23 November 2020
Rob Bilott, the attorney who sued DuPont about PFAS health harms in Clarksburg, W.Va., says next generation compounds just as dangerous.
From cell phones to bicycle helmets to IV bags, plastic has molded society in ways that make life easier and safer. But the synthetic material also has left harmful imprints on the environment and perhaps human health.
More than 60 scientists from around the world contributed to a 2009 report, the first to offer a comprehensive review of the impact of plastics on the environment and human health, and to present possible solutions.
"One of the most ubiquitous and long-lasting recent changes to the surface of our planet is the accumulation and fragmentation of plastics," wrote David Barnes, a lead author and researcher for the British Antarctic Survey. The report was published a special issue of Philosophical Transactions of The Royal Society B, a scientific journal.
As the scrutiny of the environmental toll of plastic increases, so has its usage, the scientists reported.
Since its mass production began in the 1940s, plastic's wide range of unique properties has propelled it to an essential status in society. Globally almost 360 million tons of plastic were produced in 2018. The amount of plastic manufactured in the first ten years of this century will approach the total produced in the entire last century, according to the report.
"Plastics are very long-lived products that could potentially have service over decades, and yet our main use of these lightweight, inexpensive materials are as single-use items that will go to the garbage dump within a year, where they'll persist for centuries," Richard Thompson, lead editor of the report, said in an interview.
Evidence is mounting that the chemical building blocks that make plastics so versatile are the same components that might harm people and the environment. And its production and disposal contribute to an array of environmental problems, too. For example:
People are exposed to chemicals from plastic multiple times per day through the air, dust, water, food and use of consumer products.
For example, phthalates are used as plasticizers in the manufacture of vinyl flooring and wall coverings, food packaging and medical devices. Eight out of every ten babies, and nearly all adults, have measurable levels of phthalates in their bodies.
In addition, bisphenol A (BPA), found in polycarbonate bottles and the linings of food and beverage cans, can leach into food and drinks. The U.S. Centers for Disease Control and Prevention reported that 93 percent of people had detectable levels of BPA in their urine.
Polybrominated diphenyl ethers or PBDEs, which are flame-retardants added to polyurethane foam furniture cushions, mattresses, carpet pads and automobile seats, also are widespread.
The plastics industry maintains that its products are safe after decades of testing.
"Every additive that we use is very carefully evaluated, not just by the industry, but also independently by government agencies to look at all the materials we use in plastics," said Mike Neal, a consumer and environmental affairs specialist at PlasticsEurope, an industry trade association, and a co-author of the report.
But some of these chemicals have been shown to affect reproduction and development in animal studies, according to the report. Some studies also have linked these chemicals with adverse effects in people, including reproductive abnormalities.
"We have animal literature, which shows direct links between exposure and adverse health outcomes, the limited human studies, and the fact that 90 to 100 percent of the population has measurable levels of these compounds in their bodies," said John Meeker, an assistant professor of environmental health sciences at the University of Michigan School of Public Health and a lead author. "You take the whole picture and it does raise concerns, but more research is needed."
Shanna Swan, director of the University of Rochester's Center for Reproductive Epidemiology, conducted studies that found an association between pregnant women's exposure to phthalates and altered genital development in their baby boys.
Also, people with the highest exposure to BPA have an increased rate of heart disease and diabetes, according to one recent study. Animal tests studies of PBDEs have revealed the potential for damaging the developing brain and the reproductive system.
Yet the effects on human health remain largely unknown. To help shed more light on the issue, the report recommends more sophisticated human studies.
"It's tough to have a smoking gun with a single animal study or observational human study," Meeker said. "We need to have different types of studies indicating a consistent pattern to more definitively determine health effects resulting from these chemicals."
But testing humans for endocrine disruptors can be tricky because phthalates and BPA pass through the body so quickly. In addition, tests for each chemical cost about $100 a pop.
Deciding which chemicals to test and at what dose is also an issue. To date, most studies have addressed single chemicals, and there are limited data on the interactions between chemicals. Compounding the problem is the discovery that endocrine disrupting chemicals may have effects at doses lower than those used in the Environmental Protection Agency's standard toxicity tests.
"It's a very complicated picture and the laboratory model of just taking one isolated chemical and giving it to a genetically pure strain of rats in clean cages, clean air and clean water and seeing what it does just doesn't come close to mimicking the human situation," Swan said.
Many researchers recommend studies that test pregnant women as well as their children. The National Children's Study will do just that by examining environmental influences on more than 100,000 children across the United States, following them from before birth until age 21.
"There are so many questions now with these chemicals in relation to cardiovascular disease, age and puberty, obesity, developmental disorders," said Swan. "We don't know what's causing it, only hints, so the beauty of the National Children's Study is that we can look at all of these endpoints and it should reveal a lot of answers."
Plastic's problems extend beyond the human body, according to the report. More than one-third of all plastic is disposable packaging like bottles and bags, many of which end up littering the environment.
Although the image of a bird tangled in a plastic necklace is by now burned into the public's eye, ingestion of plastic fragments is much more common. Once inside, plastic can pack a one-two punch by both clogging an animal's stomach and poisoning it with chemicals that have concentrated in the plastic. Some chemicals are then transferred to the food web when animals eat them.
More than 180 species of animals have been documented to ingest plastic debris, including birds, fish, turtles and marine mammals, according to the report.
Unfortunately, collecting data on plasticizers' impacts on wildlife suffers the same pitfalls as studying human health. Still, there is already evidence that chemicals associated plastics might harm wildlife.
For example, laboratory studies have shown that phthalates and BPA affect reproduction in all studied animal groups and impair development in crustaceans and amphibians.
"While there is clear evidence that these chemicals have adverse effects at environmentally relevant concentrations in laboratory studies, there is a need for further research to establish population-level effects in the natural environment," according to the report.
Charles Tyler, a professor at the University of Exeter School of Biosciences in the United Kingdom and a senior author of the report, said that scientists have shown that "some of these chemical compounds are getting into the environment and are in some environments at concentrations where they can produce biological effects in a range of wildlife species."
Traveling from coast to coast, plastic can endure for thousands of years due to the reduced UV exposure and lower temperatures of aquatic habitats.
Barnes demonstrates plastic's mobility with his account of a plastic sighting during an expedition to the Amundsen Sea where he took biological samples, the first there ever. The Amundsen, located in the Pacific Sector of Antarctica, is the only sea in Antarctica with no research station on its coast and the nearest urban center thousands of miles away.
"Even for us, getting in was a challenge because there's so much ice and it's so difficult to get there," said Barnes. "But even in that remotest of environments, there was plastic floating on the sea surface.
Plastic also serves as a floating transportation device that allows alien species to hitchhike to unfamiliar parts of the world, threatening biodiversity. Global warming further aids the process by making previously inhospitable areas like the Arctic livable for invasive species, which can be detrimental to local species.
For example, plastic items are commonly colonized by barnacles, tubeworms and algae. Along the shore of Adelaide Island, west of the Antarctic Peninsula, ten species of invertebrates were found attached to plastic strapping that was littering the ice.
