Wednesday, November 25, 2009

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.


Polly Palumbo, Ph.D. said...

It's great hearing an objective toxicologist's perspective on the current BPA controversey! I think it will be quite some time until we know this chemical's real risks. Like you I've grown tired of the mud-slinging over BPA too but am even more aggrieved by the crappy studies that snag the media attention. And as a psychologist I do worry about the fall-out should we ever learn BPA is relatively safe. Will write about your post this week.

Emily Monosson said...

Hi Polly, thanks for your comments. That was a difficult post to write - because I realize it's a touchy issue. That said, I had just returned from SETAC - the national env. tox. meeting - where I spoke to a couple of commonly cited scientists who in private suggested that yes - sometimes they'd rather work on what's really important, but sometimes the hot button issues are where the money is. I don't know about BPA one way or the other, but right now it is where the money is. Maybe that'll help sort out the question of toxicity.

Another issues is the funding structure. For toxicology, I think at least in the past, there tends to be more funds for directed, applied research, rather than basic. So if these hot button issues help researchers answer interesting basic research questions - then they'll be used that way (e.g. this is a big problem so we need more funds.) That's not a good thing, but sometimes a necessary thing for some researchers I think. It's too bad - it tends to turn science into a commodity - and once you're selling something - you open the door for some natural bias.

Hopefully I'm overly skeptical! But that seems to be the way funding works sometimes.

Polly Palumbo, Ph.D. said...

Emily, isn't that the truth about funding! It's true - someone recently asked me if there's a bias amongst researchers studying breastfeeding (i.e. do they all think BF is so much better than infant formula?) - but it's much the same issue, with lots of funding going towards it (and of the null bias in publishing).