Another Plastics Ingredient Raises Safety Concerns

Bisphenol A's 'twin' may have more potent hormone effects.

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By Janet Raloff, Science News

A largely ignored contaminant doesn’t just resemble bisphenol A, the chemical found to leach out of hard plastic water bottles. It’s BPA’s fluorinated twin — on steroids.

New laboratory studies in Japan indicate that the twin, called bisphenol AF, or BPAF, may be even more potent than BPA in altering the effects of steroid hormones such as estrogens in the body.

The unusual way that BPAF blocks some estrogen actions and fosters others “could make this a vicious compound, a very toxic compound,” says Jan-Åke Gustafsson, a molecular endocrinologist at the University of Houston. The chemical is an ingredient of many plastics, electronic devices, optical fibers and more.

The last letter in bisphenol AF’s name denotes the substitution of fluorine atoms for six hydrogens and explains why the compound is sometimes referred to as hexafluoro-BPA. These fluorines also make BPAF behave differently than BPA in the body, biochemist Yasuyuki Shimohigashi of Kyushu University in Fukuoka, Japan, and his colleagues report online April 28 in Environmental Health Perspectives.

Both chemicals act on estrogen receptors, molecular locks found in cells throughout the body. Estrogen hormones serve as their keys, turning on genes that control time-sensitive activities such as ovulation in young women. Certain contaminants, such as BPA and BPAF, can mimic those keys.

But some mimics are better than others and may even, like skeleton keys, act on a variety of locks. Most of BPA’s estrogen-mimicking effect, Shimohigashi’s group found in 2006, comes from activating a cellular switch known as human estrogen-related receptor gamma, or ERR-gamma.  It’s an “orphan” receptor, meaning a lock with no known natural key.

In its latest study, the Japanese group performed tests in isolated cells and receptor proteins. And BPAF, the researchers now report, all but ignores ERR-gamma. Instead, the chemical’s fluorine atoms appear to give it a strong affinity for the two best-studied estrogen receptors, ER-alpha and ER-beta. Indeed, the fluorines bind to ER-alpha some 20 time more effectively than BPA does, and to ER-beta almost 50 times more effectively.

After binding, BPAF proved a potent activator of ER-alpha, unleashing its actions just as the body’s own estrogen would. The big surprise, Shimohigashi says, was finding that despite BPAF’s even stronger affinity for ER-beta, it elicited no activity from this lock. The chemical enters the receptor and then just sits there like a dud. In so doing, it blocks the receptor’s access to the body’s own estrogen — preventing it from unlocking any of the myriad operations normally controlled via this important receptor.

Where ER-alpha can promote reproductive cancers, actions triggered through ER-beta tend to inhibit cancer development and foster health in a range of tissues throughout the body. “So simplistically speaking,” Gustafsson says, “ER-alpha is the bad guy and ER-beta is the good one.” Generally, he says, their actions tend to balance one another.

And that’s what appears to make BPAF such a “double-edged sword,” he contends. By increasing ER-alpha activity and shutting down ER-beta’s countervailing functions, BPAF appears to shift endocrine action toward greater toxicity, he says.

Early hints of BPAF’s hormonal alter ego prompted the National Toxicology Program in late 2008 to target it for federal toxicity testing in rodents. Shimohigashi says his team will soon begin similar studies to investigate how the newly unveiled endocrine effects play out in whole animals.

Little is known about the quantity of BPAF produced each year or likely human exposures. One federal study conducted nearly three decades ago estimated that some 4,400 U.S. workers likely encountered the chemical at the time, according to a brief online report by the National Toxicology Program. That report also notes that the contaminant has been detected in women’s fat — a sign that it could, during breastfeeding, be passed along to a baby.