"Raising the temperature just one degree can make the difference between getting to someplace and actually surviving once you get there," said Barnes.
Plastic is so resilient that even burying it deep within the earth doesn't keep it from impacting the environment. Currently it accounts for approximately 10 percent of generated waste, most of which is landfilled. But, as the report notes, placing plastics in a landfill may simply be storing a problem for the future, as plastic's chemicals often sink into nearby land, contaminating groundwater.
In addition, production of plastics is a major user of fossil fuels. Eight percent of world oil production goes to manufacturing plastics.
As plastics grow in volume at a rate of about nine percent each year, the authors emphasize that tackling its problems means addressing its sustainability.
One solution is to treat plastic as a reusable material rather than as a disposable commodity that's quickly discarded. That means making plastic more easily recyclable from the get-go by using fewer materials in the manufacturing process and increasing recycling facility availability.
"The recycling message is simple; both industry and society need to regard end-of-life items, including plastics, as raw materials rather than waste," stated the report.
Increasing the availability of biodegradable plastic, which can be made from renewable materials from plants such as corn and soy, is another option.
"Biodegradable plastics have the potential to solve a number of waste-management issues, especially for disposable packaging that cannot be easily separated from organic waste in catering or from agricultural applications," according to the report.
However, currently production capacity for biodegradable plastics worldwide is around only 350,000 tons, representing less than 0.2 percent of petrochemical-based plastic. In addition, "most of these materials are unlikely to degrade quickly in natural habitats, and there is concern that degradable, oil-based polymers could merely disintegrate into small pieces that are not in themselves any more degradable than conventional plastic," stated the report.
To help mitigate the potentially harmful chemicals in plastics, the authors recommend that more studies be conducted on the biological mechanisms that may be affected by plastic additives and in particular, low-dose chronic exposures.
In the meantime, the report recommends reducing the use of these chemicals and developing safer alternatives, a strategy known as green chemistry.
"Had this approach been in place 50 years ago it would probably have prevented the development of chemicals that are recognized as likely endocrine disruptors," the report said.
The report also suggests that plastic waste can be reduced by using labels that allow consumers to choose packaging based on a lifecycle analysis that includes all components of the manufacturing process. For example, if the product were made of mostly recycled materials, used minimal packaging and could be easily recycled, it would get a green dot. If the product were made of excessive packaging that used a lot of virgin materials, it would get a red dot.
"Personally, I feel that's the way to do it, rather than a knee jerk reaction where legislation says we can't use certain types of plastic," said Thompson. "Having that information will help drive the system because I think consumers are keen to make the right choice when provided with all the information."
Neal of PlasticsEurope said consumers, not the industry, are responsible for making sure plastics don't wind up littering the environment.
"In my view the responsibility is fairly and squarely on the consumer," he said. "People tend to pick on plastics because perhaps it's the most visible form of litter and because it's lightweight so it can move around a bit, but actually it's only a small part of the litter problem."
The authors said that if plastics are made and used responsibly, they can help solve some environmental problems.
For example, one study found that packaging beverages in PET (a type of plastic) versus glass or metal reduces energy use by 52 percent and greenhouse gas emissions by 55 percent. And, solar water heaters containing plastics can provide up to two-thirds of a household's annual hot water demand, reducing energy consumption.
Plastics, if used wisely, "have the potential to reduce mankind's footprint on the Earth," Thompson said.
Editor's note: This article was first published in July 2009 by Environmental Health News and updated April 2020. It is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.
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.
That exposure, according to research that regulators are willfully ignoring, is increasingly linked to harmful health impacts ranging from birth defects to cancer.
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.
Exposed: The BPA Experiment www.youtube.com
Hundreds of emails obtained via the Freedom of Information Act and dozens of interviews show that science is being perjured:
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.
"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.
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.
And follow the fallout from this investigation on Twitter at the hashtag: #ExposedBPA
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.
The ongoing health concerns and mixed messaging over the chemical BPA
Is a federal study of BPA contaminated by questionable motives, methods?
"The government keeps testing chemicals for safety using the same old approaches developed 50 years ago"
What will it take to rid our store shelves of BPA and its equally hazardous cousins?
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
"The mindless clinging to outdated science is detrimental to public health and to the development of good science"
Babies are being exposed to "totally unacceptable concentrations"
"This should change how the FDA and other people look at the safety of BPA."
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.
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.
Scientists have found BPA in more than 90 percent of Americans tested. 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.
"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.
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.
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."
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.
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.
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.
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 20,000 times lower than what the FDA says is safe, comparable to levels at which most of us are exposed.
Even back in 1982, 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.
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.
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:
●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.
●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.
●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.
●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.
●Hints of potential industry influence, such as the FDA's reliance on industry-funded studies.
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.
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.
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.
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.)
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."
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.
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.
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.
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.
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, EFSA dropped its safety limit from 50 to 4 micrograms of BPA per day per kilogram of body weight.
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 $22.5 billion by 2022 and top 7 million tons by the end of 2023.
"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."
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.
University of Massachusetts-Amherst environmental health scientist Laura Vandenberg. (Credit: Umass.edu)
"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.
"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."
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."
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."
In the 1930s, a British medical researcher discovered 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.
Its future would instead be in the chemical industry.
Cheryl Rosenfeld, a biologist at the University of Missouri and another Clarity investigator. (Credit: University of Missouri)
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.
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.
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 PBS's Frontline about the threat posed by endocrine-disrupting chemicals used in plastics and other consumer products.
"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.
By 2008, 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.
"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."
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."
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 an increase in anxiety-related behaviors or attention deficit hyperactivity disorder (ADHD).
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."
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 2016 study 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.)
"This is an underestimate of an underestimate of an underestimate," Dr. Leonardo Trasande, a researcher at New York University, author of the book, Sicker, Fatter, Poorer, and an author on both studies, told EHN.
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."
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."
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.
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.
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.
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.
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 resulting dose-response relationship resembled a bell.
"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."
His guess as to why: "Nature has decided it doesn't want to have an overreaction to an endocrine hormone."
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 scientists have identified potential biological mechanisms for non-monotonic dose-responses, such as opposing effects from multiple hormone receptors.
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.)
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.
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.)
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.
Researchers Fred vom Saal and Wade Welshons at their University of Missouri lab. (Credit: Brian Bienkowski)
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."
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.
"You can't weigh a brain to find out what is going on in there," Soto said.
In 2001, the NTP appeared to agree. 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.
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.
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," wrote the authors.
The report was an update of the agency's 2008 assessment, 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.
An external FDA committee had even reviewed the 2008 report and disagreed 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."
Of note: A 2006 analysis 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.
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."
"If you don't ask the question, you're not going to get the answer," she added.
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."
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."
Gail Prins, a researcher at the University of Illinois at Chicago and Clarity investigator (right). (Credit: uic.edu)
On February 23, 2018, upon completion of the draft version of the government's Clarity Core Study, the FDA released a public statement, suggesting that the findings supported its position that "currently authorized uses of BPA continue to be safe for consumers."
