I’m the founder and chief scientist of Environmental Health Sciences, a nonprofit launched in Charlottesville, Virginia, that publishes Environmental Health News and engages in scientific research and outreach to help the public and policy makers understand that we have many opportunities to prevent diseases and disabilities that are afflicting our families, friends and neighbors today.
We can accomplish this by acting upon today’s scientific understanding that chemical exposures are contributing to those problems.
I’m going to let you in on a scientific reality that is going to transform the chemical enterprise and upend today’s unscientific approach to figuring out what’s safe and what is not. The safe dose of one of the biggest volume chemicals in the world— bisphenol A (BPA)—will have to be reduced by at least 20,000-fold.
This calculation is based upon data the US Food and Drug Administration (FDA) obtained in an ambitious, roughly $30 million collaborative program called CLARITY-BPA. CLARITY was designed to reconcile differences between traditional regulatory science as practiced by the FDA and results obtained by independent academic scientists funded by the National Institute of Environmental Health Sciences (NIEHS). Many significant effects were observed at the lowest dose tested, including data obtained by the FDA.
That means: Take today’s FDA reference dose and divide by at least 20,000.
That’s the highest exposure that would be considered safe if regulated according to existing scientific understanding. The chemical would disappear from any uses that bring it into contact with food or drinking water, human skin, or result in it evaporating into the air or melting into water.
And the same would hold for many other chemicals that disrupt hormone signaling, that is, endocrine disrupting chemicals, which have been linked to multiple health impacts including prostate cancer, breast cancer, infertility, diabetes, ADHD and autism.
Maybe not all EDCs would require a 20,000-fold reduction. Perhaps only a 1000-fold. But there are at least several hundred endocrine disrupting chemicals (EDCs) in use today that could follow this pattern. All would see greatly heightened restrictions on their uses.
And that represents an existential threat to the chemical industry.
I am not anti-chemical, nor anti-chemist. We need chemicals, including plastics, to make modern civilization work. What we need, however, is to do a much better job at designing the next generation of inherently safer materials, safer than the mix we have today, which has been deployed with far too little attention to its inherent toxicity.
I’ve spent a significant part of my work over the last decade helping chemists design safer chemicals. I want to help them grab market share in the booming demand for safer materials. I want to help them make money.
Some people claim that chemical regulations stifle innovation. Just the opposite is true. It will require tremendous innovation to move away from hazardous chemicals and toward materials that are safer. It can be done. The scientific knowledge we possess today about what causes chemical harm is deep and wide, so much better than what we knew when hazardous materials in widespread use today were designed. Let’s use that knowledge to innovate.
What’s the long-term landscape? A series of events and scientific discoveries over the last two decades are revealing that not only have long-standing chemical industry practices harmed people’s health, investors taking positions in chemical companies may be exposing their wealth to unexpected and large financial risks.
These risks arise from a core reality of the business of establishing what is safe and what is not: Chemicals are not thoroughly tested—if at all—for safety before being released into the market, resulting in widespread if not universal exposure, including to highly vulnerable populations like babies still in the womb. Serious harmful effects often are not detected until decades later.
All too often, as effects are discovered the responsible party—which made the initial mistake to incorporate a poorly understood chemical in products and take them to global scale—doubles down in efforts to hide or dismiss concerns about safety, using toolkits to manufacture doubt developed by the tobacco and lead industries.
Internal memos obtained through legal discovery reveal that the companies, sometimes decades earlier, had ignored or hidden scientific evidence that raised safety concerns. Three prominent examples emerged in in the past few years alone: Monsanto/Bayer with the Roundup herbicide, Johnson & Johnson with asbestos in its talc baby powder, and 3M and DuPont with their manufacture and use of perfluorinated Teflon-related “forever” chemicals, PFAS.
Thousands of lawsuits are being heard against those companies now. Shareholder values plummet as juries reach decisions. Billions of dollars are at stake. And there will be more.
Monsanto had earned a bad rap for misbehavior with its chemicals for decades. But Johnson and Johnson, 3M and DuPont didn’t. They had been widely regarded as good corporate citizens. If even they have laundry this dirty in their past, how many other companies have pursued similar practices? Unquestionably many.
But with the practices so widespread, perhaps the pertinent question is, can any company within this sector be presumed innocent? It’s just too common a business practice. It’s standard operating procedure.
