SUBSCRIBE TO EHN'S MUST-READ DAILY NEWSLETTER: ABOVE THE FOLD
08 May
Toxics
Is 5G going to kill us all?
A new generation of superfast wireless internet is coming soon. But no one can say for sure if it’s safe.
Read the Full Article on
newrepublic.com
07 April
Toxics
Trump’s aggressive advocacy of malaria drug for treating coronavirus divides medical community
While Dr. Anthony Fauci has urged caution in using hydroxychloroquine, some doctors are prescribing it to patients who have the virus despite the fact it has never been tested for it.
Read the Full Article on
www.nytimes.com
20 March
Toxics
With minimal evidence, Trump asks FDA to study malaria drugs for coronavirus
The president cites “tremendous promise” for existing drugs, but their use against the new virus is unproven.
Read the Full Article on
www.nytimes.com
11 March
Toxics
F.D.A. halts overseas inspections of drugs and devices, citing coronavirus
The agency said the spread of the virus globally prompted its decision. It had already pulled back from China, but this move will also affect India, a major generics manufacturer.
Read the Full Article on
www.nytimes.com
11 March
Toxics
‘It’s just everywhere already': How delays in testing set back the US coronavirus response
A series of missed chances by the federal government to ensure more widespread testing came during the early days of the outbreak, when containment would have been easier.
Read the Full Article on
www.nytimes.com
10 March
Toxics
FDA, FTC warn companies selling fraudulent coronavirus covid-19 products
One warning letter went to the televangelist Jim Bakker's show, which hawks colloidal silver and was warned last week by the New York Attorney General's Office.
Read the Full Article on
www.washingtonpost.com
06 February
Toxics
Teens find a big loophole in the new flavored vaping ban
The policy allows mint, dessert and fruit flavors to continue to be sold in disposable e-cigarettes, prompting many teens to switch from Juul to those devices.
Read the Full Article on
www.nytimes.com
29 December 2019
Climate
Science under attack: How Trump is sidelining researchers and their work
In three years, the administration has diminished the role of science in policymaking while disrupting research projects nationwide. Experts say the effects could be felt for years.
Read the Full Article on
www.nytimes.com
26 November 2019
Toxics
How Juul hooked a generation on nicotine
The company planted the seeds of a public health crisis by marketing to millennials, who had low smoking rates, and it ignored evidence that teenagers were using its products.
Read the Full Article on
www.nytimes.com
21 November 2019
Toxics
Trump’s F.D.A. nominee sidesteps question about banning flavored vaping products
The nominee, Dr. Stephen M. Hahn, said the decision to restrict flavors would not be his, if confirmed, because it was already under final review by the White House.
Read the Full Article on
www.nytimes.com
15 November 2019
Originals
Exposed: How willful blindness keeps BPA on shelves and contaminating our bodies
We all are exposed daily to bisphenol-A (BPA) and other bisphenols – estrogen-like substances added to food can liners, paper receipts and plastic containers.
<p>
That exposure, according to research that regulators are willfully ignoring, is increasingly linked to harmful health impacts ranging from birth defects to cancer.
<br>
</p><p>
A year-long investigation by Environmental Health News finds that the U.S. Food and Drug Administration has stacked the deck against such findings from independent scientists studying BPA – as well as many compounds used in "BPA-free" products.
</p><p><br></p>
<p class="shortcode-media shortcode-media-youtube">
<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="85fa98eee47306784c9062e0b47ccdf2"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/XesQeH8YU88?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span>
<small class="image-media media-caption" placeholder="Add Photo Caption...">Exposed: The BPA Experiment</small>
<small class="image-media media-photo-credit" placeholder="Add Photo Credit...">
<a href="https://www.youtube.com/watch?v=XesQeH8YU88" target="_blank">www.youtube.com</a>
</small>
</p>
<p><br></p><p>
Hundreds of emails obtained via the Freedom of Information Act and dozens of interviews show that science is being perjured:
</p><ul class="ee-ul">
<li>FDA and industry scientists continue to use decades-old study methods that fail to detect effects known to be associated with BPA exposure; </li>
<li>Emails between federal employees suggest an effort to ignore evidence of harm; </li>
<li>Biased data interpretation methods by the FDA; </li>
<li>Sharp disagreement between the FDA regulators and health officials at the National Institutes of Health on the safety of BPA and what messages are relayed to the public. </li>
</ul><p>
Significantly, the FDA's maneuvering to keep BPA unregulated extends a similar "get out of jail free" card to thousands of other suspected hormone-altering compounds.
</p><script id="infogram_0_e9cd60bd-fe58-4634-b91c-668d293885aa" src="https://e.infogram.com/js/dist/embed.js?ywx" title="BPA swimming pool" type="text/javascript"></script><p>
"Their failure to use modern science in examining the risk of BPA and other bisphenols leaves the health of the American public at significant risk," said Pete Myers, founder and chief scientist at Environmental Health Sciences, which publishes Environmental Health News.
</p><p>
Environmental Health News is an award-winning nonpartisan organization dedicated to driving science into public discussion and policy. Read the four-part series below, as well as a comic strip interpretation of the investigation.
</p><p>
And follow the fallout from this investigation on Twitter at the hashtag: #ExposedBPA<br>
</p>
Part 1: Scientific stalemate over BPA impacts on our body
<img lazy-loadable="true" src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjA1MjE5NC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTU5OTA5NTYxOH0.Ivz0KshbkGrODGV5ZkbckIjh3p9QZkxpIh_FLPXck1E/img.jpg?width=980" id="7ccea" class="rm-shortcode" data-rm-shortcode-id="43234b09633b4d8c676febf605f3e369" data-rm-shortcode-name="rebelmouse-image" alt="Researcher pipets scientific sample" /><h3><a href="https://www.ehn.org/bpa-impact-on-human-health-2641134273.html" target="_blank">A scientific stalemate leaves our hormones and health at risk</a></h3><p>American industry, aided by federal regulators, is conducting a large-scale, consequential experiment with our hormones and the developing brains and reproductive systems of our children.</p><p><br></p>Part 2: BPA explained, as a mini graphic novella
<img lazy-loadable="true" src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjA0OTg2OS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY0NjkyMTM5OH0.nAw3cqo3-nBsYEFUSV5zD2VWyN9EUH-mR3fxvqyHCRc/img.jpg?width=980" id="b0f94" class="rm-shortcode" data-rm-shortcode-id="8bdcff5eac60d6b02a564bba0ef56a99" data-rm-shortcode-name="rebelmouse-image" /><hr><h3><a href="https://www.ehn.org/bpa-chemical-comic-2640636344.html" target="_blank">Clouded in Clarity: A comic on chemicals & controversy</a></h3><p> The ongoing health concerns and mixed messaging over the chemical BPA<br> </p><p><br></p>Part 3: BPA research honesty
<img lazy-loadable="true" src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjA0OTg0NC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYxNTQ1MDg5OX0.uiPUmnwlyJu0PZ_RZpSAopIWd3C7mzer5O0DacPs1oQ/img.jpg?width=980" id="272f1" class="rm-shortcode" data-rm-shortcode-id="5f4b9868b86f84a3e126f0ff79059f46" data-rm-shortcode-name="rebelmouse-image" /><h3><a href="https://www.ehn.org/bpa-science-fda-safe-2641150483.html" target="_blank">On the edge of research honesty</a></h3><p>Is a federal study of BPA contaminated by questionable motives, methods?</p><p><br></p>Part 4: Federal BPA standards decades past their expiration date
<img lazy-loadable="true" src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjA0OTg0Mi9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYyMTYyNzYzNX0.UGBDSFJWrEDY3Flz9fCy4BLvZiKU_y7VBI4hGTgGbHA/img.jpg?width=980" id="93016" class="rm-shortcode" data-rm-shortcode-id="b7e6c887f8828939c710593f164282e1" data-rm-shortcode-name="rebelmouse-image" /><h3><a href="https://www.ehn.org/bpa-science-health-2641150585.html" target="_blank">Deciphering the real message about BPA</a></h3><p>"The government keeps testing chemicals for safety using the same old approaches developed 50 years ago"</p><p><br></p>Part 5: A BPA-free future
<img lazy-loadable="true" src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjA0OTg0MC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTU5OTA1MTg4NH0.sIAvLclpYpcE4STFkTdraz-2q1yjorjdhZzT4iDtMog/img.jpg?width=980" id="f5682" class="rm-shortcode" data-rm-shortcode-id="e64d74c296132a73dd441311c4f21585" data-rm-shortcode-name="rebelmouse-image" /><h3><a href="https://www.ehn.org/bpa-substitutions-solutions-2641150667.html" target="_blank">Toward a BPA-free future</a></h3><p>What will it take to rid our store shelves of BPA and its equally hazardous cousins?</p><p><br></p>Follow up BPA coverage
<img lazy-loadable="true" src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjEzNjAyNi9vcmlnaW4ucG5nIiwiZXhwaXJlc19hdCI6MTY1MjkxMTc5N30.w2GjVqF8hnA1YTtfguSfj2bhIaCHt1i6jStEfdu467c/img.png?width=980" id="8975e" class="rm-shortcode" data-rm-shortcode-id="b65a9ea3205de483c50c120e5efd8b4a" data-rm-shortcode-name="rebelmouse-image" /><h3><a href="https://www.ehn.org/how-much-bpa-in-our-bodies-2641524955.html" target="_blank">Federal tests 'dramatically' undercount BPA and other chemical exposures</a></h3><p>Researchers say federal agencies use highly inaccurate tests to estimate exposure to BPA—findings that extend to multiple other harmful chemicals that get into our bodies</p><p><br></p><img lazy-loadable="true" src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjc3Njg0Mi9vcmlnaW4ucG5nIiwiZXhwaXJlc19hdCI6MTYxODgxMzEwMn0.VRRhwoim8SRANcZ8TnLVnSC-jGvHw4rwu-oN4dTfxfs/img.png?width=980" id="3ff4f" class="rm-shortcode" data-rm-shortcode-id="07514521698dcb084f271bac24d84774" data-rm-shortcode-name="rebelmouse-image" /><h3><a href="https://www.ehn.org/bpa-health-effects-policy-2645127783.html" target="_blank">FDA under scrutiny: Policymakers, advocates push for stronger science, regulation of the chemical BPA</a></h3><p>"The mindless clinging to outdated science is detrimental to public health and to the development of good science"</p><p><br></p>
<img lazy-loadable="true" src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjg4Mjc3MS9vcmlnaW4ucG5nIiwiZXhwaXJlc19hdCI6MTY1MTQ4OTc3MH0.qJzcpOahEIDMNZu4ZZyytTzDK3EqUcfdhOmR93qFp3w/img.png?width=980" id="f0629" class="rm-shortcode" data-rm-shortcode-id="a679608e38fe9c33961063db38904160" data-rm-shortcode-name="rebelmouse-image" alt="BPA and babies" /><h3><a href="https://www.ehn.org/is-bpa-free-plastic-safe-2645509688.html" target="_blank">BPA and babies: Controversial chemical and substitutes pollute the womb</a></h3><p>Babies are being exposed to "totally unacceptable concentrations"</p>
Keep reading...
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BPA testing in the lab of Cheryl Rosenfeld, a University of Missouri researcher. (Credit: Cheryl Rosenfeld)
15 November 2019
Originals
Exposed: A scientific stalemate leaves our hormones and health at risk
This is part 1 of a 4-part investigation of the science surrounding the chemical BPA and the U.S. regulatory push to discredit independent evidence of harm while favoring pro-industry science despite significant shortcomings.
<p>
SEATTLE — Bisphenol A is likely coursing through your body right now. Every day, you're inadvertently consuming and absorbing trace amounts as it migrates from can and bottle linings into your food and drink, and from thermal paper receipts onto your skin.
</p><p>
Scientists have found BPA in more than
<a href="https://www.cdc.gov/exposurereport/pdf/FourthReport_ExecutiveSummary.pdf" target="_blank">90 percent of Americans tested.</a> Yet whether exposures to such small amounts of the common chemical pose any real health hazard remains highly controversial. On one side of a deep rift are academics who are adamant about the adverse effects; on the other side are U.S. Food and Drug Administration scientists who declare there are no dangers. Only one side has any control over what actually makes its way into your body.
</p><p>
"This is a chasm that is not going to be breached," Daniel Doerge, a biochemical toxicologist with the FDA for nearly 30 years, said during a panel at the European Food Safety Authority (EFSA) conference in Parma, Italy, last September.