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.
"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."
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."
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.
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."
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."
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.
As expected, the government's report stated that exposing rodents to BPA resulted in some health effects at high doses but not at the low doses to which people are generally exposed.
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.)
But that is not exactly what the government's data said, even if that sentiment was reflected in the FDA's early press release.
"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.
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."
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.
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."
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."
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."
"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."
In part 2 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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 1 ppb can result in severe obesity. 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."
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.
Scott Belcher, a biologist at North Carolina State University, and a Clarity investigator, pointed to a number of studies that provide evidence for cellular mechanisms driving these non-monotonic responses, including opposing effects from multiple hormone receptors and negative feedback loops, a key regulatory mechanism in living things.
"Most simply put, biological systems are complicated and are controlled by multiple types of regulation," he told EHN.
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."
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."
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.
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.
"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."
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.
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."
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"?
University of Missouri researchers Fred vom Saal and Wade Welshons. (Credit: Brian Bienkowski)
Which is worse, deeming something as safe when it's not or saying something causes harm when it doesn't?
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."
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.
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.
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."
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.)
Researchers Ana Soto, Carlos Sonnenschein and Silva Krause looking at mammary glands from a BPA experiment at Tufts University. (Credit: Ana Soto)
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.'"
"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.
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.
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.
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."
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.
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?
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."
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.
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.
"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 2008 risk assessment, reporters at the Milwaukee Journal Sentinel dug up evidence that the decision was influenced by the American Chemistry Council, a leading industry trade group.
Further, the FDA's science review board rejected the conclusions in that assessment.
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.
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."
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.
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."
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.
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."
Mice from Pat Hunt's lab. (Credit: Lynne Peeples)
Degraded cages from Pat Hunt's lab. (Credit: Lynne Peeples)
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."
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."
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.
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.
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."
The most recent case-in-point was a late February 2018 statement 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.
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.
"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."
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.)
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.
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."
"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."
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."
In part 4, 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.
This is part 4 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.
PITTSBURGH — A percussion of metal-on-metal echoes through the lab as empty food cans drop one by one off a conveyor belt and into rounded pockets of a rotating blue cogwheel.
As the cog circles counterclockwise, the can spins rapidly. Two spray guns blast a liquid lining inside before the can falls onto another conveyor belt and then shoots up a chute to a final belt that carries it down into a large curing oven.
These now freshly baked cans, their interiors a toasted brown, are part of a series of validation tests at the coatings company Valspar, recently acquired by Sherwin-Williams. For more than a decade, Valspar has worked to develop safe and effective replacements for food and beverage can linings historically made with bisphenol A.
Until about a decade ago, a layer of BPA-based epoxy about 20 times thinner than a human hair coated the inside of nearly all food and beverage cans. This shield excelled at preventing corrosion and, therefore, protecting us eaters and drinkers from deadly spoilage. But evidence has piled up that bits of the substance can leach from that lining and into soda, soups, Spam and sardines, among other canned products. And studies from academic laboratories show that BPA may mimic and mess with our hormones even at the tiniest of doses — increasing risks of cancer, diabetes and infertility, as well as derailing the normal development of a child's brain. That science suggests that our bodies are so sensitive to this compound that the use of BPA needs to be eliminated, not just reduced, to protect our health.
"The regulatory agencies are saying BPA is just fine," Tom Mallen, global director of packaging regulatory affairs at Sherwin-Williams, told EHN. "But there is a large voice contradicting that."
Despite this insistence from regulatory agencies of BPA's safety, some companies have been moving ahead with alternatives. With help from developments in green chemistry, and driven largely by consumer demand and policy-making outside of Washington, they are beginning to remove BPA and other endocrine-disrupting chemicals from store shelves. Still, progress is slow as the stakes are high. The global BPA market continues to grow and is predicted to surpass 7 million tons by the end of 2023. In addition to cans, the chemical is found in cash register receipts, dental sealants and the polycarbonate plastic used in reusable water bottles, among other products. Adding to the challenge: a safe and effective BPA replacement for one product may not be a suitable swap for others. And many of the alternatives that allow a manufacturer to proclaim a product "BPA free" show health effects that are just as bad, if not worse, than BPA. What will it take to ensure only our natural hormones are running the show in our bodies?
An investigation by EHN has uncovered details of a stand-off between academic scientists and federal regulators that 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. Academics had increasingly voiced disagreement with the actions, or lack thereof, of the U.S. Food and Drug Administration with regard to the hormone imposter. The methods used by FDA regulators to assess the safety of chemicals, they have argued, remains decades behind the science. Clarity aims to help these critics and regulators reach a consensus on BPA's potential health harms, and to inform future testing and regulation of BPA and hundreds of other endocrine-disrupting chemicals including BPA replacements such as bisphenol S, or BPS.
So far, no such luck. As EHN detailed—via hundreds of emails obtained through Freedom of Information Act requests, along with dozens of studies and reports, and more than 50 conversations with scientists, regulators and other stakeholders—the FDA appears to have made up its mind on BPA before Clarity even began. "They already put a stake in the ground and they don't want to budge," Heather Patisaul, a professor of biology at North Carolina State University and a Clarity investigator, told EHN.
Here at Sherwin Williams' Packaging Global Technical Center in Pittsburgh, the tone is more positive. The company is among those actively pursuing BPA alternatives that won't disrupt our hormones. Mallen and four others sit around a table in the center's conference room, a short walk from the building with the Rube Goldberg-like can machinery. This room's walls display collections of consumer products that Valspar has coated over the decades, grouped by color of the brand's label.
There is the red assemblage: a metal bottle of Budweiser Select, a can of Campbell's Chunky BBQ seasoned pork, a Coca-Cola can. Further down the wall are shelves showcasing cans of San Pellegrino Limonata, Bumblebee solid white albacore tuna and Friskies Shreds with ocean whitefish and tuna — all with varying shades of yellow. Nearly every product displayed is lined with BPA. The substance has been an integral component of modern commerce for decades. Yet a major shift is underway for the half a billion or so food and beverage cans currently made each day in North America.
Over a lunch of sandwiches, chips and blue cans of water, Mallen goes on to describe his company's decision to not wait on regulators and to enlist the help of some of the staunchest BPA critics in the development of their next generation of BPA-free can linings. Starting in 2008, through a process they call "safety by design," Valspar went looking for a high-performing chemical compound that was not only less likely to leach from the inside of a can but also lacked the hormone-mimicking behavior of BPA or BPS. The winning compound: tetramethyl bisphenol F (TMBPF).
Academic scientists have tested the compound for a range of endocrine disruptive activities — effects that regulators do not typically consider in their safety assessments — and Valspar is now using TMBPF as the basis for ValPure V70, its newest family of can linings. The BPA-free epoxy lines those oven-cured cans, our blue cans of water and a small but increasing share of the food and beverage can market across the United States. Sherwin-Williams is applying for approval in the European Union.
