Science News - February 19, 2004

Controversy clouds atrazine studies

Two years after initial reports that the world’s most popular herbicide, atrazine, is an endocrine disrupter in frogs, the issue has exploded into allegations of ethical misconduct and bad science.

The issue began to heat up in October, after U.S. EPA experts and a special pesticide Scientific Advisory Panel (SAP) determined that studies both supporting and refuting the finding are plagued with confounding effects. Later that month, this EPA analysis helped atrazine gain re-registration. However, in November, Tyrone Hayes, the leading researcher who first announced the endocrine-disrupting effect, publicly accused EPA of being unduly influenced by atrazine’s manufacturer, Syngenta.

Hayes, an endocrinologist at the University of California at Berkeley, contends that frogs can be harmed by exposure to atrazine at concentrations as low as 0.1 parts per billion (ppb). If Hayes’ claim were verified, this concentration is so low that the only way to avoid the damage would be to ban the herbicide.

Hayes publicly contends that Syngenta manipulated EPA, managed the regulatory process, and subverted science to keep atrazine on the market. Meanwhile, the EPA SAP report released in October found fault with all the studies of frogs reported so far, calling the science “flawed”.

In a statement, EPA said it decided to re-register atrazine in part because the SAP report concluded that although amphibian studies, such as those from Hayes’ group, provide evidence to support the hypothesis that atrazine may affect amphibian development, they did not provide enough evidence to show that atrazine produces a consistent, reproducible effect on amphibian development. On the other hand, because of its adherence to the precautionary principle, the European Union has already banned atrazine.

The issue was hotly debated at the last Society of Environmental Toxicology and Chemistry (SETAC) meeting in November, where Hayes, a dynamic speaker, stunned a standing-room-only crowd of environmental scientists by declaring that the issue was about subverting, not advancing, science. Hayes said that he was driven to such a conclusion by industry efforts to muddy the scientific waters with sloppy, poorly designed studies that never attempted to replicate his work.

Since 1997, Syngenta has paid millions of dollars to Ecorisk, a Ferndale, Wash., company that does consulting and project management in toxicology, to investigate environmental issues related to atrazine. Ecorisk’s atrazine panel, which was headed by Texas Tech University toxicologist Ronald Kendall, planned, funded, and executed the atrazine studies criticized by Hayes.

At SETAC, Hayes attempted to prove his point by showing e-mail messages from Ecorisk researchers to himself and others. (Hayes was at one time a member of the Ecorisk panel, but resigned after a disagreement about the significance of his work.) Hayes says that he was driven to take this action because he is appalled that EPA would attempt to objectively evaluate data from Ecorisk scientists despite knowing that they had been dishonest, manipulated data, and conducted poor studies. Kendall, a well-known scientist who has served on many government advisory panels and committees, has denied Hayes’ allegations.

Hayes’ attack came as the Natural Resources Defense Council (NRDC) filed a lawsuit in November against EPA, the White House Office of Management and Budget, and the Council on Environmental Quality for not responding to requests for information about communications between EPA and industry regarding the decision. NRDC claims that the White House and industry played an inappropriate role in shaping the October 31 re-registration.

As a basis for the SAP evaluation, EPA scientists with expertise in toxicology and frogs evaluated 7 lab and 10 field studies that were either published by Hayes and other scientists or submitted by Syngenta. This evaluation uncovered “confounding effects across all of the studies that limited, if not precluded, the utility of the data,” EPA scientist Thomas Steeger told the panel in June.

Studies by Syngenta-sponsored scientists suffered from problems that included atrazine contamination of the water in which control animals were raised. Usually EPA would throw out a study with such a flaw, but because EPA has no established protocols for frog studies, all were considered, according to Steeger. Some of the Syngenta-sponsored labs raised too many tadpoles in tanks that were too small, fed them too little, and didn’t change the water often enough. As a result, in some studies there were too many deaths and frogs were late to metamorphose.

These frog lab studies are not particularly difficult to conduct, said SAP member Werner Kloas, an endocrinologist at Humboldt University in Berlin, Germany, who is interested in amphibians and fish. Hayes accuses the Syngenta-sponsored scientists of conducting bad experiments to muddy the waters with bad data.

Although Hayes’ frog husbandry practices are not in question, experts criticize the analysis presented in Hayes’ influential 2002 paper (Proc. Natl. Acad. Sci. 2002, 99, 5476–5480), which found that atrazine has a feminizing effect on male Xenopus lavis frogs when they are exposed as tadpoles to concentrations as low as 0.1 ppb.

“Hayes lumped together different abnormalities as a single effect,” Kloas explains. “There is no justification for lumping hermaphrodism—the presence of multiple ovaries and testes—together with a lack of pigmentation in the ovaries,” he says. On the other hand, Kloas says that something is going on with atrazine, but exactly what is not clear. He notes that an Ecorisk-funded study by Texas Tech toxicologist James Carr found an effect at 25 ppb (Environ. Sci. Technol. 2002, 36, 444A–445A).

Rather than being co-opted by industry, EPA and the SAP were too generous and diplomatic, according to another panel member who said that the work from all of the parties was sloppy.

Yale ecologist and panel member David Skelly agrees. “The SAP found that the field studies we reviewed had a number of serious flaws, including inadequate toxicant sampling, poor statistical power, and inappropriate sample site selection procedures. These issues were so fundamental that they made it virtually impossible to reach any conclusions concerning the effect of atrazine on the field populations studied. Prof. Hayes’ field study was no exception in this regard,” says Skelly, who specializes in field studies of amphibian populations.

Syngenta plans to pay for a contract lab to conduct further laboratory experiments using a protocol developed by EPA, but Japanese researchers may beat them to it. Molecular biologist Taisen Iguchi and colleagues have exposed Xenopus tadpoles to doses of atrazine from 0.1 to 100 ppb. He says that preliminary results indicate that vitellogenin production was significantly increased at 1 ppb atrazine exposure in males, females, and intersex frogs. This suggests estrogen production by atrazine, he says, although he cautions that the study is not yet complete. —REBECCA RENNER