</p><p>
<span></span>Doerge and other federal scientists were attending the conference to share details of an unprecedented multimillion-dollar project co-led by the FDA, the Consortium Linking Academic and Regulatory Insights on BPA Toxicity, or Clarity for short. The effort aims to settle the long-standing dispute between government and academic scientists over the health effects of BPA.
</p><p>
Yet Doerge's words did not indicate any hope for such a reconciliation. He wore a green polo shirt, dark glasses and a grey mustache. And he exuded frustration — if not also a bit of arrogance — as he spoke. "Tribal dynamics," he said, are at play among the academics. Doerge alleged they were creating their "own narrative," and "staying in a bubble that turns into an echo chamber."
<a target="_blank"></a>
</p><p>
The struggle has been fermenting below the surface for years: Academics with modern methods and a sophisticated understanding of human physiology versus government and industry scientists who lean on decades-old established science in their evaluation of industrial chemicals.
The suite of traditional toxicology tests recommended by the FDA for assessing a chemical's health risks hasn't been meaningfully updated since the early 1980s, before Doerge took his job and well before scientists began to understand how minuscule concentrations of certain chemicals common in consumer products, such as BPA, could mimic and mess with hormones in the body.
</p><p>
Scientists have long known that a tiny change in a natural hormone concentration — the equivalent of one drop of water in 20 Olympic-sized swimming pools — is enough to trigger instructions via the human endocrine system that impact growth, metabolism, sleep, reproduction and other critical functions of the body.
</p><h3><em>Related: See our comic strip version of this story, <a href="https://www.ehn.org/bpa-chemical-comic-2640636344.html" target="_blank">"Clouded in Clarity"</a> </em></h3><p>
BPA is just the tip of the iceberg. Tens of thousands of manufactured chemicals are on the market; hundreds are believed to be endocrine disruptors — capable of scrambling hormone signals and, therefore, raising risks of health problems such as cancer, diabetes, obesity, infertility and behavioral problems. Other pervasive hormone imposters include phthalates, which are found in plastic food containers and personal care products, and per- and polyfluoroalkyl substances (PFAS), which are added to nonstick cookware and other goods to repel oil and water. Also on the list are flame retardants and pesticides such as DDT, glyphosate and chlorpyrifos. Even bisphenol S and dozens of other BPA replacements have been found to tinker with hormones.
</p><p>
Yet the FDA has remained reluctant to accept new science and independent evidence of harm. While the agency clings to the claim that BPA poses no health risks in the amounts it is used, thousands of peer-reviewed studies from academics suggest otherwise: Absorbing or ingesting the ubiquitous chemical may harm people at doses
<a href="https://www.nature.com/articles/s41574-019-0173-y" target="_blank">20,000 times lower</a> than what the FDA says is safe, comparable to levels at which most of us are exposed.
</p><p> <a href="https://onlinelibrary.wiley.com/doi/full/10.1111/1541-4337.12020" target="_blank">Even back in 1982</a>, a scientific committee established by the FDA had warned of the potential for very low concentrations of chemicals to bind to hormone receptors and that technology in the future might find this interference alters the endocrine system's influential messages. The agency continues to miss opportunities to keep pace with scientific developments, noted Maricel Maffini, an independent consultant based in Germantown, Maryland. Instead, she told EHN, they primarily rely on tests devised decades ago that aren't designed to detect some significant effects that chemicals can have on our health.</p><p>
If we followed the academics' science, BPA and its close relatives would effectively have to be banned, not reduced, in order to protect our health. "Really, if you look at the data, we shouldn't be making these compounds, period," Terrence Collins, a green chemist at Carnegie Mellon University, told EHN.
</p><script id="infogram_0_70001ab2-47e4-4ac0-bb95-1aa6f386eba7" src="https://e.infogram.com/js/dist/embed.js?sa3" title="BPA in people" type="text/javascript"></script><p>
An investigation by EHN has uncovered a pattern of dissonance between academic scientists and federal agencies, as well as between the agencies themselves, regarding the evaluation and regulation of BPA and other endocrine disruptors. No one smoking gun surfaced. Yet putting together all the pieces creates a persuasive picture of willful blindness. Based on hundreds of emails obtained via Freedom of Information Act requests — along with dozens of studies and reports, and more than 50 conversations with scientists, regulators and other stakeholders — evidence suggests that regulators may be operating at the fringes of scientific integrity, possibly with the intent to keep the current testing and regulatory regime intact and to avoid scrutiny. EHN's findings include:
</p><p>
●Insistence by the FDA on a study design that limited Clarity's robustness to reveal health effects, including the use of a strain of animal that had been shown to be insensitive to hormone disruptors, the choice of a stressful means to deliver BPA to the animals, and the allocation of small numbers of animals provided to some of the participating academic scientists.
</p><p>
●Potential BPA contamination of the control animals, which may have further masked true differences in health effects between control animals and animals receiving administered doses of BPA.
</p><p>
●Statistical approaches in the government's side of Clarity, a traditional regulatory toxicology study dubbed the Core Study, that set a high bar to detect differences and disregarded patterns in the data that did not fit outdated assumptions on the relationship between a dose of an endocrine-disrupting chemical and its health effects.
</p><p>
●Framing of the government's Clarity Core Study draft report and corresponding press release that downplayed the health effects that did emerge in the data.
</p><p>
●Hints of potential industry influence, such as the FDA's reliance on industry-funded studies.
</p><p>
Clarity, the intended remedy for the government-academics impasse, was launched in 2012 by the FDA, the National Institute of Environmental Health Sciences (NIEHS) and the National Toxicology Program (NTP). The effort combines a traditional regulatory toxicology study from the government and investigational studies from academics.
</p><p>
The FDA took the lead on raising and treating the study animals and on performing the Core Study, which was published under the auspices of the NTP. The NIEHS awarded grants to participating academics and worked with the NTP to coordinate the study. The government and most of the 14 participating academic scientists completed their respective studies for the collaborative project in the months preceding the September 2018 EFSA conference in Italy.
</p><p>
Everyone used the same breed of lab rats, and followed government-approved standards as they investigated possible health impacts. To prevent bias, all Clarity scientists were blinded to the BPA exposure levels of the animals and tissues that they received for study.
</p><p>
Earlier in the Italy meeting, Doerge and his federal colleagues presented the government's Core Study. Once again, they relayed results that they said generally absolved BPA. They did not discuss findings from the participating academics. In fact, during the panel, Doerge seems to dismiss those studies, many of which challenged BPA's safety. "I don't see a lot of advantages in, so far anyway, in what the extramural research funding initiative has brought into the Clarity project," he said. (The FDA did not make Doerge available for an interview.)
</p><p>
Sitting in the audience in Italy was Heather Patisaul, a biologist at North Carolina State University and one of the academics participating in the massive BPA study. "I was screaming in my chair," she told EHN. "He said it so smugly."
</p><p class="shortcode-media shortcode-media-youtube">
<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="a24c35869388e755885c7ea484e21d90"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/gwEGnZqV398?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span>
</p><p>
An integrated report that pulls all of the Clarity studies together is underway, co-authored by the FDA and other participants. John Bucher, a senior scientist with NTP and NIEHS, told EHN that he expects the report to be completed by the end of this year. It will then be up to the FDA whether or not those results will spur any reshaping of U.S. regulations.
<br>
</p><p>
Several of the academic scientists are concurrently working on their own independent review of the Clarity data. Cheryl Rosenfeld, a biologist at the University of Missouri and another Clarity investigator, is among the co-authors on that report. "Many of us are not happy with the FDA," she told EHN, adding that she and others are skeptical of what will end up in the official integrated report and if it will have any impact on policy.
</p><p>
In the U.S., what the government considers a safe exposure level for BPA — 50 micrograms of BPA per day per kilogram of body weight — has remained untouched for more than 30 years, leaving us all exposed daily to the chemical. Meanwhile, other countries represented at the EFSA meeting have begun reaching agreements and acting on BPA.
</p><p>
France has enacted the strictest regulations, banning the use of the chemical in all food and beverage packaging and utensils after an assessment by the French Agency for Food, Environmental Health and Safety determined that it is hazardous at much lower doses than the FDA considers hazardous. A Danish Food Institute Clarity-like study, too, recognized effects at low doses.
</p><p>
Many more countries are keeping a close eye on Clarity. EFSA, which is funded by the European Union to conduct risk assessment but not to create policy, told EHN that it will consider the results as part of its ongoing evaluation of BPA. In January 2015, based on the latest information,
<a href="https://www.efsa.europa.eu/en/topics/topic/bisphenol" target="_blank">EFSA dropped its safety limit</a> from 50 to 4 micrograms of BPA per day per kilogram of body weight.
</p><p>
The scientific, economic and political stakes are high. For decades, modern commerce across the Western world has depended on BPA. The chemical is used in the production of goods that pervade our lives: reusable water bottles, food containers, canned goods, store receipts, medical devices and dental sealants. And despite growing concerns, the manufacturing of BPA remains on the rise. The global BPA market is increasing about 3 percent per year, and is projected to reach
<a href="https://www.prnewswire.com/news-releases/global-bisphenol-a-market-overview-2016-2022---market-is-projected-to-reach-us225-billion-by-2022-up-from-156-billion-in-2016---research-and-markets-300303934.html" target="_blank">$22.5 billion by 2022</a> and top <a href="https://www.prnewswire.com/news-releases/global-bisphenol-a-market-report-2018-analysis-2013-2017--forecasts-2018-2023-300757673.html" target="_blank">7 million tons by the end of 2023</a>.
</p><p>
"BPA is very cheap to make," said Collins. "I believe the regulatory bodies of the country are locked up by the monetary implications of addressing endocrine disruption."
</p><p>
While the clash continues over how endocrine-disrupting chemicals are tested and thereby regulated, irreversible changes to our bodies and health may be happening now. Collins pointed to declining sperm counts and rising rates of endometriosis, which he suggested could be a consequence of these exposures given that the chemicals have been shown to induce such effects in animals.