"The industry's thinking was to not talk to critics, and to marginalize them," said Mallen. "We decided that wasn't a productive approach."
"This is the only time I've seen a company reach out to people with expertise." – Thomas Zoeller, UMass Amherst
Thomas Zoeller, a biologist at the University of Massachusetts, Amherst, recalled his surprise when Valspar sought his collaboration. "This is the only time I've seen a company reach out to people with expertise," he told EHN, applauding Valspar's recognition of the modern toxicity testing techniques used by academics.
When evaluating a chemical that will come into contact with food, federal regulators generally look for obvious health effects such as changes in the weight of the brain and other organs in laboratory animals, or a fast-growing tumor. Academics search for more subtle changes that can be induced by small fluctuations in hormones such as attention deficit disorders or infertility. Such impacts may not even appear for years or until subsequent generations.
Not only was Zoeller free to use his modern scientific methods to evaluate TMBPF, but he was free to report whatever his science uncovered — even if it was unwelcome news for the company. "They were big on none of this work being private," he said. "I didn't have to sign an agreement."
Zoeller's collaboration with the government as part of the Clarity project, however, has not elicited the same warm feelings. "I don't think they have dealt with us in good faith," he said. An integrated Clarity report that pulls together findings from the government's study and studies conducted by participating academics is underway and expected to be completed by the end of 2019. Zoeller said that he doesn't anticipate the report will inspire any significant moves by the FDA to increase protections for public health.
The agency's website poses and answers the seemingly simple question: "Is BPA safe?" The agency goes on: "Yes. Based on FDA's ongoing safety review of scientific evidence, the available information continues to support the safety of BPA for the currently approved uses in food containers and packaging."
Linda Birnbaum, former director of the NIEHS and the National Toxicology Program, which are leading Clarity alongside the FDA, noted that knowledge of endocrine-disrupting chemicals and their actions has expanded in recent years — including just how a tiny dose of a chemical could affect the body even while a higher dose might do little or nothing. "I think we have to understand that science changes and advances and we need to be open to those changes," Birnbaum told EHN.
EHN's investigation has uncovered various signs of deficiencies in the FDA's science on BPA, including in its handling of Clarity, that seem to have stalled any chance of progress. There was the agency's insistence on aspects of Clarity's design that limited the study's robustness to detect health effects, and its premature public statements downplaying evidence of BPA's effects in the study. But while the FDA doesn't appear to be budging, industry responses to consumer concerns may signal a paradigm shift. Michael Hansen, a senior scientist for Consumer Reports, pointed to growing public awareness and demand for products free of BPA as well as phthalates, another family of endocrine-disrupting chemicals we encounter every day. Phthalates are used to soften the plastics in food packaging and as solvents in cosmetics, fragrances and other personal-care products.
"The market is starting to respond to that," he told EHN. "But more action has to be taken."
Most BPA replacements currently used in cash register receipts and plastics were created by rapidly tweaking the BPA molecule to form similar compounds such as BPS. The focus was on functionality, as opposed to looking at safety. And only after BPS was on the market did independent researchers began to find that it has endocrine-disrupting effects very similar to, or possibly even greater than, BPA.
A similar scenario has played out for some of BPA's other chemical cousins. A 2017 study found that six BPA substitutes—all used in products promoted as "BPA free"—had as much, if not more, of an estrogen-mimicking effect on human breast cancer cells as BPA.
And it's not only replacement bisphenols that are of concern. A bisphenol-free material called Tritan, developed by the company Eastman Chemical, is now widely used in plastic water bottles and food containers. The material is marketed as not having any hormone-related effects, yet some tests have found that stuff leaching from Tritan products — including products made for babies — could interfere with our hormones.
Kristin Parker, a spokesperson with Eastman, stated in an email to EHN that tests conducted by the company and by other third parties confirm that "Tritan is safe for its intended uses."
One of the studies that called Tritan's safety into question also found that some BPA-free plastic products didn't show any endocrine-disrupting properties. Those products contained BPA alternatives such as glycol-modified polyethylene terephthalate or cyclic olefin polymer.
But George Bittner, a neurobiologist at the University of Texas at Austin and lead author on the paper, is not among those expressing optimism. He did not identify what specific products contained those alternatives, noting that companies are constantly changing their formulations and may well be using different chemicals now. Bittner blamed a weak-to-nonexistent regulatory and consumer push on the lack of motivation for companies to prioritize getting endocrine activity out of their products.
Companies seem content with just "BPA-free." "It is like if Johnson & Johnson were selling a bandage that says it doesn't have Staph. aureus," said Bittner, who also founded CertiChemi, a company that tests products for endocrine activity, and PlastiPure, a company involved in making plastics without estrogenic chemicals. "That's nice. But how about Streptococcus or E. coli? And their response is only, 'There is no Staph. aureus.'"
"'BPA-free' is a fantastic marketing tool, but it is not evidence to the consumer of a safe product," Pat Hunt, a geneticist at Washington State University in Pullman, told EHN.
Of course, TMBPF, the basis for V70, is itself a bisphenol. This fact has made convincing people of its safety an uphill battle, according to Mallen. He underscored that Valspar has taken a novel approach, assessing the compound's safety alongside functionality throughout the entire process.
Some researchers seem to vet his stance that we may not need to immediately toss out every BPA relative. "Are all bisphenols bad? Maybe the answer is yes, until you can show certain ones are better," Joel Tickner, a pioneer in green chemistry at UMass Lowell, told EHN. Terrence Collins, another green chemist at Carnegie Mellon University, added that V70 is a "step in the right direction."
"They are providing a model for changing the chemical enterprise to deal more adequately with endocrine disruption," he said. Still, Collins told EHN that he is waiting on further data regarding the compound's potential endocrine-related activity: "I'm optimistic, but I want more convincing."
In a lab upstairs from the conference room, chemist Nusrah Hussain wears a pink and black headscarf and blue lab coat. She stands over a five-liter glass vessel, mixing an epoxy resin and other ingredients together to formulate a new polymer. If all goes well, the polymer could ultimately be used in a can coating for a new recipe of Campbell's Chunky soup.
Valspar is developing various versions of its ValPure V70 coating with specific characteristics for various foods and beverages. "Different end uses need different properties," Hussain told EHN. The expanding variety of products sold in cans today — from water to wine, even coffee and cannabis-infused alcoholic drinks — has added to the challenge.
Of course, cans are just one of the many sources of BPA in our everyday lives. And, unfortunately, V70 doesn't make a good polycarbonate for that array of other bisphenol-loaded plastics on the market, noted Collins. Beyond BPS and Tritan, few alternatives are in the works for plastics. A Korean research team is currently investigating a glucose-derivative bioplastic, for example.
Although, to date, bioplastics haven't proven to be a panacea. Martin Wagner, a biologist at the Norwegian University of Science and Technology, told EHN that he found "strong and abundant" toxic effects in the bioplastics he recently tested.
Just how well a material serves its intended purpose, along with affordability, are requisite for replacements pushing out toxic predecessors. And that's a central challenge with all BPA substitutes.
