Internal documents reveal industry ‘pattern of behavior’ on toxic chemicals by David Heath for The Center for Public Integrity
Sixty-six years ago, a professor at the Harvard School of Public Health wrote a report linking leukemia to benzene, a common solvent and an ingredient in gasoline. “It is generally considered,” he wrote, “that the only absolutely safe concentration for benzene is zero.”
The report is remarkable not only because of its age and candor, but also because it was prepared for and published by the oil industry’s main lobby group, the American Petroleum Institute.
This document and others like it bedevil oil and chemical industry executives and their lawyers, who to this day maintain that benzene causes only rare types of cancer and only at high doses.
Decades after its release, a lawyer for Shell Oil Company flagged the 1948 report as being potentially damaging in lawsuits and gave out instructions to “avoid unnecessary disclosure of sensitive documents or information” and “disclose sensitive benzene documents only on court order.”
Plaintiff’s lawyers like Herschel Hobson, of Beaumont, Texas, wield such documents in worker exposure cases to demonstrate early industry knowledge of benzene’s carcinogenic properties.
“It shows a pattern of behavior,” Hobson said. “It shows how industry didn’t want to share bad news with their employees. None of this information was made available to the average worker … Most of this stuff kind of gets lost in the weeds.”
No more. Today, the Center for Public Integrity; Columbia University’s Mailman School of Public Health and its Center for the History and Ethics of Public Health; and The Graduate Center at the City University of New York are making public some 20,000 pages of benzene documents — the inaugural collection in Exposed, a searchable online archive of previously secret oil and chemical industry memoranda, emails, letters, PowerPoints and meeting minutes that will grow over time.
The aim is to make such materials — most of which were produced during discovery in toxic tort litigation and have been locked away in file cabinets and hard drives — accessible to workers, journalists, academic researchers and others.
Some are decades old, composed on manual typewriters; others are contemporary. Combined with journalism from the Center — such as today’s story on a $36 million benzene research program undertaken by the petrochemical industry — and articles and papers from Columbia and CUNY faculty and students, the archives will shed light on toxic substances that continue to threaten public health.
Exposed: Decades of denial on poisons
The benzene documents are just the start. In coming months, we’ll be posting hundreds of thousands of pages of discovery material from lawsuits involving lead, asbestos, silica, hexavalent chromium and PCBs, among other dangerous substances. And we’ll be on the lookout for other documents.
The inspiration for the project came when we realized that in CPI’s reporting on environmental and workplace issues, we routinely obtained reams of court documents. Often, these documents hold secrets found nowhere else.
Last year we reached out to William Baggett Jr., a lawyer in Lake Charles, Louisiana, who had acquired more than 400,000 pages of documents from a decade-long case against manufacturers of vinyl chloride, a cancer-causing chemical used in plastics. Baggett agreed to give us all of them.
At the same time, public health historians Merlin Chowkwanyun, David Rosner and Gerald Markowitz were collecting court documents to create a public database and had approached Baggett. We decided to collaborate. Chowkwanyun is currently a Robert Wood Johnson Foundation Health & Society Scholar at the University of Wisconsin-Madison, and will be an assistant professor of sociomedical sciences at Columbia next year. Rosner is Ronald Lauterstein Professor of Sociomedical Sciences and History at Columbia. Markowitz is a professor of history at the City University of New York. Both Rosner and Markowitz have served as expert witnesses in a number of major cases related to these documents and have written Deceit and Denial: The Deadly Politics of Industrial Pollution and other books and articles based on them.
This is not the first database of its ilk. The University of California, San Francisco, maintains a massive collection of documents from tobacco-related lawsuits called the Legacy Tobacco Documents Library, which exceeds 80 million pages.
How to search the documents
Our database allows you to search for a word, combination of words or an exact phrase in any of the documents. You can also:
Do a search that excludes a word by putting a ‘-‘ sign in front of the word.
Do a fuzzy search that includes variations of a word by putting a tilde ‘~’ at the end of a word with the numbers of characters that don’t have to match exactly. For example, ‘planit~2’ will match ‘planet.’
Do a search that optionally contains a word by putting a ‘|’ between the words.
Do a search with a phrase by putting double quotes around the phrase.
Each document will include the court case from which it came, including the case title, case number, court as well as date filed and date terminated. The original complaint for each lawsuit is also part of the database.
Soon, we will make available a robust set of text-mining tools that will allow researchers to construct chronologies of documents; generate lists of common words, phrases and names; and sort documents in a number of ways. Qualified researchers will also have access to an even larger set of documents that will eventually contain millions of pages.
Robert Proctor, a professor of the history of science at Stanford, has used the UCSF tobacco archive extensively to do research for several books. He called it “an unparalleled treasure” that gives researchers the ability “to look through the keyhole of the mansion of this hidden world and see [corporate officials’] private thoughts, their intent, their ruminations, their jokes, their plans, how they treat their workers, how they treat the public…”
Proctor said he sees value in a similar archive on toxic chemicals. “The internal records of the chemical industry are known only to a tiny group of lawyers and journalists,” he said. “This is going to create a new kind of democracy of knowledge. It also will set the stage for whistleblowers to come forward with documents.”
That’s our hope. The search interface includes options to send us documents or contact us. The ultimate goal, to borrow Proctor’s phrasing, will be to give users “a strong magnet to pull rhetorical needles out of archival haystacks.”
Click on the link below to access the original article at The Center for Public Integrity
AMY GOODMAN: “Are any plastics safe?” That’s the title—that’s the question of a new exposé by Mother Jones that may shock anyone who drinks out of plastic bottles, gives their children plastic sippy cups or eats out of plastic containers. For years, public campaigns have been waged against plastic containing BPA, Bisphenol-A, a controversial plastic additive. But a new investigation by Mother Jones magazine has revealed that chemicals used to replace BPA may be just as, if not more, dangerous to your health than their cousin compound.
BPA is still widely used in everything from the lining of soup cans to printed receipts, even though studies show it mimics the behavior of estrogen in the human body, and have linked it to breast cancer, diabetes, obesity and heart disease. Just last week, a study estimated the use of BPA in food and beverage containers is responsible for some $3 billion a year in healthcare costs. But because BPA can hamper brain and organ development in young children, it’s been banned in bottles and sippy cups since 2012. Now new studies show the plastic products being advertised as BPA-free, and sold by companies such as Evenflo and Nalgene, Tupperware, are still releasing synthetic estrogen.
The Mother Jones report goes on to look at how the plastics industry has used a Big Tobacco-style campaign to bury the disturbing evidence about the products you use every day.
We’re joined in Washington, D.C., now by Mariah Blake, staff reporter with Mother Jones magazine.
Mariah, welcome to Democracy Now! Just lay out what you have found.
MARIAH BLAKE: Well, essentially, there is relatively new research showing that the vast majority of plastics, at least commercially available plastics that are used for food packaging, contain BPA-like chemicals, so chemicals that are what they call estrogenic. And the—
AMY GOODMAN: And explain what BPA is.
MARIAH BLAKE: So BPA is a chemical that mimics the hormone estrogen. And estrogen plays—we all have estrogen in our bodies. It plays an essential role in various bodily functions and is also very important in human development, so the development of our brain, the development of our organs. However, too much or too little of this hormone, basically, especially during early childhood or prenatally, can set you up for disease later on in life. So, exposure—what the research shows is that exposure in the womb can then lead to breast cancer, diabetes, increased aggression, really sort of a staggering list of health problems later on in life.
AMY GOODMAN: And so, talk about what has happened since BPA has been banned.
MARIAH BLAKE: So, yes, and many people will recall that in 2008 the dangers of BPA became very widely known. There was a scare. Major retailers pulled BPA from their shelves. Customers began demanding BPA-free products, especially for children. And many manufacturers began introducing products that were BPA-free. And all of us who have children have these BPA-free products in our home, most likely. One of the—so—and in many cases, it turns out that the chemicals that were used to replace BPA, or the plastics contained chemicals that were, you know, similar to BPA—at any rate, many of these chemicals had not been tested to see whether they had similar properties to BPA, whether they mimicked estrogen, in essence. And it turns out that many of them do. So, the implication is that they could have similar effects on human health.
AMY GOODMAN: You begin your piece by telling us the story of Michael Green and his daughter.
MARIAH BLAKE: Yes.
AMY GOODMAN: Talk about that experience.