</p>
<img lazy-loadable="true" src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjA0ODY5My9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYyODc2NTMyMn0.EraYLqYJztPgD3vzRlwekEfIhrwsKAvFG4ZmHHgTHSM/img.jpg?width=980" id="737be" class="rm-shortcode" data-rm-shortcode-id="ce82f09f7fb4ee1f378901138d585268" data-rm-shortcode-name="rebelmouse-image" />
University of Massachusetts-Amherst environmental health scientist Laura Vandenberg. (Credit: Umass.edu)
<p>"Endocrine disruptors are harming people and we're not regulating them to any extent right now," Carol Kwiatkowski, executive director of The Endocrine Disruption Exchange, a nonprofit research institute that advocates against the production and use of chemicals that interfere with healthy hormone function, told EHN. </p><p>"A lot of endocrine scientists have been banging their heads against that wall for a long time and haven't made any progress in changing the risk assessment process."</p><p>It is clear that the FDA is not using modern science in protecting the public from potentially toxic chemicals. It is also clear that BPA and other endocrine disruptors threaten to disrupt the status quo of toxic chemical regulation. "BPA creates a tipping point," Laura Vandenberg, an environmental health researcher at the University of Massachusetts-Amherst's School of Public Health, told EHN. "If the FDA finds out that they have been wrong about BPA — or wrong about how they evaluate chemicals for safety — that means they are wrong about the 10,000 other chemicals behind BPA in line for the same sort of evaluation."</p><p>Vandenberg, who is not involved in Clarity, is among scientists skeptical that the groundbreaking effort will result in a fair assessment of BPA. The FDA, she said, has "a vested interest in not being wrong."</p>Imposter's poster child
<p>In the 1930s, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2774166/" target="_blank">a British medical researcher discovered</a> that BPA could mimic the activity of estrogen — a female sex hormone — in the human body. The chemical was briefly considered for use as a pharmacological hormone but ultimately lost to another synthetic estrogen, diethylstilbestrol (DES). While DES was prescribed to millions of pregnant women over the next 30 years before its own health risks became known, BPA was never turned into a drug.</p><p>Its future would instead be in the chemical industry.</p><img lazy-loadable="true" src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjA0OTM1Ni9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY0NzkzOTgxMn0.1KqYsYVqvirkVAgTKCib2xW8FKUxsspgcOaAsNwIMuk/img.jpg?width=980" id="e83a5" class="rm-shortcode" data-rm-shortcode-id="1c60970321514da5b79b06bd7666f583" data-rm-shortcode-name="rebelmouse-image" />
Cheryl Rosenfeld, a biologist at the University of Missouri and another Clarity investigator. (Credit: University of Missouri)
<p>Beginning in the 1950s, BPA became a key ingredient in polycarbonate plastic and epoxy resins — finding its way into everything from Tupperware to the lining of food cans. "That's where the problem starts," Ana Soto, an endocrinologist at Tufts University and another Clarity investigator, told EHN.</p><p>The FDA officially approved BPA for use in food and beverage containers in 1963. They classified it as a "generally regarded as safe" (GRAS) compound, since it had already been around for a few years and there was no obvious evidence of harm. By the late 1980s, the U.S was producing nearly a billion pounds of BPA a year. Even scientific laboratories began working with BPA-laden instruments. In 1993, endocrinologists at Stanford University discovered that BPA was leaching from polycarbonate flasks in their laboratory.</p><p>The first published studies to raise concern about BPA's low-dose health effects came a few years later, in 1997. Frederick vom Saal and his colleagues had found exposure to tiny amounts of BPA altered the prostates and reproductive systems of laboratory mice. Vom Saal, a professor of biology at the University of Missouri-Columbia and another Clarity investigator, warned viewers in a February 1998 episode of <a href="https://www.pbs.org/wgbh/pages/frontline/shows/nature/interviews/vomsaal.html" target="_blank">PBS's Frontline about the threat posed by endocrine-disrupting chemicals</a> used in plastics and other consumer products.</p><p>"We understand now, with new techniques, that, in fact, cells are extremely responsive to these chemicals," vom Saal stated on the show. "What you have now is clearly enough scientific information to warrant concern and a change in the regulatory approach to these chemicals." Concern grew, as did the body of research.</p><p><a href="https://ntp.niehs.nih.gov/ntp/ohat/bisphenol/bisphenol.pdf" target="_blank">By 2008</a>, enough evidence had accumulated that the NTP labeled the chemical as possibly harmful for babies. Canada responded by declaring BPA toxic and manufacturers across North America, including baby bottle and sippy cup makers, started phasing it out of their products. Wal-Mart, REI, Lululemon, Toys-R-Us and other retailers, too, began pulling products with BPA off their shelves. The market was soon flooded with BPA-free products — although most of the substitutes that landed in stores share similar chemistry with BPA and pose similar health concerns.</p><p>"The science is growing exponentially. We can't keep up with it," said Kwiatkowski, of The Endocrine Disruption Exchange. "And we have to take it all very seriously, because the preponderance of endocrine-related disorders in humans today is just skyrocketing."</p><p>Pregnant women, infants and young children face the greatest risks, as a healthy functioning endocrine system is especially critical during development. "If you perturb it, it is not going to be reversible," Linda Birnbaum, former director of the NIEHS and the NTP, told EHN. "Whatever happens, it is done."<br></p><p>
In-utero BPA exposure, for example, may derail the normal growth of the brain and other organs and manifest later in life as early puberty or
<a href="https://www.ehn.org/does-bpa-cause-hyperactivity-adhd-2543584567.html" target="_blank" rel="noopener noreferrer">an increase in anxiety-related behaviors or attention deficit hyperactivity disorder (ADHD)</a>.
</p><p>
And, again, BPA is just one of many chemical threats to our hormones. We are exposed daily to a cocktail of stuff suspected of altering our endocrine system. "When we talk about endocrine-disrupting chemicals, it might be that the real story is in the mixture," Chris Gennings, the director of biostatistics and an environmental medicine researcher at the Icahn School of Medicine at Mount Sinai in New York, told EHN. While the level of exposure to any single chemical might not surpass a safety threshold, she explained, "if you put all of them together, then the mixture can reach a level of concern."
</p><p>
It is not only the potential health consequences that are leading many scientists to urge a more substantial overhaul of the testing and oversight of endocrine-disrupting chemicals. There are economic concerns: In 2014, researchers conservatively estimated that just the cases of childhood obesity and adult heart disease attributable to BPA cost the U.S. $3 billion annually. <a href="https://www.ncbi.nlm.nih.gov/pubmed/27765541" target="_blank">A 2016 study</a> that considered a few endocrine-disrupting chemicals and a few specific diseases calculated an annual $340 billion in U.S. health costs and lost wages — or about 2.3 percent of the GDP. (Editor's note: Pete Myers, CEO and chief scientist of Environmental Health Sciences, was a co-author on the paper. He is also the founder of EHN, though the publication is editorially independent.)
</p><p>
"This is an underestimate of an underestimate of an underestimate," Dr. Leonardo Trasande, a researcher at New York University, author of the book,
<em>Sicker, Fatter, Poorer</em>, and an author on both studies, told EHN.
</p><p>
Trasande noted his initial hope that Clarity would result in "progress toward a consensus" on methods to evaluate BPA. But the FDA, he said, "has taken the approach that its science and its mindset are superior to that which has been published in peer-reviewed scientific literature."
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Maurice Whelan, head of the Chemical Safety and Alternative Methods Unit of the Directorate for Health, Consumers and Reference Materials of the European Commission's Joint Research Center, shared similar thoughts while sitting next Doerge on the panel in Italy. Clarity was "institutionally biased," he said, with "the science strategy dictated" and a "very clear mindset about how to go about this."
</p>
Recipe for a poison
<p> Core to the discord is a historical assumption about toxic chemicals. Nearly 500 years ago, Swiss physician and chemist Paracelsus coined an adage that would become a basic principle of toxicology: "The dose makes the poison." In other words, the higher the concentration of a toxic chemical, the more toxic it is. </p><p> The FDA generally assumes this increasing-dose-increasing-harm relationship in its evaluation of chemicals that come into contact with food, whether directly or indirectly through production, processing, packaging and distribution. A dose-response curve should therefore always be monotonic, according to the agency, meaning it will never change direction from positive to negative, or vice versa. </p><p> As a result, when the agency deems a dose of a chemical safe, their investigation has not necessarily tested health effects at that dose — or at any lower doses. Rather, industry and government scientists typically follow an efficient, seemingly common-sense method. They start by exposing lab animals to extremely high doses of the chemical, incrementally drop the doses until they no longer detect obvious harm, then cut that last number down by a margin of safety to create a conservatively "safe" exposure limit. </p><p> Endocrinologists, on the other hand, expect craziness in their data. At least for hormone-mimicking chemicals, a relatively high dose might prove innocuous while a far lower dose wreaks havoc on the body. And they've observed that different doses can cause different effects. Such a non-monotonic dose-response curve might take the shape of a "U" or a bell. Take, for example, a 1997 paper co-authored by vom Saal. At 200 nanograms of DES per gram of body weight per day, the prostates of the mice in his study were significantly smaller than prostates in the control mice and prostates in mice receiving other doses. </p><p> At a mid-range of 20 nanograms of DES, no effect was seen. And that, under traditional toxicology, is where regulators would stop testing. But drop the dose further, to 2.0, 0.2 and 0.02 nanograms, and vom Saal found prostates were significantly larger than prostates in all of the other animals. The <a href="https://www.pnas.org/content/pnas/94/5/2056.full.pdf" target="_blank">resulting dose-response relationship</a> resembled a bell.</p><p>"What we've learned from literally tens of thousands of papers, is that endocrine activity is stimulated by very tiny quantities of endocrine hormones," said Collins, the green chemist. "If you raise the concentrations, you turn the effect off."</p><script id="infogram_0_8abe54eb-d6e4-4710-8b53-ac271ec9cb4d" title="Pull quote" src="https://e.infogram.com/js/dist/embed.js?zGP" type="text/javascript"></script><p> His guess as to why: "Nature has decided it doesn't want to have an overreaction to an endocrine hormone." </p><p> Birnbaum compared the phenomenon to the body's response to vitamins and minerals, where "too little is a problem and too much is a problem." And <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4429934/" target="_blank" rel="noopener noreferrer">scientists have identified</a> potential biological mechanisms for non-monotonic dose-responses, such as opposing effects from multiple hormone receptors. </p><p> Still, others push back on the notion of non-monotonicity. "It's illogical. It flies in the face of every mechanism we know in science," Patrick McKnight, a measurement scientist at George Mason University in Fairfax, Virginia, told EHN. "In toxicology you really have to demonstrate that there's an effect of some sort, and I think a lot of these investigators are searching for these effects." (McKnight is on the advisory board at Sense About Science USA, formerly the Statistical Assessment Service, which has industry ties and a record of downplaying the dangers of products.) </p><p> Steven G. Hentges, senior director of the Polycarbonate/BPA Global Group at the American Chemistry Council, an industry trade group, stated that "experimental evidence" to support non-monotonic dose-response has been "limited." He pointed to a recent European review that supported that view. Of 179 datasets evaluated in the paper, the authors concluded that only 10 met criteria for a non-monotonic dose response. They acknowledged difficulty in identifying relevant studies and applied strict rules for inclusion in the review, including a requirement that studies include at least five dose groups. This is rare. Even guidelines for traditional regulatory toxicology studies recommend just three dose groups.</p><p> The FDA, meanwhile, has stuck to its guns, repeatedly dismissing data on low-dose effects or non-monotonicity. Marianna Naum, an FDA spokesperson, told EHN in an email that the FDA and other federal agencies have determined that non-monotonicity "is not often found in toxicology of the endocrine system," and that "current regulatory testing methods are sufficient" to pick it up. (EHN tried for months through multiple emails and phone calls to arrange a phone interview with someone at the FDA. The agency repeatedly ignored and denied those requests.) </p><p> The agency also has a history of brushing off study results because they did not fit its strict study criteria adopted in the 1980s to calculate doses of chemicals that are expected to be safe for humans. These traditional "guideline" studies, as they are called, follow validated "good laboratory practice" (or GLP) protocols. Together, the rigorous study guidelines and lab rules dictate the number and type of animal used, levels of exposure to the chemical of interest, the outcomes to evaluate and record-keeping methods, among other details. And these studies remain the evidence preferred by the FDA, because they "provide risk assessors and risk managers with reproducible results upon which science-based decisions and policy may be based," Naum stated in the email.</p><img lazy-loadable="true" src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjA0ODY0NS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY0OTU2MjkwMH0.R4rjJFhetnhAYNZwgIeVoOXPDkDHG1hnH0OiNhIiYf0/img.jpg?width=980" id="102d2" class="rm-shortcode" data-rm-shortcode-id="8408f6a25ff7407d4b8dfafcd825c6f0" data-rm-shortcode-name="rebelmouse-image" />
Researchers Fred vom Saal and Wade Welshons at their University of Missouri lab. (Credit: Brian Bienkowski)
