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The Price of Research (31/10/2003)

A Berkeley scientist says a corporate sponsor tried to bury his unwelcome findings and then buy his silence. Not directly GM, but Syngenta, Berkeley and atrazine plus a host of familiar themes.
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The Price of Research
The Chronicle of Higher Education
From the issue dated October 31, 2003
http://chronicle.com/free/v50/i10/10a02601.htm

A Berkeley scientist says a corporate sponsor tried to bury his unwelcome findings and then buy his silence

By GOLDIE BLUMENSTYK
Berkeley, Calif.

Tyrone Hayes wasn't all that concerned about who was signing the checks when he agreed to do some consulting on one of the most widely used pesticides in the country.

And when the early studies from his laboratory at the University of California at Berkeley began producing hints that the product, the herbicide atrazine, might be inhibiting the sexual development of male frogs, he was excited. Maybe, he thought, his research would lead to some breakthrough findings. He never imagined just how unenthusiastic his research sponsors -- and others with a financial stake in atrazine -- would be about his discovery.

Six frustrating years later, Mr. Hayes and his defenders say they know only too well the lengths to which those companies will go to undermine his findings that atrazine may be harmful. This week the U.S. Environmental Protection Agency is expected to make its final ruling on the reapproval of atrazine. Mr. Hayes and some other scientists believe that the campaign to discredit him will have played a part in helping the herbicide's primary manufacturer, a company called Syngenta, win that approval.

His colleagues here at Berkeley and around the country say the story is a classic example of the subtle and not-so-subtle tactics that companies sometimes use to influence the outcome of university research that they pay for.

Mr. Hayes maintains that Ecorisk Inc., the consulting company that hired him and several other academic scientists to study atrazine on behalf of Syngenta, stalled and delayed his research progress once he began finding that the substance had damaging effects on frogs. It turned out that in the contracts covering Mr. Hayes's work and that of many of the other researchers, Syngenta and Ecorisk retained final say over what and whether the scientists could publish.

Even after he quit working as an Ecorisk consultant, in November 2000, he asserts, the company tried to buy his silence: He says the Ecorisk consultant in charge of the atrazine studies told him that it would arrange with Syngenta to provide him with as much as $2-million in lab support if he would continue his research "in a private setting," unencumbered by the academic ethos that promotes publication of results.

The Ecorisk consultant, Ronald J. Kendall, of Texas Tech University, says the charge is "absolutely" untrue.

Whatever the truth of that allegation, what happened next is undisputed: Freed from the contractual constraints on publication and confidentiality, Mr. Hayes repeated and expanded upon the original frog studies. He continued to find damaging effects of atrazine at low levels.

His work, which has appeared in Nature and other journals, has been attacked by Syngenta and a host of other critics -- including the Kansas Corn Growers Association, a Fox News commentator known for minimizing the potential threat of global warming, and the Center for Regulatory Effectiveness, an organization based in Washington that is challenging the use of academic studies in federal rule making.

As part of its rebuttal of Mr. Hayes's work, Syngenta cited studies by three
other teams of university scientists, working for the company through Ecorisk, who could not replicate his findings showing the same effects at low doses. Several of those academics, contacted by The Chronicle, said that Syngenta did not influence the outcome of their work. They also take pains to describe their differences with Mr. Hayes as an example of the kind of scientific disagreement that is typical of academe. If the debate is heated, they say, that is largely because the stakes are so high. Atrazine, an important product for Syngenta, is widely used by farmers to kill weeds.

Mr. Hayes says some of those studies are flawed, and he has gone public with allegations that Ecorisk was interested only in bending its panel of scientists to benefit Syngenta.

"It's very directly involved with the hubris of corporations that think, 'We can fund the research we want,'" says Sheldon Krimsky, a professor at Tufts University who studies conflicts of interest in academe. "Corporations think they can fund academic science in their own interests. Hayes is a case where they made a miscalculation. For every miscalculation, how many accurate ones are out there?"

A Man Who Knew Frogs

The case is not the first in which Berkeley scientists have found themselves entwined in a controversy involving Syngenta. This is the same university that was pilloried, sometimes unjustly, for an unusually close $25-million research relationship with another arm of Syngenta that began in 1998. But that association, which involved biologists from another college in the university, had nothing to do with the Hayes research. Swiss-based Syngenta was formed in November 2000 from the merged agriculture operations of two other companies, Novartis and Zeneca.

Mr. Hayes says he probably never would have begun looking at atrazine had Ecorisk not approached him. He knew very little about the herbicide at the time.

