Monday, July 23, 2012

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

Another Plastics Ingredient Raises Safety ConcernsBy 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.

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The Chemical Marketplace Series - Bisphenol AF
by Bill Chameides

Introducing bisphenol AF, BPA’s more toxic sibling.
By now, you've no doubt heard about Bisphenol A (aka BPA) and its potential for toxic mischief when leached from various plastic containers. You’ve probably also heard that companies are now falling all over themselves to declare their products ”BPA-free." (And some people claim that the public can't catalyze a national green movement.)

All in the BP Family



But you may not know that BPA is only one of a cornucopia of chemical bisphenols, or BPs, running amok in the world. (The "BP” referred to here should not be confused with a certain petroleum company that has received a good deal of media attention of late.)

Among the alphabet soup of chemical BPs are BPB, BPC, BPF, BPAF, BPE, and BPS. In fact, the National Toxicological Program lists 38 compounds [pdf] that are structurally similar to BPA. The common thread is that they all begin with the same basic bisphenol chemical structure of C12H10(OH)2 — two phenyl groups each bonded to a hydroxyl (OH) group — then are subtly added to and/or otherwise modified. For example, in the case of BPA, two methyl groups (CH3) are added along with an extra atom of carbon (C) to the basic bisphenol building block.

What About Bisphenol AF (BPAF)?


Well, not all that surprising, given the "F" in its appellation, BPAF has the same configuration as BPA except the hydrogen atoms in the methyl group have been replaced by fluorine atoms. (Technically speaking, substituting fluorine for hydrogen in the methyl groups turns them into trifluoromethyl compounds.)

From the point of view of a chemical engineer, the addition of the fluorine atoms improves BPA’s chemical, thermal and mechanical properties, making it attractive for lots of applications in plastics, electronic devices, optical fibers, and more. Thus, BPAF is one more example of a compound with wondrous new properties produced by replacing hydrogen atoms with halogen atoms (in this case fluorine) in an organic molecule.

But, alas, there is a problem: many of those halogenated compounds turn out to be mixed blessings at best. They can be quite toxic and they can be slow to break down or metabolize in the environment and in the human body. Examples include PBDEs, PCBs [video], DDT and Freons.

Lots of Unknowns With BPAF

As for BPAF, the fact is we don't know very much about its toxic properties. But recent results from short-term studies have suggested that it may act as an aggressive endocrine disruptor. Indeed, in 2008 it was one of only six chemicals accepted for further study by the National Toxicological Program.

While that work is just getting started, data trickling in from other sources are not reassuring. There are signs that BPAF may be a more effective endocrine disruptor than BPA. For example, a study published last spring in Environmental Health Perspectives by Ayami Matsushima of Kyushu University in Japan and colleagues suggests that BPAF packs a one-two punch on the reproductive system: effectively shutting off gene receptors that promote reproductive health and inhibit reproductive cancers, while activating the receptor that can promote reproductive cancers.

Okay, that's not great, but what are the chances any of us are being exposed to BPAF in dangerous quantities? I can't give you a definitive answer, but here's what TheGreenGrok team has been able to find out.

It's rather incredible to me but the National Toxicology Program reports [pdf] that there does not yet exist a comprehensive database on the types of products that contain BPAF. One application that has been documented: BPAF is used in food-contact polymers such as fluoroelastomer gaskets and in hoses used in food-processing equipment. BPAF may also be used in dental resins and plastics used to wrap foods. Not exactly what one would want to hear for a potentially toxic compound.

Patent records [pdf] indicate that we haven’t been making BPAF all that long, only since the late 1970s. According to the Environmental Protection Agency’s most recent chemical inventory database from 2006 (the inventory is updated every four years), between 10,000 and 500,000 pounds of BPAF are manufactured, imported or used annually in the United States. Why such a large range? That’s the way EPA does it; here’s the agency's explanation [pdf].

These amounts, reports EPA, have remained essentially flat since 1986. But are they significant? It's hard to say since we don't know that much about how BPAF moves through the environment or whether a significant amount leaches from products and gets into our bodies. Two relevant things to note:
  • On the positive side, the amount of BPAF in use in the United States is considerably less than that of BPA (at one billion pounds or greater).
  • On the other, BPAF has been detected in the environment (albeit at levels lower than that of BPA). A study in Germany found detectable levels of BPAF in about three-fourths of the surface water and sewage samples collected and in more than half of the sediment samples collected.
So that's the story on BPAF. One of some 80,000 chemicals used here that go unregulated and virtually unstudied. Are the products you use exposing you to BPAF? Your guess is as good as mine.