Is there bias in bi(a)sphenol A?

Over the past two years the debate about bisphenol A (BPA) has become a quagmire where highly regarded scientists who once worked side by side, now sit across the fence virtually flinging insults at one another. You wouldn’t know this reading the Sunday paper or countless mainstream press articles, blogs and even academic journals which have successfully vilified this ubiquitous chemical. Like many Americans, you’re probably tossing away your polycarbonate bottles and looking askance at the stash of cans in your pantry.

Yet two summary panel reports on BPA prepared by the National Toxicology Program (NTP) and by the Food and Drug Association (FDA)* downplayed the risks of BPA, while at the same time, NTP highlighted the need for more research - and as of January 2010 the FDA indicated they too have concluded there is some cause for concern, particularly in infants and children. As a writer I find this disconnect fascinating. As a mother who replaced the polycarbonate bottles shortly after the first round of BPA press, I wonder if the chemical is deserving of its reputation as the evil twin of estrogen. As a toxicologist, I am dismayed by the apparent bias found on both sides of the fence.

Years ago, while interviewing for a job, I was asked if science was objective. I quickly answered in the affirmative. My future employer’s brow wrinkled, but she remained silent – giving me time to think. While science is objective, it is carried out by mere humans. And we all have our biases. I wouldn’t have been interviewing with a group whose mission was to support communities affected by industrial contaminants and who could only offer a pittance in salary if I didn’t lean towards the affected. Yet, I pondered, when reviewing the literature in support of their mission would I be biased? Here’s the truth – when reading studies funded by either the military or industry my sci-dar is on full alert. Likewise, I’m just as wary when reading studies conducted by environmental activist organizations, yet I am more trusting of studies produced by academics, particularly those funded by sources that tend not to have a stake in the outcome. Really, my sci-dar should be on full alert at all times, and in the end, I am careful not to cherry-pick studies from any one source, just to support a position.

Are there concerns about bias in the bisphenol A analysis? As a recent memoirist who shall not be named, likes to say, “You Betcha.” Just Google “BPA bias” and you’ll find over one million pages.

One need only read Environmental Health Perspectives, published by the National Institute of Environmental Health Sciences (NIEHS), where the most recent BPA battle is playing out. But the stakes are higher than simply resolving BPA’s toxicity. Bisphenol A has brought to the fore the very nature of toxicity testing and regulation, questioning the role or (or lack of) basic research in chemical testing and regulation.

That toxicity testing, particularly of endocrine disrupting chemicals like BPA is in dire need of overhaul is not in question. Says Dr. L. Earl Gray**, Research Biologist and Team Leader of the Reproductive Toxicology Division at the US EPA, about updating routine chemical testing:

“There is a lot more awareness of the issues with endocrine disrupting chemicals and thoughts about screening….they are also trying to shorten the multigenerational protocol [one of the standard toxicity tests required of industry]…hopefully and likely the new assays will be able to replace the old ones fairly quickly.”

Problem is, it took a decade to develop and validate those new assays. A snail’s pace, and a significant chunk of time for those at greatest risk, the very young. Even so, when it comes to BPA, there are those who suggest reviewers and regulators stick with studies based on regulatory testing protocols, because those methods have been rigorously validated, even if they don’t incorporate the latest science.

Of the hundreds of scientific articles on BPA many could be classified as basic science, while only a fraction use regulatory testing protocols. Studies in rodents report that BPA causes diabetes, weight gain, mammary gland cancer, early onset puberty, infertility and behavioral changes. Some of these findings cannot be repeated (reproducibility is a central tenet of science). Meanwhile studies in human populations report associations (which are not cause and effect linkages) between BPA and heart disease, diabetes, infertility in industry workers, and behavioral changes in toddlers born to mothers whose urine concentrations during pregnancy mirror those in the general population.

Despite the uncertainties, aren’t all of these studies enough to require that industry remove the chemical from our food and drink? While I am skeptical of studies produced by industries whose bottom line depends upon a particular chemical and in sticking with decades old testing procedures, I also know that a chemical posing an imminent danger is good for academic business, generating more grant money, more publications, and more consulting. It’s not an ideal system, but given time the scientific method prevails – and in the interim we have guidance from the expert panels. In the case of BPA both panels had the freedom to consider any and all relevant and valid studies.

