Scientists Warn of Low-Dose Risks of Chemical Exposure

Sunday, March 25, 2012 by Yale Environment 360

A new study finds that even low doses of hormone-disrupting chemicals — used in everything from plastics to pesticides – can have serious effects on human health. These findings, the researchers say, point to the need for basic changes in how chemical safety testing is conducted.

by Elizabeth Grossman

Since before the publication of Rachel Carson’s Silent Spring 50 years ago, scientists have known that certain synthetic chemicals can interfere with the hormones that regulate the body’s most vital systems. Evidence of the health impacts of so-called endocrine-disrupting chemicals grew from the 1960s to the 1990s. With the 1996 publication of Our Stolen Future by Theo Colborn, Dianne Dumanoski, and J. Peterson Myers, many people heard for the first time how such exposures — from industrial pollution, pesticides, and contact with finished consumer products, such as plastics — were affecting people and wildlife. Since then public concern about these impacts has grown.

In 2009, the American Medical Association called for reduced exposure to endocrine- disrupting chemicals. Last year, eight scientific societies, representing some 40,000 researchers, urged federal regulators to incorporate the latest research on endocrine-disrupters into chemical safety testing.

Last week, 12 scientists – including such experts as Colborn and the University of Missouri’sFrederick vom Saal — published a paper that they say significantly advances the debate. Their research, based on a review of 800 scientific studies, concludes that it is “remarkably common” for very small amounts of hormone-disrupting chemicals to have profound, adverse effects on human health. Hormone-disrupting chemicals, the paper explains, challenge a fundamental tenet of toxicology — “the dose makes the poison” — which contends that the greater the dose, the greater the effect. Hormone-disrupting chemicals don’t necessarily behave like this. Significant health effects, the researchers say, sometimes occur at low rather than high doses.

"Whether low doses of endocrine-disrupting compounds influence human disorders is no longer conjecture, as epidemiological studies show that environmental exposures are associated with human diseases and disabilities,” the paper’s authors write. The study, published in the journal Endocrine Reviews, maintains that the low-dose and special dose-response effects of hormone-disrupting chemicals means that “fundamental changes in chemical testing and safety determination are needed to protect human health."

The study’s lead author, Laura Vandenberg, a post-doctoral associate at Tufts University’s Department of Developmental and Regenerative Biology, said in an interview said that this low-dose and special dose-response behavior “should be expected of any chemical that acts like a hormone."

Not all experts in biology and toxicology agree with the study’s conclusions. Some scientists in academia, industry, and the U.S. Environmental Protection Agency said there is not yet convincing proof that extremely low doses of endocrine-disrupting chemicals have ill health effects or consistently produce low-dose effects that are not predicted by their effects at higher doses.

"There’s no question that both natural and synthetic compounds can mimic hormones,” said George Gray, director of the Center for Risk Science and Public Health at The George Washington University. But that a chemical produces effects at one level, no effects at another, and different effects at yet another level of exposure, “that’s not yet widely accepted in toxicology,” said Gray. “It’s something toxicologists are not yet convinced of and comfortable with,” he added.

Hundreds of such hormone-disrupting chemicals have now been identified, and exposure to these compounds is virtually ubiquitous. Among the chemicals the new paper discusses are bisphenol A, used in plastics, can liners, and receipt papers; common pesticides, including atrazine and chlorpyrifos; methyl paraben, a preservative used in cosmetics and personal care products; triclosan, an antibacterial agent used in soaps and toothpaste; nonylphenol, a detergent ingredient; the flame retardant PBDE-99; perchlorate, a fuel compound; and dioxin, an industrial and incineration by-product. The paper also cites DDT and PCBs — discontinued but very environmentally persistent compounds.

"This is the first time anyone’s tried to synthesize this whole field and show that this is not a single chemical issue,” Vandenberg said of the new study.

Very small amounts of hormones, including endocrine system hormones — those that regulate many of the body’s most important systems, among them development, metabolism, and reproduction — can have significant biological effects. So, it’s been discovered, can synthetic compounds with similar chemical compositions. Research indicates that exposure to a small amount of such a chemical at a particular stage of development can prompt effects that can impact not just that particular individual, but, in some cases, several generations.

"It’s not just sex hormones but also thyroid hormones, and insulin among others, that are involved,” said Vandenberg. “We’re really complicated instruments."

