The chemical bisphenol A (BPA), widely used in products such as food cans, milk container linings, water pipes and even dental sealants, has now been found to disrupt important effects of estrogen in the developing brain.

A University of Cincinnati (UC) research team, headed by Scott Belcher, PhD, reports in two articles in the December 2005 edition of the journal Endocrinology that BPA shows negative effects in brain tissue "at surprisingly low doses."

The research was supported by funding from the National Institutes of Health and the Pediatric Brain Tumor Foundation.

"These new studies are also the first to show that estrogen's rapid signaling mechanisms are active in the developing and maturing brain in regions not thought to be involved with sexual differences or reproductive functions," Dr. Belcher said.

BPA has often been implicated in disease or developmental problems.

Long known to act as an artificial estrogen, the primary hormone involved in female sexual development, BPA has already been shown to increase breast cancer cell growth, and in the January 2005 edition of the journal Cancer Research, another UC research team reported that it increased the growth of some prostate cancer cells as well. Warnings about other possible long-term health risks associated with fetal exposures to BPA have also been discussed in recent scientific literature.

"BPA molecules are linked into polymers used to create polycarbonate plastics and epoxy resins that are widely used in many products," said Dr. Belcher, an associate professor in the pharmacology and cell biophysics department at UC College of Medicine. "While plastics are typically thought of as being stable, scientists have known for many years that the chemical linkage between BPA molecules was unstable, and that BPA leaches into food or beverages in contact with the plastics."

Dr. Belcher and his colleagues worked with rats at a period in their development equivalent to the third trimester of human fetal development through to the first few years of childhood.

Although best known for its function as a female sex hormone, Dr. Belcher explained, estrogen also has very important roles in the developing brain of both males and females.

In the absence of estrogen, Dr. Belcher said, BPA alone was found to mimic the actions of estrogen in developing neurons, and very low doses of BPA completely inhibited the activity of estrogen. Because estrogen normally increases the growth and regulates viability of developing neurons, he said, these results support the idea that BPA may harm developing brain cells.

In fact, Dr. Belcher said, while high doses cause little effect, analysis of cellular and molecular markers of estrogen signaling revealed that near-maximal effects of BPA on rat brain neurons not only occurred "at surprisingly low" doses of 0.23 parts per trillion, they also happened in a matter of minutes.

"From other studies it's clear that these low concentrations are in line with human fetal exposures, and at levels one might even see in the water supply," said Dr. Belcher.

This "low-dose" effect of BPA is troubling, Dr. Belcher points out, since its maximal effects occur at the level typical of human exposure. This means that the harmful effects of BPA could easily be missed using standard approaches for determining the risks of chemical exposure.

"These are important considerations in view of the widespread presence of low concentrations of BPA in the environment," said Dr. Belcher

In earlier research, which showed estrogens could control the survival of maturing neurons in the brain region involved in movement and coordination, Dr. Belcher and his co-workers found the effects of estrogen were the same in both males and females.

"Estrogen's actions on these neurons appear to be a double-edged sword," he said. "During certain periods of development estrogen can kill specific subsets of neurons, but at a later developmental stage it actually appears to increase their viability." Disruption of either of these actions of estrogen could be considered potentially harmful, he added.

"We have now shown that environmental estrogens like BPA appear to alter, in a very complicated fashion, the normal way estrogen communicates with immature nerve cells," Dr. Belcher explained. "The developmental effects that we studied are known to be important for brain development and also for normal function of the adult brain," he said.

What remains unclear, he said, is how inappropriate hormone signaling, or blocking the normal signaling at a critical time during development, will influence later life.

In the face of more than 100 studies published in peer-reviewed journals showing the detrimental effects of BPA, Dr. Belcher said, the chemical industry and federal regulatory agencies have resisted banning BPA from plastics used as food and beverage containers, despite the fact that plastics free of BPA and other toxic chemicals are available.