The first beverage can was made back in 1935, shortly after the end of Prohibition. That can of red Krueger Beer was comprised of three steel pieces with a solvent-based PVC coating supplied by Valspar. But it wasn't long before BPA emerged as the superior substance for protecting the quality and flavor of whatever was inside a can. By the late 2000s, the majority of food and beverage cans were lined with BPA epoxy.
Consumer concern over BPA had begun escalating by that time — a result of accumulating research by academic scientists. In 2015, California responded by adding BPA to its Proposition 65 list of chemicals known to cause cancer or reproductive harm. That same year, France banned the use of BPA in all food packaging and containers. Because it's inefficient for manufacturers to use different products for different markets, industry was motivated to look for alternatives, Jeff Niederst, marketing director for beverage at Valspar, told EHN.
As makers of plastics looked to BPS and other chemical cousins, most can coating companies including Valspar initially sought non-bisphenol alternatives such as polyesters and acrylics. But those materials have significant performance limitations. Niederst wanted a better solution. He convinced his upper management that they had to look back to bisphenols, and work from the ground up to find one that did not have endocrine-disrupting characteristics.
Valspar scientists started by screening hundreds of molecules, searching for a bisphenol that would not physically fit into hormone receptors. One strong candidate, TMBPF, emerged. They then began working with environmental health advocates and academic scientists, including Zoeller, to determine how much of the compound might migrate from coated cans and make sure that whatever did make it into our bodies wouldn't scramble our hormones.
Although there are well-established tests for signs of a chemical causing cancer, there is "no widely accepted tests for androgen or estrogen activity and so forth," said Mallen. "We had to depend on people in academia to help educate us and guide us."
Scientists found that very little TMBPF could leach out of a can and into food: less than the 0.2 parts per billion that their testing method could even detect. Ana Soto, another Clarity participant and an endocrinologist at Tufts University, however, suggested that the more pertinent information came in testing endocrine activity of can extracts. It's not necessarily a single compound but rather a chemical cocktail that could leach out of a can lining. The additional substances may, too, have endocrine activity. So, she tested samples of the can extracts, for estrogenic activity. None.
Further tests, included in a paper published in October, looked to see if TMBPF could disrupt the delicate levels of androgen and aromatase, an enzyme that converts testosterone to estrogen, in the body. Some subtle anti-androgenic activity was seen at the highest dose studied; otherwise, all appeared clear.
"I don't eat anything canned," said Soto. "But I understand people do that. And a person who eats canned food is better off, in principle, with this one than the conventional one."
Companies that are shifting away from BPA, such as Coca-Cola and Campbell's Soup, still referenced FDA's continued assurance of its safety. Mallen, too, was hesitant to suggest that more regulation is needed from the government on BPA. And he never said that low-dose BPA exposures actually posed a threat to public health. "The problem with the whole endocrine thing is there is no consensus," said Mallen. "We have to, as a society, get to a consensus on that first. Then the regulators would be able to do something with that."
Nevertheless, Valspar appears motivated to phase out BPA and avoid its equally troublesome cousins. The company is responding to consumer demand, much like the Campbell Soup Company. "Although the FDA has determined that BPA is safe to use in food packaging, we understand that some people would prefer to avoid it," Amanda Pisano, a spokesperson with Campbell's, told EHN in an email.
As more companies follow their lead, scientists hope they will also do the extra legwork to ensure any replacement is not just another endocrine disruptor. Rachel Simon, a researcher at the Lowell Center for Sustainable Production at UMass Lowell, is optimistic. "We're seeing companies move more quickly to trying to find innovative solutions. It doesn't matter what the driver is — regulatory or consumer demand," she told EHN. "Previously, people spent energy trying to fight about whether it is or it isn't safe. By focusing on innovation, we're able to find solutions faster than if trying to defend the legacy incumbent. I think we're seeing a shift."
Simon and Tickner are working to propel that shift, developing methods for chemists and toxicologists to evaluate potential substitutions for chemicals of concern, including the other thousand or so chemicals on the market that are believed to have endocrine-disrupting properties. Multiple strategies exist for creating chemical substitutes.
"You can look at less hazardous, structurally-similar molecules, or you could look at totally new molecules that achieve the same function, or you could make process changes that eliminate the need for a chemical," said Tickner. "Or you could just find another way to get the service that the chemical provides."
For example, there are efforts to bypass plastics in packaging, such as Tetra Brik, the paper-based liquid cartons used for various soups and beverages. A substitution toolbox has been expanding over the last several years. In 2013, a team of biologists, chemists and toxicologists developed a "Tiered Protocol for Endocrine Disruption" to help industrial scientists detect endocrine-disrupting tendencies early in the chemical development process. (Editor's note: Pete Myers, CEO and chief scientist of Environmental Health Sciences, was involved in the development of the protocol. He is also the founder of Environmental Health News, though the publication is editorially independent.)
Among the most useful tests to detect potential effects on the human endocrine system, according to the 23 authors, involves zebrafish. The tiny fish are fast to develop, transparent and absorb compounds through water. "It's a very powerful assay for signaling a lot of effects. And it's not expensive," said Collins, one of the authors of the protocol. "It is now possible to the highest levels of contemporary science to say whether or not you've got an endocrine disruptor." A separate nonprofit, Advancing Green Chemistry, helps connect people wanting to have chemicals tested and the experts to do the appropriate testing.
"Using this framework, chemists could refine chemicals and design toxicities out of those molecules," said Wagner of the protocol. "It takes a lot of time and resources, but eventually you end up with chemicals that you know right from the start are not toxic."
In addition to bioplastics, Wagner's recent paper analyzed the chemical mixtures in a range of plastics products and found that most showed some potential toxicity. His team found far more androgen-blocking effects across chemicals than the more well-known estrogenic impacts associated with BPA. The usual suspects, bisphenols and phthalates, played only a minor role. In fact, many of the suspect chemicals were unknown. Of the 1,400 substances they detected in a sample of plastic products, his team could identify only 260 compounds. "It's impossible for consumers to know what plastic contains what chemicals, and what's safe," he added. "It should be on the producers' responsibility to make sure their products are safe."
Wagner acknowledged that manufacturers are unlikely to start doing that by themselves given the added costs. Pressure is needed from the public and from regulators. "Industry has to strive to prevent the problem, but we will always need the regulatory part," added Soto. "The way the FDA does regulation has to change."
Tickner and Simon are among those arguing that the federal government should take advantage of the tools now available to build a regulatory framework for industry that includes the appropriate assays to detect low-dose endocrine-disrupting effects. Meanwhile, Europeans are already starting to employ assays very similar to those detailed in the tiered protocol. And they're creating incentives for its use. EU's Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) regulation states that endocrine disruptors can be identified as substances of very high concern alongside chemicals known to cause cancer, mutations and toxicity to reproduction.
In July, the General Court of the European Union confirmed that BPA must be listed as such a substance, potentially subjecting the chemical to further regulation and restrictions under REACH. The implications could reach back to the U.S., much like how California's stricter rules impact markets across the country. "EU's regulations shape the world's regulations," said Simon.