But Tyrone B. Hayes knew frogs.

He has been fascinated with the creatures since his childhood in South Carolina. A trim man with a compact frame and an easygoing manner, Mr. Hayes, now 36, has passed that enthusiasm on to the students who work with him. "My lab works 24 hours a day, and it's not because I pay anybody to work 24 hours a day," he says.

Hired at Berkeley in 1994, he had already published 10 peer-reviewed papers on amphibian development when he was asked by Ecorisk, on behalf of Syngenta, to review the available scientific literature on atrazine's effects on amphibians. The company was collecting the information as part of its application for a required reapproval of atrazine by the EPA.

A year later, in 1998, Ecorisk invited Mr. Hayes to join a panel of scientists who would be examining atrazine's impact on the development of fish, frogs, and other animals, with a focus on hormonal systems that control development. The group was called the Atrazine Endocrine Disruption Panel. Syngenta, through its crop-protection division, in North Carolina, says it provided about $2-million to Ecorisk for the scientists' studies.

By 1999, working with African clawed frogs that he had raised in his lab, Mr. Hayes began to see indications that doses of atrazine in concentrations as low as one part per billion would inhibit the growth of the larynxes of male frogs. He says he shared the information with colleagues on the Ecorisk panel and with Syngenta. The findings were noteworthy, he says, because under EPA guidelines, atrazine is considered safe in drinking water as long as it is found in levels no greater than three parts per billion.

Panel members asked for additional confirmation of his findings, but Mr. Hayes says they would not provide payment or approve guidelines for the additional work. By controlling the money, "they had control over the pace of the work," he says. By mid-1999, "I started to feel like they were stalling progress." He agreed that analyses of additional samples were necessary, but was frustrated that the money for the work was not forthcoming. He says he eventually did the additional analysis with his own funds.

By early 2000, Mr. Hayes was eager to begin a second round of analyses, but he still could not get approvals for the financing or the research protocols. By September, he says, he was growing so impatient that he decided to begin that work on his own, assuming that Ecorisk and Syngenta would eventually reimburse him for his costs. He paid for some of the work with money from grants from his department and from awards he had won. His rapport with his students helped. Many of them volunteered their time.

The new studies looked not only at the larynxes but also at the sex organs of the frogs treated with atrazine. Mr. Hayes says that by early fall, he began seeing signs that the effects of atrazine on the sex organs of male frogs were occurring at levels as low as 0.1 parts per billion -- a concentration a tenth of that affecting the larynxes. "The testes essentially start changing," he says, because atrazine triggers production of estrogen. "They grow ovaries and eggs."

'Trying to Buy the Data'

In his lab, amid shelves crammed with jars and beakers containing dead frogs suspended in a sickly-looking green preservative, Mr. Hayes explains why atrazine's effects on frogs concern him.

As a developmental endocrinologist in Berkeley's department of integrative
biology, Mr. Hayes looks at how hormones promote development. In frogs and humans, "the hormones are the same, the mechanisms are the same," he explains. So if atrazine seems to be feminizing frogs by increasing the production of estrogen, it might also be having the same effect over the production of estrogen in people. High levels of estrogen, he notes, have been linked to breast cancer.

Mr. Hayes says that he kept the Ecorisk panel informed of his work through the fall of 2000. But by early November, still waiting for the panel to approve money for the work he had already begun, he decided to quit and complete the work on his own.

In his November 7, 2000, resignation letter, sent to Syngenta and several Ecorisk panel members, Mr. Hayes said the panel was not interested in pursuing his proposals to study the effects of low concentrations of atrazine. He also expressed his concern about the panel's plan to hold off on publishing the results of his and others' work until the following year.

"It will appear to my colleagues that I have been part of a plan to bury important data," he wrote. "This fear will be particularly realized when independent laboratories begin to publish data similar to data that we (Novartis and my laboratory) produced together as early as 1999."

The letter was part of a cache of documents and e-mail exchanges obtained from the Environmental Protection Agency under the Freedom of Information Act by the Natural Resources News Service, which provided them to The Chronicle and other news organizations.

It was after he quit the panel, Mr. Hayes says, that Mr. Kendall, the Texas Tech professor who was directing the Ecorisk panel, approached him about continuing to work on atrazine not as a Berkeley scientist, but under the auspices of a start-up company owned by Mr. Hayes's wife.

"Ron Kendall said he was going to take me to Syngenta and we were to make a proposal, and they would give me enough money to continue the work in a private setting," Mr. Hayes says.