<p> Jennifer Sass, a senior scientist with the Natural Resources Defense Council, said that the guidelines are "a good starting point to see if there's evidence of harm," and "allow regulators from Japan to Sweden to North Africa to look at data the same way." However, she added, these guidelines "should not be used to eliminate evidence of harm." </p><p> Such standardized studies can also be pricey to conduct, often beyond the budgets of academics. And the FDA's traditional targets for tests, such as weighing organs and looking for other overt signs of toxicity, generally do not consider the unique effects of endocrine-disrupting chemicals — some of which can be subtle such as behavioral changes or infertility years down the road. </p><p> "You can't weigh a brain to find out what is going on in there," Soto said. </p><p> In 2001, the <a href="https://ntp.niehs.nih.gov/ntp/pressctr/mtgs_wkshps/2000/lowdosepeerfinalrpt.pdf" target="_blank">NTP appeared to agree</a>. They concluded in a report that published studies had provided evidence for the effects of BPA exposure at or below the safety standard set by the FDA. And they recommended a reconsideration of the current testing paradigm. </p><iframe src="https://e.infogram.com/e9cd60bd-fe58-4634-b91c-668d293885aa?src=embed" title="BPA swimming pool" width="700" height="273" scrolling="no" frameborder="0" style="border:none;" allowfullscreen="allowfullscreen"></iframe><p> The plastics industry pushed back, funding the Harvard Center for Risk Analysis, a group that had received financial support from chemical companies in the past, to do a separate review of the literature on BPA. That assessment determined that only two large studies—both funded by industry—were relevant and reliable enough to consider. Both studies would go on to make regular appearances in subsequent FDA reports. </p><p> Doerge was a co-author on FDA's most recent safety assessment of BPA, released in 2014, which reaffirmed its position that the chemical is safe at levels of exposure from food contact uses. "No new information was identified to suggest revision of the existing safety assessment level," <a href="https://www.fda.gov/media/90582/download" target="_blank"> wrote the authors</a>. </p><p> The report was an update of the agency's <a href="http://docplayer.net/102806848-Scientific-peer-review-of-the-draft-assessment-of-bisphenol-a-for-use-in-food-contact-applications.html" target="_blank">2008 assessment</a>, for which the FDA relied heavily on the same two industry-funded guideline studies considered in the Harvard group's analysis and discarded hundreds of non-GLP studies published by academics that nonetheless found low-dose effects of BPA. </p><p> An external <a href="https://www.researchgate.net/publication/237734993_Scientific_peer-review_of_the_draft_assessment_of_bisphenol_A_for_use_in_food_contact_applications" target="_blank">FDA committee had even reviewed the 2008 report and disagreed</a> with the agency's decision to exclude those other peer-reviewed papers. "The draft FDA report does not articulate reasonable and appropriate scientific support for the criteria applied to select data for use in the assessment," they wrote. "Specifically, the Subcommittee does not agree that the large number of non-GLP studies should be excluded from use in the safety assessment." </p><iframe src="https://e.infogram.com/f013adea-774f-4e13-86e8-8408f9cdcd61?src=embed" title="Annual health costs" width="700" height="676" scrolling="no" frameborder="0" style="border:none;" allowfullscreen="allowfullscreen"></iframe><p> Of note: A <a href="https://www.ncbi.nlm.nih.gov/pubmed/16256977" target="_blank">2006 analysis</a> found that 11 out of 11 industry-funded studies found BPA had no significant action, while 109 of 119 studies that had no industry funding did find effects of BPA. </p><p> Yet those industry-funded studies tend to use more expensive GLP protocols and qualify as guideline studies. "The non-guideline studies are basically ignored. To me, that's like wearing blinders," said Birnbaum. "Science has continued to advance, and I think there are questions that we really didn't know about 30, 40, 50 years back that people are asking today." </p><p> "If you don't ask the question, you're not going to get the answer," she added. </p><p> Jerry Heindel, the health scientist administrator at the National Institute for Environmental Health Sciences (NIEHS) when Clarity was initiated, agreed. "Maybe these guideline studies aren't as gold standard and terrific as people have thought," he told EHN. "Problem is, the endpoints are so simplistic and old-fashioned." </p><p> But he and other scientists also acknowledge that the FDA has an extremely high bar to justify adoption of new approaches, let alone bans on a chemical. Regulatory agencies are in a tight spot and have to first ensure they can't be sued, added Heindel, who retired from NIEHS in 2016 and founded Commonweal's Healthy Environment and Endocrine Disruptor Strategy (HEEDS), a hub for scientists working on endocrine disruptors. "If they come out and say a chemical is toxic and we need to ban it," he said, "then they have to feel confident they have the data that will stand up in the court of law." </p>Deepened divide
<img lazy-loadable="true" src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjA0ODU5NC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYyNDQ0MDU0Mn0.khmBkEbxU5QMefYsIoFB56pO1nQ8T_PFtxd1YOJ2bdU/img.jpg?width=980" id="8f5c4" class="rm-shortcode" data-rm-shortcode-id="33edf4dd8bc3fc4a517710831108edeb" data-rm-shortcode-name="rebelmouse-image" />Gail Prins, a researcher at the University of Illinois at Chicago and Clarity investigator (right). (Credit: uic.edu)
<p> On February 23, 2018, upon completion of the draft version of the government's Clarity Core Study, <a href="https://www.fda.gov/news-events/press-announcements/statement-stephen-ostroff-md-deputy-commissioner-foods-and-veterinary-medicine-national-toxicology" target="_blank" rel="noopener noreferrer">the FDA released a public statement</a>, suggesting that the findings supported its position that "currently authorized uses of BPA continue to be safe for consumers." </p><p> The move stirred significant press, mostly reassurances to the public of the chemical's safety; FDA's collaborators were not pleased. Some suggested that the very agency responsible for ensuring our safety is actively working to avoid dealing with a massive experiment that is disrupting our hormones from birth. </p><p> "I smell a big fat rat here," Gail Prins, a researcher at the University of Illinois at Chicago and Clarity investigator, wrote in an email to Nigel Walker of NIEHS after learning of the statement. "The FDA is not playing fair." </p><p> Walker, a toxicologist who helped lead Clarity, responded by sending a scathing email to officials at the FDA. Members of that agency's upper management, he wrote, were "reneging on their own values in regulatory science," and "using the Clarity core study as a quasi-definitive human risk assessment document to affirm the current FDA policy on safety of BPA." In additional emails obtained by EHN, Walker went on over subsequent days to write of FDA officials' "shenanigans," calling their actions "disingenuous" and "disrespectful." He referred to himself as "peeved." </p><p> He also made a point to state that he had no conflicts of interest himself: "I don't have a horse in this race," wrote Walker. </p><p> The FDA declined to comment on the statement, or on the subsequent criticisms from collaborators. A culture clash of sorts continues between the FDA and NIEHS. Multiple scientists with the latter agency shared similar sentiments about the FDA's conduct in Clarity. Walker declined a phone interview but stated in an email to EHN that "there may from time to time be disagreements on various issues or topics." </p><p> Birnbaum said that while she was not surprised by the FDA's conclusions from the government's portion of Clarity — it was, after all, consistent with their historic stance on the chemical's safety — she did not share their opinion. "I think we reserve the right to disagree, respectfully," she said. And Bucher of the NIEHS and NTP offered his take: "The FDA conclusions are the FDA's view of how they look at data from these kinds of studies... To us, it would be more valuable to try to integrate this information and then come up with statements as to interpretations." </p><p> In September 2018, the government released the final version of its Core Study report. The FDA also advertised and hosted a webinar to detail their findings, which was preempted by outside academics who held their own webinar to present contrasting conclusions. The academic webinar was organized and moderated by Myers of Environmental Health Sciences.</p>Webinar: CLARITY-BPA: Achieving clarity on low dose effects of bisphenol A
<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="45e4d88777bd7a42be7214f9b244c404"><iframe lazy-loadable="true" src="https://www.youtube.com/embed/Dkiefk-hGps?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span><p>As expected, the <a href="https://www.ehn.org/bpa-harmful-at-low-levels-2604683710.html" target="_self">government's report stated that exposing rodents to BPA resulted in some health effects at high doses but not at the low doses</a> to which people are generally exposed. <br></p><p>Hentges, of the ACC, praised the report. "The scope and magnitude of the FDA study are unprecedented for BPA, and the results clearly show that BPA has very little potential to cause health effects, even when people are exposed to it throughout their lives," he told EHN in an email. (The ACC declined multiple requests for a phone interview.)</p><p>But that is not exactly what the government's data said, even if that sentiment was reflected in the FDA's early press release.</p><p>"They have a bunch of data that says BPA is doing something. But they're ignoring that data," Patisaul, the North Carolina State University biologist and Clarity investigator, said.</p><p>This March, Vandenberg co-authored an opinion paper with two other scientists also not involved in Clarity, to see what data the feds may be missing. After a close look at the government's Core Study results, they identified 41 endpoints with statistically significant effects. As with the academics' studies, the lowest doses were associated with the greatest number of effects, such as mammary gland cancer, kidney damage, increased body weight and altered gene expression in the brain. "There are a lot more effects at low doses than high doses. A lot more," Vandenberg said. "It's hard to ignore that and say everything is fine here. Even the FDA's own data suggests there is harm."</p><p>During another session at last September's EFSA meeting in Italy, Barry Delclos, a biochemical toxicologist with the FDA, responded to a question from Patisaul regarding these low-dose results. He answered that his team had looked to see if "consistent responses" would explain the statistically significant results they had found. "We didn't feel that was the case," he said. Delclos also stated in the September 2018 webinar that his team questioned the biological significance of findings that didn't fit a consistent dose-response relationship.</p><p>The frustrations of academics and health advocates, as well as of FDA scientists, is tangible. Patisaul argued that Delclos, Doerge and their colleagues are in their "own echo chamber," doing the "same thing they are accusing everyone else of doing," and unwilling to recognize that their science might be outdated. Doerge went on during the EFSA panel discussion: "You come to someone that has all the responsibility mandated by law to protect the public from this or that, and you're saying, 'Oh, these basic tenets that you've used to do your job for all these years is no longer valid. Dose-response doesn't exist any longer,'" he said. "This is a fundamentally unbreachable barrier, in my opinion."</p><p>In the 1998 PBS interview, vom Saal detailed a "distinct pattern" that comes with any paradigm shift in science — especially one, he said, that could impact billions of dollars of profits for chemical companies. "The first thing is absolute denial," he said. "The second is a feeling that it may be true, but it's only true in very limited circumstances. The third is, it's true but the economic consequences are so great that we can't do anything about it."</p><p>Lisette van Vliet, a senior policy coordinator with Breast Cancer Prevention Partners, a San Francisco-based nonprofit, likened it to the times of Galileo. "A bunch of scientists were saying the Earth is the center of the universe; other scientists were saying the sun is the center," she told EHN. "They were using very different ways of ascertaining reality."</p><p>"These paradigm fights tend to be long and protracted and don't always have a complete 'aha' moment," said van Vliet. "The Clarity study was as good of a stab as anyone could make… The integrated final version of the study is going to be a really important point in this discussion, but it is not going to be the end of the story. And, meanwhile, public health will suffer because of continued exposure to this harmful chemical."</p><p><em>In <a href="https://www.ehn.org/bpa-science-fda-safe-2641150483.html" target="_blank">part 2</a> of this series, EHN details how the FDA operates on the edge of research honesty, inconspicuously misleading the public with regard to the testing and regulation of BPA.</em></p>
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15 November 2019
Originals
Exposed: On the edge of research honesty
This is part 2 of a 4-part investigation of the science surrounding the chemical BPA and the U.S. regulatory push to discredit independent evidence of harm while favoring pro-industry science despite significant shortcomings.
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PULLMAN, Wash.—Tiny pink lab mice disappear then quickly reappear again from within a cage's hardwood chip bedding. The squirmy newborns are part of Patricia Hunt's latest series of experiments on the health impacts of industrial chemicals widely found in products we all use.
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Here, in a dim basement at Washington State University, where metal shelves are stacked high with rows of plastic cages, Hunt has made multiple discoveries that call into question claims made by U.S. federal regulators about the safety of one of those chemicals: bisphenol A, or BPA.
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<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2920080/" target="_blank">Virtually all of us have tiny amounts of it in our blood and bodies</a> – at least two millionths of a gram per liter of blood, the equivalent of about
14 pinches of table salt in an Olympic-sized swimming pool. The Food and Drug Administration maintains that the chemical, known to mimic and mess with natural hormones, poses no real health threat at such levels.
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<a href="https://www.sciencedirect.com/science/article/pii/S0960982203001891" rel="noopener noreferrer" target="_blank">Hunt's results</a> say otherwise. Since being among the first scientists to report on the harmful effects of BPA on mice in 2003, Hunt has further identified genetic abnormalities, fertility problems and other health impacts in animals at very low doses.
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We encounter the chemical every day in food and beverage cans, plastic packaging and cash register receipts. And it doesn't appear to be going away anytime soon: The global BPA market is predicted to surpass $30 billion by the mid 2020s. "I'd like to vote the bisphenols off the planet. But that's not likely to happen," Hunt later tells me in an upstairs room flanked with microscopes used to view tissues from the mice. "The more immediate goal should be to change the way we do toxicity testing for these types of chemicals."
</p><h3><em>Related: <a href="https://www.ehn.org/bpa-impact-on-human-health-2641134273.html" rel="noopener noreferrer" target="_blank">A scientific stalemate leaves our hormones and health at risk</a></em></h3><p>
Her findings—and those of others—have implications far beyond BPA to the hundreds of other chemicals capable of wreaking similar havoc on our hormones.
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Discoveries in Hunt's lab also hint at how an evaluation of a chemical can easily conclude that it is safe even if it may cause harm. Twice now, Hunt has found BPA or one of its equally troublesome replacements, such as bisphenol S, coursing through the bodies of her control mice — animals not intentionally dosed with a chemical in her experiments. The source: those plastic cages housing the mice.