While the NTP panel concluded there was cause of “some concern,” noting the need for more research, the FDA concluded that current exposures to BPA do not present a health risk. So began the fireworks. Critics charged the panels were biased omitting too many basic studies from their final analysis. In his congressional testimony, Gray who was a member of the NTP panel disagrees. Testifying before congress about BPA, Gray noted, that “the criteria [for inclusion in the review] provided minimum standards for experimental design and statistical analysis. Many studies failed to meet these minimal criteria – these studies came from industry, government and academic laboratories.

“The controversy,” says Gray “resides over the fact that standard and enhanced multigenerational studies are negative for low dose effects and many academic studies were positive…. several of the multigenerational studies have added low dose groups, estrogen sensitive endpoints and tried to replicate the low dose effects to no avail... These differences are due in part to differences in how a chemical is administered in a study.” Differences which also include the use of live animals versus test tube studies (which preclude metabolism and excretion of a chemical), the timing of exposure and the range of doses tested.

Yet based on accounts by the popular press, enviro-blogs and magazines – if you still drink from a polycarbonate bottles or serve your kids canned foods then you must be an irresponsible parent. When I replaced our reusable bottles with BPA free – but didn’t toss the canned goods, my inner toxicologist reasoned that we are exposed to a myriad of natural estrogenic chemicals in foods like soy, plants, and milk – was BPA any worse? Meanwhile the environmentalist in my brain reminds me that we don’t choose to consume industrial chemicals like BPA. Shouldn’t we have that choice? But since BPA does not accumulate in humans (a quality that may trigger a chemical ban), “that choice” depends primarily upon the amount and frequency of BPA exposure, how it’s metabolized and its potency.

So is it or isn’t it? Maybe the nearly 30 million dollars recently committed by NIEHS for BPA research will solve the question, and maybe BPA will be one more example for the scientific flip-flopper pile along with fiber, mammograms, and therapeutic estrogens. For now, there’s FDA’s final report due at the end of the month, and Consumer Report’s recent investigation of BPA in canned goods – both of which will surely add a few feet to the fence separating some very good scientists.

*This report is the 2008 draft, a final report was just published you can find FDA's current position on BPA here.

Here is a recent article on the relationship between BPA in urine and heart disease

CHECK OUT the US DEPT Health and Human Services site for the latest on BPA (added Jan 16 2010)

AND a Jan 28 2010 interview with Dr. Linda Birnbaum of NIEHS

**In the spirit of disclosure, I worked for Earl back in the early nineties, he was not only a great guy to work for, but I also respect his science and opinions.

Silencing Spring: WWRD

First Pulished September 2008 in the Montague Reporter

In her 1962 publication, Silent Spring, Rachel Carson wrote about a spring in the near future potentially silenced by “indiscriminate use of pesticides,” with names like DDT, lindane, aldrin and mirex. What she didn’t write about back then, are the now infamous perfluorinated chemicals used in nonstick and waterproof surfaces, the polybrominated flame retardants that are infused into textiles and plastics, or the triclosan and triclocarban antibacterials in soaps, toothpastes and a range of consumer goods. Back then, no one knew that these chemicals used primarily in consumer products, would eventually find their way into not only you, but also your neighbor, and your neighbor’s neighbor, and, depending on the chemical possibly their uncle in Alaska and definitely the polar bear that just roamed through your neighbor’s neighbor’s uncle’s town.

Instead, Carson chronicled what in retrospect seems obvious now, but clearly wasn't back then. That spraying long-lasting (and by long - I mean decades) chlorinated chemicals like DDT, which accumulate in the fat and are designed to be toxic, on farms, suburbs, even cities just wasn’t smart. But if her expose seems obvious now, then why almost fifty years later are scientists finding, in addition to the remnants of chlorinated pesticides banned years ago, industrial fluorinated and brominated chemicals in water, sediments, wildlife and in humans? And why is one of the “next generation,” shorter lived, barely-bioaccumulative pesticides, atrazine, turning up in surface and groundwater supplies across the nation?

There is no doubt that the publication of Silent Spring wakened the American public to the very real consequences of “better living through chemistry.”

“I was in 8^th or 9^th grade,” recalls my neighbor Jeff, “and learned about it from the mainstream media. It had a pretty big impact – it started to frame the way you looked at things. I remember kayaking down the Connecticut. It was disgusting. But,” he conceded, “none of us were really sure what to do about these things.”