MARIAH BLAKE: So, Michael Green is—he had a two-year-old daughter. He’s somebody who works in the environmental health field. And he had heard—he had seen research suggesting that BPA-free plastics may have posed some of the same problems to human health. And—but he told me this very moving story about himself and his two-year-old daughter. Somebody else in the family had given his two-year-old daughter this pink plastic sippy cup with a picture of a princess on it, which she just loved. And every night at dinner time, they would have this battle of the wills over this pink plastic sippy cup: He wanted to give her the stainless steel sippy cup; she wanted the pink plastic sippy cup. And in the interest of maintaining peace in the household, occasionally he gave in and gave her this pink plastic sippy cup. But the decision really weighed on him. And I think that those of us who have children—I have a three-year-old son—can relate to this situation, where sometimes you do the expedient thing in the interest of peace, but you wonder if it’s the best thing for your child. And in this case, he decided that he would try to answer that question. And he runs this environment health organization, and he collected sippy cups from Wal-Mart and Toys”R”Us—Babies”R”Us, I’m sorry—and he sent them to an independent lab in Texas to be tested. And he found out that in fact roughly a third of them did contain estrogen-like chemicals.
AMY GOODMAN: And that pink sippy cup?
MARIAH BLAKE: His daughter’s sippy cup was leaching estrogenic chemicals. So his fears were founded.
AMY GOODMAN: And what can that do to her?
MARIAH BLAKE: This is the big question. We know a lot about BPA. BPA is one of the most studied chemicals on the planet. And we know that these chemicals generally are associated with a range of negative health effects. But the specific effect of any given chemical varies slightly from chemical to chemical, and we actually don’t know what chemical is leaching out of that sippy cup. So it’s impossible to know. I mean, there’s a very high correlation with breast cancer, for example, with all of these estrogenic chemicals, and with certain developmental problems. But other specific diseases vary from chemical to chemical. So, Michael Green, the way he describes it is an unplanned science experiment that we’re doing on our families all of the time.
AMY GOODMAN: We’re going to break and then come back to this discussion and talk about Big Tobacco, what Big Plastic has learned from Big Tobacco. We are talking to Mariah Blake, a staff reporter with Mother Jones. Her story is in the new issue of the magazine. It’s called “The Scary New Evidence on BPA-Free Plastics: And the Big Tobacco-Style Campaign to Bury It.” Stay with us.
[break]
AMY GOODMAN: This is Democracy Now!, democracynow.org, The War and Peace Report. I’m Amy Goodman. We are with Mariah Blake, staff reporter for Mother Jones magazine. “The Scary New Evidence on BPA-Free Plastics: And the Big Tobacco-Style Campaign to Bury It” is her new piece. What is the campaign to bury the information, Mariah Blake?
MARIAH BLAKE: Well, there are multiple facets to the campaign, but the primary—the primary objective is to cast doubt on the scientific evidence linking these chemicals to human health problems. So—and there are various ways this is done. In the case of BPA, for example, the industry funded studies, which were biased studies that found that this—that the chemical was not harmful to health. And there’s a sort of network there. They published them in certain journals that, in many cases, had links to the tobacco industry. They relied on scientists that, in many cases, had helped to discredit the science linking smoking and secondhand smoke to disease. So, in many ways, this is—they didn’t only borrow strategies and tactics from Big Tobacco; they are actually relying on the same cadre of experts that Big Tobacco relied on to bury—to bury the truth about smoking.
AMY GOODMAN: I want to turn to a video made by the plastics industry featuring the vice president of Eastman’s specialty plastics division, Lucian Boldea, speaking in the video made by the company. A pregnant woman is one of the people shown buying plastic products as Boldea speaks.
LUCIAN BOLDEA: We understand that there are concerns about plastic materials that are used in consumer products that consumers use every day. Those products include water bottles, baby bottles and food storage containers. We can see how available information about plastic materials can be confusing and how it can be difficult for consumers to tell what is really safe. We want you, the consumer, to know the facts behind our clear, tough material named Tritan. Consumers can feel confident that the material used in the product is free of estrogenic activity.
Consumers should have high expectations of the products that they use, and no one is tougher on our products than the researchers and engineers at Eastman Chemical. Most importantly, we have used reputable, independent, third-party laboratories that have used well-recognized scientific methods to prove that Tritan is free of estrogenic activity. Numerous regulatory agencies around the world have independently reviewed our data and have approved the product for use in food contact applications. Some of the world’s most recognized brands trust Tritan as their ingredient.
AMY GOODMAN: That was Lucian Boldea, who is president of Eastman Chemical’s specialty plastics division. Can you respond to this, Mariah Blake?
MARIAH BLAKE: Well, the Eastman product, called Tritan, which is the product that Boldea is speaking about in this video, is actually one of the primary focuses of my investigation. A number of independent scientists have tested this product and found that it is actually more estrogenic than polycarbonate, which is the plastic that contains BPA. And Eastman Chemical, according to internal documents which were released as part of a lawsuit, has taken pains to suppress the evidence showing that its products—or that this product, in particular, is in fact estrogenic.
AMY GOODMAN: So how is it the EPA isn’t regulating this?
MARIAH BLAKE: Well, and this is one of the most surprising things to me when I read this—when I was reporting the story. So, there are about 80,000 chemicals in circulation in the United States. Virtually none of those chemicals has been tested for safety, or a very, very small fraction of those chemicals has been tested for safety. In general, chemicals are presumed safe until proven otherwise under the U.S. regulatory system. So, when a chemical like BPA is removed from a production line, the industry will substitute another chemical that is untested, and we really, in many cases, just don’t know the health effects of that chemical. So, it’s largely an unregulated realm.
AMY GOODMAN: Tell us about George Bittner.
MARIAH BLAKE: OK. George Bittner is a neuroscientist at the University of Texas, and he has launched an independent lab called CertiChem—it also has a sister company called PlastiPure—and it tests products for estrogenic activity. And he—working with a prominent Georgetown professor, he and his staff tested, I think it was, 455 commercially available plastics that are on the market and published a paper in Environmental Health Perspectives, which is the premier NIH journal, which found that virtually all commercially available plastics have estrogenic activity. And among the plastics he tested were Tritan products, several Tritan products. And this publication, this finding, prompted a pretty big backlash from the industry. So he ended up being targeted by the industry as a result and, in fact, was sued by Eastman, which is—many of the documents that formed the basis of my story were released as a result of that lawsuit.
AMY GOODMAN: I want to read from a memo that Eastman’s senior chemist, Emmett O’Brien, wrote after customers began asking about George Bittner’s tests that showed that Tritan may still be estrogenic. O’Brien describes a meeting with Whole Foods executives who were considering replacing their polycarbonate bulk food bins with ones made from Tritan. He wrote, quote, “We called Bittner a mad scientist. They didn’t know his name actually. They asked twice, by two independent people, what we thought of them. I hemmed and hawed (ducked and dodged) saying I prefer not to comment, but we joked and pushed and flat out said the guy was ‘shady’ — with this non-stereotypical crowd it was a good term.” O’Brien added, “They asked if they could do their own tests — I mentioned the cost is very high and they were quick to chime in that the tests take very long.” Can you respond to that, Mariah Blake?
MARIAH BLAKE: I think you chose the most telling possible quote. So this was effective—this was the strategy they used. Firstly, they worked to discredit Bittner, and they did this through a campaign of personal character assassination and by calling his business practices into question. And secondly, they worked to discredit the science. So, one of the things that Eastman did was they claimed that the test that Bittner is using, which relies on a specialized line of breast cancer cells, had been rejected by the EPA, when in fact it hadn’t. The EPA is considering using this very line of breast cancer cells for its own screening program for what they call endocrine-disrupting chemicals. BPA is one of those.
So, the other thing they did was they commissioned their own research, so they paid labs to perform research which found that Tritan was not estrogenic. And—but if you look at—if you look at the research closely, you’ll see that it is—the studies are essentially designed in a way that guarantee that estrogenic activity will not be found. So, for instance, they use a type of rat; it’s called a Charles River Sprague Dawley rat. This rat is known to be insensitive to estrogen, so it can withstand doses, according to one Japanese study, a hundred times higher than a human female can withstand, with—and show absolutely no effect. They also used doses that are below what is known as the no-observable-effect level, so the doses that are known not to cause an effect. And they then published their own study in a scientific journal, which is—has numerous tobacco industry ties, finding that Tritan was in fact not estrogenic. So, that is essentially how they responded to the finding that their product contained these chemicals that are potentially harmful to human health: They attempted to cover it up.