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Natural wear and tear of Hunt's cages and, more recently, potential cross-contamination in a shared wash area from another facility's damaged plastic cages, likely led to tiny amounts of the chemicals getting into the animals. She has had similar misadventures with contamination from phytoestrogen-laden mice chow, wildfire smoke and cleaning products. Such unplanned exposures could dilute differences in health outcomes between a study's experimental and control animals, making it difficult to detect if a chemical truly poses a health risk and, ultimately, making it all the easier for hazardous things to continue finding their way into our bodies.
</p><p>
Both times Hunt found bisphenol contamination, she essentially lost her experiment. "It was a whole lot of déjà vu all over again," said Hunt, who is in her mid-60s, her face framed by rimless glasses, cropped gray hair and small hoop earrings.
</p><p>
Hunt's repeated frustrations point to just one of the myriad ways a study's design, implementation, analysis, interpretation and presentation can diminish, obscure or even totally hide any true health effects of a chemical. The risk of such oversights may be especially high for BPA and other chemicals that interfere with the action of hormones in the body, a class called endocrine disruptors.
</p><iframe allowfullscreen="" frameborder="0" height="650" mozallowfullscreen="" src="https://cdn.knightlab.com/libs/timeline3/latest/embed/index.html?source=1qWh3aMBC2innBIXWMxCZrV19JbrGtYka2_ylKLKYOTA&font=Default&lang=en&initial_zoom=2&height=650" webkitallowfullscreen="" width="100%"></iframe><p>
An investigation by Environmental Health News suggests that an ongoing multimillion-dollar project called Consortium Linking Academic and Regulatory Insights on BPA Toxicity, or Clarity, includes a number of these potentially harm-hiding elements. Launched in 2012 by the U.S. Food and Drug Administration (FDA), the National Institute of Environmental Health Sciences (NIEHS) and the National Toxicology Program (NTP), Clarity combines a traditional regulatory toxicology study from the government and investigational studies from academics who wield more modern techniques. The goal is to reconcile a long-standing dispute over data and conclusions on BPA's health effects. But it's bigger than BPA—the collaboration aims to determine if the study methods used by government regulators are sufficient to determine the safety of the hundreds of chemicals suspected of being endocrine disruptors. The implications could reverberate through the entire U.S. chemical regulatory structure.
</p><p>
FDA officials continue to claim that concerns over low-dose effects of BPA are unfounded; academic scientists continue to publish studies that underscore risks such as altered brain development, cancer and diabetes.
</p><p>
Through interviews and emails obtained via Freedom of Information Act requests, EHN has uncovered various signs of deficiencies in the FDA's science on BPA and its handling of Clarity. While each sign alone could be considered a red flag, viewed as a whole, they suggest that the FDA is missing some big warning signs about BPA and, therefore, likely misleading the public about its safety.
</p><p>
Some of these signs can be traced back to before the study began. For example, evidence of BPA contamination emerged during a preliminary Clarity study. If the animals in the main Clarity study had been contaminated, that would dilute any true differences between exposed and unexposed groups. And during the study's design, the FDA insisted on using a specific type of rat that had been shown to be insensitive to the effects of estrogen and its mimics, including BPA. Michael Hansen, a senior scientist for Consumer Reports, compared using this rat to operating a radar gun that doesn't detect speeds under 100 mph and then concluding that no one is speeding. "It is almost as though they were trying not to find differences," Hansen told EHN.
</p><p>
Other potential red flags popped up during the course of the study, such as the small number of animals provided to some of the academic scientists — also limiting their ability to detect differences — and a public statement on BPA's safety made by the FDA before all the data was in.
</p><p>
"Is it total incompetence or fraud? I don't know their thinking. But neither choice is pleasant, and it represents the waste of about $15 million in public funding," Pete Myers, CEO and chief scientist of Environmental Health Sciences, told EHN. (Editor's note: Myers is also the founder of Environmental Health News, though the publication is editorially independent.)
</p><p>
An integrated report that pulls together government and academic findings is in preparation and
expected by the end of 2019. Eight of the 14 academic investigators have so far published 14 papers based on their findings in a scattering of different peer-reviewed journals such as <em>Endocrinology</em> and <em>Toxicological Sciences</em>. Many found health effects in rats exposed to very low levels of BPA. "There isn't one big publication coming out with the academics' results," Gail Prins, a researcher at the University of Illinois at Chicago and Clarity investigator, told EHN. "I'm afraid that significant findings across academic studies are going to be buried."
</p><p>
Federal regulators have also now published their part of Clarity, one big publication known as the Clarity Core Study that was widely publicized. Their results, too, reveal some effects at low doses. Yet they again concluded in their report — and in the accompanying press — that exposing rodents to BPA did not result in health effects at the low doses to which people are generally exposed.
</p><p>
"I think that a lot of this is failure by design," Laura Vandenberg, an environmental health researcher at the University of Massachusetts-Amherst's School of Public Health and who was not involved in Clarity, told EHN.
</p>
Strains on relationships
<img lazy-loadable="true" src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjA0ODc4MC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTU5NzA0MTI4OX0.M3SPsqTugkWDygIpWtEZE4WHI4jwiAo2hQiaFhOOAhE/img.jpg?width=980" id="a5304" class="rm-shortcode" data-rm-shortcode-id="3578f1f88e62f6c909047c95c7875996" data-rm-shortcode-name="rebelmouse-image" />The lab of Cheryl Rosenfeld, a biologist at the University of Missouri and another Clarity investigator. (Credit: Cheryl Rosenfeld)
<p> Ila has just returned from her first puppy training class as I arrive at Hunt's home in Moscow, Idaho. Labradoodles are known to have a lot of energy, and Ila's bouncy greeting of this newcomer corroborated that reputation. Hunt tells me she is surprised Ila has yet to hurdle the childproof gate that separates the mudroom from the dining room. "I keep thinking she could hop over it so easily, but she just never does," says Hunt. </p><p> Other dog breeds may be calmer, but Hunt and her husband had good reason to go with a labradoodle: The breed sheds less fur and other allergy-triggering substances than other breeds. "We had a lab once before and the hair was everywhere, and our allergies were terrible," she says. Sure enough, I made it out of her house without any of Ila's dark brown fur. </p><p> Like dogs, lab animals can be diverse in their behavior and biology. </p><p> To determine the impact of a chemical, scientists track various changes, called endpoints, in an animal such as organ weight, tumor development, changes in behavior or insulin levels. Different strains of different rodents are often used in different studies. Hunt and many others who investigate the impacts of hormones and hormone mimics often opt for strains of mice. For one, the animals can be more practical — they eat less and take up less space than rats. Certain strains of mice are also known to be particularly sensitive to hormone changes. </p><p> "If your animal model can't respond to your experimental manipulation, then you can never determine if the manipulation does anything, ever," Scott Belcher, a biologist at North Carolina State University, and a Clarity investigator, told EHN. </p><p> Belcher, too, tends to use mice in his studies of impacts on the heart. "Rats and mice aren't the same things," he said. </p><p> The FDA's go-to animals for chemical toxicity testing are Sprague-Dawley rats bred at the FDA's National Center for Toxicological Research in Jefferson, Arkansas. These were the animals chosen for Clarity, despite objections from some academic investigators. The rats <a href="https://academic.oup.com/biolreprod/article/89/5/108,%201-10/2513941" target="_blank">have long been used</a> in government regulatory studies, and they have long been known to have low sensitivity to BPA. </p><h3><em>Related: Want this story in comic strip form? Check out <a href="https://www.ehn.org/test-comic-post-2640636344.html" target="_blank" rel="noopener noreferrer">"Clouded in Clarity"</a></em></h3><p> Jerry Heindel, the health scientist administrator at NIEHS when Clarity was initiated, noted one particularly unusual characteristic of the rats. "Estrogen stimulates puberty in a female animal. You can generally make puberty come up two, three days earlier by giving an animal extra estrogen," he told EHN. "But in this animal, you can't." A couple days early is relatively significant for an animal that, on average, hits puberty at 38 days. </p><p> "So some endpoints are going to be insensitive or much less sensitive. There's no getting around that," said Heindel. (The FDA did not respond when asked about the choice of study animal.) </p><p> Of course, animal studies all have their limitations. The only way to be relatively sure of a chemical's effect in humans would be to study the effect of that chemical in humans. In a first-of-its-kind study published in 2018, <a href="https://www.ehn.org/bpa-linked-to-diabetes-2604258226.html" target="_blank">researchers exposed a small group of people to a very small amount of BPA</a> and saw a link to a precursor of type 2 diabetes. The researchers first lowered participants' BPA levels and then brought those levels back up to the normal range. (Myers was an author on the paper.) Still, to knowingly expose people to something suspected of being harmful can raise some ethical concerns. Epidemiological studies do the next best thing — they take advantage of the natural experiment currently underway by estimating levels of exposure and health outcomes in people and then determining if and how the measures might be related. </p><p>In his epidemiological studies, John Meeker, an environmental health scientist at the University of Michigan School of Public Health, has uncovered evidence that BPA may alter circulating levels of hormones and birth outcomes. He laments how regulators have remained reliant on animal toxicology studies. "We need more harmonization of animal and human research in the regulatory setting," he told EHN.</p><p>Both research methods have their place. Toxicology studies allow scientists to directly compare exposed and unexposed animals, control the experimental environment and precisely measure outcomes. Meeker noted that his epidemiological findings do not always match up with toxicology studies. "When they do match up, it gives you more confidence," he said. "When they don't, it could be due to chance in human studies or due to species differences in their responses to exposure."</p><img lazy-loadable="true" src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjA0OTA0Ny9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYxNzI4NTMzM30.bzydhkgsSa-qCZhjzTJtFHHuuYfIkKQgP3X4W1yfq0E/img.jpg?width=980" id="0ae64" class="rm-shortcode" data-rm-shortcode-id="560da7db926792cbca73882e346f7f4f" data-rm-shortcode-name="rebelmouse-image" />
Thomas Zoeller, a biologist at the University of Massachusetts, Amherst, and Clarity investigator in his lab. (Credit: Umass.edu)
<p>Thomas Zoeller, a biologist at the University of Massachusetts, Amherst, suggested such species differences resulted in what he called "unprecedented" findings in his Clarity study. "This is a very odd strain of animal," he told EHN.</p><p>For a century, explained Zoeller, researchers including himself have studied the impact of thyroid hormone insufficiency on brain development in animal models. "Nobody sees a lack of effect," he said. Zoeller treated some of his Clarity rats with a medication used for hyperthyroidism, propylthiouracil, that suppresses thyroid activity. And while it did succeed in altering thyroid hormone levels, as expected, the brains of his rats appeared almost unfazed.</p><p>"The data that we have show that these animals are different," added Zoeller. "They may just be different with respect to the thyroid system. But I doubt that." He suggested that because the strain was selectively bred to be prolific breeders over many generations, other changes likely accompanied the increased fecundity.</p><p>The impact of species differences can go both ways, explained Patrick McKnight, a measurement scientist at George Mason University in Fairfax, Virginia. Using a model animal that is overly sensitive to the agent of interest can artificially inflate the size of an effect, he told EHN.</p><p>Still, Linda Birnbaum, former director of the NIEHS and the NTP, shared the academics' concerns. "When we started this study, I remember having nightmares thinking, 'What happens if we don't find anything?' Because we really didn't have much data on using this strain of rat and BPA," she told EHN. "In retrospect, if I were to do this study again, I probably would've done it in mice and I probably would've used a strain which had been reported to have clear effects."</p><p>Vandenberg added her worries. "Why are we using this strain to test all chemicals if we now have evidence that it is not the right strain?" she added. "Have we made a mistake on everything?"</p>Power struggles
<img lazy-loadable="true" src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjA0ODgxMy9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYwMjc5ODk1MX0.U7eI4wRkEq5qXVrxjksGO_wMsU8m1DR2lPTBL2FE0og/img.jpg?width=980" id="5051b" class="rm-shortcode" data-rm-shortcode-id="2616c241866658111b05c13b25d6a407" data-rm-shortcode-name="rebelmouse-image" />Linda Birnbaum, former director of the NIEHS and the NTP, speaking at Northeastern University's Our Environment, Our Health event in 2016. (Credit: Matthew Modoono/Northeastern University)