Barely a year old at the time of publication, and not cognizant of books except maybe as suitable teething material, I don’t recall its publication or the impact it had on my suburban life, although I do recall tanker trucks trundling along our road, spraying for mosquitoes and gypsy moths; the shelf in the garage full of bottles and spray cans that my father used to combat whatever ailed his beloved trees and shrubs; and, befitting my current occupation, I recall mixing up my own toxic potions – from cleaning materials stashed under the sink or in the laundry room, and testing them out on the earwigs and carpenter ants that raced along our swing set. Unlike Jeff, I was clueless.

Thankfully, there were plenty of folks who were neither clueless, nor baffled about what could be done to avert the impending environmental disaster described so elegantly by Ms. Carson. Eight years after Silent Spring, the US Environmental Protection Agency, the primary body responsible for registration, release and management of chemicals was born.

Of the December 2, 1970 launch of the agency Jack Lewis, writing for EPA Journal noted, “…Surely no factor was more pivotal in the birth of EPA than decades of rampant and highly visible pollution. But pollution alone does not an agency make. Ideas are needed--better yet a whole world view--and many environmental ideas first crystallized in 1962. That year saw the publication of Rachel Carson's Silent Spring….In fact, EPA today may be said without exaggeration to be the extended shadow of Rachel Carson. The influence of her book has brought together over 14,000 scientists, lawyers, managers, and other employees across the country to fight the good fight for "environmental protection."”

That’s an impressive legacy. But sometimes, I wonder what Ms. Carson would think of her legacy today?

Reading Silent Spring for the first time (I am ashamed to admit), it’s unsettling that nearly fifty years later, albeit on a different scale, Carson’s writing is still relevant. I don’t mean the the details – I think for anyone who didn’t live through those times – or who doesn’t live near farms where aerial spaying is still used – the events Carson described are hard to imagine. It’s been over thirty years since DDT fell from the sky like snow, and “housewives” swept pellets from their front steps or washed the stuff out of their kids’ hair, and the death of so many songbirds suggested a bleak future.

No doubt, we are all better off thanks to the EPA’s slew of chemical regulations and policies, but on a different scale, pesticides and industrial chemicals continue to contaminate water, consumer products, wildlife and us. And scientists, rather than focusing on lethality and reproductive success are now measuring more subtle changes in wildlife like altered reproductive function and development. The perfluorinated and polybrominated chemicals provide examples of history repeating itself – even with regulations in place. Sometimes chemicals slip by because scientists haven’t figured out how to measure them in the environment. Sometimes they slip by because no one expected them to be there, and sometimes they slip by because the industry that produced and released them didn’t provide all the relevant data. But thanks to greater collective environmental awareness ( by consumers, activists, scientists, policy makers and even industry), unlike DDT, it won’t take over a decade to phase-out fluorinated and brominated chemicals – phase-outs for these chemicals are already in progress.

But then there’s Atrazine. The top selling herbicide in the United States, banned by the European Union in 2003, atrazine is an example of a “new and improved” pesticide gone awry. Applied primarily to corn, with minor uses including lawns and golf courses, the EPA estimates that roughly 73 million of pounds of atrazine are applied to crops each year. Compared with the longevity of the chlorinated pesticides like DDT atrazine lasts for merely a blink in time with a half-life 146 days or so (although in these more enlightened days even that’s considered long-lived.) Unfortunately once Atrazine works its way into ground water it may last for years. The result? In the midwest, Atrazine is one of the most commonly detected contaminants in surface and groundwater, additionally it’s been detected although to a lesser extent in groundwater in the Northeast, including Massachusetts. Though detected concentrations often fall well below EPA’s 3 part-per-billion drinking water standards, there are a growing number of studies suggesting that other species, particularly amphibians may be susceptible to much lower concentrations.