The health effects documented in the studies the paper reviews have been observed in live animal and cell culture studies and in human epidemiological studies. Their effects include adverse impacts on reproductive and sexual development and fertility; cognition and neurological systems; immune system function; and metabolic effects, including diabetes and obesity. 

“The weight of the available evidence suggests that EDCs (endocrine-disrupting chemicals) affect a wide range of human health endpoints that manifest at different stages of life, from neonatal and infant periods to the aging adult,” write the authors.

Hormones interact with cellular receptors like locks and keys, explained Vandenberg. The hormone or hormone-like chemical is the key, and the receptor, the lock. “Touch the receptor and it starts to produce a response,” said Vandenberg. Too much chemical stimulus (the wrong-size key), however, can overwhelm the receptor, causing it to shut down and produce no response.

A key concept of the paper is that endocrine-disrupting chemicals are non-monotonic, meaning that the responses of animals or people to the chemicals do not necessarily intensify or diminish based on the dose. To illustrate this concept, Vandenberg said, “Picture a line of people, where those on the left have no exposure and those on the right have the most exposure. For endocrine-disrupting chemicals, where the greatest effects occur may not follow that line of increasing exposure level from left to right."

While complex and challenging, the studies gathered in this paper demonstrate that this phenomenon is now well documented, say the authors. “I hope that this paper opens the door to the realization that the endocrine system is the overarching control system of all other body systems,” said Theo Colborn, president of the Endocrine Disruption Exchange, whose work has been instrumental in popularizing knowledge of endocrine-disrupting chemicals. “It controls how we develop, function, and reproduce from the moment we are conceived — in other words, the quality of our lives and our existence."

While epidemiological studies show environmental exposure to EDCs are associated with human diseases, linking a specific environmental chemical exposure to an individual’s health disorder remains difficult, particularly given the many variables that contribute to health outcomes — life stage, genetics, and other environmental factors.

"There are different susceptibilities in different populations that may cause very minute amounts of a hormone to prompt effects in some people but not others,” said Linda Birnbaum, director of the National Institute of Environmental Health Sciences, who was one of the paper’s reviewers. This literature, she said, points to the importance of investigating low doses and timing of exposure when assessing chemicals for endocrine and other hormonal health outcomes, she explained in an interview.

Some scientists think more research is needed to confirm how endocrine disrupting chemicals behave. L. Earl Gray, Jr., a research biologist at the EPA’s Reproductive Toxicology Branch, said these low-dose effects are “certainly biologically plausible.” But he questioned whether there is sufficient evidence to firmly establish the non-monotonic responses of endocrine-disrupting chemicals.

The American Chemistry Council (ACC), which represents chemical manufacturers, issued a statement saying that it “has committed substantial resources” to better understanding the potential effects of chemicals on the endocrine system, and cited a Michigan State University professor emeritus of toxicology who concluded that “low-dose effects have not been proven, and therefore should not be applied to real-world conditions and human exposures.” (Corporate shill, yeah?--jef)

To verify these effects, studies must prove the mechanism of these responses and be replicable, said Lorenz Rhomberg, principal at the Gradient Corporation, a private environmental and risk analysis consultancy. “In my experience that’s been lacking,” said Rhomberg, co-author of an ACC-funded study that found low doses of BPA to be without adverse human reproductive and developmental health effects.

But, said Vandenberg, that’s exactly what the new paper shows. “We don't just know that these effects occur, we know how they occur,” she said, noting that for some chemicals like BPA, non-monotonic responses are reported by dozens of labs.

Thomas Zoeller, a University of Massachusetts biologist and paper co-author, said that regulatory testing of chemicals for endocrine-disrupting impacts lags behind the growing evidence of the compounds’ health effects, particularly at levels to which people are routinely exposed. “There is a very large disconnect between regulatory toxicology and the modern science of endocrinology that is defining these issues,” said Zoeller.

How much will testing chemicals at low, environmentally relevant levels improve human health, the paper authors ask? While it’s not currently possible to quantify in dollars, current evidence “linking low-dose EDC exposures to a myriad of health problems, diseases, and disorders suggests that the costs of current low-dose exposures are likely to be substantial,” they conclude.

"People can easily get overwhelmed by this issue,” said Laura Vandenberg. “But from a public health perspective, we can’t see this problem as too big to deal with. We wouldn’t do that with any other medical problem.”