Collins underscored the urgency, calling for a global movement with regard to endocrine disruptors that parallels the one for climate change. As machines continue to print cash register receipts, mold hard plastic bottles and spin metal cans, we remain part of a massive experiment with far greater implications than any designed by Rube Goldberg.
"It's just as bad as the climate in terms of its impact on living things," he said. "It's arguably faster acting, and hardly anyone knows about it."
Yes, the sweet smell of perfumes, even the most expensive ones you invest in, can leave you bewildered with dangerous reactions.
Kids exposed to phthalates prenatally and as 3-year-olds have decreased motor skills later in their childhood, according to a new study.
The study is concerning because phthalates are so widely used. Previous research found that phthalate exposure is linked to decreased motor skills for infants and toddlers but this is the first study to suggest these problems may persist as the children age.
"As lower scores on measures of motor development have been associated with more problems in cognitive, socioemotional functioning and behavior, the findings of this study have implications related to overall child development," the researchers wrote in the study published online in Environmental Research.
"This is a crucial public health challenge given the globally ubiquitous nature of phthalates," they added.
Phthalates—used widely in vinyl flooring, cosmetics, detergents, lubricants and food packages—are endocrine disrupting chemicals, meaning they alter the proper functioning of people's hormones. They've also recently been found in diapers and women's sanitary pads.
The chemicals have been linked to multiple health problems, including birth and reproduction problems, diseases, impaired brain development, diabetes and cancer. Just last week researcher linked phthalates to reduced lung function as well.
Researchers looked at the prenatal phthalate exposure of 209 children, as well as exposure when they were 3 years old. They found girls that were exposed to higher levels of phthalates while in the womb had decreased motor skills at age 11; and boys exposed to higher levels of phthalates at age 3 had decreased motor skills at age 11.
The women and children are from an ongoing study cohort in New York City; the mothers are all either Black or Dominican.
Senior author of the paper Pam Factor-Litvak, a professor and epidemiologist at the Columbia University Medical Center, told EHN the motor skills tests included "fine motor skill" tests such as whether or not kids can put a peg in a peg board or coordinating with their upper limbs, and a focus on larger muscle groups, with tests such as walking on a balance beam or running.
She said the importance of motor skills is often overlooked in research. "Motor function is so important and it has a lot to do with cognitive and social development as well," she said.
The researchers didn't look at how the phthalates might be impacting motor skills; however, previous studies have shown the chemicals to alter proper function of the thyroid, which is crucial to proper motor skills and brain development. The chemicals could also disrupt vital neuron activity in the kids' brains, which are involved in motor skills' development.
Factor-Litvak said it's not entirely understood why they saw different impacts on boys and girls but that phthalates are known to disrupt sex steroid hormones such as estradiol and androgens, which could impact boys' and girls' brains in different ways.
The study alone doesn't prove the compounds are causing these impacts, however, it adds to mounting evidence. Multiple previous studies have found a link between phthalate exposure and decreased motor skills.
Those studies focused on newborns to children around preschool age. This study suggests that these prenatal and early life exposures may continue to impact children well into their childhood years—and maybe beyond, Factor-Litvak said.
"That's what we worry about – the downstream impacts after childhood. [Those impacts] haven't been studied," she said.
As reporters, we're used to asking questions.
When it comes to questions we ask before we even start reporting, two stand out: why is this is a story? And, if the first answer is sufficient, how will we tell it?
This year our small newsroom added another question: What will we accomplish with this reporting?
It's a simple question, but it has transformed our thinking. By asking this question on the front end, and re-framing our reporting with a bias for action, I feel we've had one of our most impactful years of reporting since EHN opened shop more than 15 years ago.
Impact—that's what defines my mission as EHN's editor.
And I don't mean page views, comments on Facebook, or awards. In our coverage of pollutants and environmental injustice this year, we went beyond bringing attention to the issues. We moved the needle toward less human exposure to toxics and correcting injustices.
Let me give you some examples:
And we're damn proud. We remain as dedicated as ever to objective journalism—but fully acknowledge that speaking truth to power is more important than ever as those in power increasingly try to create their own truth.
In the coming year, several initiatives will further our mission of driving science into public discussion and policy on environmental health issues:
It is an exciting time at EHN and we remain grateful for your attention and your continued support.
We're wishing you all happy, healthy holidays and, to borrow a phrase from longtime reader and donor, George Ball, Jr., "Go get 'em!"—because that's exactly what we'll be doing in 2019.
Editor's note: This is adapted from a lecture Zoeller gave at the 51st Session of International Seminars on Planetary Emergencies: Science for Peace the World Over, in Erice, Italy, in August. It has been lightly edited.
Chemicals are manufactured for use in almost everything with which humans come into contact including food, plastics, personal care products, clothing and building materials.
In addition, manufactured chemicals contaminate our environment in ways not always anticipated in air, dust, food and water.
Most of these chemicals are derived from crude oil; in fact, petrochemical production is now driving oil demand. This demand for petrochemicals is expected to increase.
It is therefore important to recognize that only a few – and a minuscule percentage – of chemicals with which we come into contact have been tested for human safety.
The cause of chemical exposures to the human population is profit and convenience. If the production and use of chemicals resulting in human exposures were not profitable, they would not be produced and used.
If consumers did not feel that products containing petrochemicals were worth the money, they would not buy them.
A hidden issue is that consumers most often are unaware of the chemicals to which they are being exposed.
Would they think it was worth the money if they knew?
Credit: Edward Cisneros/Unsplash
Every baby born – at least in the developed world – has well more than 100 industrial chemicals in their bloodstream at birth, demonstrating that they are exposed in utero.
In other words, humans are born pre-polluted.
This is a well-known situation among governments, so it is important to ask not only why and how the human population has become exposed to hundreds of chemicals, but also why we allow it to continue.
If a man in a suit were to knock on your door every morning offering a teaspoon of clear liquid to your children, you would certainly decline the offer, even if they said it was "government approved."
So why do we accept it when the exposures are "hidden"?
If chemical exposures are benign, then these questions are not important. However, there is sufficient scientific evidence to conclude that chemical exposures are currently causing harm to the human population, and that their effects profoundly increase health care costs, decrease the quality of life for millions of people, reduce cognitive function and increase the expression of neurobehavioral disorders, and that at least some of these effects can be passed from one generation to the next without further chemical exposure.
These are observations that have been confirmed by many of the world's most credible scientific organizations including the World Health Organization, the United Nations, many medical societies, and international groups of independent health science professionals.
We are, in short, affecting not only individuals and populations, but also human society and its future as we know it.
Credit: Jonathan Chng/Unsplash
To begin to understand why we continue to contaminate the human population, it may be useful to break this large question down into more focused questions.
Within this context, it is germane to emphasize that an important mechanism by which chemical exposures can harm the general population is by interfering with hormones. This is important because hormones control many – if not most – processes of human development and physiology.
In addition, the few chemicals that are evaluated for safety are evaluated by a strategy that is tuned to identify acute toxicity, not endocrine disruption.