AMY GOODMAN: Your report cites some leaked minutes from a 2009 meeting of the BPA Joint Trade Association, whose members include the American Chemical—the American Chemistry Council, Coca-Cola, Del Monte. During the meeting, they explored messaging strategies that included using what they called, quote, “fear tactics.” For example, “Do you want to have access to baby food anymore?” The attendees agreed that the “holy grail” spokesperson was a, quote, “pregnant young mother who would be willing to speak around the country about the benefits of BPA.” Mariah?
MARIAH BLAKE: Yes, and this is one of the most disturbing things I discovered during the course of reporting this, is that in their efforts to portray plastics as safe, they oftentimes target the groups who are most vulnerable to the effects of these chemicals. So, prenatal exposure and exposure during early childhood is potentially the most harmful, and oftentimes the marketing of these products targets pregnant women, targets families with children. And also, Eastman, for example, in their efforts to portray their products as safe, also targeted these specific groups.
AMY GOODMAN: Can you talk about Nalgene bottles, Evenflo—is it Evenflo?—Tupperware, Rubbermaid, CamelBack?
MARIAH BLAKE: Yes, all of these companies produce at least some products that are made with Tritan, so—and they’re not alone. There are hundreds, probably, of companies that use this. This is the only plastic on the market that markets itself as being free of all estrogenic activity, so many companies that cater to consumers who are concerned about their health and many of the high-end consumer brands have started using this plastic. I think the thing to keep in mind is that Eastman misrepresented their product to their customers, as well. So these brands are not necessarily to blame for this. They have been told by Eastman that Eastman produced—performed independent, third-party testing and found no evidence of estrogenic activity. And so, in many cases, it appears that these companies are trying to do the best thing for their customers, but they were not given—they were not given accurate information about the plastic that they use in their products.
AMY GOODMAN: Last week, NPR did a report, “Maybe That BPA In Your Canned Food Isn’t So Bad After All.” Can you talk about that?
MARIAH BLAKE: Yes. So, this is based on a recent study that was performed by FDA scientists. This is a $30 million taxpayer-funded study. And the FDA used many of the same tactics that the industry uses. For instance, they used the Charles River Sprague Dawley rat. The other thing about this study is that the lab appears to have been contaminated. So the control group of rats—these are the rats that are supposed to not be exposed to BPA, so that you can—you have some sort of a baseline to measure the animals that have been exposed to this chemical—they were somehow accidentally exposed to BPA. I have been talking to scientists about this and am planning to write about this later this week. And the academic scientists I have been speaking to say that this essentially—this raises very serious questions about the validity of the findings, and it’s unclear whether any conclusions can be drawn based on this study.
AMY GOODMAN: What most shocked you in all your research, Mariah?
MARIAH BLAKE: Boy, that’s a good question, because there were a lot of—a lot of shocking things I discovered. I would say there’s a couple things. One, the fact that so few of the chemicals that are in the products we use every day have been tested for safety. So, as I said, there are 80,000 chemicals that are in commercial use in the United States; only a tiny fraction of those have been tested for safety.
Two, how easy it is for the industry to bias that safety testing in their favor. I had—obviously, many of us know about Big Tobacco and the way they were able to essentially buy science saying their products were safe. But I was not aware that that was happening on such a grand scale today. And it really is. You know, plastics—as I worked on the story, it became evident to me that plastics—that this is not the only industry—the plastics and chemical industry are not the—is not the only one that is using these tactics. These tactics are fairly widespread.
And I guess, on a micro level, one of the things that surprised me most, in Bittner’s testing, he looked at various types of commercially available plastics, and one of the types of plastic that was most frequently estrogenic was the corn-based plastic, so the plastic that is biodegradable, that you often find in restaurants—health food restaurants, health food stores, that this is potentially one of the most harmful types of plastic.
AMY GOODMAN: Explain that again.
MARIAH BLAKE: So, Bittner looked at various kinds of plastic, Bittner and his colleagues, when they tested plastics. There’s a variety of different kinds of plastic—polyurethane, PET-P, polycarbonate—all these different kinds of plastic. So he broke it down by types of plastic. He tested a number of samples of each one. And he—in the final paper, they showed which ones—what percentage of each type of plastic tested positive in their tests. And there is a type of plastic that is—frequently you’ll find it in Whole Foods, you’ll find it in health food stores. It is corn-based, and it is marketed as biodegradable. Oftentimes there are forks made out of this, for example, in health food restaurants. I believe the statistic was 95 percent of samples made out of this kind of plastic tested positive for estrogenic activity.
AMY GOODMAN: So what are you going to do with your three-year-old? What have you decided to use?
MARIAH BLAKE: Well, what I’ve already done is removed all plastic from my home. So, I have switched to natural materials. We use glass or stainless steel for our Tupperware, for our sippy cups, for everything that we possibly can. Plastic is unavoidable, so we still buy food packaged in plastic, because there is no alternative. But we try to minimize it.
AMY GOODMAN: Saran Wrap?
MARIAH BLAKE: Saran Wrap, actually, in Bittner’s tests, I believe it was somewhere around 99 to 100 percent of plastic wraps tested positive for estrogenic activity.
AMY GOODMAN: And where does the EPA come down when you question them about when they’re going to be regulating some of this, in the way that they regulated BPA?
MARIAH BLAKE: Well, the EPA still does not regulate BPA. The FDA—the FDA banned BPA in sippy cups and bottles at the request of the industry. So—and they still—the agency still insists that BPA is safe. So the industry asked the FDA to ban it, because they wanted to reassure parents that their products are safe. There has been no meaningful regulation of any of these chemicals, with the exception of phthalates. And in the case of the EPA, they have a program which was supposed to screen these 80,000 chemicals for what’s called endocrine disruption. So, endocrine-disrupting chemicals are chemicals that mimic hormones, like BPA. And they—this was supposed to be at least partially done by 2000. They still haven’t fully vetted a single chemical. So the industry has managed to throw stumbling blocks in their path. And delay is the name of the game, essentially, sowing doubt and delay. So—
AMY GOODMAN: And how much does the plastic in water bottles and juices leach into the water and the juices?
MARIAH BLAKE: PET or PETE, which is most commonly used for water bottles, is—I believe 75 percent of samples in Bittner’s study leached estrogenic activity. There is another study performed by a scientist in Germany which also found that this particular type of product was estrogenic. So, it seems, based on the available evidence, that many or most of these bottles leach estrogen.
AMY GOODMAN: And the longer the bottle of water you buy sits, is the water becoming increasingly contaminated?
MARIAH BLAKE: Well, there are certain factors that increase the risk of these chemicals being released. So, exposure to UV rays, heat, if they’re put in a dishwasher, these are the things that are known to increase—increase the risks that these chemicals leach out of plastics. So, with reusable plastics, in particular, this is a concern. If you boil them, if you put them in your dishwasher, if you leave them in your car, that causes plastics to break down, and it’s more likely that estrogenic chemicals will leak into whatever those containers contain.
AMY GOODMAN: Well, Mariah Blake, we want to thank you for your research, staff reporter with Mother Jones magazine. Her story is just out in the new issue; it’s called “The Scary New Evidence on BPA-Free Plastics: And the Big Tobacco-Style Campaign to Bury It.” We’ll link to it at democracynow.org. You can also follow her on Twitter. Later today, she’ll be doing a Twitter chat with readers.
An excerpt from the chapter, “The Polycarbonate Problem.”
BPA, Benzene, Phenols, & Carbonyl Chloride (also known as Phosgene)
Although it’s only in the past few years that news of bisphenol A’s health impacts began to reach a nonscientific general public–news that has since spread rapidly–it was first recognized as a synthetic estrogen in the 1930s. Papers published in the journal of Nature in 1933 and 1936 describe its estrogenic effects on lab rats. These papers also commented on the possible carcinogenic activity of materials with similar or comparable composition to bisphenol A–specifically materials synthesized from petroleum (from which bisphenol A is ultimately derived) and coal tar.
Some two decades later, bisphenol A was launched into everyday life with the development of commercially produced polycarbonates. Major production of these plastics began in the United States in the late 1950s after a General Electric engineer named Daniel W. Fox formulated a material based on BPA that GE called Lexan. The invention was not so much deliberately planned as it was the result of what Fox called his ability to take “a few clues and jump to conclusions that frequently panned out.”
While experimenting with different materials that might ultimately make a good moldable polymer, Fox decided to work with bisphenols, compounds derived from petroleum processing that were then being used to make various epoxy resins. As molecules, bisphenols have a structural feature that makes them useful as potential chemical building blocks. Attached to their hydrocarbon ring is what’s called a hydroxyl group, an oxygen and hydrogen that together form a site to which other molecules can bond. This structure is common to both synthetic and naturally occurring compounds, a coincidence that will later turn out to be important to how bisphenol A behaves.