Low doses of Atrazine in weed killer Threat to Male Sexual Development Revealed

Thursday, August 26, 2010 by Environment News Service (ENS)

RESEARCH TRIANGLE PARK, North Carolina - Male rats exposed before birth to low doses of the weedkiller atrazine are more likely to develop prostate inflammation and to go through puberty later than non-exposed animals, finds a new study conducted by federal government scientists.

One of the most common agricultural herbicides in the United States, some 80 million pounds of atrazine are applied across the country every year to control broadleaf and grassy weeds in crops such as corn and sugar cane. It is the main ingredient in about 40 name-brand herbicides.

"Atrazine is a staple product for producers, who use it as a critical tool for weed control in growing the vast majority of corn, sorghum and sugarcane in the United States.

Atrazine is sprayed on an Iowa cornfield. (Photo credit unknown)

Use of atrazine fights weed resistance, reduces soil erosion and increases crop yield," according to the Triazine Network, an association of growers and researchers.


But atrazine and its byproducts are known to be endocrine disrupters that are persistent in the environment, making their way into both surface water and groundwater supplies.

This study on how atrazine affects male rats was led by Suzanne Fenton, PhD, and Jason Stanko, PhD, of the National Institute of Environmental Health Sciences, part of the National Institutes of Health. The scientists tested male rats using atrazine concentrations close to the regulated levels in drinking water sources.

The current maximum contamination level of atrazine allowed in drinking water is three parts per billion.

"We didn't expect to see these kinds of effects at such low levels," Fenton said, releasing the findings Tuesday.

Dr. Fenton, a reproductive endocrinologist, will be presenting the research findings in September to the U.S. Environmental Protection Agency, as part of its ongoing reassessment of atrazine.

In 2009, the EPA began a comprehensive new evaluation of atrazine to determine its effects on humans. At the end of this process, in September 2010, the agency has said it will decide whether to revise its current risk assessment of atrazine and whether new restrictions are necessary to better protect public health.

This is the third time since the early 1990s the EPA has evaluated atrazine. In each of the two previous reviews the EPA ruled in atrazine's favor, most recently in 2006 after considering 6,000 studies and 80,000 public comments.

"We hope that this information will be useful to the EPA, as it completes its risk assessment of atrazine," said Linda Birnbaum, Ph.D., director of the National Institute of Environmental Health Sciences and the National Toxicology Program.

Fenton began the work as a researcher at the EPA, but completed the research at NIEHS, working closely with NIEHS pathologists. Both agencies provided financial support for the study.

The researchers found that the incidence of prostate inflammation went from 48 percent in the control group of rats to 81 percent in the male offspring who were exposed to a mixture of atrazine and its breakdown products before birth. The severity of the inflammation increased with the strength of the doses.

"It was noteworthy that the prostate inflammation decreased over time, suggesting the effects may not be permanent," said David Malarkey, DVM, PhD, an NIEHS pathologist and co-author on the paper.

The scientists also found that puberty was delayed in the animals who exposed to atrazine.

This new study is Fenton's second paper showing low dose effects of atrazine metabolite mixtures.

Fenton was the senior author on a 2007 paper which demonstrated low doses of the atrazine mix delayed mammary development in female siblings from the same rat litters used in this current study.

Fenton points out that these findings may extend beyond atrazine alone, and may be relevant to other herbicides found in the same chlorotriazine family, including propazine and simazine. All three of the herbicides create the same set of breakdown products.

Fenton says more research is needed to understand the mechanism of action of the chlorotriazines and their metabolites on mammary and prostate tissue.

"These tissues seem to be particularly sensitive to the effects of atrazine and its breakdown products," Fenton said. "The effects may be due to the stage of fetal development at the time the animals were exposed."

Another point of view on the safety of atrazine and the related chemicals comes from the Triazine Network. A five-person executive committee leads the network: Jere White, chairman, Kansas Corn Growers and Kansas Grain Sorghum Producers Associations; Dan Botts, Florida Fruit and Vegetable Association; Joel Nelsen, California Citrus Mutual, Stephanie Whalen, Hawaii Agriculture Research Center, and Gary Marshall, Missouri Corn Growers Association.

In a letter to EPA Administrator Lisa Jackson, the Triazine Network argues that atrazine is safe and necessary to growers.

