomic DNA hypomethylation (Bastos Sales et al., 2013). Besides, several studies using animal models showed that prenatal BPA exposure would induce behavioral and neuronal disorders due to the epigenetic changes in the brain (Wolstenholme et al., 2013; Aiba et al., 2018; Xin et al., 2018). Early-life BPA exposure in rat would induce gene-specific promoter methylation changes, which might serve as predictive epigenetic biomarkers of prostate cancer recurrence (Cheong et al., 2016). In addition, a cohort study among Egyptian prepubescent girls found that urinary BPA levels was correlated with methylation status of genes involved with immu-nity and inflammation, suggesting that BPA increased human im-mune and inflammatory response through epigenetic mechanism (Kim et al., 2013). Several studies have also shown that BPA could induce epigenetic changes in breast epithelial cells in vitro. Decrease on the level of global cytosine methytion level after BPA exposure was observed in MCF-7 cells (S¸ enyildiz and Ozden, 2015). Low-dose BPA exposure induced epigenetic changes as well as gene expression level changes in MCF-7 cells (Weng et al., 2010). Besides, exposure of BPA increased the levels of H3K27me3 accompanied with increasing expression level of EZH2 in MCF-7 cells (Doherty et al., 2010). Another study showed that BPA downregulated cell regulatory genes including cyclin A2, cyclin E1 and p16 and induced promoter hypermethylation of p16 and cyclin A1 genes in human mammary epithelial cells (Qin et al., 2012).