It's in Baby Bottles, Soda Cans And 93% of US
It Causes Breast Cancer, Testicular Cancer, Diabetes And Hyperactivity in Lab Animals, According to 80% of Studies Analyzed by the Journal Sentinel. But U.S. Regulators Side with the Chemical-makers And Say It's Safe.; Chemical Fallout /; a Journal Sentinel Watchdog Report
The Milwaukee Journal Sentinel
For more than a decade, the federal government and chemical- makers have assured the public that a hormone-mimicking compound found in baby bottles, aluminum cans and hundreds of other household products is safe.
But a Journal Sentinel investigation found that these promises are based on outdated, incomplete government studies and research heavily funded by the chemical industry.
In the first analysis of its kind by a newspaper, the Journal Sentinel reviewed 258 scientific studies of the chemical bisphenol A, a compound detected in the urine of 93% of Americans recently tested. An overwhelming majority of these studies show that the chemical is harmful - causing breast cancer, testicular cancer, diabetes, hyperactivity, obesity, low sperm counts, miscarriage and a host of other reproductive failures in laboratory animals.
Studies paid for by the chemical industry are much less likely to find damaging effects or disease.
U.S. regulators so far have sided with industry by minimizing concern about the compound's safety.
Last week, a panel commissioned by the National Toxicology Program released a report finding bisphenol A to be of some concern for fetuses and small children. It found that adults have almost nothing to worry about.
Its recommendations could be used by the U.S. Environmental Protection Agency and other regulators to assess federal policies on how much bisphenol A is safe and may have huge ramifications for the multibillion-dollar chemical industry.
The panel said it considered more than 700 studies by university scientists, government researchers and industry-funded chemists. It picked the work it felt was best and threw out the rest.
The Journal Sentinel found that panel members gave more weight to industry-funded studies and more leeway to industry-funded researchers.
-- The panel rejected academic studies that found harm - citing inadequate methods. But the panel accepted industry-funded studies using the same methods that concluded the chemical does not pose risks.
-- The panel missed dozens of studies publicly available that the Journal Sentinel found online using a medical research Internet search engine. The studies the panel considered were chosen, in part, by a consultant with links to firms that made bisphenol A.
-- More and more university researchers and foreign governments are finding that bisphenol A can do serious damage in small doses. But the panel rejected studies mostly submitted by university and international government scientists that looked at the impact at these levels.
-- The panel accepted a Korean study translated by the chemical industry's trade group that found bisphenol A to be safe. It also accepted two studies that were not subjected to any peer review - the gold standard of scientific credibility. Both studies were funded by General Electric Co., which made bisphenol A until it sold its plastics division earlier this year.
"This undermines the government's authority," said David Rosner, professor of history and public health at Columbia University. "It makes you think twice about accepting their conclusions."
Panel chairman Robert Chapin, a toxicologist who works for Pfizer Inc., the pharmaceutical giant, defended his group's work.
"We didn't flippin' care who does the study," said Chapin, who worked as a government scientist for 18 years before joining Pfizer.
If the studies followed good laboratory practices and were backed with strong data, they were accepted, Chapin said.
Created to act as hormone
Bisphenol A was developed in 1891 as a synthetic estrogen. It came into widespread use in the 1950s when scientists realized it could be used to make polycarbonate plastic and some epoxy resins to line food and beverage cans.
With the advent of plastic products such as dental sealants and baby bottles, the use of bisphenol A has skyrocketed. The chemical is used to make reusable water bottles, CDs, DVDs and eyeglasses. More than 6 billion pounds are produced each year in the United States.
In recent decades, increases in the number of boys born with genital deformities, girls experiencing early puberty and adults with low sperm counts, uterine cysts and infertility prompted some researchers to wonder whether the prevalence of bisphenol A could be interfering with human development and reproduction.
Scientists began looking for a link between bisphenol A and spikes in cancer, obesity and hyperactivity. Others, such as Patricia Hunt, simply stumbled onto it.
Hunt, a scientist at Case Western Reserve University, was investigating the connection between maternal age and Down syndrome in 1998 when all of her laboratory mice, including those not treated in any way, began exhibiting chromosomal abnormalities.
Her investigation revealed that bisphenol A was leaching from the animals' polycarbonate cages, and it was the chemical that had caused the problems.
Ana Soto, a researcher at Tufts University, began noticing that her lab mice treated with bisphenol A were a lot fatter than her other mice.
More alarming still was the work scientists found in their breast and prostate cancer research. They injected cancer cells in test tubes of bisphenol A and watched as the cells grew rapidly, even at doses lower than what people are normally exposed to. Reports such as these sparked fear that bisphenol A could become the new lead or asbestos.
As scientists' suspicions grew, regulators repeatedly reassured the public that the chemical was safe. The Food and Drug Administration and the EPA routinely pointed to studies by government regulators in the 1980s that found no serious effects.