The growers say they are "increasingly concerned by the serious irregularities in the EPA's current re-review of the herbicide atrazine."

"No one cares more about the safety of the herbicide atrazine than those of us who use it in the fields where we raise our families," says the letter, signed by White. "We drink the local water. We swim and fish in local lakes, rivers, and ponds. We look forward to passing our way of life onto our children and grandchildren. Simply stated, we care about keeping our environment healthy and our foods safe and abundant."

"Atrazine and its companion triazine herbicides have a 50-year history as safe and effective weed-control products used on more than 30 commodities in over 40 states and 60 countries," the growers state in their letter.

"Five decades of continued and rigorous EPA testing has shown time and again that atrazine poses no danger to public health. Over the last half century, more than 6,000 atrazine studies have been submitted to EPA. These studies confirmed, and EPA agreed, that atrazine does not affect human health," the letter asserts.

"EPA's current 3 parts per billion limit for lifetime exposure or the 298 ppb limit for short-term exposure, are standards that are more than 1,000 times safer than a level shown to have no effect," maintains the Triazine Network.

But Professor Tyrone Hayes in the Department of Integrative Biology at the University of California, Berkeley, who specializes in the study of atrazine, calls the chemical, "a potent endocrine disruptor with ill effects in wildlife, laboratory animals and humans."

"Atrazine chemically castrates and feminizes wildlife and reduces immune function in both wildlife and laboratory rodents," says Hayes, who has published research showing that exposure to atrazine caused male tadpoles to turn into hermaphrodites - frogs with both male and female sexual characteristics.

"Atrazine induces breast and prostate cancer, retards mammary development and induces abortion in laboratory rodents," Hayes warns. "Studies in human populations and cell and tissue studies suggest that atrazine poses similar threats to humans."

Other scientists support the use of atrazine when it is used correctly. Purdue University weed scientist Bill Johnson says, "Farmers need to understand both the rate restrictions of atrazine for different soil types and the setbacks from water sources. Like any chemical, they shouldn't apply atrazine right before a big rain in order to prevent runoff."

Other safe-handling techniques include establishing 66-foot grass buffer strips along bodies of water and ditches to help filter out atrazine from water flowing across fields and choosing crops that don't require the use of atrazine when planting near water sources.

"There are a lot of herbicides labeled for corn, but only a select few control as many weeds at as low a cost as atrazine," Johnson said. "Herbicides with more narrow spectrums drive up costs and eliminate the simplicity atrazine offers."

But in March, 16 communities in six Midwestern states filed a federal lawsuit seeking to force atrazine manufacturer, the Swiss company Syngenta, to pay for removal of the herbicide from their drinking water. The class action lawsuit was filed in U.S. District Court for the Southern District of Illinois by 16 towns and villages in Kansas, Illinois, Indiana, Ohio, Missouri, and Iowa.

Atrazine has been banned in Europe, even in Switzerland, the home of manufacturer Syngenta.

Click here for more information about the EPA risk assessment.

Report targets 20 possible cancer causes

Most are familiar names, such as chloroform and formaldehyde, but the list includes indium phosphide, a compound used in flat-screen TV.

By Maggie Fox | Reuters | July 15, 2010

The American Cancer Society and three federal agencies named 19 chemicals and shift work on Thursday as potential causes of cancer that deserve more investigation.

The group published a report with the backing of international experts who said the 20 potential causes they identified had fairly good evidence that they may be a danger and deserved more follow-up.

Most are familiar names, such as chloroform, formaldehyde and polychlorinated biphenyls or PCBs, but the list includes indium phosphide, a relatively new compound used in making flat-screen televisions.

All have been classified as possible carcinogens by the International Agency for Research on Cancer or IARC, the United Nations cancer agency.

"These particular ones were picked for two reasons. One is there is more of a hint in most cases that they might be involved with cancer," Elizabeth Ward of the American Cancer Society, who helped lead the work, said in a telephone interview.

But at the same time, she said, the studies that could make a definitive link are missing.

The second reason is that some of the potential agents or causes are very common. "We are focusing on things like formaldehyde, where there really has been widespread exposure in many industries," Ward said.

"Or in some cases the exposure is not widespread but is something that is increasing and there is insufficient data."

