Maternal and Fetal Pharmacokinetics of Oral Radiolabeled and Authentic Bisphenol A in the Rhesus Monkey.

Catherine A Vandevoort,Anne Hillenweck,Daniel Zalko,Alice F Tarantal,Frederick S Vom Saal,Patricia A Hunt,Roy R Gerona,Angel Nadal

doi:10.1371/journal.pone.0165410

Abstract

The present study was conducted in pregnant rhesus monkeys to determine the rapidity and extent to which BPA reaches the fetal compartment following oral ingestion, and the 24-hr fate of BPA. To assess metabolism changes during the course of pregnancy, we compared BPA biotransformation during the second and third trimesters in the same animals, measuring the levels of sulfated, gluronidated, and free BPA in maternal serum, amniotic fluid, and fetal serum. All animals showed measurable unconjugated and conjugated BPA in the fetal compartment and slow clearance compared to maternal serum. There were higher levels of BPA-G in amniotic fluid at 150 days gestation compared to 100 days gestation, as well as higher levels of BPA-G than BPA-S. We also monitored 3H-BPA (and metabolites) in key tissues and excreta from a mother and fetus and from a non-pregnant female. The elimination of radioactivity was rapid, but residues were still detectable 24 hr after dosing in all tissues analyzed. These data suggest that, in primates, rapid maternal processing of BPA does not alleviate the risk of exposure to the developing fetus. This study elevates concerns about levels of current BPA human exposure from potentially a large number of unknown sources and the risks posed to developing fetuses.

Highlights

The use of bisphenol A (BPA) in a wide range of consumer products brings humans into daily contact with this chemical, and data from biomonitoring studies suggest that BPA and its metabolites can be detected in most human subjects [1]
Levels of unconjugated BPA (Fig 1) were generally within a similar range in maternal and fetal serum at both gestational time points assessed, with the exception of one monkey at gestation day 100 that showed a spike in fetal serum unconjugated BPA 2 hours after maternal gavage, that resulted in a 20-fold higher level in fetal serum compared to maternal serum
It is important to note that maternal levels of both BPA-G and BPA-S were higher than fetal levels at 1 and 2 hr after exposure, but not at the 4 hr time point

Summary

Introduction

The use of bisphenol A (BPA) in a wide range of consumer products brings humans into daily contact with this chemical, and data from biomonitoring studies suggest that BPA and its metabolites can be detected in most human subjects [1]. Data from numerous biomonitoring studies, have reported far higher levels of unconjugated BPA in serum than expected based on the assumption that BPA is absorbed from the gastrointestinal tract [3,4], and growing evidence suggests that non-oral routes contribute significantly to human BPA exposure [2,3,5,6,7]. This is important, because it means that inferences about the levels and duration of human exposure to unconjugated (bioactive) BPA that have been based on the assumption that BPA is rapidly conjugated and inactivated significantly underestimate human exposure

Methods

Results

Discussion

Conclusion