Fox’s interest in the hydroxyl group was as a polymer building site, not for its biological activity. But when attached to a hydrocarbon ring as it is in bisphenol A, the entire chemical grouping becomes a molecule known as a phenol–an aromatic hydrocarbon, a ring made up of six carbon atoms and five hydrogen atoms plus a hydroxyl group. Phenols are commonly made by oxidizing benzene, which essentially means adding oxygen to benzene. Phenols are toxic, but they are also known for their antiseptic properties and so were used to kill germs in the nineteenth century surgical procedures.
This molecular group consisting of six carbon-five hydrogen rings with a hydroxyl group attached, however, is also part of the structure of substances produced naturally by the human body, compounds that include estrogen and thyroid hormones. Introducing a manufactured chemical that includes the phenol group into a cellular environment may therefore pose a problem because the synthetic material may compete biochemically with the similarly structured naturally occurring chemical. Thinking in green chemistry terms, the presence of a phenol group on a synthetic, therefore, should be a sign to investigate that substance’s potential as an endocrine disruptor.
The potential cellular toxicity of phenols has actually been known for decades. Research done in the 1950s, written about by Rachel Carson in Silent Spring, discussed the mechanisms by which pesticides constructed with phenols had the ability to prompt oxidation processes that upset cellular metabolism. These reactive chemical groups can disrupt formation of enzymes vital to energy production, which in turn may interfere with how an organism produces and differentiates cellular material. These processes of cellular reproduction are involved in virtually every bodily system, from how an individual processes sugars and calcium to how its reproductive system functions. Carson described the introduction of xeniobiotic phenols as thrusting “a crowbar into the spokes of a wheel. Had Fox been a green chemist, our current synthetic landscape might look very different.
But because Fox and his colleagues were focused on functional performance and on working with readily available chemical ingredients, bisphenols seemed a good choice. As an additional building block that might combine with the bisphenol molecules’ hydrocarbons to yield a useful polymer, Fox chose a chlorine compound called carbonyl chloride. Carbonyl chloride was then–and is currently–a common ingredient in the synthetics known as isocyanates that are used to make any number of products, including polyurethanes that go into varnishes, paints, and plastic foams. By the 1950s it was known that chlorinated hydrocarbons made useful synthetics so this was a logical route for Fox to follow–but no one had yet made the kind of moldable, shatter-resistant plastic that Lexan turned out to be.
If you’re building a polymer, a linked chemical chain in effect, you need lots of the same repeating pieces; ideally you’ll work with shapes that are easy to find and lend themselves to chemical bonding. It’s here that a Tinkertoy or Lego analogy comes to mind. To add pieces to a chemical structure, you need sites where new sticks and building blocks can be attached. So it was with the choice of bisphenols and carbonyl chloride, which lend themselves to such bonding and were both readily available industrial chemicals. Had Fox been practicing green chemistry, however, he would never–even with what was known in the 1950s–have launched a product that required copious quantities of carbonyl chloride.
Carbonyl chloride is also known as phosgene and is so toxic that it was used as a chemical weapon during World War I. The isocyanates it’s used to make are also highly toxic. One such compound, methyl isocyanate, was the gas involved in the deadly 1984 disaster at the Union Carbide plant in Bhopal, India. Lest anyone wonder if nerve gas is lurking in your bike helmet or CD cases, however, let me quickly explain that no phosgene or even any chlorine ends up in the final bisphenol A polymer; the chlorine compound is simply a reagent, an ingredient that enables the desired chemical bonding to take place.
Yet speaking to an interviewer in 1983, Fox acknowledged that using large quantities of a chemical such as phosgene was indeed hazardous. But, Fox continued, it “was not a totally frightening undertaking because we had good advice. I would say that we have been tightening up our whole phosgene handling ever since, investing in an awful lot of money in trying to make the stuff doubly safe and then triply safe and quadruply safe.” Still, the interviewer pressed, “Has there ever been a problem?” To which Fox responded, “We have had one or two small discharges. To my knowledge, I don’t think GE advertised it, but I think we probably had a ‘casualty’ from phosgene.” Did this give anyone second thoughts about going into business? “I don’t think it did,” Fox replied.
At the time Fox was working, new material inventions like carbonates were just that–inventions that came first, with applications and markets found later. “When we invented polycarbonates in the early 1950s we had a polymer with an interesting set of properties and no readily apparent applications,” Fox said in 1983. But what was known about polycarbonates’ behavior early on that might have hinted at what’s since been discovered about their physical and biological behavior” Could this information have been used to prevent what are clearly problems of chemical contamination? Endocrine-disruption science is relatively new, but some of what was known early on about bisphenol A and polycarbonates would seem to indicate a material perhaps not ideally suited for use, say, with food, heat, and dishwashing detergents.
That polycarbonates built from bisphenol A were vulnerable to certain detergents, solvents, and alkali solutions (household ammonia would qualify) has been known since at least the 1970s. Ammonium hydroxide (essentially a solution of ammonia in water) was discussed as a possible way to break polycarbonates down to its chemical constituents–for materials recovery and reuse and as a way to remove unwanted polycarbonate from another surface. It was also known that various additives used to modify polycarbonate mixtures could leach from the finished plastics when they came into contact with certain liquids. Documents filed with the Federal Register in 1977 list chloroform, methylene chloride, and chlorobenzene among these additives. (The U.S. Department of Health and Human Services considers chloroform and methylene chloride suspected carcinogens, while chlorobenzene is known to cause liver, kidney, and nervous system damage and produce a precancerous condition in lab rats.) Correspondence between GE Plastics Division personnel in the 1970s and 1980s also voiced concern over the presence of chlorobenzene in water stored in polycarbonate bottles (but not bottles made by GE as it happened) and about how the stability of these polymers might affect their ability to be used with food.
A memo circulated within the Lexan division of GE in 1978 also noted that “through reaction with water,” polycarbonate resin can degrade. “The two largest applications of Lexan resin for which hydrolytic stability is critically important are baby bottles and water bottles,” ran the 1978 memo.
In each application the finished parts are subjected to conditions which will cause, after prolonged treatment, molecular weight reduction. However, in each application, actual product failure is usually observed before significant molecular weight reduction is detectable by the usual techniques…..Baby bottles are subjected to autoclaving at 250 degrees F in saturated steam and fail under these conditions by becoming opaque, and sometimes by shrinking and deforming. Milk and water bottles are washed in aqueous solutions of alkaline or caustic cleaning agents and fail by stress cracking. The relationship between practical failure modes and the fundamental physical and chemical processes involved is not fully understood.
That polycarbonates might degrade when heated, washed, or exposed to sunlight was also discussed in company memos in the late 1970s and early 1980s. Three decades later, the plastics industry assures consumers that such wear and tear of polycarbonate baby bottles poses no health concerns for infant users.
Pages 58 – 62
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Infertility in Spanish Pigs Has Been Traced to Plastics. A Warning for Humans?
A scientist has connected infertility in pigs to compounds in plastic bags.
By Josie Glausiusz
for National Geographic
PUBLISHED JUNE 5, 2014
A strange catastrophe struck Spain’s pig farmers in the spring of 2010. On 41 farms across the country—each home to between 800 and 3,000 pigs—many sows suddenly ceased bearing young.
On some farms, all the sows stopped reproducing. On others, those that did become pregnant produced smaller litters.
When investigators examined the sows and the semen that had been used to artificially inseminate them—it had been collected from different boar studs and refrigerated—they couldn’t find anything wrong. The sperm cells weren’t misshapen. None of the sows were diseased. No microbes or fungal toxins were detected in their feed or water.
Only one factor was common to all the farms and studs: The plastic bags used for semen storage all came from the same place.
Investigating those bags has led Cristina Nerín, an analytical chemist at the University of Zaragoza who studies packaging materials, to publish new research that traces the pigs’ infertility to chemical compounds in the plastics.
This is “the first time that the correlation between reproductive failures and compounds migrating from plastic materials [has been] studied and demonstrated,” says Nerín, whose team published last month in the journal Scientific Reports.
The implications could extend far beyond the farm.
Some of the same chemicals found in the pigs’ semen storage bags are routinely used in packaging food for humans and are known to migrate into food. The strange case of the Spanish pigs, Nerín says, “shows the real risks we face.” (Explore an interactive showing toxic chemicals that may be lurking in your home.)