The National Institute for Occupational Safety and Health or NIOSH, National Institute of Environmental Health Sciences and the National Cancer Institute also helped sponsor the report, which names the following agents:

• Lead and lead compounds
• Indium phosphide
• Cobalt with tungsten carbide
• Titanium dioxide
• Welding fumes
• Refractory ceramic fibers
• Diesel exhaust
• Carbon black
• Styrene7,8oxide and styrene
• Propylene oxide
• Formaldehyde
• Acetaldehyde
• Dichloromethane, methylene chloride (DCM)
• Trichloroethylene (TCE)
• Tetrachloroethylene (perc, tetra, PCE)
• Chloroform
• Polychlorinated biphenyls (PCBs)
• Di(2ethylhexyl) phthalate (DEHP)
• Atrazine
• Shift work

The study is published in the journal Environmental Health Perspectives and at http://monographs.iarc.fr/ENG/Publications/techrep42/index.php.

Ward said indium caught the group's attention because it is becoming increasingly common. Used to make microelectronics, animal data suggested it might cause lung damage and genetic changes when breathed in, she said.

"It is a particularly important component of the flat displays of TVs that have been so popular," she said. Workers in assembly plants and those recycling discarded televisions might be most at risk, she said.

"Some of this kind of work done is in developing countries," she noted. "They are broken apart and valuable components extracted. It is an example of a newly emerging hazard."

Cancer is the No. 2 killer of Americans and people in most industrialized countries, after heart disease.

In May the President's Cancer Panel said Americans are being "bombarded" with cancer-causing chemicals and radiation but many experts said it overplayed some causes for which there is very little evidence of a cancer-causing effect, such as cell phones.

Weighing Safety of Weed Killer in Drinking Water, EPA Relies Heavily on Industry-Backed Studies

Agency Says Company's Evidence 'Scientifically More Robust' than Independent Research
by Danielle Ivory, Huffington Post Investigative Fund

Thursday, July 8, 2010 

Companies with a financial interest in a weed-killer sometimes found in drinking water paid for thousands of studies federal regulators are using to assess the herbicide’s health risks, records of the U.S. Environmental Protection Agency show. Many of these industry-funded studies, which largely support atrazine’s safety, have never been published or subjected to an independent scientific peer review.

Meanwhile, some independent studies documenting potentially harmful effects on animals and humans are not included in the body of research the EPA deems relevant to its safety review, the Huffington Post Investigative Fund has found. These studies include many that have been published in respected scientific journals.

Even so, the EPA says that it would be “very difficult for someone to put a thumb on the scale” to slant the outcome.

Atrazine is one of the most widely used herbicides in the U.S. An estimated 76 million pounds of the chemical are sprayed on corn and other fields in the U.S. each year, sometimes ending up in rivers, streams, and drinking water supplies. It has been the focus of intense scientific debate over its potential to cause cancer, birth defects, and hormonal and reproductive problems. As the Huffington Post Investigative Fund reported in a series of articles last fall, the EPA failed to warn the public that the weed-killer had been found at levels above federal safety limits in drinking water in at least four states. Some water utilities are suing Syngenta to have it pay their costs of filtering the chemical.

Now the EPA is re-evaluating the health risks of atrazine, which was banned in the European Union in 2004 due to a lack of evidence to support its safe use. That ban includes Switzerland, where atrazine’s manufacturer, Syngenta, is headquartered. The EPA expects to announce results of its re-examination of the herbicide in September 2010. It could take action ranging from restrictions on its use on crops to an outright ban. Or it could permit continued use without additional restrictions.

The company, one of the world’s largest agribusinesses, says the chemical has been used safely for decades and restrictions could prove devastating to farmers who are heavily dependent on the inexpensive herbicide. Atrazine poses “no harm” to the general population or to drinking water supplies, said company spokesman Steven Goldsmith.

EPA records obtained by The Huffington Post Investigative Fund show that at least half of the 6,611 studies the agency is reviewing to help make its decision were conducted by scientists and organizations with a financial stake in atrazine, including Syngenta or its affiliated companies and research contractors.

More than 80 percent of studies on which the EPA are relying have never been published. This means that they have not undergone rigorous “peer review” by independent scientists, a customary method to ensure studies are credible and scientifically sound before they can be published in major journals.

At the same time several prominent studies by independent academic scientists in well-respected scientific journals – showing negative reproductive effects of atrazine in animals and humans – are absent from the EPA’s list.