Mr. Hayes says he found the timing puzzling. "Right after I left, I told them I had repeated the work and intended to go ahead with publication," he recalls. "What is it that they were trying to purchase?"

He has a theory. Mr. Hayes says that several members of the panel knew what his research showed. "They were trying to buy the data."

Mr. Kendall, who directs the Institute of Environmental and Human Health at Texas Tech, says the panel did ask Mr. Hayes to do additional studies, but only because the initial results he found on the larynxes were unexpected. "We felt it prudent, as a panel, that the experiment be repeated," Mr. Kendall says. "That's just good science."

If there were delays, he says, they were the result of the panel's trying to agree on the conditions for additional studies. As for the $2-million offer, Mr. Hayes has it wrong, Mr. Kendall says, explaining that he had no authority to pay anyone. "I had no discussion with Syngenta authorizing that money," he says. "I had no discussions with Ecorisk to authorize that money."

Mr. Kendall says he did make entreaties to Mr. Hayes during that period, but says they were on behalf of the panel, which hoped that Mr. Hayes would reconsider his resignation.

In an e-mail message in December 2000 to Mr. Kendall and to the president of Ecorisk, Mr. Hayes mentions his findings on the effects on atrazine on the frogs' sex organs. But Mr. Kendall says he had not been shown any data backing that up. "And I don't believe something until I see it," he says.

Robert Bruce, president of Ecorisk, which is based in Ferndale, Wash., did not respond to several telephone and e-mail messages seeking comment. A spokeswoman for Syngenta says both it and Ecorisk "have consistently acted in a straightforward and ethical manner."

'Anything but Collegial'

Any thought of further collaboration between Mr. Hayes and the panel would all but vanish by the end of January 2001 after a contentious meeting he had at Berkeley with several of the panel members and Syngenta officials. Some of Mr. Hayes's students attended, as did a few of his faculty mentors and deans. One of them was Paul Licht, who has been a professor and dean at Berkeley for 40 years and now runs the university's botanical garden.

According to minutes of the meeting prepared by Ecorisk, Mr. Hayes again accused the panel of trying to keep his data out of public view. Mr. Kendall and the other panel members said that was not true, arguing that the panel "was and still is unsure of the findings in his investigations." They also said his data contained errors.

A letter from an Ecorisk consultant working at the University of Florida,
who could not attend the meeting, was then read aloud, reminding Mr. Hayes that the work he was doing "is much different than a research grant" and that it carried confidentiality requirements and other restrictions. "I am in the same situation and have always understood that this is contract research and therefore not simply my property," wrote Tim S. Gross. "The strict critical review by the panel is not a negative nor to hinder progress or diminish results or their impacts, rather it is to ensure the highest quality and at a high level and high quality of peer review."

Ernest Smith, another professor at Texas Tech who coordinated the scientific
studies for the panel, says the letter was not an indication of the panel's desire to control Mr. Hayes's research but a reminder that its members had a right to approve what would be presented publicly, since they all shared responsibility for designing the studies.

"Neither I nor Mr. Smith nor any panel member attempted to bury his data," concurs Mr. Kendall.

Mr. Hayes, who by then was already preparing a manuscript describing the findings from his second round of frog studies -- conducted with his own resources -- says the panel's concerns about high-quality science were disingenuous.

Later that day he presented the completed findings from his first study, on atrazine's effects on frogs' larynxes. A statistician hired by Syngenta then offered his own interpretation of Mr. Hayes's data. He reported that in his analysis, he found many instances in which the data did not match Mr. Hayes's findings. Mr. Hayes, who says he had never been told of such a problem with his data, disputed the conclusion.

Mr. Licht says that the tone of the meeting and, in particular, the appearance of the statistician as a sort of "surprise witness" was unlike any academic presentation he had ever attended, and that it was anything but collegial.

"What I saw was an attempt at character assassination," he says.

War of Words

Mr. Hayes and the panel went their separate ways. But Mr. Hayes did not go quietly.

With new financing, including money from the W. Alton Jones Foundation, the World Wildlife Fund, and the National Science Foundation, he set out to repeat the atrazine studies and publish them. His first article appeared in the April 2002 Proceedings of the National Academy of Sciences.

The article did not go unnoticed. Two months later the Natural Resources Defense Council petitioned the EPA to withdraw atrazine from the market, citing Mr. Hayes's study and another that linked the herbicide with cases of prostate cancer among factory employees working with the substance.