Not Just About Pigs
Cyclic lactone, for instance, is a common by-product in adhesives used in potato chip bags and sliced meat packages. It was one of the chemicals found in high levels in the semen bags that had been used on the farms with the highest rates of reproductive failure.
Another chemical found in high levels on those farms: a compound called BADGE, a derivative of the notorious bisphenol A (BPA). It’s the building block of epoxy resins that form the basis for 95 percent of food and beverage can linings in the U.S. (Also see “Chemical BPA Linked to Heart Disease, Study Confirms.”)
In one recent study led by analytical chemist Kurunthachalam Kannan of the New York State Department of Health in Albany, BADGE, which is also found in household dust, was detected in 100 percent of 127 urine samples collected from people in the U.S. and China.
BPA, the precursor of BADGE, is a known endocrine disruptor: It mimics and interferes with the action of a human hormone, in this case estrogen. A derivative of BADGE called BADGE-2H2O—which forms when BADGE meets water—is an even more potent estrogen mimic.
A lot of research—epidemiological, lab-animal, and clinical studies—has linked endocrine disruptors to adverse health effects, including abnormal testicular development, early puberty, prostate cancer, breast cancer, and even obesity.
Damaging DNA?
Nerín thinks the suspect chemicals in the pigs’ bags came from adhesives used to glue together the multilayer plastic that made up the bags. But the chemicals in question aren’t normally used for that purpose. Their presence in the Spanish pig semen bags may reflect some kind of unusual contamination.
The supplier of the bags, a company named Magapor, had contacted Nerín because of her expertise. “They were desperate,” she says, “because they didn’t find a reason why reproduction failed.”
Nerín confirmed her suspicion that the high levels of cyclic lactone and BADGE were to blame by “spiking” a new batch of semen with a mix that included those two chemicals and inseminating two groups of 50 sows with either the spiked mixture or a control. Just 58 percent of the sows inseminated with the spiked semen became pregnant, compared with 84 percent of the controls.
Magapor had purchased the semen storage bags from a Chinese manufacturer. When the company switched to a different bag producer, the Spanish pigs’ fertility returned to normal.
To complicate the story further, Nerín didn’t find any evidence that BADGE was acting as an endocrine disruptor at the levels at which it was present in the semen bags. But lab experiments suggest BADGE is a mutagen as well as an endocrine disruptor: Besides binding to hormone receptors inside cells, it can bind to DNA, causing mutations.
Because the sperm cells in Nerín’s pig study looked normal and moved and penetrated eggs normally, she believes many of the pregnancy failures may have resulted from damage to the sperm’s DNA—which somehow caused fertilized embryos not to develop normally and not to implant in the sow’s uterus.
Effects in Humans?
Meanwhile another paper published last month revealed a specific mechanism by which endocrine disruptors might indeed interfere with fertilization in humans.
One of the authors, physician Niels Skakkebaek of the Rigshospitalet, a university hospital in Copenhagen, has been studying testicular disorders and endocrine disruptors for decades. In a 1992 paper in the British Medical Journal, he reported evidence indicating that sperm quality had deteriorated among men in the United States and elsewhere over the previous 50 years.
In the new study, Skakkebaek; Timo Strünker of the Center of Advanced European Studies and Research in Bonn, Germany; and their colleagues exposed human sperm in lab tests to 96 common endocrine disruptors—chemicals, they write, that are “omnipresent in food, household, and personal care products.”
They looked at the effects of the chemicals on a specific signaling conduit in sperm (and other cells) called a calcium channel. The calcium channel in sperm is usually activated by female hormones in the female reproductive tract, including progesterone released by cells surrounding the egg. Activation of the calcium channel allows calcium ions to flood into the sperm cells, which in turn affects their motion, causing them to swim toward an egg and penetrate it.
Skakkebaek and Strünker found that about one-third of the chemicals they tested in the lab evoked a “sizable” response by the calcium channel.
For example, some caused the sperm’s tail to curl up rather than flick from side to side. The chemicals that had the strongest effects included ultraviolet light-filtering agents in sunscreens; plastic-softening phthalates used in food and drink containers; and fungicides and antibacterial compounds such as triclosan, which are commonly found in soaps, toothpaste, and toys.
“That was quite unexpected to find so many that could have an effect,” Skakkebaek says. “This is the first time this has been shown.”
If endocrine-disrupting chemicals are present in the female reproductive tract, Skakkebaek says, they may desensitize the sperm to signals from progesterone. “The sperm cells may have more difficulty in sensing where the egg is,” he says. “They could also be swimming in the wrong direction, because they had wrong signals on the way.”
That, in turn, might disrupt the process of fertilization.
Skakkebaek’s lab tests, like the Spanish semen bags, placed the suspect chemicals in direct contact with sperm cells. But it’s not known whether those chemicals are in fact present in the female reproductive tract in dangerous concentrations.
Some researchers question whether everyday exposure to such chemicals in food packaging, say, would have the same detrimental effects on sperm; after the chemicals were ingested, they would be metabolized in the human body, which could change their structure and toxicity.
One skeptic is Allan Pacey, a senior lecturer in andrology at the University of Sheffield in the U.K. He and his co-workers conducted two large epidemiological studies on thousands of British men, examining both occupational exposures to chemicals and lifestyle issues, such as drinking and smoking. They found that only two risk factors—exposure to glycol ether (a paint ingredient) and wearing tight underwear—were associated with “low motile sperm count.”
“It is possible to measure effects on ejaculated sperm in the lab, but this is a long way removed from what may be happening in the real world,” Pacey says.
Skakkebaek agrees that more studies of how chemical exposure affects actual humans are needed.
“Most of these chemicals are found in almost everybody,” he says, referring to the ones in his recent study. “We know for sure that they are in our bodies, because we know for sure that they are excreted in our urine. But what we don’t know for sure is the concentration.”
As for Nerín’s study of the Spanish pigs, “they really found a clear association” between chemical exposure and infertility, Skakkebaek says. “I believe it should be taken as a warning.”
TedX talk with Tyrone Hayes & Penelope Jagessar Chaffer
Filmmaker Penelope Jagessar Chaffer was curious about the chemicals she was exposed to while pregnant: Could they affect her unborn child? So she asked scientist Tyrone Hayes to brief her on one he studied closely: atrazine, a herbicide used on corn. (Hayes, an expert on amphibians, is a critic of atrazine, which displays a disturbing effect on frog development.) Onstage together at TEDWomen, Hayes and Chaffer tell their story.
General Electric agreed today to sell its plastics division for $11.6 billion to the largest public company in Saudi Arabia, the Saudi Basic Industries Corporation.
The deal for the G.E. division, which has 11,000 employees in 20 countries, is one of the largest yet by the Saudi company, known as Sabic. Sabic prevailed in a sometimes crowded race, with other top bidders being Basell, the Dutch plastics maker, and Apollo Management, the American private equity firm led by Leon Black.
In a statement, Mohamed al-Mady, the vice chairman and chief executive of Sabic, said: “This business is complementary to our existing business without any overlaps. Sabic’s intention is to grow the business globally.”
In a separate statement, Jeffrey R. Immelt, the chief executive of G.E., said the sale made equal sense for G.E.
“Sabic is the right owner for our customers and our employees,” Mr. Immelt said. “This transaction will transform the plastics industry by combining Sabic’s low-cost materials position and global reach with GE Plastics’ strong marketing and technology capabilities. Sabic also has a record of investing in acquired businesses and their people.”
Neither the buyer nor the price came as a surprise to analysts who follow General Electric. In January, when G.E. confirmed long-standing rumors that it was putting its plastics business on the block, most analysts expected the unit to go for $8 billion to $10 billion, and for the probable buyer to be a private equity firm.
But in recent months, G.E. executives had signaled to analysts that they expected to get $10 billion to $12 billion for the unit, and that it would likely go to a strategic buyer — that is, a company that would utilize the division and its products, rather than groom it for an eventual public offering or resale. Most analysts quickly honed in on Sabic, because of its access to Saudi Arabia’s vast petroleum supplies. After all, it was the ever-rising cost of benzene, a petroleum derivative and a key raw material for G.E.’s plastics products, that had sucked the profitability out of the unit for G.E. A company like Sabic, with an inexpensive and inexhaustible supply of benzene could far more easily turn a profit.
The sale, which is expected to close in the third quarter, is unlikely to have much of a strategic impact on G.E. In January, G.E. agreed to spend $4.8 billion to buy the aerospace business of the Smiths Group, $1.9 billion to buy the oil and gas operations of Vetco Gray and $8.1 billion to buy a diagnostics business from Abbott Laboratories. G.E. said it will use most of the proceeds from the plastics sale to buy back stock, but analysts expect that some of the money will be used to pay for those acquisitions.
