Bisphenol-A (BPA), BPA Glucuronide, and BPA Sulfate in Midgestation Umbilical Cord Serum in a Northern and Central California Population

Abstract

Bisphenol-A (BPA) is an endocrine disrupting chemical used in numerous consumer products, resulting in universal exposure in the United States. Prenatal exposure to BPA is associated with numerous reproductive and developmental effects in animals. However, little is known about human fetal exposure or metabolism of BPA during mid-gestation. In the present study, we present a new liquid chromatography-tandem mass spectrometry method to directly measure concentrations of BPA and two predominant metabolic conjugates – BPA glucuronide and BPA sulfate – in umbilical cord serum collected from elective 2nd trimester pregnancy terminations. We detected at least one form of BPA in all umbilical cord serum samples: BPA (GM 0.16; range <LOD-52.26 ng/mL), BPA glucuronide (GM 0.14; range <LOD-5.41 ng/mL) and BPA sulfate (GM 0.32; range <LOD-12.65 ng/mL). Levels of BPA ranged from less than 1/100th to over 400 times higher than levels of BPA in conjugated form. Although levels of BPA in conjugated form exceeded BPA levels in about 3/4 of the samples, BPA levels were higher in samples with Total BPA above the median. Our findings suggest universal fetal exposure to BPA in our study population, with some at relatively high levels, and we provide the first evidence of detectable BPA sulfate in mid-gestation fetuses.

Conjugation and Deconjugation Reactions within the Fetoplacental Compartment in a Sheep Model: A Key Factor Determining Bisphenol A Fetal Exposure

“…In early-stage fetuses, the unbound intrinsic sulfoconjugation clearance of BPA was 4-fold higher than that of glucuronidation. These data are in accordance with the exposure to BPA-S observed in human umbilical cord blood at midgestation (Gerona et al, 2013). Conversely, BPA's sulfoconjugation hepatic clearance was very low in adult sheep and humans, accounting for only 2.2% and 0.26% of the total conjugation hepatic clearance.…”

“…These reactions are usually considered as mechanisms of detoxification because these metabolites are not estrogenic (Nakagawa and Tayama, 2000;Matthews et al, 2001). In humans, in the fetoplacental compartment, highly variable BPA and BPA-G levels have been reported in cord blood, placenta, and amniotic fluid (Vandenberg et al, 2010;Gerona et al, 2013). However, these biomonitoring data remained limited and were therefore unlikely to reflect fetal exposure throughout pregnancy.…”

Evidence that bisphenol A (BPA) can be accurately measured without contamination in human serum and urine, and that BPA causes numerous hazards from multiple routes of exposure

“…In responding to this criticism the authors of the breast density study pointed out that numerous steps had been taken to ensure the absence of contamination (also identified in the initial published article), that method blanks were below the limit of detection, and that random contamination would tend to decrease, not increase, the likelihood of a statistically significant association (Sprague et al, 2013b). The conclusion by Ye et al (2013) that eliminating contamination by environmental BPA “is practically impossible” directly contradicts that they did successfully eliminate BPA contamination, as did laboratories that participated in the Markham et al (2010) study, the NIH round robin study, and many other laboratories for both biological (Gerona et al, 2013; Schonfelder et al, 2002) and environmental (Watabe et al, 2004) samples.…”

Pharmacokinetics of bisphenol A in humans following a single oral administration

“…Exposures during fetal life or early postnatal development are of most concern because of the susceptibility of normal development to potential disruption and because BPA is metabolized and eliminated through conjugation enzyme systems that may not be fully developed in early life (Divakaran and others in press; Gerona and others 2013). …”