University of California, Berkely researcher Tyrone Hayes reported back in 2003 that exquisitely low concentrations of atrazine, as low as 0.1 ppb, altered the steroid hormone balance in frogs, feminizing male frogs and resulting in hermaphrodism and demasculization of the vocal cords. And just recently, Krista McCoy and others, publishing in Environmental Health Perspectives, reported a link between hectares of farmland and feminization in local frogs. Although the authors didn’t measure specific pesticides, among the suspects is atrazine. All this got me wondering – where’s our EPA? Atrazine was recently up for reregistration, an opportunity for EPA to review data accrued over the years since a pesticide is first registered. For atrazine that was 1958. This was well before scientists were clued in to subtle reproductive and developmental impacts caused by small concentrations of chemicals. Nor was consideration given back then, and only rarely now, to the reality that seldom are individuals or wildlife exposed to single chemicals. We are all exposed to complex mixtures of contaminants released by industry, agriculture and from consumer products like soaps, sunscreens and pharmaceuticals.

Surely, I thought, given the pervasive groundwater contamination and the recent data on frogs, atrazine’s registration if not revoked would at least be restricted. At the very least maybe the allowable environmental concentrations (the “chronic criterion”) would be reduced below those found to impact amphibians? Unable to find the appropriate numbers on EPA’s website, I emailed EPA. “We anticipate this chronic criterion, when finalized later next year, will fall within the range of 10 to 20 ug/l [ppb]” wrote Frank Gostomski of EPA’s Health and Ecological Criteria Division. I asked if Hayes’ studies had been included. Yes, was the answer. But if Hayes’ studies hold up to scientific scrutiny –and there seems to be a growing body of literature that suggests that they do - then EPA’s concentrations are way higher than those found to feminize male frogs.

Though hard to imagine in our own backyard where spring peepers and cluckers keep us awake, is it possible that some day thanks once again to “indiscriminate use of pesticides” spring could still be silenced?

Polycarbonate redux

I am listening to NPR’s All Things Considered – it’s a story about bisphenol A, a common chemical that many of us have heard about by now. You know the estrogenic chemical that’s in those colorful polycarbonate clear plastic bottles that we all bought when we didn’t want to use bottled water, as well as in the linings of food tins and clear plastic baby bottles – that yes, I’m sure I used with my kids. And I’m thinking maybe we all ought to drink a little bisphenol A if it’s true that a little estrogen is good for improving memory.

Here’s why.

There is no question that exposure to estrogenic contaminants is problematic – particularly when exposure occurs during fetal development and in young children. There are reams of data that demonstrate adverse impacts on the development of reproductive organs, timing of puberty, and other effects on both male and female offspring of test animals exposed in utero and during lactation. Then there is the unfortunate example of diethylstilbesterol or DES, the synthetic estrogen prescribed to women back in the twentieth century to stem complications during pregnancy. It was found to be ineffective in the 1950’s but prescribed until the ‘70s (go figure) when the consequences of exposure to extraneous estrogenic chemicals during development first reared its ugly head in the form of clear cell adenocarcinoma in the daughters exposed in utero.

But did you know that at one time, back in the 1930’s scientists seeking synthetic estrogens like DES found that bisphenol A also behaved as a weak estrogen? That’s right. Back in the 30s this was known. Then some genius discovered that it could be linked together to make plastic. And voila – perimenopausal women like me just have to drink from our polycarbonate bottles to replenish our estrogen. Apparently back then no one figured anyone would be drinking from the plastic, or storing food in it, or sealing children’s teeth – and then when they did discover these uses of the plastic they must have forgotten that it was a known estrogen.

Seriously, we could all use a memory boost. Here’s a Science News article from back in 1999 by Janet Raloff which, besides being so last century, is so similar to recent reports about leaching of bisphenol A from polycarbonate that I did a double take when I came across it on the web (actually I probably read it back then, being a fan of Ms. Raloff, but have since forgotten.) It’s uncanny. Right down to reports that bisphenol A is more likely to leach from well-used polycarbonate and when liquids are heated in polycarbonate.

If that was then, why has it taken us ten years to toss our bottles? Maybe it’s because as Raloff pointed out, the jury was out. Well, almost ten years later it has returned in the form of a report by the National Toxicology Program’s Expert Panel evaluation of bisphenol A, here’s what they conclude (their emphasis):

“The NTP concurs with the conclusion of the CERHR Expert Panel on Bisphenol A that there is some concern for neural and behavioral effects in fetuses, infants and children, at current human exposures. The NTP also has some concern for bisphenol A exposure in these populations based on effects in the prostate gland, mammary gland and an earlier age for puberty in females.”