It is also unlikely that the divestiture is heralding a larger-scale trimming of the G.E. portfolio. Many investors have tried to pressure G.E. into selling NBC Universal, the entertainment division that suffered through many quarters of lackluster profits. And there has been widespread speculation that, if G.E. did decide to sell the unit, it would also divest its consumer finance division. The reason is that NBC Universal is part of G.E.’s industrial group, and a sale would skew the company’s portfolio too far toward financial products. Shares of financial services companies generally trade at lower multiples than those of industrial companies, and G.E. would not want to risk having itself recategorized in investors’ minds.
But NBC Universal’s profits have been rising, and consumer finance is a growing area for G.E., and many analysts say G.E. would have no reason to sell either. Still, while plastics seemed to play no role in G.E.’s vision of its future, it played a huge role in the company’s past. G.E. formed its first plastics department in 1930, and by 1941 it had become the country’s largest plastics producer. In 1953, a G.E. scientist discovered a high-strength polycarbonate that the company branded Lexan. To this day Lexan is a huge seller, used for bulletproof glass, water bottles and even Apple iPods. Neil Armstrong and Buzz Aldrin were wearing Lexan visors on their journey to the moon in 1969. Four years later, G.E. made the booming plastics department an official division of the company.
Since then GE Plastics has become a major supplier to industries as diverse as automaking, electronics and appliances. Both Mr. Immelt, G.E.’s current chairman, and John F. Welch Jr., his predecessor, worked at the plastics group. But competition and price increases in raw materials have squeezed profit margins, even though the unit increased product prices. For 2006, the plastics division reported about $6.6 billion in revenue, virtually unchanged from the previous year. Profit fell to $674 million, down 22 percent from 2005.
An excerpt from the chapter, “The Polycarbonate Problem.”
BPA, Benzene, Phenols, & Carbonyl Chloride (also known as Phosgene)
Although it’s only in the past few years that news of bisphenol A’s health impacts began to reach a nonscientific general public–news that has since spread rapidly–it was first recognized as a synthetic estrogen in the 1930s. Papers published in the journal of Nature in 1933 and 1936 describe its estrogenic effects on lab rats. These papers also commented on the possible carcinogenic activity of materials with similar or comparable composition to bisphenol A–specifically materials synthesized from petroleum (from which bisphenol A is ultimately derived) and coal tar.
Some two decades later, bisphenol A was launched into everyday life with the development of commercially produced polycarbonates. Major production of these plastics began in the United States in the late 1950s after a General Electric engineer named Daniel W. Fox formulated a material based on BPA that GE called Lexan. The invention was not so much deliberately planned as it was the result of what Fox called his ability to take “a few clues and jump to conclusions that frequently panned out.”
While experimenting with different materials that might ultimately make a good moldable polymer, Fox decided to work with bisphenols, compounds derived from petroleum processing that were then being used to make various epoxy resins. As molecules, bisphenols have a structural feature that makes them useful as potential chemical building blocks. Attached to their hydrocarbon ring is what’s called a hydroxyl group, an oxygen and hydrogen that together form a site to which other molecules can bond. This structure is common to both synthetic and naturally occurring compounds, a coincidence that will later turn out to be important to how bisphenol A behaves.
Fox’s interest in the hydroxyl group was as a polymer building site, not for its biological activity. But when attached to a hydrocarbon ring as it is in bisphenol A, the entire chemical grouping becomes a molecule known as a phenol–an aromatic hydrocarbon, a ring made up of six carbon atoms and five hydrogen atoms plus a hydroxyl group. Phenols are commonly made by oxidizing benzene, which essentially means adding oxygen to benzene. Phenols are toxic, but they are also known for their antiseptic properties and so were used to kill germs in the nineteenth century surgical procedures.
This molecular group consisting of six carbon-five hydrogen rings with a hydroxyl group attached, however, is also part of the structure of substances produced naturally by the human body, compounds that include estrogen and thyroid hormones. Introducing a manufactured chemical that includes the phenol group into a cellular environment may therefore pose a problem because the synthetic material may compete biochemically with the similarly structured naturally occurring chemical. Thinking in green chemistry terms, the presence of a phenol group on a synthetic, therefore, should be a sign to investigate that substance’s potential as an endocrine disruptor.
The potential cellular toxicity of phenols has actually been known for decades. Research done in the 1950s, written about by Rachel Carson in Silent Spring, discussed the mechanisms by which pesticides constructed with phenols had the ability to prompt oxidation processes that upset cellular metabolism. These reactive chemical groups can disrupt formation of enzymes vital to energy production, which in turn may interfere with how an organism produces and differentiates cellular material. These processes of cellular reproduction are involved in virtually every bodily system, from how an individual processes sugars and calcium to how its reproductive system functions. Carson described the introduction of xeniobiotic phenols as thrusting “a crowbar into the spokes of a wheel. Had Fox been a green chemist, our current synthetic landscape might look very different.
But because Fox and his colleagues were focused on functional performance and on working with readily available chemical ingredients, bisphenols seemed a good choice. As an additional building block that might combine with the bisphenol molecules’ hydrocarbons to yield a useful polymer, Fox chose a chlorine compound called carbonyl chloride. Carbonyl chloride was then–and is currently–a common ingredient in the synthetics known as isocyanates that are used to make any number of products, including polyurethanes that go into varnishes, paints, and plastic foams. By the 1950s it was known that chlorinated hydrocarbons made useful synthetics so this was a logical route for Fox to follow–but no one had yet made the kind of moldable, shatter-resistant plastic that Lexan turned out to be.
If you’re building a polymer, a linked chemical chain in effect, you need lots of the same repeating pieces; ideally you’ll work with shapes that are easy to find and lend themselves to chemical bonding. It’s here that a Tinkertoy or Lego analogy comes to mind. To add pieces to a chemical structure, you need sites where new sticks and building blocks can be attached. So it was with the choice of bisphenols and carbonyl chloride, which lend themselves to such bonding and were both readily available industrial chemicals. Had Fox been practicing green chemistry, however, he would never–even with what was known in the 1950s–have launched a product that required copious quantities of carbonyl chloride.
Carbonyl chloride is also known as phosgene and is so toxic that it was used as a chemical weapon during World War I. The isocyanates it’s used to make are also highly toxic. One such compound, methyl isocyanate, was the gas involved in the deadly 1984 disaster at the Union Carbide plant in Bhopal, India. Lest anyone wonder if nerve gas is lurking in your bike helmet or CD cases, however, let me quickly explain that no phosgene or even any chlorine ends up in the final bisphenol A polymer; the chlorine compound is simply a reagent, an ingredient that enables the desired chemical bonding to take place.
Yet speaking to an interviewer in 1983, Fox acknowledged that using large quantities of a chemical such as phosgene was indeed hazardous. But, Fox continued, it “was not a totally frightening undertaking because we had good advice. I would say that we have been tightening up our whole phosgene handling ever since, investing in an awful lot of money in trying to make the stuff doubly safe and then triply safe and quadruply safe.” Still, the interviewer pressed, “Has there ever been a problem?” To which Fox responded, “We have had one or two small discharges. To my knowledge, I don’t think GE advertised it, but I think we probably had a ‘casualty’ from phosgene.” Did this give anyone second thoughts about going into business? “I don’t think it did,” Fox replied.
At the time Fox was working, new material inventions like carbonates were just that–inventions that came first, with applications and markets found later. “When we invented polycarbonates in the early 1950s we had a polymer with an interesting set of properties and no readily apparent applications,” Fox said in 1983. But what was known about polycarbonates’ behavior early on that might have hinted at what’s since been discovered about their physical and biological behavior” Could this information have been used to prevent what are clearly problems of chemical contamination? Endocrine-disruption science is relatively new, but some of what was known early on about bisphenol A and polycarbonates would seem to indicate a material perhaps not ideally suited for use, say, with food, heat, and dishwashing detergents.