<p>Even when assuming a chosen animal is a reasonable model to test a chemical of interest, the next critical factor for a successful study is enlisting a large enough number of those animals to detect health effects if there are effects to be detected. The more animals, the more so-called statistical power a study has to reveal the true effects of a chemical. </p><p> Prins believes that the FDA shortchanged her on animal numbers. She had determined prior to the study that she would need at least 18 animals per treatment group to have adequate power to detect differences between the groups. Yet for one of her treatment groups she received just four animals. "When you get that number of animals, you can't get a significant effect," Prins told EHN. "I would go out on a limb and say this was done intentionally." </p><p> In a 2008 federal review of the evidence on BPA, the FDA excluded a study of hers from their risk assessment because, in part, her study didn't include enough animals. That FDA assessment, which ended up relying on just two studies — both funded by industry — restated the agency's stance that BPA is safe. </p><p> "The FDA wants to tell a story," said Prins. "They want to tell the story that BPA is fine. And it's not." </p><p> Another Clarity researcher, Jodi Flaws, struggled with a similar power problem in her Clarity research. She ended up with just three animals in one of her treatment groups, Flaws told EHN, because the tissue sent to her by the government was not collected on the same day of the animals' menstrual cycle — a critical detail that she had requested. </p><p> Her team still managed to publish a paper with their results, which indicated that BPA exposure at some doses altered hormone production and the number of developing eggs in female rats. But she told EHN that the small number of animals underpowered them to see the stronger results in Clarity that they had seen in their prior studies. </p><p> "There was no way to make sense of anything," said Flaws, who studies genetic and environmental factors that affect the female reproductive system at the University of Illinois at Urbana-Champaign. (The FDA did not respond to a question regarding the number of study animals provided some researchers.) </p><p> John Bucher, a senior scientist with NTP and NIEHS, and one of the Clarity leads, acknowledged this shortcoming of Clarity. "We recognize that some of the investigators didn't get as many samples as they would have liked. And that's regrettable," he told EHN. "This was an enormously complicated study and we tried to accommodate as many requests as possible.... We probably overpromised." </p>Dirty data
<p> On Hunt's office wall in Pullman hangs a framed quilt made by the Sarum Quilters of Salisbury, England. The primary-color design depicts the DNA double helix, genes, eggs and sperm that have been the primary characters in her 40-plus years of research. Other genetics references fill the room — there is the thick blue Dictionary of Genetics, and the half-moon table braced by arms and a back that are shaped as x and y chromosomes. </p><p> Human-made chemicals only began to take center stage in the latter half of Hunt's research career. In fact, before 1998, Hunt knew nothing about BPA. She was simply investigating at the time how hormonal changes in mice might affect the quality of a female's eggs. Then, some unexpected data began to emerge: Abnormal eggs appeared in both her experimental and control animals. "We knew we had a problem," said Hunt, wearing a dog-fur-free blue long-sleeve t-shirt and dark blue jeans, along with a multi-colored stone pendant. "It took me a month to track down what was going on." </p><script id="infogram_0_24590e35-148f-4e04-8224-e3d659b4c5f7" title="Copy: Pull quote 2" src="https://e.infogram.com/js/dist/embed.js?ZfE" type="text/javascript"></script><p> At first, she suspected everything — from construction project debris to pesticides sprayed nearby. Then she took a closer look at the plastic cages. As they were repeatedly washed and autoclaved, she could see that the cages were starting to degrade. Across the street from her lab was the university's polymer sciences building. She recalled running over to those scientists and learning from them that BPA was likely leaching out of her cages. </p><p> While some health effects of BPA were already suspected by the late 1990s, impacts on female eggs — and, therefore, potentially increased risks of miscarriages and birth defects — were not yet among them. Hunt spent the next three years confirming her data. Today, female reproductive problems are included with the published risks associated with BPA exposure. Hunt has continued to investigate how BPA and other endocrine disruptors might further affect genes and reproduction. And, while not a participating scientist, she is also keeping a close eye on Clarity. </p><p> In emails and PowerPoint slides obtained by EHN, FDA scientists acknowledged as far back as <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038784/" target="_blank">July 2013</a> that contamination occurred in a study done to determine Clarity's feasibility. During this preliminary study, which was carried out at the same facility that later housed the animals used in the large-scale Clarity study, tests had revealed that BPA levels in control rats were similar to those in the four lowest exposure groups. </p><p> That's a problem: Endocrine disruptors, like natural hormones themselves, can impact the body at extremely low levels. So, unintentionally exposing controls to a tiny dose of a chemical may result in those animals showing similar effects as experimental animals intentionally exposed. In a comparison of health effects between the control and experimental animals, any true differences between the groups would be diluted. </p><p> In January 2014, Barry Delclos, a biochemical toxicologist with the FDA, wrote in an email that, while data from the preliminary study revealed "the potential for significant effects in the low BPA dose range," the BPA contamination "confounds the interpretation of the changes observed in the lowest BPA exposure groups." </p><p> Marianna Naum, an FDA spokesperson, told EHN in an email that data suggesting contamination of the control rats might have been due to "the housing of the animals in the same room as animals treated with high BPA doses." Although Naum also noted that the agency has still not confirmed the source of contamination, and that it remains unclear to what extent any contamination might have affected the rats in Clarity. Still, the government's Core Study report asserts that contamination was not an issue. </p><img lazy-loadable="true" src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjA0OTEwNS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTU5MTE2NDMzMH0.kjbS69gbiyOk2nlQ-0yWlSzgMXQcxZLbBuKJA6dgjvE/img.jpg?width=980" id="0c2fc" class="rm-shortcode" data-rm-shortcode-id="c6a2b2d299e519b669529630cb36ac7d" data-rm-shortcode-name="rebelmouse-image" />
Heather Patisaul, a professor of biology at North Carolina State University and a Clarity investigator. (Credit: NCSU)
<p>"The fact is, they don't know where the contamination came from and they don't know if the Clarity controls were contaminated," said Zoeller. "They didn't measure it."</p><p>"If you can't ferret it out, it's like shooting yourself in the head before you even start the study," added Hunt.</p><p>Birnbaum expressed little concern about that potential contamination. "When we deal with environmental chemicals, almost everyone — or every animal — has some exposure," she said. "Control doesn't have to mean zero — it means you know what you have and it is lower than the intentionally exposed."</p><p>Hunt still maintained that contamination with an endocrine-disrupting chemical could derail a study. "If you have contamination, you don't have a control. There's no way around it," she said. "It puts a shadow over the whole thing."</p>Food issues
<p> It was unlikely a pleasant experience to be a Clarity rat. Every day, while restrained, a lab technician stuck a tube down its throat and into its stomach to deliver a solution. For the experimental animals, the solution contained BPA. For the controls, it either contained a dose of ethinyl estradiol, the synthetic estrogen in oral contraceptives, or nothing. The method is called gavage. </p><p> FDA scientists argue that gavage is a better way to ensure the correct dose is getting into an animal than putting the chemical in its food. Academic scientists counter that gavage triggers chronic stress and can therefore significantly alter hormone levels — another means by which any actual differences between experimental and control animals could be artificially diminished. Because the control animals were also exposed to the stress of gavage, they argue, there was no true control group of rats in Clarity. </p><p> Heather Patisaul, a professor of biology at North Carolina State University and a Clarity investigator, co-authored a 2013 study in which she found that gavage alone was enough to change the expression of hormone receptors and other genes in areas of the brain that are <a href="https://www.ncbi.nlm.nih.gov/pubmed/23457122" target="_blank">known to respond to stress</a>. </p><p> "Clearly animals gavaged and not gavaged are not the same," she told EHN. </p><p> During the planning of Clarity, the FDA made it clear that use of gavage was non-negotiable, noted Heindel, the former NIEHS health scientist administrator. The academics could accept that or simply not participate. </p><p> So, many reluctantly signed on, despite believing that gavage and other design factors dictated by the FDA would make it extra difficult to show effects that many of them had identified in their previous studies. Use of gavage was among the criteria adopted by the government decades ago for studies that evaluate the safety of chemicals. In addition to standardizing the number and type of animal used, and levels of exposure to the chemical of interest, these so-called "guideline" studies also generally focus only on traditional endpoints such as overt signs of toxicity, rather than the unique effects of endocrine-disrupting chemicals that academics tend to investigate. </p><p> Academics usually use other means of administering chemicals to animals. Prins delivers BPA into a mouse's mouth with a pipette tip. Andrea Gore, a neuroendocrinologist at the University of Texas at Austin, said her lab is starting to administer chemicals to animals via vegetable oil placed on a piece of cookie. "There is evidence that gavage is stressful," Gore, who was not involved in Clarity, told EHN. "When you're talking about low doses of endocrine-disrupting chemicals, that is extremely relevant." </p><p> Hunt, too, feeds her mice BPA via corn oil. "We gently pipette oil into the mouth and the animals actually like it," she said. </p>Losing control
<img lazy-loadable="true" src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjA0OTA5OC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY1MDM5NDA3NH0.yle7wszkcyurVaT3YEYneWovi6Db_AMin_AwRspTXKQ/img.jpg?width=980" id="d19c9" class="rm-shortcode" data-rm-shortcode-id="9df56bb017b1900604c2899418e77336" data-rm-shortcode-name="rebelmouse-image" />Researcher Pat Hunt with lab mice. (Credit: Lynne Peeples)
<p> Whenever it is wet outside, Hunt makes sure to clean off Ila's four paws before they come inside. "We pause for paws," she said. Given the puppy's high energy, it is a given that the outside mud would end up just about everywhere inside her house. Yes, Hunt is familiar with both dirty dogs and dirty data — and the struggle to keep puppies and studies under control. </p><p>Contamination is one of the ways in which a study and its results might become tainted; a lack of control is another. </p><p>Standard protocol for research on endocrine disruptors demands the inclusion of both "positive" and "negative" controls — groups of animals that researchers can then use as a baseline comparison against their exposed group of animals. A negative control is your typical study control animal that doesn't receive any exposure. (Again, in the case of Clarity, academics argue that this purity was spoiled by potential contamination.) A positive control is exposed to something with a known response. </p><p>For example, <a href="https://www.maryvillecollege.edu/media/dsx/manager/Faculty/NaturalSciences/dcrain/publications/Vom%20Saal%20et%20al%202010.pdf" target="_blank" rel="noopener noreferrer">academic studies of BPA</a> have generally included a group of animals exposed to a synthetic hormone for which effects are well known: ethinyl estradiol, the estrogen mimic in oral contraceptives. This positive control helps scientists decipher whether or not a lack of an effect in BPA-exposed rats compared to negative controls was because the experiment simply did not have the sensitivity to detect estrogen-like effects or because BPA really had no such effect. </p><p>When the government initially declared their plan not to include positive controls in Clarity, according to emails reviewed by EHN, 11 of the academic researchers pleaded for them to reconsider. In one of the emails from April 2012, Frederick vom Saal, a professor of biology at the University of Missouri-Columbia and a Clarity investigator, stated that without these controls, the experiment could "waste millions of dollars and generate uninterpretable data."</p><p>Positive controls were eventually provided and used for most, but not all, of the Clarity studies. Kim Boekleheid, a toxicologist at Brown University, was the only academic scientist not to use a positive control in his study of male reproduction. His decision ignited ire among some of his Clarity co-investigators, especially upon the release of his results. While previous academic studies have found that male reproduction is very sensitive to BPA, Boekleheid's study concluded that exposure to BPA did not harm the testes or sperm in rats. Hunt and others question how he could be so sure without a positive control. Boekleheid declined to be interviewed for this story. </p><p>An additional type of control was enlisted by the government in their Core Study. When they found higher rates of mammary cancer in rats exposed to low doses of BPA compared to negative controls, the FDA authors then also looked to a control group from a somewhat similar study conducted about a decade earlier. Turned out those non-BPA-exposed animals, considered "historical" controls, developed more mammary tumors than the non-BPA-exposed rats in the Clarity study. The government used this as one of their reasons to disregard the mammary cancers as a true BPA effect. </p><p>Outside scientists questioned their motives and noted, for example, that the animals not exposed to BPA in the old study would have been housed in plastic cages made partially of BPA. So, those rats may, too, have been inadvertently exposed to small doses of BPA. Gore added that "things change over 10 years." In work in her own lab, she has found that animals vary across generations — "even if they are the same strain, fed the same food and all animal husbandry is done the same."</p><img lazy-loadable="true" src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjA0OTEyMS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYyODc1MzMxMH0.5p6z7RqPOmq9i9SW-L9_qcODRKTNnuPbEpVLcGqt8Qk/img.jpg?width=980" id="75738" class="rm-shortcode" data-rm-shortcode-id="6f55dc6dd08c7a7b335332a991591f67" data-rm-shortcode-name="rebelmouse-image" />
Ana Soto, an endocrinologist at Tufts University and a Clarity investigator, with fellow Tufts researcher, Carlos Sonnenschein (Credit: Tufts University).