In 1998, the National Toxicology Program formed the Center for the Evaluation of Risks to Human Reproduction to look at why so many people were unable to conceive or carry their babies to term. Scientists were suspicious of the environmental impact from chemicals, including hormone-mimicking chemicals such as bisphenol A.
Last year, two groups of scientists were appointed by the federal government to gauge bisphenol A's risks.
One panel was purely academic, made up of 38 international experts in bisphenol A who work for universities or governments. In an August report, they found a strong cause for concern.
Levels of bisphenol A in people were higher than the levels found to cause harm in lab animals, the panel said. The average level found was above what the EPA considered safe.
The other group, led by Chapin, included 12 scientists. The members were chosen because of their lack of detailed knowledge about bisphenol A. The idea was that the group would serve as an impartial jury, Chapin said.
It considered 742 studies conducted over the past 30 years.
The non-expert panel was less alarmed about bisphenol A's effects.
The non-expert panel's report was posted Monday on the center's Web site without a press release or fanfare. When the panel released an earlier draft, critics assailed it as arbitrary, biased and incomplete.
The sharpest response came from bisphenol A experts, many of whom had their work rejected by the non-expert panel. Even those whose work was accepted were critical of the findings.
"When panels that are sponsored by the government come out with reports and say that there is not convincing evidence yet, that gives me great concern, knowing what I do about some studies showing that there are effects," said Gail Prins, professor of physiology at the University of Illinois at Chicago and an expert in bisphenol A.
The federal government will now weigh the reports of both the expert and non-expert panels before assessing safe levels of bisphenol A.
Studies found widespread effects
Before reviewing the panel's reports, the Journal Sentinel analyzed 258 studies spanning two decades. All studies involved live animals with spines - those species scientists consider most relevant to people. The studies were found on PubMed, an online search engine used by researchers.
Four out of five studies found that bisphenol A caused problems in the lab animals tested, ranging from allergies to reproductive deformities. The vast majority of these studies were funded by government agencies and universities.
One federally funded study found that rats exposed to bisphenol A before birth were at increased risk of developing precancerous prostate lesions. Another study, funded by the U.S. and Argentine governments, found that the chemical increased the likelihood of rats developing mammary tumors.
Just 12% of the studies found that bisphenol A had no ill effects. Most of those studies were paid for or partially written by scientists hired by the chemical industry.
A study funded by the Society of the Plastic Industry found that bisphenol A did not pose harm to developing rats. Another study discounted any reproductive effects on exposed rats. The authors included scientists affiliated with Shell Chemicals, Dow Chemical Co. and General Electric - all then makers of bisphenol A.
Two studies actually determined that bisphenol A may be beneficial. One funded by drug-maker Eli Lilly & Co. said it could lower cholesterol in rats. The other study said the chemical might prevent or cure breast cancer in rats.
Industry scientists dispute any claims that bisphenol A is harmful to humans.
"Our view is consistent with what has been concluded by government and scientific bodies around the world, which is that bisphenol A is not a risk to human health based on the weight of scientific evidence," said Steven G. Hentges, executive director of the American Chemistry Council's Polycarbonate/BPA Global Group. Hentges called the newspaper's review superficial.
Norman Fost, founder and director of the medical ethics program at the University of Wisconsin-Madison, said industry and academic studies come to radically different conclusions all the time. Fost would not comment directly on the panel's work because he hadn't studied it. But he said the universe of scientific research is replete with studies conducted by organizations with a vested interest.
"It's up to us to be skeptical, cautious and critical when we consider how much of their work to believe," said Fost, who is chairman of an FDA committee looking at the ethics of pediatric studies.
Human safety levels
Bisphenol A is just about everywhere. But trying to get a handle on how much of the chemical a person can tolerate is not easy.
The government established a safety level for bisphenol A about 20 years ago - well before most scientific studies on the chemical had been conducted. The government considers a safe daily level of bisphenol A to be 50 micrograms per kilogram of body weight. For a 200-pound person, that would be the equivalent of no more than one drop of the chemical every five days.
The American Chemistry Council says an average adult would have to ingest more than 500 pounds of canned food and beverages every day for an entire lifetime to be at risk. The chemical industry based those conclusions on its own research.
Others say there is no way to know how much bisphenol A one is exposed to when microwaving dinner in a plastic container, eating tuna from a can or drinking from a reusable plastic water bottle.
"Even if you go out of your way to avoid products, you don't know all of your exposures," said Soto, the bisphenol A expert from Tufts. "At the end of the day, you may have cut your exposure by 5 percent or by 95 percent. We just don't know."
Because bisphenol A is so ever-present in the environment, there are many ways to be exposed to it. But the biggest risk comes from those products that people put in their mouths or that come directly into contact with food, scientists say.
