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Plastics chemical alters female brains

Research renews debate over the toxicity of bisphenol A, a plastics chemical found in humans.

20.06.2006 |Sascha Gabizon

Science News – June 7, 2006

A chemical that leaches out of plastics has been discovered to modify the developing brains of female mice, who later behave much more like their brethren. This latest study builds on a growing body of literature about the toxicity of bisphenol A (BPA) and raises questions about its effects in humans.
Low doses of bisphenol A make female mice behave more like males.

In 1936, researchers found that BPA acts much like the hormone estrogen. Scientists now estimate that more than 6 billion pounds of the chemical are manufactured for use in products such as polycarbonate plastic—the resin lining food cans—and dental sealants. Citing the precautionary principle, city supervisors for San Francisco recently banned the chemical for use in products, such as baby bottles, that are intended for use by children under 3 years of age.

In the latest study, published in the journal Endocrinology, Beverly Rubin, an associate professor of cellular biology at Tufts University, and colleagues placed tiny pumps into female mice. From the 8th day of pregnancy until the 16th day of nursing, these pumps released doses of BPA into the mothers. This time period is critical because on the eighth day of development, embryonic mice begin growing neurons in a region of the brain that is critical for sexual behavior.

Most importantly, says Rubin, the concentrations administered were very tiny. One set of mothers was exposed to doses of 250 nanograms per kilogram per day (ng/kg/d) of BPA, while the other set was dosed at only 25 ng/kg/d.

“The levels of bisphenol A that were used are within the range that is estimated to be found in humans,” she says. Last year, the Centers for Disease Control and Prevention reported that 95% of Americans excrete at least 100 parts per trillion (ppt) of BPA in their urine.

The scientists then examined the brains and behavior of the new generation of mice. In a section of the brain that controls the sexual cycle, female mice have 2–3 times as many neurons as males. But female mice who had been exposed to BPA while still in the womb were found to have fewer neurons than usual in this area of the brain. Female mice are typically more energetic than males, but the activity level of females who had been exposed to BPA dropped and mirrored that of their brothers.

“We found that the differences between males and females, at least for these two markers, were obliterated,” adds Rubin.

But Steve Hentges, executive director of the American Plastics Council, says he finds little that is compelling in the research. “This study is of limited relevance to human health. A more robust study should be done,” he says.

“We are within the human exposure range,” counters Ana Soto, a Tufts professor of cellular biology and coauthor of the paper. She points out that other studies have found that BPA can lead to problems of the reproductive tract in both male and female rodents. “There is plenty of evidence now that low-dose levels lead to problems,” she adds.

Few studies have reported on how BPA might harm humans. One study found that exposure to BPA is associated with recurrent miscarriage.

For almost two decades, Fred vom Saal, a professor of biology at the University of Missouri, has been investigating chemicals that alter the hormone system. “The findings reported in this study show permanent changes to the brain at doses that are 2000–20,000 times lower than what is estimated to be safe,” he says. In January, vom Saal published an article that examined 120 papers on BPA. Of these studies, 109 found effects on experimental animals from low doses—40 of them at concentrations below the U.S. EPA’s recommended safe level of 50 micrograms/kg/d.

However, he reported that 11 studies funded by industry found no effect from BPA.

And in a paper published in Cancer Research, scientists discovered that BPA can permanently alter DNA in rats. Like in the Rubin study, researchers exposed fetal rats to BPA at similar levels to those found in humans. When later tested, the male rats had DNA with an altered methylation pattern. Methyl groups act like switches and when attached to DNA can shut down gene expression. In this case, the excess methylation occurred on genes that regulate the function of the prostate, a gland that is influenced by hormones. Rats with this disrupted methylation pattern showed an increased incidence of precancerous prostate lesions.

Commenting on Rubin’s research, Scott Belcher, an associate professor of pharmacology at the University of Cincinnati, says that the work does an excellent job of measuring low-dose responses in classic behavior and neuroanatomical studies.

Last December, Belcher published an article in Endocrinology reporting that rat brains were affected by BPA at doses below 1 ppt. “It was very surprising to see how the effects correlate with levels that have been found in humans,” he says. —PAUL D. THACKER