<p>Ana Soto, an endocrinologist at Tufts University and a Clarity investigator suggested that historical controls are typically only used when a difference is not seen between an experiment group and control group. "They are doing the opposite. They seem to be trying to minimize the fact that they found differences between BPA-treated and the simultaneous control," she told EHN. "That is where you start wondering whether this choice is plainly inept or disingenuous."</p><p>Vandenberg too was curious about the government's use of historical controls in guideline studies, such as the Clarity Core Study. So she took a closer look at how the government dealt with other outcomes. For example, they found a significant increase in pituitary cancer in female rats exposed to ethinyl estradiol and used that as support that the positive control worked in Clarity. However, the same historical controls the government referenced for cases of mammary cancer also had a rate of pituitary tumors comparable to the ethinyl estradiol group. "If they had applied the same logic to the ethinyl estradiol pituitary data in Clarity as they did to the BPA mammary gland data, they would have had to conclude that the positive control had no effect," she said.</p><p>And that would have called into question the rest of their results.</p><p>"When the FDA didn't like the data they got, they went back into their own lab to try to dismiss it," added Vandenberg. "But then they don't do that for the data they like. This asymmetric treatment of data is one more example of how the FDA seemed to manipulate the interpretation of the Clarity data."</p><p>Zoeller agreed. "They at least appear — by their inconsistency — to have a preconceived conclusion that they arrive at by selective logic," he said.</p><p><em>In <a href="https://www.ehn.org/bpa-science-health-2641150585.html" target="_blank">part 3</a> of this series, EHN further details critical questions surrounding how the FDA assesses the evidence and frames their conclusions on BPA, as illustrated in the agency's handling of Clarity.</em></p>
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15 November 2019
Originals
Exposed: Deciphering the real message about BPA
This is part 3 of a 4-part investigation of the science surrounding the chemical BPA and the U.S. regulatory push to discredit independent evidence of harm while favoring pro-industry science despite significant shortcomings.
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MOSCOW, Idaho—Patricia Hunt, a geneticist at Washington State University, and I walk a long, curved route through the arboretum at the University of Idaho — past the big red barn, through the woods and up a hill by the water tower painted with a big yellow "I". It's the same water tower we could see directly out from her back patio. Yet our path back to the house was a far more natural course than any straight-line path.
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Such a lack of linearity, Hunt explained, can also describe the relationship between the dose of a chemical — say, bisphenol A (or BPA) — and its level of impact on the body.
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Historically, government toxicologists have assumed that the greater the exposure to a toxic chemical, the greater the harm — or, as the old adage goes, "the dose makes the poison." A dose-response curve should therefore always be monotonic, meaning it will never change direction from positive to negative, or vice versa. But academic scientists, especially those who study endocrinology, are finding that this principle is not always true, at least not for chemicals such as BPA that mimic and mess with our hormones. These endocrine-disrupting chemicals, studies show, can wreak havoc at extremely small doses.
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<a target="_blank"></a>This disagreement is just one of many front lines in an ongoing conflict between federal regulators and academics, which intensified with the launch in 2012 of a multimillion-dollar government-led project called Consortium Linking Academic and Regulatory Insights on BPA Toxicity, or Clarity for short. The project combines a traditional regulatory toxicology study from the government — dubbed the Core Study — and investigational studies from academics. The government and most of the 14 participating academic scientists have completed their respective studies for the collaborative project. An integrated report that pulls together all the findings is currently underway and expected to be completed by the end of 2019.
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The goal of Clarity is to reconcile a long-standing dispute over data and conclusions on BPA's health effects, although the implications could be far broader. BPA is just one of hundreds of chemicals we're exposed to in our everyday lives that are suspected of scrambling the natural hormone messages in our bodies.
</p><h3><strong><em>Related: Check out <a href="https://www.ehn.org/bpa-chemical-comic-2640636344.html" target="_blank">"Clouded in Clarity,"</a> a comic strip adaptation of this series </em></strong></h3><p>
Through interviews and emails obtained via Freedom of Information Act requests, EHN found a series of red flags concerning deficiencies in the FDA's science on BPA, including how it dictated much of the Clarity study design and methods. As EHN detailed, a number of these factors limited Clarity's robustness to detect health effects — from insistence by the FDA to use of a strain of animal that had been shown to be insensitive to hormone disruptors, to the choice of a stressful means to deliver BPA to the animals, to the provision of small numbers of animals to some of the academic scientists.
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But then there's the question of what happened as the data came in. What patterns did researchers look for when plotting the dose of the chemical versus the response of the animals? Where did they draw the line on what is considered significant evidence of an effect? And how did they present what they found? Once again, a number of contentious issues emerged in the course of EHN's investigation.
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Take North Carolina State University biology professor Heather Patisaul's research on the brain: In three studies now, including one that was published as part of Clarity, she has found effects of BPA on the developing rodent brain at just 2.5 micrograms per kilogram of body weight. For context, that is approximately 120,000 times below the lowest dose that has been shown in other studies to alter uterine weight — one of the traditional tests looked at by the FDA.
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In some cases of what scientists call non-monotonicity, a chemical may have effects at low doses and no effects at higher doses; in others, further effects may only appear as doses get really high. In either case, the result is a curve that changes direction, such as a U-shape. But if researchers were to only look for a strictly increasing line, by enlisting the statistical methods best suited to identify a linear trend, then their calculations would likely conclude that the chemical has no impact on that endpoint of interest.
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It's also possible that the health effects of a chemical differ across doses. "Very high and very low doses can do entirely different things," Frederick vom Saal, a professor of biology at the University of Missouri-Columbia and a Clarity investigator, told EHN. Take, for example, diethylstilbestrol (DES), the estrogenic drug that was once commonly prescribed to pregnant women. Studies have found that exposures in the womb to 100 parts per billion of DES can cause mice to become scrawny as adults, while exposures to <a href="https://www.ncbi.nlm.nih.gov/pubmed/15959888" rel="noopener noreferrer" target="_blank">1 ppb can result in severe obesity</a>. There is only one way to fairly evaluate a dose-response relationship, Richard Stahlhut, a biologist at the University of Missouri-Columbia, told EHN. "You look for straight lines, you look for curves," he said. "Then you tell people what you found."
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However, A. John Bailer, chair of the department of statistics at Miami University in Ohio, is among scientists not fully convinced of non-monotonic dose responses. He underscored a need to better understand their biologic basis. "A mechanistic understanding would give us the real insights," he told EHN.
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Scott Belcher, a biologist at North Carolina State University, and a Clarity investigator, pointed to a <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4429934/" rel="noopener noreferrer" target="_blank">number of studies</a> that provide evidence for <a href="https://www.ncbi.nlm.nih.gov/pubmed/24569941" rel="noopener noreferrer" target="_blank">cellular mechanisms</a> driving these <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260535/" rel="noopener noreferrer" target="_blank">non-monotonic responses</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3275382/" rel="noopener noreferrer" target="_blank">including opposing effects from multiple hormone receptors</a> and negative feedback loops, a key regulatory mechanism in living things. </p><p>"Most simply put, biological systems are complicated and are controlled by multiple types of regulation," he told EHN.</p><p>Despite the large body of evidence from vom Saal and others, the FDA continues to deny the relevance of very low dose exposures and non-monotonicity. In an email to EHN, Marianna Naum, an FDA spokesperson, said that the agency had "extensively reviewed the low-dose BPA literature and was "unable to construct a plausible or logical comprehensive toxicological profile or explanation for the many claimed effects of BPA, largely due to the inconsistencies that currently exist within this literature." </p><p>This attitude keeps the stalemate alive, while we all remain Guinea pigs in a grand experiment on our hormones. "We thought Clarity would help, but the way the results turned out, it has kind of exacerbated the difference between people who think of low-dose effects as important and non-monotonic dose-responses as real and physiologically important, and those that don't," said Jerry Heindel, the health scientist administrator at NIEHS when Clarity was initiated. "That's the biggest hurdle we still have to get through."</p>
On the hunt
<p>Hunt abruptly stops during our stroll through the arboretum, which is just across the state border and a few miles from her lab at Washington State University. "Look, a wild orchid," she said. Pink petals pop in the otherwise predominantly green landscape.</p><p>Unexpected discoveries may be a relatively frequent occurrence for Hunt: She has twice found bisphenols coursing through the bodies of animals not intentionally dosed with a chemical in her studies, a result of degrading plastic cages housing the mice. Generally, however, scientific research tends to be a bit more prescribed. To find any particular effect of a chemical, you usually need to look for it — or at least recognize it. The problem is, government regulators and academics tend to look for and recognize different things: Regulators look for the obvious – changes in body weight, or a fast-growing tumor. Endocrinologists look for subtle changes – learning behavior, anxiety, memory – that may not appear until years later, or even subsequent generations. This has been another major point of contention in the ongoing debate over the testing and regulation of endocrine-disrupting chemicals.</p><p>"Typically, the tests they use for regulatory purposes are a little more rigid. They are not as cutting edge as you might see from academic labs doing it on their own," said John Meeker, an environmental health scientist at the University of Michigan School of Public Health, who is not involved in Clarity. "This can lead to big differences in study conclusions, as well as the overall view of the toxicity of a particular agent." </p><h3><em>Related: <a href="https://www.ehn.org/bpa-impact-on-human-health-2641134273.html" target="_blank" rel="noopener noreferrer">A scientific stalemate leaves our hormones and health at risk</a></em></h3><p>In one of University of Illinois at Chicago researcher Gail Prins' studies, for example, she found that while BPA didn't appear to stimulate prostate cancer by itself, if there was an early life exposure to BPA, an additional estrogen or testosterone exposure later in life then significantly increased the risk of prostate cancer. The most significant effects appeared in the lowest dose groups. </p><p>Other Clarity studies by academic investigators found a number of low-dose BPA effects, including changes in gene expression within specific regions of the brain, ovarian follicle development and spatial navigation. "The government keeps testing chemicals for safety using the same old approaches developed 50 years ago, and then they tell us that everybody is good to go," said Laura Vandenberg, an environmental health researcher at the University of Massachusetts-Amherst's School of Public Health and who was not involved in Clarity. "You don't have to see a tumor to determine something adverse is going on."<strong> </strong></p><p>In an email to National Institute of Environmental Health Sciences (NIEHS) colleagues in February 2018, Nigel Walker, a toxicologist at NIEHS who helped lead the study, highlighted one of the key questions that Clarity aimed to answer: "Are we missing any signals using 'traditional' approaches that newer technologies and approaches pick up"?</p>High bars
<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjA0OTI2MC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY0Njc1MTY3Nn0.1CyzwTcyEXosukuLFTZBFEc_JhERoOOuI8kQr0pEaRM/img.jpg?width=980" id="5034b" class="rm-shortcode" data-rm-shortcode-id="467c1b1ebb5891ff6c5a5b03744eee76" data-rm-shortcode-name="rebelmouse-image" />University of Missouri researchers Fred vom Saal and Wade Welshons. (Credit: Brian Bienkowski)