Another example: Bill Moyers’ 2001 documentary Trade Secrets unveiled an early 1970s conspiracy by several seemingly respected chemical companies to hide devastating scientific discoveries about the health risks of vinyl chloride, one of the most important chemicals for the plastics industry. The conspiracy involved Conoco, BF Goodrich, Dow, Shell, Ethyl and Union Carbide, some of the founding fathers of the chemical revolution.
A new weapon against these bad practices has emerged and matured since the tobacco settlements of the late 1980s: the creation of large, searchable databases of internal documents obtained through legal discovery in lawsuits, showing what the companies knew and when they knew it, and also how they conspired with federal agencies to derail needed safety regulations.
The two biggest databases are the Chemical Industry Documents Library at the University of California San Francisco, and ToxicDocs, a similar database of 20 million internal documents dating back as far as 1920, hosted by Columbia University and City University of New York. The UCSF library now includes a large set of documents released by the Attorney General of Minnesota upon settlement of an $850 million suit against 3M last February.
The lawsuits currently underway against Monsanto/Bayer, 3M and Johnson & Johnson will undoubtedly add additional documents that provide yet more evidence of cover-ups that commenced long ago. It already is a positive feedback loop, as new documents add to the body of evidence, which then stimulate more lawsuits.
Science of harm
Financial risks arise for chemical industry investments from a different direction as well: the advance of science demonstrating harm, and the evolution of science to determine what is safe.
The discovery of harm can be slow arriving—sometimes decades after a chemical is first put on the market—but impacts of harm can nonetheless be devastating.
For example, 3M’s and DuPont’s forever chemicals (perfluorinated compounds, or PFAS, which degrade very slowly in the environment, if at all) were first used in products in the 1940s. Scientific concerns about them started to appear in the 1990s, although internal documents indicate the companies had known decades earlier. Most of the concerns have been about cancer, low birth weights, immune system function and birth defects.
Last year, a science team in Italy unveiled results revealing a new, different set of adverse impacts, this time on male reproduction. They include decreased penis size, reduced sperm count and structural changes in the reproductive tract, classic signs of endocrine disruption. And the team’s research confirmed that the contaminants interfere with testosterone action.
Even without the penis effect, 3M settled that $850M suit with the State of Minnesota. DuPont settled a case in West Virginia for $671 million in 2017 and this month the film Dark Waters starring Mark Ruffalo tells the story of the company’s decades-long treachery. New Hampshire, New Jersey and New York have ongoing lawsuits.
As of the end of 2019, research by the U.S. military, the Environmental Working Group and others have documented PFAS contamination in more than 400 sites around the U.S. According to one analysis, 110 million Americans have drinking water contaminated by unsafe levels of these chemicals. This estimate is likely to grow substantially with the discovery of PFAS in artificial turf and leaching therefrom into surface water, and the haphazard disposal of untold tons of artificial turf once it wears out and must be replaced.
Many other suits will unquestionably be filed. And that’s just in the U.S. These chemicals have already created furors about public health in Australia and Canada.
Upending dangerous assumptions
But if there is an existential threat on the horizon for the chemical enterprise, it’s the compelling evidence that two of the most basic assumptions used by regulatory agencies to determine what is safe and what is not are flat out wrong. One assumption is that it’s sufficient to examine chemicals one at a time. The second bedrock assumption is that high dose testing can be used to detect low dose effects. These assumptions have underpinned literally every single risk assessment (what’s safe and what’s not) of a chemical that has ever been done anywhere in the world.
“One at a time” fails because it doesn’t acknowledge that no one is ever exposed to just one chemical at a time. We are exposed to hundreds if not thousands.
What does every physician ask a patient for whom the doc is about to prescribe a drug? What medicines are you already taking? That’s because chemicals interact. One of the most ridiculous uses of this assumption is perhaps in testing pesticides. The EPA tests the “active” ingredient of a pesticide. Yet the pesticide that is available for purchase is a mixture of dozens of chemicals, many of which are added to the product sold explicitly to ENHANCE THE IMPACT OF THE ACTIVE INGREDIENT.
How can you assess pesticide safety without considering the whole product, not just the active ingredient? You can’t.
“High dose testing” falls on the sword of what endocrinologists call “non-monotonicity.” Many syllables, but a simple concept: Hormones, and chemicals that behave like or interfere with hormones, do different things at different doses. There are many examples of this in the scientific literature of endocrinology, the study of hormones. This is an anathema to traditional and regulatory toxicology, because that “science” maintains that “the dose makes the poison,” which the regulatory agencies interpret to mean “higher doses have bigger effects.”
