BPA crosses the placenta, remains active in the fetus, show rat and human studies.

What did they do?

Nishikawa and colleagues injected either 2 or 10 micromolar concentrations of BPA-glucuronide into pregnant rats. These concentrations are relatively high and are probably not relevant to human exposure levels. However, high concentrations are necessary because they allow researchers to measure the low levels of BPA moving through the pregnant rats, the fetuses and the amniotic fluid.

The scientists collected samples of the fetal tissues and the amniotic fluid that surrounds the developing rats and analyzed the tissues and fluid for both BPA-glucuronide – the inactive form – and "free" BPA – the estrogenic and active form. From these data, they determined whether BPA-glucuronide could cross the placenta and whether it is converted to free BPA by the fetus.

They also determined whether the rat fetuses had turned on genes for enzymes that 1) break down BPA-glucuronide into the estrogenic BPA and 2) convert BPA to BPA-glucuronide, the inactive form.

In the second study, Balakrishnan and colleagues used human placentas gathered from Cesarean section births. A pump that simulated the mother's heart was hooked to the mother's blood vessels in the placenta. Solutions containing 10 nanograms per milliliter of BPA were pumped for several hours. This concentration was chosen because it is thought to be in the upper range of actual human exposures. The fluid that was pumped from the maternal side of the placenta to the fetal side was collected and levels of "free" and active form of BPA and the metabolized BPA-glucuronide were measured.

What did they find?

Taken together these studies clearly show that: 1) BPA inactive metabolites and the free active BPA can cross the placental barrier; 2) once free BPA crosses into the fetus, it mostly remains in its estrogenically active form; and 3) once the inactive BPA metabolite crosses into the fetus, it can be converted to the active form.

Both BPA and BPA-glucuronide were detected in the rat fetal tissues and in amniotic fluid at both the 2 and 10 micromolar concentrations. This means the BPA-glucuronide can cross the placental barrier and into the amniotic fluid surrounding the rat fetuses. Once across the placenta, the fetus can break it down to the active, estrogenic form of BPA.

From the smaller dose, the researchers calculated that very low amounts – less than 0.1 percent of the administered dose – crossed into the fetus.

Nishikawa et al. also found that both the rat fetal liver and heart make an enzyme that can convert the inactive BPA-glucuronide into the estrogenic and active form of BPA. Enzymes are proteins that moderate chemical reactions – like the conversion of less toxic BPA metabolites to the more toxic BPA. The presence of the enzyme explains why the BPA-glucuronide administered to the mother rat could be converted to the more toxic form of BPA in the fetuses.

In the second study, Balakrishnan and colleagues show BPA can cross the human placenta from mother to fetus. They found that 27 percent of the BPA applied to the mother's side of the placenta is carried to the fetal side. Like the results reported in rats, this indicates that the placenta does not protect the fetus from this chemical.

In addition, more than 95 percent of the BPA recovered from the fetal portion of the placenta was still in the free, estrogenic, active form. Therefore, very little of the BPA that crossed from mother to fetus was inactivated, indicating that the human fetus is exposed to the estrogenic type of BPA.

What does it mean?

These two studies clearly indicate that BPA – in both its active and inactive form – can cross the placenta into the fetus where most of the active form remains active and some of the inactive form is converted to the active form.

The results are especially concerning because they indicate the fetus may be at greater risk from BPA exposures than previously thought. In non-pregnant adults, researcher believe BPA is rapidly converted to inactive forms like BPA-glucuronide and then removed from the body in urine. The findings from both studies suggest that adults can process BPA differently and are more protected from its effects than the fetus.

BPA is regularly detected in the blood of pregnant women, in amniotic fluid, umbilical cord blood, placental tissue and breast milk. Together with the results presented in these new studies, this indicates that human fetuses are regularly exposed to the active, estrogenic form of BPA.

Exposure to BPA during fetal development is of paramount concern. BPA in its active form can act like an estrogen hormone, although its weaker than most natural hormones. In the womb, exposure to estrogens at the wrong time or in greater or lessen amounts than normal can cause adverse effects in the development of many organs and systems, including the male and female reproductive tracts, the brain, the mammary gland and the immune system.

For the past several years, scientific and regulatory experts have debated BPA's safety in light of its widespread exposure in adults, developing fetuses, infants and children. The U.S. Food and Drug Administration (FDA), the European Food Safety Authority (EFSA) and other regulatory agencies that determine whether exposure to chemicals like BPA is safe have come to different conclusions. Following the lead of the National Toxicology Program, the FDA’s latest decision is that BPA may cause adverse effects in humans, including altered brain development and behaviors.

In contrast, EFSA contends that the fetus is able to convert BPA to less harmful metabolites, like BPA-glucuronide. This would suggest that the fetus can protect itself from the harmful effects of BPA. The current studies show that this opinion may be wrong. Together, these studies address important questions about human exposures to BPA and BPA metabolites and provide solid data that are greatly needed.