That finding may raise concerns about how the agency is doing its work. Rep. Henry Waxman, chairman of the House Energy and Commerce Committee, which oversees environmental regulators, told the Investigative Fund, “it’s critically important that EPA use all of the information at its disposal.”

Agency scientists may review studies not on the list, but EPA senior policy analyst William Jordan said that the 6,611 studies are those considered “relevant to the assessment of atrazine.”

‘Not Just Atrazine’

EPA spokeswoman Betsaida Alcantara said the list was not exhaustive and that some studies may not be on the list because they were not given an eight-digit “master record identification number,” which the agency uses to keep track of studies. There is “no uniform practice” for assigning numbers to studies submitted by people other than those working for herbicide, fungicide or pesticide manufacturers, she added.

EPA officials said that with a limited budget the agency must rely heavily on research sponsored by parties with a stake in the outcome. The agency’s “test guidelines” governing how experiments are conducted – the types and number of lab animals to be used, for instance. These provide sufficient safeguards against skewed results, officials said.

“Companies have a very strong incentive to follow the guidelines,” said EPA senior analyst Jordan. “We hope and think that we have written the guidelines with enough detail that it would be very difficult for someone to put a thumb on the scale, as it were, to slant the outcome, [or] to make something look safer than it is.”

Jennifer Sass, a senior scientist specializing in health issues at the Natural Resources Defense Council, argues that relying on a company to test the safety of its own product – an “inherent conflict” of interest – is part of a larger pattern at the EPA. “It’s not just happening with atrazine,” she said.

Hundreds of herbicides, pesticides, and other chemicals are regulated by the EPA, whose decisions can have significant implications for public health and on the abilities of an array of multinational companies to earn billions of dollars in the U.S.

By law, industry influence often is built into the regulatory process of the federal government. At the Food and Drug Administration, for instance, clinical trials conducted by pharmaceutical companies are used to determine whether pills and devices work and are safe. Makers of pesticides, herbicides, and fungicides also must pay for studies on their products. If they meet agency rules for conducting the testing, the EPA must accept them.

The ‘Funding Effect’

But is industry-funded research always reliable? A pair of scientists funded by the National Science Foundation, the U.S. Department of Agriculture, and the EPA scrutinized a Syngenta-funded Canadian study – one that is not on the EPA’s list. The scientists said they found numerous inaccuracies and misleading statements.

The scientists who questioned the study, University of South Florida biologists Jason Rohr and Krista McCoy, published their critique in the March 2010 issue of the journal Conservation Letters. In all, they tallied what they said were 122 inaccurate and 22 misleading statements, of which 96.5 percent appeared to support atrazine’s safety. The widely cited study focused on the herbicide’s effects on fish and other aquatic creatures.

Rohr and McCoy also asserted that the Canadian study, which was done in 2008, misrepresented more than 50 other studies. For example, it incorrectly suggested that only one scientist had demonstrated the chemical’s gender-altering effects on frogs. In fact, several other scientists demonstrated such effects.

The study dismissed one of Rohr’s papers as invalid, noting wrongly that the researcher had filtered atrazine out of a water tank while trying to assess the chemical’s effect on the aquatic organisms in the tank.

The Canadian study also misrepresented results, figures, and conclusions of other studies, according to the University of South Florida biologists.

Rohr, who served on an EPA advisory panel examining atrazine last year, told the Investigative Fund that he felt compelled “to set the record straight given the potential policy and environmental implications of these misconceptions and inaccuracies.”

The author of the Canadian study, University of Guelph (Ontario) biologist Keith Solomon, declined to respond to questions from the Investigative Fund about his financial ties to Syngenta, the company’s influence, or the inaccuracies and mischaracterizations the South Florida biologists said they had uncovered. Solomon noted that other scientists had come to similar conclusions, and that governments in the U.S. and Australia had not found any significant risk to creatures living in water.

While the critiqued study is not on the EPA’s list, several other studies by Solomon are.

Wendy Wagner, an expert in environmental policy at the University of Texas law school, said that the criticism of the Canadian study demonstrates a phenomenon sometimes referred to as “the funding effect.”

“It is next to impossible to squeeze all of the discretion out of a researcher, and when he has a strong incentive to find a particular result, the result can be unreliable and badly biased research,” said Wagner, an authority on the influence of politics and special interests on science. “There is compelling evidence that bias still pervades sponsored pesticide research – research that presumably is done in accord with EPA’s guidelines.”

