The bountiful fields of the U.S. are awash in atrazine. About 36 million kilograms of the odorless, white powder are applied on farms to control grassy weeds. Every year some 225,000 kilograms of the herbicide become airborne and fall with the rain, up to 1,000 kilometers from the source. All that atrazine may have a sexual effect: turning male frogs female.

As described in the March 1 Proceedings of the National Academy of Sciences USA, biologist Tyrone Hayes of the University of California, Berkeley, and his colleagues exposed 40 African clawed frogs (Xenopus laevis) to 2.5 parts per billion (ppb) of atrazine continuously for three years—a level below the 3 ppb allowed in drinking water by the Environmental Protection Agency. As a result, 30 of the frogs were chemically castrated, incapable of reproducing, among other consequences. Also, four of the treated frogs actually turned female, going so far as to mate with other males and produce viable eggs despite being genetically male. Only six of the treated frogs resisted atrazine or at least showed normal sexual behavior.

To be sure of their results, the researchers used males bearing only the ZZ sex chromosomes. In previous studies “if we got hermaphrodites, there was no way to know if they were males with ovaries or females with testes,” Hayes says. “By using all ZZ males, we were assured that any hermaphrodites or females were indeed sex-reversed males.” Frogs follow the ZZ (male), ZW (female) sex determination scheme, rather than the more familiar XX (female), XY (male) pattern of humans.

A key culprit in the sex change may be aromatase, a protein that spurs the production of the female hormone estrogen, causing originally male gonads to become ovaries. Atrazine may be boosting the production of aromatase.

Hayes has a long history of studying atrazine, starting in the 1990s with research funded by its maker, now known as Syngenta, which first raised the prospect that the herbicide might be interfering with the natural hormones of animals, including humans. A barrage of studies on such endocrine disruption has followed—some confirming that amphibians such as frogs are suffering from an atrazine onslaught, others finding no effect and others even uncovering evidence of reduced sperm count in men from agricultural regions. Atrazine and other herbicides can be found in 57 percent of U.S. streams, according to the U.S. Geological Survey.

Hayes’s sex-changing experiment, however, is not without criticism. Biologist Werner Kloas of Humboldt University in Berlin charges that samples may have been contaminated by endocrine disruptors such as bisphenol A (BPA) leaching from plastic containers or being introduced during screening. He also questions the single exposure level and lack of measurement of female hormone levels in the affected frogs. For his part, Kloas in the past reviewed atrazine’s effects for Syn­gen­ta and found no impact on African clawed frogs at concentrations comparable to those investigated by Hayes.

In their native habitats, African clawed frogs do not appear to be suffering from the herbicide. “Atrazine has been used widely in South Africa for the past 45 years, and our studies showed that Xenopus are doing equally fine in agricultural and nonagricultural areas,” says zoologist Louis du Preez of North-West University in South Africa. “If atrazine had these adverse effects on Xenopus in the wild, surely we would have picked it up by now.”

Nevertheless, the European Union has banned atrazine because of its ability to contaminate water. “I personally prefer our European habit to use the precautionary principle concerning environmental chemicals to phase out persistent compounds,” Kloas says.

After declaring the chemical treatment safe in 2006, the EPA announced yet another review of the herbicide last October because of human health concerns. The chemical, after all, affects many species. “Atrazine increases aromatase and/or estrogen production in zebra fish, goldfish, caimans, alligators, turtles, quail and rats,” Hayes points out. “So this is not just a frog problem.”