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Boyish Brains: Plastic chemical alters behavior of female mice

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10:49am, May 3, 2006
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Exposure to the main ingredient of polycarbonate plastics can modify brain formation in female mouse fetuses and make the lab animals, later in life, display a typically male behavior pattern, scientists have announced.

The chemical, bisphenol-A, is measurable in 95 percent of U.S. residents, according to past research. The chemical mimics the hormone estrogen, which in mammalian fetuses affects anatomical development that distinguishes male and female brains.

Neuroendocrinologist Beverly S. Rubin and her colleagues at Tufts University School of Medicine in Boston pumped bisphenol-A into the bodies of female mice while they were pregnant and while they were nursing their offspring. Some of the mice received 250 nanograms of bisphenol-A daily per kilogram of body weight (ng/kg/day); others received 25 ng/kg/day. Another group of mice wasn't given any bisphenol-A.

The researchers then examined the brains of some of the male and female offspring, and they placed other offspring into an empty arena to monitor their behavior.

In offspring that had not been exposed to bisphenol-A during development, a brain structure that influences fertility-related hormone cycles was larger in females than in males. However, that sex difference was not evident among animals receiving either dose of bisphenol-A, Rubin's group found.

Compared with unexposed female offspring, those given 250 ng/kg/day of bisphenol-A had fewer neurons of a type critical to the function of the fertility-controlling brain structure. The results will appear in an upcoming Endocrinology.

"Exposure to very low doses of bisphenol-A results in masculinization of the female brain," says coauthor Ana M. Soto.

Furthermore, the team reports, females exposed to either dose were less distinguishable from males on the basis of their behavior. Female mice normally explore more avidly than do males in an open environment.

Several scientists have estimated that the average person's daily exposure to bisphenol-A is similar to the lower dose given to animals in this study. That dose is the lowest that's been shown to affect the sexual differentiation of a mammalian brain, Soto says.

"This study is a strong addition to a series of recent reports on the long-term effects of bisphenol-A on sexual differentiation," says John G. Vandenbergh, a zoologist emeritus at North Carolina State University in Raleigh. "It shows significant effects at remarkably low doses that are well within the range of known human exposures."

But Steve Hentges, a chemist with the American Plastics Council in Arlington, Va., says that effects observed in these animals aren't relevant to people because food that's been in contact with polycarbonate is the main source of human exposure to bisphenol-A. The body metabolizes the chemical into a non-estrogenic form when it's ingested, says Hentges, whose organization represents plastics manufacturers.

Researchers "would have to confirm this kind of result with an oral exposure to make it relevant for people," Hentges says.

Frederick vom Saal of the University of Missouri–Columbia counters that the Tufts researchers, by exposing animals continuously day after day, "are mimicking to the best degree possible the human exposure to bisphenol-A."

The bisphenol-A concentrations used were "so staggeringly low" that people will inevitably be exposed to similar amounts as long as polycarbonate remains in commerce, vom Saal says.

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