“The NTP has negligible concern that exposure of pregnant women to bisphenol A will result in fetal or neonatal mortality, birth defects, or reduced birth weight and growth in their offspring.”

Although I’ve confiscated my kids bottles I might keep them around for a few years in case I’m needing a little extra estrogen – if I can remember where I’ve stashed them!

It’s TOXICANTS stupid

Whenever I have the opportunity to teach, I quickly learn how little I know. Maybe that’s what draws me towards the classroom. Besides the opportunity for human contact – especially contact with students who are so eager to learn about how we’ve managed to muck things up and what we can do about it.

A few months ago, I took on two challenges 1) introducing students at Mount Holyoke College to the fascinating world of toxicants, which, as they all now know– it’s toxi-c-a-n-t-s – unless of course it's a biologically produced toxin (and each time I reminded them of this, I was reminded of my graduate school advisor, the one we called “the pedant,” and shudder,) and 2) asking them to write about toxicants (and in one case, a toxin) for publication in the very public Encyclopedia of Earth or EOE (www.eoearth.org). (And write they did - articles ranging from PBDEs to Atrazine to Synthetic musks - something I hadn't know even existed!)

For some it was a slog. As one student wrote, and I’m sure more than a few students thought, “I never realized writing for the EOE would be so tedious.” For others it seemed a breeze. For me it was nerve-wracking. Particularly after I had the brilliant idea that each student should send her article out for review to whatever expert on her topic she felt most appropriate.

When they sent their work out for expert review, writing letters of introduction, attaching their articles and sending a small part of themselves out into the unknown – I warned them,

“Don’t be surprised if you don’t hear back.”

But then something amazing happened. Scientists wrote back. Scientists - many who are respected in their field, who are pressed for time, who let reviews for prestigious journals sit on their desk until pinged for the tenth time by the journal editor - these scientists took the time to review articles written by undergraduates struggling to comprehend and communicate their research.

It was frightening.

“I didn’t open the response for a day,” said one student about her “expert review.” Another found a sea of red marks – comments, corrections, and No! Wrong! Wrong again – followed by helpful suggestions and further reading.

I wondered if I’d thrown my students to the wolves. Though I’d commented, edited and corrected as best I could before review, the fact is – I could never claim expertise on the breadth of topics covered by this group of young women. This was the lesson I'd learned. I hadn't planned for that level of expert review - but when the drafts came rolling in, I knew I was over my head. Without reading each and every reference - there was no way I could truly comment on the accuracy of what they'd written.

So was it worth the ego-bruising effort? (And I'm not referring just to the students here.) I had asked my students to write not only for the highest level of review, but also in the end, to put themselves out there in a way that many scientists haven’t dared, communicating a highly technical topic - one which they'd just learned about virtually on their own, to the public and in plain language. 

It’s something that I never felt comfortable with until I was out of the lab. Until I felt I had nothing to lose. But these days it is often necessary for scientists to communicate not just with each other but with the public, and it is my hope that that’s the lesson that sticks.

Maybe the difference between “toxicant” and “toxin” is pedantic. But sometimes you’ve just got to get it right. I think they did.

Check out their articles on the Encyclopedia of Earth:

PBDE
Pfeisteria
CFC-11
Pthalates
Atrazine
Perchlorate
Synthetic musks

Well, we're better off than in the '70s right?

Toxicology fascinates me, and I love passing that fascination on to students eager to learn about how chemical contaminants impact their environment, and what they can do about it. But it’s a difficult science to teach to undergraduates. It’s hard not to talk about environmental contaminants without the doom and gloom. Particularly this semester, when I’ve decided to run a new course, introducing students to emerging contaminants, by having them investigate and write - for this site and others - about what they’ve discovered.

Because really, there’s nothing “new” or “emerging” about these chemicals, except that we’re now aware of their existence in the environment, and in us. As most of my students now know, many of these contaminants have been around for decades. Some were never regulated; some were regulated, but ended up contaminating land and water across the country anyway; some, have taken environmental scientists and regulators by complete surprise.

“How do you not get depressed?” asked one student, head in hands, slouching into the desktop.

“Well,” I reply, “we’re a lot better off than we were back in the ‘70s.”

Whoa, did I really say that?! The ‘70s? Do I have to harken back to the 1970’s to make us look OK now? A time when many environmental regulations were new, and couldn’t help but improve the condition of air, water and land?

