**Conflict of interest**

partially BPA-glucuronide/sulfate diconjugate in males. During pregnancy, bilious excretion of BPA-GA decreases, and reciprocally, venous excretion may increase through MRP. BPA-GA remaining in systemic blood circulation is metabolized by placental or fetal β-glucuronidase, and the resultant BPA would permeate the fetal tissues. MRP, multidrug resistance-associated

Some members of the Oatp [71–73] and Mrp [74, 75] transporter families are known to transport conjugates of steroid hormones such as DHEAS and 17β-estradiol-GA, suggesting that BPA-GA is transported across the placenta by these transporters. In light of the studies cited above and our present results, we surmise that if BPA-GA remaining in systemic blood circulation is metabolized by placental or fetal β-glucuronidase, the resultant BPA would permeate the fetal tissues (**Figure 3**). Due to a low UGT2B1 expression in fetal rat liver, we also reported that this metabolic system is weak in the fetus [70, 76, 77]. Numerous recent studies in rodents have found that maternal BPA exposure causes adverse effects in the offspring [17, 78–84]. In light of these findings, the present results suggest that the risk of BPA exposure to the fetus is high, despite preservation of BPA

Many reports have suggested that human health may be affected by exposure to even low levels of BPA, especially during the gestation period. However, the detailed mechanisms of BPA's effects remain unknown. To further elucidate the mechanism governing the detrimental effects of EDCs on target organs, it is essential to clarify both the metabolism and elimination pathways of such chemicals in the body. However, BPA is highly glucuronidated in the intestine and liver, and the resultant formation of BPA-GA prevents a complete understanding of metabolism and disposition by facilitating deconjugation during enterohepatic circulation and systematic circulation in the body. Given that exposure to BPA could adversely affect the fetus in pregnant animals, it is critical that further work be done to determine the fate of

In modern society, we are continually exposed to many chemical substances. We have to deal with all of these chemicals to ensure good health. Many studies of the effects of chemical substances have focused only on terminal mechanisms. We originally developed the prominent drug metabolism systems to eliminate various chemicals in the process of evolution. The various mechanisms that determine the effects of EDCs can only be productively discussed after a more complete understanding of their metabolism systems is achieved. At that point,

This study was supported by the Rakuno Gakuen University Research Fund (No. 2018-04).

venous GA compounds in the complete BPA pathway before excretion.

new precautions to avoid the risks of adverse effects could be developed.

protein; UGT, UDP-glucuronosyltransferase; ST, sulfotransferase.

glucuronidation in the maternal liver.

**2. Conclusion(s)**

70 Endocrine Disruptors

**Acknowledgements**

The authors declare no conflict of interest.