That polycarbonates built from bisphenol A were vulnerable to certain detergents, solvents, and alkali solutions (household ammonia would qualify) has been known since at least the 1970s. Ammonium hydroxide (essentially a solution of ammonia in water) was discussed as a possible way to break polycarbonates down to its chemical constituents–for materials recovery and reuse and as a way to remove unwanted polycarbonate from another surface. It was also known that various additives used to modify polycarbonate mixtures could leach from the finished plastics when they came into contact with certain liquids. Documents filed with the Federal Register in 1977 list chloroform, methylene chloride, and chlorobenzene among these additives. (The U.S. Department of Health and Human Services considers chloroform and methylene chloride suspected carcinogens, while chlorobenzene is known to cause liver, kidney, and nervous system damage and produce a precancerous condition in lab rats.) Correspondence between GE Plastics Division personnel in the 1970s and 1980s also voiced concern over the presence of chlorobenzene in water stored in polycarbonate bottles (but not bottles made by GE as it happened) and about how the stability of these polymers might affect their ability to be used with food.
A memo circulated within the Lexan division of GE in 1978 also noted that “through reaction with water,” polycarbonate resin can degrade. “The two largest applications of Lexan resin for which hydrolytic stability is critically important are baby bottles and water bottles,” ran the 1978 memo.
In each application the finished parts are subjected to conditions which will cause, after prolonged treatment, molecular weight reduction. However, in each application, actual product failure is usually observed before significant molecular weight reduction is detectable by the usual techniques…..Baby bottles are subjected to autoclaving at 250 degrees F in saturated steam and fail under these conditions by becoming opaque, and sometimes by shrinking and deforming. Milk and water bottles are washed in aqueous solutions of alkaline or caustic cleaning agents and fail by stress cracking. The relationship between practical failure modes and the fundamental physical and chemical processes involved is not fully understood.
That polycarbonates might degrade when heated, washed, or exposed to sunlight was also discussed in company memos in the late 1970s and early 1980s. Three decades later, the plastics industry assures consumers that such wear and tear of polycarbonate baby bottles poses no health concerns for infant users.
Pages 58 – 62
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Researchers soon realized the estrogenic effect was due to a contaminant rather than a hormone that was causing the breast cancer cells to rapidly multiply. They determined that the contaminant was bisphenol-A – BPA and that the source of the contamination was the polycarbonate lab flasks used to sterilize the water used in the experiments….
In a 1993 paper, the Stanford team reported their discovery and their discussions with the manufacturer of polycarbonate, GE Plastics Company. Apparently aware that polycarbonate will leach, particularly if exposed to high temperatures and caustic cleaners, the company had developed a special washing regimen that they thought had eliminated the problem.
In working with the company, however, the researchers discovered that GE could not detect bisphenol-A in samples sent by the Stanford lab-samples that were causing proliferation in estrogen-responsive breast cancer cells. The problem proved to be the detection limit in GE’s chemical assay-a limit of ten parts per billion. The Stanford team found that two to five parts per billion of bisphenol-A was enough to prompt an estrogenic response in cells in the lab. pages 130 – 131
Bisphenol-A: an estrogenic substance is released from polycarbonate flasks during autoclaving.
AV Krishnan, P Stathis, SF Permuth, L Tokes and D Feldman
Division of Endocrinology, Stanford University School of Medicine, California 94305
Endocrinology, Vol 132, 2279-2286
In studies to determine whether Saccharomyces cerevisiae produced estrogens, the organism was grown in culture media prepared using distilled water autoclaved in polycarbonate flasks. The yeast- conditioned media showed the presence of a substance that competed with [3H]estradiol for binding to estrogen receptors (ER) from rat uterus. However, it soon became clear that the estrogenic substance in the conditioned media was not a product of the yeast grown in culture, but was leached out of the polycarbonate flasks during the autoclaving procedure. [3H]Estradiol displacement activity was monitored by ER RRA, and the active substance was purified from autoclaved medium using a series of HPLC steps. The final purified product was identified as bisphenol-A (BPA) by nuclear magnetic resonance spectroscopy and mass spectrometry. BPA could also be identified in distilled water autoclaved in polycarbonate flasks without the requirement of either the organism or the constituents of the culture medium. Authentic BPA was active in competitive RRAs, demonstrating an affinity approximately 1:2000 that of estradiol for ER. In functional assays, BPA (10-25 nM) induced progesterone receptors in cultured human mammary cancer cells (MCF-7) at a potency of approximately 1:5000 compared to that of estradiol. The BPA effect on PR induction was blocked by tamoxifen. In addition, BPA (25 nM) increased the rate of proliferation of MCF-7 cells assessed by [3H]thymidine incorporation. Thus, BPA exhibited estrogenic activity by both RRA and two functional bioresponse assays. Finally, MCF-7 cells grown in media prepared with water autoclaved in polycarbonate exhibited higher progesterone receptor levels than cells.grown in media prepared with water autoclaved in glass, suggesting an estrogenic effect of the water autoclaved in polycarbonate. Our findings raise the possibility that unsuspected estrogenic activity in the form of BPA may have an impact on experiments employing media autoclaved in polycarbonate flasks. It remains to be determined whether BPA derived from consumer products manufactured from polycarbonate could significantly contribute to the pool of estrogenic substances in the environment.
Editorial: Estrogens from Plastic—Are We Being Exposed?
David Feldman M.D.
Stanford University School of Medicine Division of Endocrinology, Gerontology and Metabolism Stanford, California 94305-5103
Address all correspondence and requests for reprints to: David Feldman, M.D., Stanford University School of Medicine, Division of Endocrinology, Gerontology and Metabolism, Stanford, California 94305-5103. E-mail: feldman@CMGM.Stanford.edu.
Introduction
Top
Introduction
References
The controversy over the potential negative impact on public health of environmental chemicals with estrogenic activity has spilled over from scientific journals (1, 2) into the public domain. News articles on the subject have appeared in multiple sources including Science (3), Journal of the American Medical Association (4), Chemical and Engineering News (5), Science News (6) and Newsweek (7), and in many newspapers, as well as on National Public Radio. The book Our Stolen Future (8) has emphasized the effects of environmental chemicals on wildlife and their long-term effects on the environment. Some stories have hyped the risk of environmental chemicals with provocative terms such as “Ecocancers” (6) and titles such as “Can environmental estrogens cause breast cancer? (9). Proponents of the position that environmental estrogens are hazardous raise concerns about birth defects due to fetal exposure (8, 10), the increased incidence of breast cancer (9, 11), falling sperm counts and decreased fertility (12), and numerous other conditions (3, 4, 5, 6, 7, 8, 9, 10, 11, 12). However, in each case there is controversy over the findings with opponents making strong counter-arguments. In all of these conditions, the risk is hypothetical, with no data yet proving a causal relationship between environmental estrogens and illness or disease in people.
The claim that environmental estrogens are causing a decline in sperm counts has been especially contentious. Investigators in this field have so far failed to agree on whether sperm counts are, in fact, falling. If sperm counts are in decline, they certainly cannot agree on whether environmental estrogens are even remotely involved (12, 13). Similarly, the proposal that environmental estrogens contributed to an increased incidence of breast cancer (11) was quickly refuted (14).
Scientifically sound experiments have documented that various environmental chemicals are capable of acting as endocrine disrupters, either hormone agonists or antagonists, which can potentially alter the hormonal balance in animals and people. A number of studies, including our own (15), have clearly shown the estrogenic activity of some environmental chemicals. What remains controversial and open to serious debate is the level of exposure of the population to these agents and an ascertainment of whether these levels are sufficient to cause harmful effects. The critical question is whether the population is exposed to a high enough concentration of chemicals to cause, in the in vivo setting, the effects that these agents have been demonstrated to initiate in vitro. This question is not easily answered. Although the estrogenic activity of these substances is very much weaker than estradiol, as discussed below, new chemicals with endocrine disrupting potential continue to be discovered, unanticipated pathways of exposure continue to be found, and concern about the cumulative effects of these agents continues to grow. However, the level of exposure is difficult to quantify and the array of potential target organs in the body continues to rise.
In this issue of the journal, Ben-Jonathan and her group extend the accumulated data on the estrogenic activity of Bisphenol-A (BPA), a compound used to manufacture the plastic called polycarbonate. In this article, Steinmetz et al. (16) argue that the pituitary cells that regulate PRL release are a new target for environmental estrogens in general and BPA in particular. Although there are many substances considered to be environmental estrogens, including pesticides, pollutants, and various chemicals, this paper deals with the estrogenicity of BPA, and I will therefore focus my discussion primarily on the estrogenic substances derived from plastics.