I can relate to my students' sense of loss. It’s like having the rug pulled out from under. We all want to believe that all the regulations and regulatory agencies that serve to protect us from harmful chemicals really are effective. And, for the most part they are, and we are better off for it. But these emerging chemicals are more insidious. For decades many of these chemicals have contaminated food, water, us – in part because they were beyond the reaches of the analytical chemist. No one knew they were there - although some might have been predicted to be a problem, others were thought to degrade, break apart into harmless products.

But now, with improved techniques we know that we are not only stardust, but we’re synthetic chemicals as well.

So I point out that there’s hope. I say that even though PFOA and PFOS, which belong to a class of perfluorinated contaminants, were a big regulatory “whoops,” they now are undergoing the appropriate scrutiny, and within a fairly short timeframe, scientists have begun to measure their decline in the environment.

Shortly after that discussion, I sent the students off to investigate their favorite “emerging contaminant.”

Now I’m depressed.

Of the seven different “emerging contaminants” they chose to investigate, four of them, Pthalates, Atrazine, PBDEs, and Nitro-musks are banned by the European Union. But here in the United States? All four are still legal. (OK, California recently banned pthalates and many states have issued bans on specific PBDEs .)

As Mark Schapiro, editorial director of the Center for Investigative Reporting, reveals in his book Exposed , the differences in chemical regulation between the U.S., once an environmental leader, and the EU the rapidly emerging new leader are vast, and like the universe, rapidly expanding.

“All this makes me want to move to Europe,” commented one student, or maybe California.

Bisphenol A in the news again

For those interested in reading more about the estrogenic plasticizer bisphenol A (BPA), the Milwaukee Journal Sentinel just published its own review of BPA literature in response to the recently released National Toxicology Program (NTP) report, which according to the Sentinel, found "bisphenol A to be of some concern for fetuses and small children. It found that adults have almost nothing to worry about."

The article discusses conflicting conclusions by two different panels one convened by the NTP the other by National Institutes of Environmental Health and Safety) and NTP's recently released BPA report.

The Sentinel analyzed 258 studies, although a search of the links provided along with the article didn't lead to a list of those articles, nor the depth of their analysis, and who actually did the analysis, they do provide a graphic summarizing general conclusions of each study (found an effect, vs. did not find effect or were not looking); the dose range (low verses high); and the funding agency for each study (industry, nonindustry.)

If you want to read more about the scientific reports (those produced by government panels rather than the Sentinel), check out what J.Lowe has to say over at Impact Analysis in his blog about the "Tangled story of bisphenol A."

Cross posted from the earthportal forum

What's Emerging in your Water?

There is a nice review of Emerging Contaminants, recently published in the journal Analytical Chemistry, by Susan Richardson. In it is a review of the "oldies" like PFOA, PFOS, and polybrominated flame retardants and newbies like nanomaterials and ethylene dibromide or EDB, a gasoline additive from back in the day when gasoline was leaded.

In the excerpt below she discusses the term “Emerging,” a term over which I sometimes stumble. Which chemicals fit into the category of emerging contaminants? Why are some chemicals which have been around for decades suddenly appear as “emerging” and, why are others, which have yet to be detected in major quantities (like the category of nanomaterials – which describes a type of chemical rather than any one specific chemical) on the list?

“Emerging environmental contaminants were the focus of a recent issue of Environmental Science & Technology (December 1, 2006), where current research on emerging chemical and microbial contaminants was highlighted. This is a must-read issue, and several of those papers will be discussed in this review. The guest editors of this issue also published an excellent perspective on "What is emerging?" as a lead-off editorial to this issue, which points out that the longevity of a contaminant's "emerging" status is typically determined by whether the contaminant is persistent or has potentially harmful human or ecological effects (2). It is often the case that emerging contaminants have actually been present in the environment for some time (in some cases, decades), but they are discovered through a wider search of potential contaminants (as in the case of ethylene dibromide, in this current review) or through the use of new technologies (such as LC/MS) that have enabled their discovery and measurement in the environment for the first time (as in the case of many pharmaceuticals).”

Although a bit technical in spots (this is Analytical Chemistry afterall,) the current literature for each emerging contaminant is reviewed in a readable manner, and there is an impressive list of over 200 citations for those looking to learn more.