Here's how we think it works. Testosterone is a precursor to estrogen. In male frogs, it makes their voice boxes grow and their vocal sacs develop. But atrazine, in frogs, switches on a gene that makes the enzyme aromatase; it's silent. In these males, the estrogen induces the growth of ovaries, eggs and yolk. So you've got two things happening: the frog is demasculinized, and it's also feminized (Sobel, 2004).
Previous findings by Tyrone Hayes, a comparative endocrinologist at the University of California Berkeley, brought together emerging concerns about amphibian declines, endocrine disrupters, and chemical contamination of the environment. In a series of high-profile papers, Hayes reported that tadpoles exposed to levels of atrazine as low as 0.1 parts per billion (ppb) could develop gonadal abnormalities or become hermaphrodites, apparently because of disruptions in their endocrine system (Proc. Natl. Acad. Sci. U.S.A. 2002, Environ. Health Perspect. 2003,).
He proposed that atrazine-induced production of aromatase, which is an enzyme that converts testosterone to estrogen in vertebrates (including humans), and that this was feminizing the male frogs. Other researchers reported that atrazine had a range of endocrine-modulating effects on amphibians. But studies funded by Atrazine manufacturer Syngenta did not find adverse effects. The official report from the U.S. EPA Scientific Advisory Panel (SAP) report in 2003 found fault with all the studies.
But Hayes and the Natural Resources Defense Council still contend that, in its regulatory deliberations on atrazine, the U.S. EPA is biased in favor of Syngenta, and Hayes now actively campaigns for a ban on the use of atrazine."
But Hayes disagrees. The increase in female frogs is an important effect consistent with his findings, he says. "You don't know how many females you start with, but when you progressively get a 10% loss in males with every 10 ppb [increase in] atrazine, that is very statistically significant; something is real."
EPA's review
The paper from the Japanese researchers comes in the wake of an EPA review, which concluded in Oct. 2007 that Atrazine does not adversely affect gonadal development of the frogs. The panel evaluated the results of two large Syngenta-funded studies that adhered to an experimental protocol recommended by the SAP in 2003. Studies were conducted by 2 independent labs.
One was a contract lab, Wildlife International in Easton, Md., and Werner Kloas's lab at the Leibniz Inst. In Berlin (of Freshwater Ecology and Inland Fisheries). Both labs raised the tadpoles in glass tanks set up with a flow-through water system. The protocol: Five groups of 200 frogs each, were exposed to 0.01–100 ppb atrazine. The researchers looked for changes in sex ratio and the presence of mixed-sex animals, but they did not find any statistically significant changes.
The fact that the two studies that found no correlation between Atrazine and sex changes in the frogs just happened to be funded by Syngenta, seemingly escaped everyone's notice.
Differences in response to estrogen, bisphenol A, and dioxin have been reported in rats and mice, and difference in response to chemicals has been reported in Daphnia reproduction also, according to Osamu Tooi, one of the Japanese researchers. "The discrepancy of the present results and Hayes's studies may be caused by various factors, such as genetic differences in X. laevis used, water quality, including iodide ions, food, and the composition of aquaria," he says.
However Kloas argues that differences among subpopulations or strains still need to be proven. "Even in different species of frogs, the response to estrogen under similar conditions is close, within an order of magnitude…With concerns over feminization, all frog species tested so far react similarly," he said.
Amphibians and especially frogs are obviously in decline, but pinning down the evidence on Atrazine has been very tricky. Something or some number of things that we don't understand is going on with frogs, says Skelly.
SOURCES:
Blumenstyk, Goldie, The Story of Syngenta & Tyrone Hayes at UC Berkeley:
The Price of Research, http://www.mindfully.org/Pesticide/2003/Syngenta-Tyrone-Hayes31oct03.htm, Oct. 31, 2003.
Renner, Rebecca, Atrazine effects in Xenopus aren't reproducible, Environmental Science & Technology, http://pubs.acs.org/subscribe/journals/esthag-w/2008/apr/science/rr_atrazine.html, April 9, 2008.
Suzawa and Ingraham, The Herbicide Atrazine Activates Endocrine Gene Networks via Non-Steroidal NR5A Nuclear Receptors in Fish and Mammalian Cells, PLoSOne.org,
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0002117, 2008.
Dini, Jack, on Junk Science.com, December 2007,
http://www.junkscience.com/jan08/fearing_frog_deformities.html
Sobel, Dava (editor), The Best American Science Writing, P.158, 2004. (for excerpt about how Hayes thinks Atrazine feminizes frogs) forthwith: http://books.google.com/books?id=HbT6AU_n7_YC&pg=PA157&lpg=PA157&dq=atrazine+frog+dieoff&source=web&ots=YHq5T8aIyg&sig=7Lq-RTpj0z4p0xh50APBax2e-9Y&hl=en#PPA158,M1