A number of studies looked at how bisphenol A affects lab animals at low doses. Bisphenol A experts say that the chemical works like a hormone and, therefore, needs to be tested at low doses where much damage can be done.
"This is basic endocrinology," said Frederick vom Saal, a biologist at the University of Missouri who has been studying bisphenol A for more than a decade. "You learn this in any introductory class. Hormones work on an extremely sensitive system."
For instance, it only takes 40 parts per billion of the hormone MIS to produce male sexual organs in the human embryo. That's about one drop in 15 bathtubs of water.
Two groups of scientists - from the National Academy of Sciences and the National Toxicology Program - have called for the U.S. government to radically overhaul the way it tests chemicals to include these low doses. But the government has yet to do so. Instead, it continues to cite the government studies from the early 1980s that focused only on high doses.
Of the 258 studies reviewed by the Journal Sentinel, 168 studies looked at low-dose effects of bisphenol A.
The vast majority - 132 studies - found health problems at low doses, including hyperactivity, diabetes and genital deformities. All but one of those studies were conducted by non-industry scientists. Nearly three-fourths of the studies that found the chemical had no harmful effects were funded by industry.
But Chapin's panel did not accept any studies that found an effect at low doses in its review of 742 studies.
Once the panel weeded out studies it believed had been done poorly, no studies remained that showed effects from low doses, Chapin said.
"There's a lot of bad science out there," he said.
Most of the low-dose studies the Journal Sentinel reviewed - including some the panel rejected - were published in reputable scientific journals.
Prins, the bisphenol A expert from the University of Illinois at Chicago, said she was a late convert to the idea that the chemical causes harm at low doses. She changed her mind after reading repeated studies.
Then she saw it in her lab.
"We gave very small doses to male rats and saw cancerous lesions form on their prostates," Prins said.
For the panel to dismiss low-dose effects is a fatal flaw, she said.
Chapin conceded that the panel did not give equal weight to studies that considered low-dose effects, the levels that most people are exposed to every day.
"I'll admit it. We may be off in like totally uncharted territory," Chapin said.
The chemical industry defended the panel's choice of studies, noting that their scientists have been unable to replicate the work of some university scientists.
"Replication is a hallmark of science, and studies that cannot be replicated cannot be accepted as valid," said Hentges of the chemistry council.
Panel's work studied
The Journal Sentinel reviewed the work that the panel did, comparing each of its two drafts and the final report, together totaling more than 1,000 pages.
Two of the panel's four chapters considered the same kind of studies the newspaper reviewed - looking at the effects of bisphenol A on live animals. In one of those chapters, focusing on reproductive toxicology, 20 studies by either government or academia were tossed. No study that disclosed it had been funded by industry was rejected.
Chapin said they gave greater weight to studies that used more animals. Critics say only the chemical-makers can afford to conduct studies with more animals.
The panel failed to apply consistent standards, the newspaper's review found.
Not all studies recorded the kind of feed, caging, bedding or specific type of animal used. Those factors can influence the studies' results.
Chemical industry researchers used the same methodology in studies the panel accepted that caused other studies to be rejected. They included studies that used a single high dose and injected rats with bisphenol A rather than having the chemical administered orally. Chapin's panel rejected some studies, including those conducted by Soto, because they used an oil called DMSO to administer bisphenol A to rats.
"That just helps compounds waltz into cells," Chapin said.
But Chapin's panel accepted another study that used DMSO, never citing that oil as a limitation or concern.
The panel also accepted a study by Shell Chemical, Dow Chemical and General Electric that found no effects from bisphenol A. The same study also found no effects when rats were exposed to the powerful chemical diethylstilbestrol, or DES - a compound known to cause reproductive harm.
The rats' resistance to DES should have been an immediate red flag, critics said. But the panel accepted the research.
Consulting firm fired
Chapin's group has been dogged by controversy from the beginning. Last year, conflict-of-interest concerns were raised regarding the panel's use of Sciences International. The Virginia-based consulting firm had been hired to choose and summarize research for panel members. However, it had not been revealed that Sciences International had clients that included bisphenol A producers.
The company was fired in April, and the National Institutes of Health audited the firm's report. It found no conflict, and the company is credited in the final report.
Chapin dismissed criticisms against the panel.
"I'm tired of having my credibility as a scientist questioned when the panel bent over backwards to apply standards of good scientific conduct . . . evenly across the board," Chapin said. "My accusers have a great deal more bias than I do.
"They are not unbiased," Chapin added, "even though they keep holding themselves up as the white hats, the pure, the only holders of the cup of scientific chastity."
The newspaper found dozens of studies of bisphenol A that were not brought to the panel's attention.