BPA is the monomeric unit used to produce the ubiquitous plastic, polycarbonate. This plastic has excellent properties making it tremendously useful in many applications. In 1993, my group reported on the estrogenic activity of BPA that was released from polycarbonate flasks during the autoclaving of media (15). We showed that BPA could act on MCF-7 human breast cancer cells as an estrogen, stimulating cellular proliferation and inducing progesterone receptors. BPA could bind to estrogen receptors, and the estrogenic effects induced by BPA were blocked by the estrogen antagonist tamoxifen, thus supporting the notion that the estrogenic activity of BPA was mediated via the estrogen receptor. Although the chemical structure of BPA is quite similar to diethylstilbestrol (DES), a well known and very potent nonsteroidal estrogenic compound with a bis-phenolic structure, BPA was a much weaker estrogen, approximately 1000- to 2000-fold less potent than estradiol (15). Our results were of interest for two reasons. First, we wanted to alert other investigators about the potential risk of estrogenic artifacts causing spurious effects in laboratory experiments. Second, we wanted to raise for scientific scrutiny the possibility that BPA was a risk to public health. Because polycarbonate is used in the packaging, storing, and preparation of a myriad of foods and beverages, including water jugs, bottled beverages, baby food, and juice containers, we wondered whether BPA might contaminate the food supply and potentially harm the public. However, because limited data were available upon which to draw a conclusion, we cautiously raised the question for study and made no claim that a public health risk existed (15).
In addition to our work, Soto, Sonnenschein, and colleagues at Tufts University showed very similar results with another component of different plastics, p-nonyl-phenol (17). This alkylphenolic substance, used as plastic additive and surfactant, could be released from polyvinyl chloride and polystyrene plastics even without autoclaving. The Tufts group also developed an “E-Screen” to assay the estrogenic activity of unknown substances or mixtures based upon their ability to stimulate MCF-7 cell proliferation (18).
Two subsequent studies further demonstrated the potential public health hazard of BPA. First, Brotons et al. noted that many food cans are lacquer-coated with a plastic lining and that, within some cans, the food contained substantial amounts of BPA (19). Because the food is autoclaved in the cans, the conditions of our laboratory polycarbonate flask experiment are essentially reproduced by the canning industry. While we had found BPA at levels of 2–4 µg in the liquid contents of our plastic flasks, Brutons et al. reported that food cans that contained BPA had contents ranging between 4 and 23 µg. Almost all of the estrogenicity was due to BPA based upon the results of the E-Screen.
A second study found that some routine dental procedures could potentially cause significant amounts of BPA exposure (20). Resin based composites and sealants commonly used in dentistry are made of BPA or BPA-dimethacrylate. Olea et al. found 90–931 µg of BPA in the saliva of patients 1 h after a sealant was applied to their teeth. Unfortunately, we have no data on how long the BPA persisted in the saliva and the total level of exposure after various dental treatments.
In this issue of Endocrinology, Steinmetz et al. (16) confirm by additional methods that BPA is estrogenic, and they estimate that its potency in vitro is 1000- to 5000-fold less active than estradiol. This study raises three additional important issues. First, Steinmetz et al. examined the estrogenic activity of BPA in vivo. Although the administration was from sc implanted SILASTIC (Dow Corning, Midland, MI) brand “capsules” and not the oral route, it is highly significant that the estrogenic effects of BPA were demonstrated in ovariectomized rats. From the data presented on PRL secretion in vivo, it can be surmised that BPA may only be 100- to 500-fold less active than estradiol. Thus, BPA may be an order of magnitude more potent in vivo than assessed by prior in vitro studies. The reasons for this increased potency in vivo are not apparent, but this finding could make estimations of BPA exposure levels based solely on in vitro potency liable to a 10-fold error.
Secondly, Steinmetz et al. raise a new BPA-target organ beyond the obvious ones of breast and uterus. The study shows BPA effects on pituitary cells that secrete PRL and speculates on a possible link between environmental estrogens and PRL secreting pituitary tumors (16).
A third intriguing concept from the paper by Steinmetz et al. is that there are genetic differences in susceptibility to estrogens including BPA; Fischer 344 rats are very sensitive, whereas Sprague-Dawley rats are resistant (16). The mechanism for this differential effect is unclear from the data available. The authors speculate that subpopulations of humans may likewise be more sensitive to BPA and other environmental estrogens than the population at large.
The public health question raised by all of these studies is: are the amounts of ingested BPA from all sources substantial enough to cause significant estrogenic effects in the population? It is difficult to answer this question because there are no data available yet on the estrogenic potency of BPA via the oral route.
Perhaps the most articulate proponent of the view that environmental estrogens are not a public health hazard is Stephen Safe, a pharmacologist/toxicologist who has studied this and related environmental issues for many years. Safe argues that the total amount of environmental estrogens that people are exposed to, especially because of their low potency, is inconsequential (2). He contends that phytoestrogens in our diet far outweigh the estrogenic potency of environmental estrogens. Furthermore, environmental antiestrogens would balance out many of the harmful effects of environmental estrogens (21). Using calculations of “estrogen equivalents,” he concludes that the exposure level to environmental estrogens is trivial in comparison with estrogen levels used in therapeutic settings and even thousands-fold lower than the flavonoid phytoestrogens in food that we routinely consume (2). Safe argues persuasively that there is no evidence proving that there is a problem due to environmental exposure.
However sound these theoretical arguments may appear, I believe, and Safe agrees [personal communication], that a number of considerations have to be taken into account that may modify these estimates of risk: 1) More exposure of the population than anticipated may be occurring due to environmental estrogens from unexpected sources and new, as yet unknown, substances including BPA and other chemicals (22). The effects of BPA and other components of plastic have not yet been accounted for in estimates of estrogen equivalents exposure. 2) Additional mechanisms may be operative that are additive to the negative effects of environmental estrogens. For example, substances that inhibit enzymatic degradation of environmental or natural estrogens or exposure to environmental substances with antiandrogen activity may provide a second negative effect (23). 3) The cumulative effect of many different agents may be additive or synergistic. Although cumulative exposure may be exceedingly important, the added possibility of synergistic interactions among the environmental estrogens, thereby increasing their estrogenic activity, is potentially alarming. This hypothesis was raised by Arnold et al. (24) but has now been refuted by two groups (25, 26) and remains equivocal and unproven. 4) Tissue-specific effects for estrogens are well documented so that some environmental estrogens may be more potent than others in certain tissues, or may be agonists rather than antagonists (27). This tissue specific activity is seen with estrogen antagonists such as tamoxifen and the new “designer estrogens” such as raloxifene and droloxifene. Thus, calculation of estrogenic potency based on actions using the breast or uterus as models may not be quantitatively predictive of effects in other tissues such as the liver, bone, or brain or in the developing fetus that may be more sensitive to hormonal influences (28). 5) Genetic susceptibility of subpopulations, as raised by Steinmetz et al. (16), may make some groups more susceptible to estrogenic effects. 6) Pharmacokinetic or other in vivo factors may cause the estrogenic effect to be greater than expected based solely on extrapolations from in vitro data, as shown by Steinmetz et al. (16). These factors might include inadequate metabolism of man-made chemicals or metabolism to more active analogs, lack of binding to serum proteins, accumulation in the body and storage in fat, or other conditions causing an increased or prolonged exposure. 7) Finally, all estrogenic substances do not behave in an identical fashion. Some might have additional unique actions, as was seen with DES and vaginal cancer in daughters of treated patients (29). Because BPA is structurally similar to DES and not estradiol, its estrogenic actions might be more predictable from DES than estradiol and might cause unanticipated effects.
Conversely, similar arguments might suggest decreased in vivo activity relative to in vitro potency. Of prime importance is the possibility that ingested BPA would be rapidly metabolized to inactive products and have no estrogenic activity by the oral route. This possibility needs to be tested before the concept that BPA is a public health hazard can be taken seriously.
In conclusion, a healthy skepticism about the risk due to BPA and other environmental estrogens is wise. In my opinion, the data do not yet prove a relationship of environmental estrogens to breast cancer, sperm counts, or any general adverse effect. However, because this potential hazard could occur on a global scale affecting the entire population, this possibility should not be discounted without further study. Although I suspect that the environmental exposure is not adequate to cause serious effects, except in unique situations where a large local contamination occurs (10), the potential hazards are too important, and more investigation is certainly warranted. Especially necessary are in vivo studies examining dose-response effects of orally ingested BPA and other potential environmental estrogens and an examination of their actions at many tissue sites. I agree with Steinmetz et al. (16) that the complex potential problems of additive, cumulative, and persistent effects of these agents must be addressed. This controversy will not go away, nor should it, until adequate experimental results are available to ascertain whether or not the population is being exposed to harmful levels of environmental estrogens.
Received February 24, 1997.
References
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Introduction
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The Silent War 