<p>Which is worse, deeming something as safe when it's not or saying something causes harm when it doesn't?</p><p>The two scenarios are referred to, respectively, as false negatives and false positives. "The FDA uses very, very conservative statistics with a low risk of false positives," said Patisaul. "That's always been a sticky wicket with the FDA versus academic scientists."</p><p>By applying conservative statistics throughout the Clarity Core Study that generally minimize false positives, noted Patisaul, the government increased the risk of false negatives — or the chance of deeming a chemical innocent when it was actually guilty of harm. </p><p>It is a balancing act, explained Bailer. With conservative methods, you may be less likely to see real effects. "But the counter response is: You are less likely to see false effects," he told EHN.</p><p>Even with a high bar, statistically significant effects emerged from the government's data. In tests for mammary gland cancerous growths, for example, the Core Study detected significant effects at the lowest dose of BPA in the part of the study where exposure stopped when the rats were weaned. But through the government's "weight-of-evidence approach," they discounted the finding as "unlikely" to be a "plausible BPA treatment-related lesion." </p><p>Their rationale: similar effects were not observed at the highest doses, the effect was not observed in animals exposed over their entire lifetimes and, as noted earlier, lesions were found in historical controls. (EHN gave the FDA a chance to comment, but the agency declined.)</p><img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjA0OTI4Ni9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYzNjA5MDg2MH0.sUn7fXOGut39SgcaMObgt3Zw_mpJ3l3UNTBGi6mhG5o/img.jpg?width=980" id="2732b" class="rm-shortcode" data-rm-shortcode-id="2f36c63c32be04af8b3fefba5deb86ba" data-rm-shortcode-name="rebelmouse-image" />
Researchers Ana Soto, Carlos Sonnenschein and Silva Krause looking at mammary glands from a BPA experiment at Tufts University. (Credit: Ana Soto)
<p>Patisaul disagreed with their methods and rationale. "There are certainly cases where developmental-only exposure has different effects than lifelong exposure," she said. "Just because you don't know why something is happening doesn't mean that the phenomenon is erroneous or 'not biologically plausible.'"</p><p>"This attitude is certainly not precautionary nor protective of public health and emphasizes the lengths to which this group will go to bury potentially important outcomes," added Patisaul.</p><p>Vom Saal said he faced a particularly high bar to uncover potentially important outcomes in his Clarity study. The weights of the rats that the FDA provided him for analysis of the effects of BPA on the development of the urogenital system, he explained, ranged widely — the heaviest rat weighed at least 250 percent more than the lightest rat. To prevent bias, all Clarity scientists were blinded to the BPA exposure levels of the animals and tissues that they received for study. Once the data were unblinded, vom Saal learned that his BPA-unexposed rats also weighed significantly less than the BPA-unexposed rats in the government's Core Study.</p><p>Increased variability in weights could cause increased variability in other measures of interest. A statistical fallout of that variability can be a watering down of the differences between exposed and unexposed rats. "This was just not done correctly," said vom Saal.</p>Deciphering data
<p> On the winding walk through a densely wooded portion of the arboretum, Hunt points out an abundance of money plants — their bright magenta blooms scattered across the forest floor. "They are weeds," she says. "Or wildflowers, depending on your point of view." </p><p> Again, two different people can be looking at the same thing yet call it two very different things — whether out in the world or in the lab. And it can be a result of bias, noted Bailer. "The eye wants to see what the eye wants to see," he said, suggesting that a scientist might, for example, see a non-monotonic pattern in data where such a dose-response effect does not actually exist. </p><p> Further, two different scientists may also take the same findings and make a number of different choices that ultimately weave a very different story for the public. What results do they include and how do they interpret those results? Which of the results do they emphasize in the study's conclusions, abstract and title? How do they publicize that end product to the rest of us? </p><p> Prins argued that the FDA has repeatedly come up with study results that show effects of BPA, "but then spin it in the discussion section to say there are no BPA effects." </p><p> Critics suggest that the FDA may spin results across studies as well. For example, FDA risk assessments have generally relied largely on a small number of older industry-funded guideline studies. "The playing field is slanted. Industry gets more input," said Hunt. </p><p> The FDA's 2014 risk assessment of BPA is one such example. Of the 36 studies that they identified as related to neurological endpoints, the FDA chose only one to include in the risk assessment. That study was funded by industry. Then, of 25 reproduction-related studies, they determined that none were appropriate for the risk assessment as they did not follow the validated protocols traditionally accepted by the FDA. </p><p> "If you cherry pick for the answer you want, you can get it," said Patisaul. "I would argue that's not in the interest of public health." When the FDA declared BPA "safe" in its previous <a href="http://wayback.archive-it.org/7993/20180126150108/https:/www.fda.gov/ohrms/dockets/ac/08/briefing/2008-0038b1_01_02_FDA%20BPA%20Draft%20Assessment.pdf" target="_blank">2008 risk assessment</a>, reporters at the Milwaukee Journal Sentinel <a href="http://archive.jsonline.com/watchdog/watchdogreports/34469194.html/" target="_blank" rel="noopener noreferrer">dug up evidence</a> that the decision was influenced by the American Chemistry Council, a leading industry trade group. </p><p> Further, the FDA's <a href="http://wayback.archive-it.org/7993/20180126150105/https:/www.fda.gov/ohrms/dockets/ac/08/briefing/2008-4386b1-05.pdf" target="_blank" rel="noopener noreferrer">science review board rejected</a> the conclusions in that assessment. </p><p> By 2008, more than 1,000 studies of BPA health effects had been published yet the FDA based its conclusion of BPA's safety on only two studies, which were funded by the plastic industry and had been deemed flawed by outside scientists and government officials. </p><iframe src="https://cdn.knightlab.com/libs/timeline3/latest/embed/index.html?source=1qWh3aMBC2innBIXWMxCZrV19JbrGtYka2_ylKLKYOTA&font=Default&lang=en&initial_zoom=2&height=650" width="100%" height="650" webkitallowfullscreen="" mozallowfullscreen="" allowfullscreen="" frameborder="0"></iframe><p> The agency defends their risk assessments of BPA. "Guideline and academic studies are independently evaluated on a case by case basis to determine if enough information is available to have confidence in the data to address the relevant risk assessment question," Naum, the FDA spokesperson, wrote in an email to EHN. "The FDA's conclusions were based on a comprehensive, transparent, review using predefined scientifically supported criteria for evaluating the available science." </p><p> Clarity provides yet another opportunity to combine a lot of data into a more comprehensive assessment of BPA. An analysis of all the data from the collaboration remains in the works. "This is where we are going to get the most compelling evidence," added Hunt. </p><p> Still, just what the feds will do with that evidence remains unclear. The FDA did not respond to questions concerning how it will use the Clarity findings, or what it would take for the results or conclusions to prompt the agency to revise its view on the safety of BPA or the criteria for determining a safe dose of a chemical. Naum only stated that the agency will "continue to monitor developments in the field," including previous reviews and the results of the Clarity Core Study, and will "take steps appropriate to protect public health." </p><p> In an email on May 8, 2012, Retha Newbold, a developmental endocrinologist with NIEHS, wrote to Walker, the toxicologist at NIEHS, of her disappointment in not getting more assurance from Jason Aungst, the toxicology branch chief at the FDA, that the agency would use the data generated from Clarity. "He is already planning his reasons why they may not use it," she wrote. Aungst helped lead that 2014 risk assessment.</p><p> Walker responded: "Like most data for FDA one can only ensure data 'can be used' for decision making, not that it 'will be.'" In February 2018, he emailed other NIEHS colleagues lamenting a lack of a "plan, timeframe or strategy" from the FDA on how it "plans to do an update to its assessment of data on BPA." </p>The final word
<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjA0OTI1NS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYwMDU0ODcwNn0.lurKlAKBuR3T_rWOvpS74y7V5BsvIza3KXO_vXVu4IE/img.jpg?width=980" id="b1e60" class="rm-shortcode" data-rm-shortcode-id="499366d94edf24b01cdf1199aa7077aa" data-rm-shortcode-name="rebelmouse-image" />Mice from Pat Hunt's lab. (Credit: Lynne Peeples)
<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjA0OTI5NC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYxNjc3MjA4Nn0.cTurjWCQK9opNqL_XCPsCsP-b0ZK1vvRX2vwVXKaD70/img.jpg?width=980" id="e2e7d" class="rm-shortcode" data-rm-shortcode-id="86e49f1dc7793974196393c168c53093" data-rm-shortcode-name="rebelmouse-image" />
Degraded cages from Pat Hunt's lab. (Credit: Lynne Peeples)
<p> Leaving a room filled with plastic cages of mice — big brown ones and tiny pink ones — Hunt and I step onto a sticky mat and change out of the Crocs we had worn inside. The process helps to ensure further contaminants including pathogens are not spread to the mice in the lab. We place the Crocs back on shoe racks just as one of Hunt's colleagues walks by holding an empty reusable pod for a Keurig coffee machine. She looks knowingly at Hunt and says, "unfortunately, it's plastic." </p><p> Hunt reassures her that, actually, this one is made of silicone. "So, you're ok," she says. "But good on you to think about that." </p><p> Not everyone thinks about the potential health risks of BPA, let alone the hundreds of other endocrine-disrupting chemicals found in common consumer products. Not surprisingly, scientists who study the chemicals for a living are more apt to consider exposures. Hunt, for example, now opts for email receipts on her stops by the Moscow Food Co-op. She knows that most cash register receipts, too, are among the everyday things that can leach BPA or one of its substitutes, such as bisphenol S, onto the skin and into the body. </p><p> Some scientists fear that the public has not been receiving accurate information on BPA. A curious consumer might look for answers online. Yet the top hit in a Google search of "bisphenol A safety" is a link to an industry-sponsored website titled "Facts About BPA." In fact, the search result appears in a stand-out box filled with material pulled from the site. Without having to click a link, you could read that BPA has a "safety track record of 50 years," and that no "cause-and-effect relationship between BPA and any human health effects" has been shown. </p><p> Patisaul suggested that the public has also not been receiving the "correct message," because "the FDA has been issuing statements before research has been done and before they've had a chance to comprehensively look at all the data." </p><p> The most recent case-in-point was a late <a href="https://www.fda.gov/news-events/press-announcements/statement-stephen-ostroff-md-deputy-commissioner-foods-and-veterinary-medicine-national-toxicology" target="_blank">February 2018 statement</a> from Stephen Ostroff, the deputy commissioner for foods and veterinary medicine at the FDA, which highlighted the agency's interpretations of the just-released draft of the Clarity Core Study. It did not mention the significant findings of effects at low doses of BPA in both the Core Study and in the peer-reviewed studies from academic collaborators that had been published by that time. National headlines appeared shortly thereafter. From NPR to Newsweek, the media was once again relaying the message from the FDA that the public need not worry about BPA. </p><p> Clarity participants had agreed at the start of the project that they would not make any policy statements, nor any conclusions, without considering all of the data. Even NIEHS was caught off-guard by the FDA's move. Earlier in February, Virginia Guidry, of the NIEHS Office of Communications and Public Liaison, emailed Walker and other colleagues about a conversation she had with a communications official at the FDA regarding the Core Study release. "I told her we were planning a reactive approach, ready for questions but no press release. They are doing the same," she wrote. </p><p> "The announcement from the FDA that has spread like wildfire is in direct contrast with that agreement," said Patisaul. "We had published four papers. Other Clarity participants had published papers. And the FDA said nothing. Then, when they issued their draft report — which was not even peer-reviewed — they made this big sweeping statement that BPA is fine. That's disingenuous." </p><script id="infogram_0_9251e230-fa7f-422a-9923-2da21c4de0d6" title="Pull quote 2" src="https://e.infogram.com/js/dist/embed.js?3df" type="text/javascript"></script><p> Pete Myers, CEO and chief scientist of Environmental Health Sciences, suggested that the move was a tactic by the FDA to control the media. The press — and the public — would pay less attention when the full report is unveiled, he told EHN. "The second wave doesn't receive the same coverage," said Myers. (Editor's note: Myers is also the founder of EHN, though the publication is editorially independent.) </p><p> A fury of emails between NIEHS colleagues followed the FDA statement. In one of those emails, Walker suggested that FDA officials had drafted "a statement to reiterate their current policy stance on the safety of BPA." The FDA did not respond to EHN's questions regarding why they issued the statement. They further declined to respond to the subsequent criticisms. </p><p> On that industry website, which belongs to the American Chemistry Council, three key findings from the government's research on BPA are listed. One of them has been front-and-center in Clarity: "No risk of health effects at typical consumer exposure levels." Hunt and other non-government scientists have co-authored a paper currently under peer review that also calls into question the other two: "Consumer exposure to BPA is extremely low" and "BPA is rapidly eliminated from the body." </p><p> "We are woefully underestimating exposure levels," said Hunt. "All of our regulatory decisions have been based on assumptions about metabolism and levels of human exposure that are questionable." </p><p> The stakes are high. With BPA just the tip of the iceberg, any conclusions and admission by the FDA of BPA's problems could cause the dominoes to really fall. It would be "like a death knell for industry," she added. "I think the feds are very sensitive to that." </p><p> <em>In <a href="https://www.ehn.org/bpa-substitutions-solutions-2641150667.html" target="_blank">part 4</a>, EHN takes a look toward the future of BPA, its alternatives and what experts suggest still needs to be done regardless of the outcome of the integrated Clarity report.</em> </p>
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