Among them was a 2005 study that determined the chemical disrupted brain development in rats at very low levels. The panel also missed a study last year by Yale University researchers that found the chemical altered reproductive tract development in female mice exposed in the womb. Again, the researchers found these effects at low levels - below what the EPA considers safe.
"I'm surprised because my understanding was after all the hoo-ha was raised about Sciences International, the NTP went out and did its own search," Chapin said. "That's weird."
In one study accepted by Chapin's panel, the work was translated into English by the American Plastics Council, a division of the American Chemistry Council. The Korean study found that the sperm density and the reproductive systems of male rats were not harmed by bisphenol A.
Rosner, the public health professor, said that practice "immediately raises eyebrows."
"You have to have a neutral party doing the translations," he said. "It's the only way to really trust the accuracy."
Michael Shelby, director of the government agency that selected the panel to evaluate bisphenol A, acknowledged that the translation could be called into question. However, he denied any conflict.
Chapin said panel members agreed that they wanted to see any data they could, regardless of how they got it.
"I hear what you're saying about the perception," Chapin said. "Too bad."
Two studies, both funded by industry, were not peer reviewed, the newspaper found. Peer review is considered the foundation of scientific credibility. Most scientific journals will not publish a study unless it is peer reviewed.
The studies found no effects from bisphenol A, and were funded by General Electric in 1976 and 1978. They were accepted despite concerns similar to those that led the panel to disqualify academic and government studies. They included a small sample size of animals, the use of high doses and questions about the statistical methodology.
The panel also accepted at least a dozen studies that had not been published in any scientific journal - another check and balance in the scientific community to maintain high standards.
Shelby said the panel considered studies that were not peer reviewed if they included sufficient details.
Even scientists on the panel who agreed with the findings say they are uneasy about broad claims that bisphenol A is safe.
Jane Adams, a professor at the University of Massachusetts, doesn't allow her teenage son to get dental sealants because of her worries about bisphenol A.
"I am concerned about this chemical," she said. "Much more research needs to be done."
Simon Hayward, another panelist, agrees.
"Where there's smoke, there's fire," said Hayward, professor of prostate biology at Vanderbilt University Medical Center. "There is definitely enough smoke to be worried."
Rosner, the public health historian, says bisphenol A's potential for danger is too great to allow its widespread use without being certain of its safety. Consider what happened with lead and tobacco, he said.
"The government needs to work with caution," he said, noting that we have lived well for thousands of years without this chemical. "Until we know that it is safe, it is more prudent to avoid it."
A Journal Sentinel investigation found:
-- The federal government's assurances that bisphenol A is a safe chemical are based on outdated and incomplete government studies and science mostly funded by the chemical industry.
-- About 80% of academically and government-funded research found that bisphenol A is harmful in laboratory animals. Most of the industry-funded studies found there was no harm.
-- A federal panel that advises the government issued a report last week downplaying the effects of bisphenol A. The panel gave more weight to industry-funded scientists and industry-funded studies.
-- What bisphenol A is in; what you can do to limit your exposure to it and other endocrine disruptors
-- See a list of members of both bisphenol A panels as well as staff members.
-- Link to reports on bisphenol A.
-- Chat Monday at noon with Steven G. Hentges of the American Chemistry Council.
To read the first installment of this series, go to www.jsonline.com/chemicalfallout
WHICH LABORATORY ANIMAL IS BEST?
Some scientists say mice are more sensitive than rats to particular endocrine disruptors. But, even within species, there are differences.
The Charles River Sprague-Dawley rat has been bred to reproduce prolifically and frequently and, over time, has become largely insensitive to the effects of estrogen - and estrogen-like chemicals such as bisphenol A.
Most scientists say that the albino F344 rat is the most sensitive to estrogen, making it the best to use in testing.
Of the 53 studies involving rats that made it into a report by a federal advisory committee, only three studies used the F344 rat. Sixteen studies used the Sprague-Dawley, and none of those found an effect at low doses.
Scientists increasingly are acknowledging the problems of using Sprague-Dawley rats and are calling for F344 rats to be used. But the government has yet to insist on the change.
"We know the Sprague-Dawley rat is not perhaps the model to be using," said Gina Solomon, a senior scientist with the Natural Resources Defense Council. "Those studies should be looked at but given less weight, just like any other study with a design flaw."
- Susanne Rust
CHEMICAL FALLOUT / A JOURNAL SENTINEL WATCHDOG REPORT
TODAY: The federal government's assurances that a common chemical is safe are based on outdated U.S. government studies and research heavily funded by the chemical industry.
LAST SUNDAY: Congress ordered the federal government in 1996 to begin testing and regulating certain chemicals suspected of causing cancer and a host of developmental problems. Eleven years later, not a single compound has been put to that test.
Copyright 2007, Journal Sentinel Inc. All rights reserved. (Note: This notice does not apply to those news items already copyrighted and received through wire services or other media.)
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