We know for certain that a variety of chemicals and chemical classes affect human health by interfering with hormone systems. These include lead, mercury, polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and other flame-retardants, perchlorate, some pesticides, BPA and other estrogenic chemicals.
In general, there are two inter-dependent reasons to explain each of these questions posed above. The first is that governments employ an antiquated discipline that informs us about toxicity and safety. This system is based on the 400 year-old concept that the "dose makes the poison."
The implication of this concept is that everything is toxic at some dose. In this way, arsenic is the same as water – it just takes more water to kill a person than it does arsenic.
This false equivalency supports a regulatory system that calculates the risk of harm to humans exposed to a variety of chemicals from pesticides designed to interact with biological systems to plasticizers, flame-retardants or heavy metals that are used only for their product functionality.
But, what is the harm that risk calculations are designed to prevent? Operationally, those harms, or adverse effects, are defined by the tests employed to evaluate the hazard. Cancer studies identify carcinogens; reproductive studies identify reproductive toxicants; endocrine studies identify endocrine disruptors; immunology studies identify immune toxicants.
These tests are prescribed studies with measurements that have been approved by various committees. However, there is good reason to question both the sensitivity of these measurements to identify hazards, and the degree to which they reflect hazards to the human population.
In addition, hazard identification is only the first step in calculating risks; the potency of the chemical and the exposure of humans to the chemical must then be determined to calculate risk.
A significant issue is that "potency" is a relative measure.
For example, researchers who work for or with industry defined the potency of chemicals that act like the female hormone estrogen by their ability to affect the weight of a rat uterus. This is a standard measure of estrogen activity used by industry and by the government, but there are other, more sensitive measures, such as the ability of estrogen to affect brain development.
Therefore, risk calculations of chemicals that act like the female hormone estrogen (e.g., BPA) are often based on its ability to affect the weight of a rat uterus. The lack of sensitivity of traditional measures of potency of chemicals to interfere with hormones is generalizable across endocrine systems.
In addition, if the measurement (e.g., uterine weight) is not plausibly reflective of a risk of disease or disability in the human population, it is difficult to understand why it is employed other than that it is the traditional measure.
Likewise, estimates of exposures are error prone at best. For example, reports of the effect of perchlorate in drinking water on thyroid function in newborn babies used measures of perchlorate exposure in municipal water supplies in Las Vegas, Nevada (contaminated) compared to Reno, Nevada (not contaminated) as a surrogate measure of exposure.
Perchlorate is known to inhibit thyroid function and thyroid hormone is essential for normal brain development. Therefore, calculating the risks associated with perchlorate exposure has important public health implications. However, more recent studies demonstrate that everyone is exposed to perchlorate, independent of municipal water contamination; therefore, risk estimates were flawed based on these early reports using city of residence as a surrogate for exposure to perchlorate.
A second reason that the status quo of human chemical exposures continues is that financial self-interest motivates campaigns to confuse both the public and regulatory agencies with the goal of limiting or avoiding regulations. The strategies employed, well-documented in a number of legal cases, range from outright fraud and corruption to the selective manipulation of information to make a chemical or product appear safe.
These two categories of explanations for the status quo are not mutually exclusive. The "principle" that the "dose makes the poison" lends itself quite readily to manipulation because it creates a false equivalency between chemicals that are causing harm in the human population and those (e.g., water) that are not. Moreover, it relies on potency as a primary metric, when potency is neither relevant to hazard identification nor an absolute metric.
There are two additional issues: One is that regulatory decisions are made by government agencies in secret collaboration with the industries that manufacture the chemical. It is secret because the data provided to regulatory agencies are proprietary.
However, the people from government and industry involved in these negotiations and decisions are not experts in human health and therefore must necessarily make decisions based on traditional ways of interpreting traditional data.
The second is that there seems to be a general acceptance that petrochemical-based products are required for modern life and that environmental regulations negatively impact market competitiveness.
The concept that petrochemical-based products are required for modern life implies necessarily that we cannot manufacture safer products using bio-based feedstocks and green chemistry. This is a particularly unflattering and pessimistic view of human society and it should be summarily rejected.
The concept that environmental regulations negatively impact market competitiveness has been refuted over and over again by a variety of economic studies.
Thus, when governments overtly move to restrict or eliminate environmental regulations, they are acting neither to protect public or environmental health nor to protect the market. Rather, they are acting to protect the market share of industries currently dominating the market.
In other words, the chemical industry and regulatory system has evolved to maintain itself rather than to protect public health.
The consequence of this status quo is becoming increasingly clear. Non-communicable disease now results in more deaths per year than communicable diseases, and these chronic diseases profoundly impact quality of life and the global economy.
The human health effects of exposures to only a few endocrine disruptors for which there is sufficient data alone cost the economy hundreds of billions of dollars per year, not to mention impacting quality of life.
In addition, there is a cultural cost to the status quo of chemical regulations.
A large number of chemicals are known to affect brain development and cognitive function. Loss of IQ as well as increasing the incidence of neurobehavioral disorders in generations of children can have profound effects on society. It is germane here that the U.S. Centers for Disease Control and Prevention has recently reported that the incidence of autism in the U.S. is now 1 in 40 children.
Moreover, there is increasing evidence that the health effects of endocrine disrupting chemicals can be passed from one generation to the next.
What will be required for the status quo to change?
We must first admit that this status quo is not sustainable and is responsible for contributing significantly to human health and global economic challenges. That admission will provide the political will to begin to change this status.
It isn't simply a matter of loving our children more than we love money.
Rather it is a matter of clearly evaluating the system we have created and the price we are paying for its maintenance. It may not be uncommon that human enterprises reach a point where more effort goes into maintaining the status quo than adapting to new data to refine and improve the system.
But we can and should do better, both for our future and for our economy.
Reducing chemical exposure should be considered "low hanging fruit."
Dr. R. Thomas Zoeller, Ph.D., is Professor of Biology at the University of Massachusetts, Amherst. His research focuses on the role of thyroid hormone in brain development and the mechanisms by which environmental endocrine disruptors can interfere with thyroid hormone action in the developing brain.
Pennsylvania environmental officials are bracing for a future filled with lawsuits and angry citizens as the state tries to get a handle on widespread chemical contamination that some other states have already begun to mitigate.
At a public hearing on Friday held by the Pennsylvania Department of Environmental Protection [DEP], experts from states, like New Jersey and Michigan, testified about a group of chemicals referred to as PFAS (perfluoroalkyl and polyfluoroalkyl substances).
Hundreds of sites across the country, including at least 20 in Pennsylvania, have been contaminated by PFAS.
PFAS chemicals have been used in hundreds of consumer products that repel water or oil, such as waterproof clothing and non-stick pans. But, so far the biggest contamination sites have been discovered around industrial sites and military bases that used fire-fighting foams containing PFAS. The biggest threat to the public, according health officials, is how these chemicals are leaching into the water supply.