Syngenta, too, took notice. That same June the company posted a news release on its Web site announcing that "three separate studies by university scientists have failed to replicate" Mr. Hayes's findings.

The release cited research by three teams of academics working for Ecorisk. None of the studies had been reported in a peer-reviewed journal. Since then, one of them, led by James A. Carr of Texas Tech, was published in the journal of the Society of Environmental Toxicology, in February 2003, after being presented at a meeting in August 2002. The other studies were led by John P. Giesy, of Michigan State University, and Louis du Preez, of Potchefstroom University for Christian Higher Education, in South Africa.

Mr. Hayes has argued to the EPA and in public forums that the Carr study is flawed and that its researchers understated the effects of atrazine in their analysis and in the way they applied the dosages. It was as if two people had each been given 25 jars of cough syrup for the sick children in their houses, he says, "but his house has 16 times more kids in it than mine."

What's more, many of the frogs in the Carr study died before the effects of atrazine could be assessed, Mr. Hayes notes. But even so, he says, the study does show that atrazine affects the sexual development of frogs.  Mr. Carr says that his research speaks for itself, and that he is not responsible for how Syngenta chooses to characterize it. "I don't think it contradicts Hayes," he says. "I think it shows that we weren't able to find a low-dose effect. We weren't able to find an effect in the larynx."

Restricted Research

In the company's submissions to the EPA, Syngenta said Mr. Carr's study "was conducted under the direction and auspices of an independent scientific panel." But documents show otherwise. The Ecorisk contract with Texas Tech, covering more than $600,000 worth of research, states that all research data and analyses belong to Ecorisk "and/or its client."

The university says the contract is actually an improvement over what Ecorisk first proposed. The final version includes an added sentence stating that Ecorisk intends the research for publication in scientific journals, although only with "appropriate review and written permission by Ecorisk."

It was the best the university could get, says Robert M. Sweazy, vice president for research, graduate studies, and technology transfer. "In our estimation," he says, "this is not a real favorable contract." (Ecorisk's restrictions initially covered Mr. Hayes because his first atrazine studies were conducted under a contract between Ecorisk and his wife's company, which then subcontracted with Berkeley for the lab work.)

Although Ecorisk designed the studies, Mr. Carr says his findings were not influenced by either company.

But copies of a February 2003 e-mail exchange between Mr. Carr and Mr. Hayes, made available by Mr. Hayes, suggest that Mr. Carr did have some reservations about how the panel was interpreting data from other studies. Mr. Carr wrote: "My differences with other panel members have to do with how the new data are being interpreted. (I am a biologist, others will be using statistics to minimize the impact of the new data sets.)"

Asked about the comment last week, Mr. Carr played down its significance. He says those analyses were prepared for the studies that Ecorisk was submitting to the EPA, and were among many standard statistical analyses that the scientists used. He adds that Ecorisk also supplied the agency with the raw data. "If there was something in the raw data that we missed, the EPA would have picked it up in their independent analyses," he says.

New Salvo

In October 2002, Mr. Hayes made news again, when his follow-up research, including additional information on American leopard frogs taken from field studies in the Midwest, was published online in Environmental Health Perspectives. A shorter version appeared in Nature.

The research was promptly questioned by members of the Ecorisk atrazine panel, including the three lead investigators in the studies trumpeted in June, and by Mr. Gross, the Florida scientist whose letter had reminded Mr. Hayes that the Ecorisk-sponsored work was not independent research. The critique appeared on a Web site that promotes the use of pesticides. The Web site is run by an arm of the Hudson Institute, an Indianapolis-based organization that promotes free-market economy.

Criticism of Mr. Hayes's new study also appeared on the Fox News Web site, where the commentator Steven Milloy said he'd "rather kiss a frog" than trust the professor's peer-reviewed studies. Mr. Milloy is founder of a Web site he calls Junk Science, on which he mocks studies he says are used by "lawsuit-happy trial lawyers, the 'food police,' [and] environmental Chicken Littles."

More seriously, Mr. Hayes's work was now being challenged in Washington, where the Environmental Protection Agency was nearing the final stages of its review of atrazine.

In November 2002, the Center for Regulatory Effectiveness, the Kansas Corn Growers Association, and the Triazine Network, petitioned the EPA to ignore Mr. Hayes's studies in considering the scheduled reapproval of atrazine, arguing that the studies did not conform with the 2001 Data Quality Act, which prohibits federal agencies from using scientific findings for which there are no established standards. They said that since Mr. Hayes's studies could not be replicated by the Ecorisk panel, and there were no such standards, his work should be excluded from consideration.