EHN recruited a reporter, Lynne Peeples, to investigate the FDA’s execution of the roughly $30 million project to reconcile their conclusions with the work of 14 independent academic labs showing harm at low levels for over a year. The investigation found that the FDA worked to ignore or discredit independent evidence of harm while favoring pro-industry science despite significant shortcomings. Key to their conclusions was rejecting statistically significant non-monotonic patterns in their own data, because, they asserted, the non-monotonic findings were not biologically meaningful. In other words, non-monotonic patterns aren’t real.
“The dose makes the poison” seems like common sense, but common sense has failed us many times in the past. Think about quantum physics or plate tectonics. Our understanding of the modern world depends upon the practical implications of those discoveries. Non-monotonicity isn’t nearly as revolutionary as those scientific fields, but it is profoundly important for human health. And it is a standard, widely accepted concept in endocrinology and pharmacology. In 2012, the then-Director of NIEHS, Linda Birnbaum, editorialized that non-monotonicity should be the default assumption in the study of EDCs.
While there are multiple molecular mechanisms leading to non-monotonicity, the easiest (but incomplete) way to think about it is this: Hormones and endocrine disrupting compounds turn on one set of genes at one dose, and another at higher. Sometimes the higher dose turns on genes that shut down the genes that were stimulated by the low dose. In this case, the effect of the low dose is not visible when using high doses. It’s analogous to the way a thermostat works. If the room is cold, the furnace is on. But when the temperature hits the desired temperature, the thermostat turns the furnace off.
Sometimes the high dose is so high that instead of turning on genes it becomes overtly toxic. Here’s an example: doses of one part per billion of a specific endocrine disrupting chemical delivered to an infant rat causes morbid obesity as the animal matures. This is research by the U.S. National Institute of Environmental Health Sciences. In contrast, a dose of the same compound 1,000 times higher causes weight loss.
The vital piece of information needed to understand why this invalidates today’s chemical safety testing requires understanding how the regulatory tests are performed. The lab doing the safety testing starts at high doses and then delivers lower and lower doses to different test groups. Once they find a dose that no longer causes a difference between the exposed and the control animals, testing stops. They use a series of safety factors, usually dividing that no effect dose by 1,000, to estimate the safe dose.
Seems logical. Seems common sense. If dose X doesn’t cause an effect, dose X divided by 1,000 is surely safe. But endocrinology doesn’t work that way. That might defy common sense, but it is scientific reality.
And unfortunately, because it seems so logical, the regulatory agencies in standard mode NEVER test at the estimated safe dose. 1,000-fold below? Why bother.
To save money and time, they assume that the dose 1,000-fold lower is safe.
Unfortunately, many published scientific papers now show that doses way below the “no effect” dose can cause serious adverse effects. It isn’t that the high doses are safer. They, too, cause problems. It’s that the effects are different. The low dose effects are serious too—like morbid obesity and reduced fertility.
Here’s the one very practical implication I mentioned at the beginning: If the FDA were to acknowledge statistically significant non-monotonicity in their test of BPA—which analysis by independent scientists has confirmed—the safe dose of would be reduced by a factor of more than 20,000-fold. BPA would become virtually unusable.
For a webinar from Carnegie Mellon University featuring four of the world’s leading experts on BPA explaining this calculation, go here. This webinar contains four presentations all focused on the FDA-NIEHS collaboration called CLARITY-BPA. The presentations work through why CLARITY was launched, what was found by the FDA ‘guideline’ study (conducted like a standard regulatory test but including low doses), what was found by 14 independent academic laboratories who also were part of CLARITY, and analysis of what it means.
Bisphenol A is one of the plastics industry’s most important molecules. Incredibly cheap to make, incredibly abundant in production, incredibly important to the bottom line. Also—incredibly dangerous to human health.
Removing that one molecule alone would send tectonic signals throughout the chemical enterprise. And yet BPA is but one of at least a hundred or more molecules that have non-monotonic patterns. The replacement chemicals for BPA currently touted as ‘BPA-free’ are likely to be among them, although many have not been tested. ‘BPA-free’ does not mean ‘safe.’
Non-monotonicity is truly an existential threat to today’s chemical enterprise. If that enterprise is to become sustainable, it must embrace this basic endocrinological reality.
Embracing it is a path to reversing today’s epidemics of chronic diseases that are driven, at least in part, by chemical hacking of the hormone messaging system by endocrine disrupting compounds.
Pete Myers, is board chair and chief scientist of Environmental Health Sciences. He is also the founder of EHN, though the publication is editorially independent.