Exposure to these chemicals, even at very low levels, is associated with a wide range of health impacts including cancer, thyroid disease, ulcerative colitis and birth defects. And, while it's not clear if the chemicals are to blame, Pennsylvania residents who attended the hearing and live near PFAS-contaminated sites rattled off dozens of family members—and pets— who have struggled with cancers.
Most of the 11 Pennsylvania residents who spoke at the hearing demanded more action from the state. They say the towns, rather than the polluters, are picking up the cleanup costs, and residents are being burdened with paying for their own medical tests.
"When is someone going to step up to the plate?" said Hope Grosse, whose family lives near a contamination site at the former Warminster Naval Air Warfare Center. She testified that PFAS contamination was found in her family's private well and the local public system in 1996. She and family members have been stricken with various cancers.
"These chemicals are destroying lives," she said. "We need you to make changes today, not tomorrow."
In the absence of federal regulations, many states are just beginning to test for the chemicals and launch cleanup efforts. In September, Gov. Tom Wolf formed a PFAS Action Team to address the issue in Pennsylvania.
Some other states started investigating and taking action much earlier. Michigan has spent tens of millions organizing cleanups.
New Hampshire organized health studies with thousands of participants. New Jersey has implemented a more stringent drinking water standard. Michigan has implemented standards for groundwater and surface water, which empower the state to initiate cleanup efforts.
Two of the 20 contamination sites identified so far in Pennsylvania are near Pittsburgh: the Pittsburgh Air National Guard base in Moon Township and Pittsburgh Air Reserve Station in Coraopolis. Rick Rogers, the associate director of the Office of Drinking Water at the U.S Environmental Protection Agency [EPA], testified that there may well be hundreds of more contamination sites at existing Superfund sites.
In January, Pennsylvania will start testing some of the more than 14,000 sources of drinking water. The DEP is trying to prioritize which sites to test first because there isn't funding to test them all, according to Lisa Daniels, the department's acting deputy for water programs.
"It's not a simple problem and it won't have a simple fix," said Patrick McDonnell, the DEP secretary. "What we're doing is beginning a journey here along a path that starts with a lot of hard work."
The EPA's health advisory limit of 70 parts per trillion (ppt) sets a standard for the amount of PFAS chemicals a person can be exposed to over their lifetime without experiencing adverse health effects.
New Jersey went beyond the federal standard and set its limit at 13 ppt.
Michigan has spent at least $23 million to address its PFAS problem since its own action team was assembled in November 2017. In one year, they've managed to test every water system in the state that serves more than 25 people and the water supplies to all schools and daycare centers. The state has also provided filters and bottled water to communities where testing detected contamination.
Michigan has confirmed PFAS contamination in at least 35 sites across the state; its investigation continues and 10 state departments are involved in a collaboration to address the crisis. The state has also begun testing fish and deer for the chemicals, and issued several notices not to consume those animals in regions where they were found to be contaminated with high levels of PFAS.
Michigan's PFAS Action Response Team intends to issue drinking water standards by the end of the year, Carol Isaacs, director of the Michigan PFAS Action Response Team, said at the hearing. In the meantime, they've already set standards for groundwater (70 ppt) and surface water (11-12 ppt), so they can start cleanup initiatives.
The Minneapolis-St. Paul area has experienced one of the most severe exposures detected in the country because of its proximity to 3M, the manufacturer of Scotchgard. Scotchgard was made with certain strands of PFAS that were discontinued in 2015.
Local scientists refer to Minnesota's exposure as the "Megaplume" because it impacted five public water supplies and more than 1,000 private wells, all of which serve more than 140,000 residents.
Minnesota sued 3M in 2010 and settled in February for $850 million.
Mark Cuker, a lawyer in Eastern Pennsylvania who is handling several cases related to PFAS contamination in the state, urged the state Action Team on Friday to follow rules of common courtesy: When you make a mess, clean it up. Right now, he said, the local communities, rather than the Department of Defense, are paying to clean up the contamination from the former military bases.
But if Pennsylvania creates a more stringent standard for PFAS contamination, like Vermont and New Jersey, the military may be forced to pay. "It's really that simple," he said. "The time is now for action."
Pennsylvania Action Team members called for additional research. "What we know is that there's much more science that we need," said Sarah Boateng, executive deputy secretary with the state Department of Health.
This approach elicited frustration from community members.
"We've heard so much from the Action Team about how much we don't know and how much more research is needed," said community member Phil Baiocchi. "What we do know is that there are filtration systems available that can protect our drinking water. Where I live, the private water supplier brazenly refuses to take action to filter because they don't have to yet. You could change that right away by declaring this a hazardous substance. Please."
Baiocchi was referring to some carbon filtration systems believed to be capable of filtering out PFAS; the systems can be installed at water plants, homes or wells.
Credit: US EPA
Lisa Cellini, a resident from Horsham Township in Eastern Pennsylvania, lives near a former Navy base contaminated by PFAS. At Friday's hearing, she said she's sick and many people around her are sick. She wants the state set a more stringent standard for what constitutes PFAS contamination, so the Navy will have to do a comprehensive cleanup around the base and provide free blood testing for residents to detect contamination.
The lack of clear regulations is hurting the local economy, according to Mike McGee, the executive director of the Horsham Land Redevelopment Authority. The Navy's ability to transfer the former Navy base over for redevelopment has been limited by a lack of guidelines for how to remediate PFAS contamination.
Joanne Stanton, a member of the Buxmont Coalition for Safer Water outside of Philadelphia, said her son was diagnosed with a brain tumor when he was 6. Two other women who grew up on the same street also had children with the same brain tumors.
"That's not normal," she said. "Children that have been exposed should be entitled to testing and monitoring to ensure the healthiest future possible."
At a public meeting in May 2017, the Pennsylvania Environmental Quality Board voted unanimously to accept a petition asking them to set a state-specific maximum contaminant level for PFOA — a particularly dangerous type of PFAS.
The environmental group Delaware Riverkeeper Network submitted the petition. "But after almost a year of doing nothing, they were telling us they couldn't do it because they didn't have a toxicologist on staff," said member Tracy Carluccio.
Toxicologists research what levels of chemicals are harmful to human health. Pennsylvania (and many other states) generally rely on the EPA to set drinking water standards, so neither the DEP nor the Department of Health have a toxicologist on staff.
The topic wasn't discussed at Friday's hearing beyond a promise from a DEP spokesperson that they'll continue looking for a qualified candidate.
"Pennsylvania is lagging behind other states," Carluccio said during the hearing.
Grosse agreed. After experiencing illness and witnessing deaths at early ages, she is demanding action.
"In 1990, I was diagnosed with stage 4 cancer at 25 years old," she said. "I watched my father die at 52...my sister is sick. All our pets died from cancer and tumors.
"We deserve cleanup and remediation now. After sitting here watching all these states talk about what they've been doing — we're behind."
Oliver Morrison is PublicSource's environment and health reporter. He can be reached at email@example.com or on Twitter @ORMorrison.
Correction: A previous version of this story contained a misleading definition of Superfund site.
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