The Triazine Network, named for the class of herbicides that includes atrazine, is an organization of about 1,000 growers and herbicide makers. It was formed after the EPA announced in 1994 that it would seek re-registration of several triazines. Jere White, director of that group and the corn growers association, says it has received some financial support from Syngenta, mostly for events designed to keep members apprised of the status of atrazine at the EPA.

Mr. White says the organizations challenged Mr. Hayes's data because they found it unfair to impose new restrictions on atrazine when the EPA itself did not have any standards against which to assess his findings.

Corn growers and other farmers like using atrazine, he says, because it works as a general herbicide and improves the efficacy of other herbicides when used in combination with them. This year a Kansas farmer using atrazine would probably get a yield of about 130 bushels of corn per acre, worth about $260, of which at least $20 would be attributable to atrazine, Mr. White says.

Mr. White says he doesn't question Mr. Hayes's integrity but wonders about his objectivity in analyzing what he finds. "I have a hard time believing there's anything as dramatic as Dr. Hayes is saying" about atrazine, he says. "After almost 50 years of using it, if these were real-world effects, you'd be able to go out and see them."

Harassment by Innuendo?

Mr. Hayes has his defenders, too, most notably on a Web site called Our Stolen Future. John Peterson Myers, the former director of the foundation that provided $5,000 to Mr. Hayes in 2001, helps run the site. After an EPA scientific advisory panel met in June 2003 to consider the studies by Mr. Hayes, Ecorisk, and others, the Web site took the company to task, saying it had used misleading news releases against Mr. Hayes.

Hiring academic scientists and portraying them as an independent panel is the kind of tactic that "creates this aura of scientific respectability," says Mr. Myers.

The site also raised questions about Mr. Kendall's role, noting that he had served as a member of the EPA's main scientific advisory board until 2002, a period that overlapped with the time he was coordinating the atrazine panel for Syngenta as it sought reapproval for atrazine. He also has been an editor of the toxicology journal where the Carr study was published. (The journal's chief editor says Mr. Kendall took no part in publication decisions related to atrazine. Mr. Kendall says he recused himself from discussions on atrazine while serving on the agency panel.)

Rena Steinzor, a professor of law and director of the Environmental Law Clinic at the University of Maryland School of Law, says the Data Quality Act challenge against Mr. Hayes's studies is part of a broader assault on academic freedom, amounting to harassment. "It's the innuendo that surrounds a data-quality petition," she says. "This is a very well-funded campaign that serves not the quality of science but serves industry self-interest."

Ultimately, the EPA did consider Mr. Hayes's studies, along with 15 others. Twelve of them were produced by Ecorisk, including the one by Mr. Carr's group that has been published. (Mr. Kendall says other Ecorisk studies will be published soon.)

Based on what it found, the EPA preliminarily recommended further studies on the effects of atrazine on amphibians.

In June, the agency's scientific advisory panel concurred. "Sufficient data were available to establish the hypothesis" that atrazine interferes with the sexual development of frogs," it concluded. But the panel also found that many of the studies had serious flaws of design or methodology.

In its final ruling, scheduled to be released this week, the EPA is expected to reapprove atrazine, while also requiring Syngenta to conduct further studies on its effects on amphibians.

The Natural Resources Defense Council says such a ruling would be inadequate because it includes no trigger for further restricting atrazine's use, even if the new research finds negative effects. Syngenta says it will involve Ecorisk to help with the additional studies.

Sticking With His Cause

Mr. Hayes says he never set out to be a folk hero of the "keep industry out of academe" crowd. Even now, he says, he would still work for companies, though only under the right circumstances.

He recognizes that his persistence in defending his studies to the EPA and to others against his critics might lead some observers to question his motives.

But, he says, he does not have the luxury of sitting back and letting the debate play out as a simple controversy among scientists. "The truth is, we get this effect" in frogs, he says. "My responsibility -- as a scientist, as an academic, as a citizen -- wouldn't allow me not to care."

He has not given up on studying atrazine either. Soon to be named a full professor, and with a new $100,000 grant from the National Science Foundation in hand, Mr. Hayes, together with the students in his lab, continues to examine how the herbicide affects frogs' development. Now he is expanding the work. Along with atrazine, he is studying how atrazine affects frogs in combination with S-metolachlor.

S-metolachlor, as it happens, is another herbicide sold by Syngenta.