Meanwhile, some independently-funded academic research published in major scientific journals is missing from the list of papers the EPA is using to make its decisions on atrazine. Absent are studies published in Proceedings of the National Academy of Sciences, Environmental Health Perspectives, and Nature. Many works by independent academic scientists such as Tyrone Hayes and Rohr – who have demonstrated a range of potential reproductive and hormonal effects of the chemical – are not on the list.

Some peer-reviewed studies from prestigious journals fail to meet the agency’s standards, said EPA analyst Jordan, citing as an example work by scientists such as Hayes, who recently found that low doses of atrazine could turn male frogs into female frogs.

Jordan explained that the agency couldn’t rely on Hayes’ and the other scientists’ research in part because the government lacked protocols for testing chemicals on frogs. So the EPA developed those guidelines and asked Syngenta to study the issue. The company’s researchers reported that they were unable to replicate Hayes’ findings. Jordan said the Syngenta study “superceded” Hayes’ and the other scientists’ studies. The EPA, on its Website, currently states that atrazine causes no such adverse effects on frogs and that “no additional testing is warranted” to address the issue.

Environmental groups have in the past criticized the EPA for allowing chemical companies to wield disproportionate influence over regulatory decisions. While evaluating the safety of atrazine in 2003, the EPA allowed representatives from Syngenta to participate in closed-door negotiations with the agency, according to documents obtained by the NRDC in 2004.

Missing Evidence

Dale Kemery, an EPA spokesman, defended the practice of omitting some studies. The agency’s safety “review may not include every study that has been conducted, since some may not meet the standards that are appropriate for a regulatory setting or they may not be on target for the issues to be assessed.”

The EPA considers industry-sponsored studies “scientifically more robust than are the studies generated by people in academia,” said Jordan, the agency's senior policy analyst. “That’s generally because companies spend more money on their studies and can attend to details that are potentially important that people in academia just can’t afford to do.”

Jordan added that agency oversight of the thousands of unpublished studies on the list is just as rigorous as a peer-review by scientists prior to publication in a scientific journal. “I know that people might not agree with this proposition, but I believe that the scientists at EPA constitute a peer-review,” he said. “Our scientists go over the studies with a fine tooth comb.”

EPA officials said they were not able to provide a list of all omitted research.

A spokeswoman for CropLife America, the Washington D.C.-based trade association that represents pesticide and herbicide manufacturers, said EPA oversight is thorough, regardless of whether studies have appeared in peer-reviewed journals.

“Whether or not they have been published, the studies submitted to EPA for registration support of pesticide products are subject to scientific review by EPA scientists that is equally, if not more, rigorous and demanding than the pre-publication peer review conducted by any scientific journal,” said spokeswoman Mary Emma Young.

Some people are skeptical about the rigor of the EPA’s scrutiny. “What worries me,” said the University of Texas’ Wagner, “is the possibility that there isn’t time or energy within EPA to give a lot of oversight to this unpublished, industry-funded research, especially when the number of unpublished studies for a chemical like atrazine are in the thousands.”

A former EPA official, epidemiologist Lynn Goldman, said it is normal and necessary for the agency to accept unpublished and industry-funded studies, most of which would not be interesting enough to publish in scientific journals.

“This is the way that the system was built by Congress. It could be changed but the EPA does not have the authority to turn the system upside down,” said Goldman, a former assistant administrator for toxic substances during the Clinton administration.

The existence of a list of relevant research for EPA review has played a prominent role in public arguments for the herbicide’s safety. Journalists, scientists, and advocates for atrazine have frequently cited the “6,000” studies.

In 2005, Anne Lindsay, then a top official in the EPA’s Office of Pesticide Programs, brought up the number of studies during congressional testimony. “Atrazine is one of the most well-examined pesticides in the marketplace,” she said, noting that “there are nearly 6,000 studies in EPA files on the human health and environmental effect of atrazine.”

Syngenta now cites the number in its press materials and on its website – not merely as a tally of studies but as proof of its safety. “Atrazine passes the most stringent, up-to-date safety requirements in the world,” said spokesman Paul Minehart. “In 2006, the U.S. Environmental Protection Agency (EPA) re-registered atrazine in 2006 based on the overwhelming evidence of safety from nearly 6,000 studies.”

EPA's List of Scientific Studies on Atrazine