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HOW A RESEARCH PROJECT BECAME A CORPORATE CONFLICT

August 1997:
Tyrone Hayes, a scientist at the U. of California at Berkeley, is retained by Ecorisk, on behalf of Syngenta, to analyze published studies on frogs and atrazine, a widely used herbicide.

1998:
Mr. Hayes is retained by Ecorisk to test the effects of atrazine on African clawed frogs.

1999:
Mr. Hayes finds that atrazine inhibits development of the larynx in male frogs at low doses.

2000:
Mr. Hayes finds that atrazine, at even lower doses, feminizes male frogs by altering the testes so they will produce eggs. He proposes further studies.

November-December 2000:
Mr. Hayes resigns from the Ecorisk panel of consultants studying atrazine, questioning the panel's willingness to pursue certain avenues of study and accusing it of trying to bury his findings. According to Mr. Hayes, the director of the Ecorisk panel offers him substantial financial support from Syngenta to pursue his research "in a private setting."

January 15, 2001:
Syngenta reports Mr. Hayes's findings concerning atrazine's effects on frogs' larynxes to the Environmental Protection Agency, but says that aspects of the study "prevented clear conclusions" from being drawn.

January 26, 2001:
At a meeting in Berkeley, Mr. Hayes accuses Ecorisk of trying to delay release of his work because he has turned up negative findings about atrazine. Ecorisk reminds Mr. Hayes that his work is confidential. Syngenta analysts say Mr. Hayes's studies were flawed.

April 2002:
Mr. Hayes's lab research on the effects of atrazine and frogs, financed and conducted without Ecorisk involvement after he quit, is published in "Proceedings of the National Academy of Sciences."

June 2, 2002:
The Natural Resources Defense Council petitions the EPA to withdraw atrazine from the market, citing Mr. Hayes's research and another study.

June 20, 2002:
Syngenta and Ecorisk issue a news release announcing that "three separate studies by university scientists have failed to replicate" Mr. Hayes's findings.

October 2002:
Mr. Hayes's follow-up research, including additional data from new research on frogs taken from field studies in the Midwest, is published online in "Environmental Health Perspectives." A shorter version of the study appears in "Nature."

November 2002:
The Kansas Corn Growers Association and two other groups petition the EPA to ignore Mr. Hayes's studies in considering the reapproval of atrazine, claiming the studies do not conform to the 2001 Data Quality Act.

June 2003:
The EPA Scientific Advisory Panel considers the two studies by Mr. Hayes, 12 by Ecorisk scientists, and three others, and concludes that the research shows that atrazine interferes with the sexual development of frogs. But the panel also says that many of the studies had serious design or methodological flaws, and recommends further study.

October 31, 2003:
Deadline for the EPA to issue its final recommendations on atrazine.

ABOUT ATRAZINE

What it is: Atrazine, a white, crystalline, solid organic compound, is the second-most heavily used herbicide in the United States.

Where it's used: According to its main manufacturer, the Swiss corporation Syngenta, atrazine is used on two-thirds of all cornfields and sorghum fields in the United States and on 90 percent of sugar-cane fields. It is also used on residential lawns, golf courses, and Christmas-tree farms. More than 76 million pounds of atrazine are applied annually, mostly in the Midwest and Southeast. It is applied to the soil before planting to control broadleaf weeds and some grassy weeds.

An ingredient: Atrazine is sold on its own or as an ingredient in about 130 other products. It was first approved for use as an herbicide in the United States in 1958 and is now nearing reapproval by the U.S. Environmental Protection Agency.

Effect on humans: Atrazine has been detected in groundwater, surface water, and in water systems. People exposed to unsafe levels of the compound may develop diarrhea, eye or skin irritation, and stomach pain. Experts disagree on whether atrazine causes cancer; the EPA recently determined that it is "not likely to be carcinogenic to humans."

Effect on animals: In animals, a number of studies show that atrazine disrupts the endocrine system, and that it has a noticeable effect on the production of hormones that control sexual development. Most of those studies have focused on frogs.

Sales: Syngenta does not release information about atrazine sales but reports that its overall revenues from "nonselective herbicides," including atrazine, exceeded $1.6-billion in 2002, more than one-quarter of its total revenues. Atrazine is one of the company's five biggest-selling herbicides in the United States.

Restricted in Europe: Although popular with farmers in the United States, atrazine is either banned or severely restricted in several countries in Europe. This month the European Union announced that it would withdraw its approval of atrazine for European use because of health and environmental concerns.

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