SY N G EN TA
GOVERNMENT & POLICY
information on the relevance of animal toxicology findings to human health. The goal of the reevaluation is to determine whether EPA’s risk assessment for atrazine should be revised, according to Anna Lowit, a health effects scientist in EPA’s pesticide office. EPA also wants to determine whether the frequency of drinking-water monitoring is adequate to assess atrazine exposure, Lowit noted at a Sept. 14 meeting of EPA’s pesticide scientific advisory panel. WEED-FREE Atrazine
has been used for more than 50 years in the U.S. to keep weeds away, but EPA is reevaluating the safety of the endocrinedisrupting chemical.
ATRAZINE DEBATE INTENSIFIES EPA zeroes in on hormone effects, grapples with CONTRADICTORY DATA BRITT E. ERICKSON, C&EN WASHINGTON
IT’S BEEN ONE YEAR since the Envi-
ronmental Protection Agency decided to reevaluate the toxicity of atrazine, one of the most commonly used herbicides in the U.S. The agency’s review was expected to be nearly complete by now, but a plethora of new and contradictory studies on the health effects of atrazine have bogged down the process. EPA assessed the risks of atrazine in 2006 and determined that the 50-year-old weed-killing chemical is safe for use on corn, sorghum, and other crops when ap-
plied as directed. Last year, however, the agency decided to take another look at the herbicide because of a handful of studies showing an association between atrazine exposure and birth defects, premature births, and low birth weight in humans (C&EN, Oct. 12, 2009, page 36). The agency now acknowledges that the quality of those human epidemiology studies is insufficient for use in a quantitative risk assessment of atrazine. Nonetheless, EPA plans to continue with the reevaluation and use the studies qualitatively to provide
LAST MONTH’S meeting was the panel’s
third meeting this year on the health effects of atrazine. In February, the panel debated ways to incorporate human epidemiology and poisoning-incident data into EPA’s risk assessment of atrazine (C&EN, March 1, page 31), and in April, the group examined the endocrine-disrupting effects of atrazine in various animal toxicology studies. Last month, the panel wrestled with integrating all of the information, including human epidemiology, experimental toxicology, and drinking-waterexposure data. With respect to human epidemiology, EPA considered hundreds of published studies, but only 19 of them met the agency’s criteria, Carol H. Christensen, an epidemiologist in EPA’s pesticide office, noted
The Powerhouse for API Solutions
www.sintesicomunicazione.it
2 production sites 186,000 m2 total surface area (about 46 acres) 6 manufacturing units 1 launch/small cGMP production plant 1,711 m3 production capacity (about 450,000 US gal) 86 reactor trains 5 micronization mills 500 tons/year active ingredients produced 40 active ingredients 600 employees 1,000 partners worldwide
www.fisvi.com
F.I.S. - Fabbrica Italiana Sintetici SpA Viale Milano, 26 - 36075 Montecchio Maggiore - (Vicenza) - Italy
WWW.CEN-ONLINE.ORG
31
OCTOBER 11, 2010
Preeminent Researcher, Preeminent Journal. When you publish your research in the Journal of the American Chemical Society, you are joining the most preeminent researchers in the chemical & related sciences. Ahmed H. Zewail, the 1999 Nobel Prize winner in chemistry has published several articles in JACS and other ACS journals, including “Structure of Isolated Biomolecules by Electron Diffraction−Laser Desorption: Uracil and Guanine” as featured on the March 4, 2009 cover of the journal.
pubs.acs.org/JACS March 4, 2009 Volume 131 Number 8 pubs.acs.org/JACS
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
www.acs.org
Your Research. Your Journal. The Journal of the American Chemical Society.
at last month’s meeting. To meet the critezine (Toxicol. Sci. 2005, 87, 255), and anria, studies had to measure an association other showed the same effect at low doses between atrazine exposure and a chronic (Environ. Health Perspect. 2007, 115, 541). health effect, as well as measure atrazine But a paper reporting research funded by exposure specifically. The paper could not Syngenta, the primary manufacturer of be an editorial, and the full text of the paper atrazine in the U.S., and recently submitted had to be available, Christensen said. to Toxicological Sciences, found no delay in The studies that made the cut showed mammary gland development in rats exassociations between atrazine and reposed to atrazine in utero. productive effects, including delayed menopause, increased ATRAZINE IN THE FIELD gestational diabetes, and poor Herbicide’s use bounced back in 2007 after semen quality. They also showed several years of decline birth defects and low birth weight associated with atrazine Atrazine, millions of lb 90 exposure during pregnancy. But EPA concluded that these 80 human epidemiology studies are of insufficient quality to 70 include in a quantitative risk assessment. As a result, “EPA will 60 continue to rely on animal toxi50 cology data in quantitative risk assessment,” Christensen said. 40 The problem is that EPA can’t link atrazine to the reported 30 outcomes. “The lack of an exposure-response measurement for 20 ■ Corn ■ Sorghum many of these studies, the lack of ■ Sugarcane 10 individual-level exposure mea■ Other crops surement, and the lack of valida0 tion for use of surrogates for indi1992 94 96 98 00 02 04 06 vidual exposure” are also factors SOURCE: U.S. Geological Survey’s Scientific Investigations Report limiting the use of these studies 2010-5034 in quantitative risk assessment, Christensen explained. Nonetheless, EPA sees some value in the One reason for the discrepancies may human studies because many of the results have to do with differences in when an orare consistent with animal toxicology studganism is exposed. Several studies hint at ies. For example, the reported observation critical windows of exposure, Christensen of “small for gestational age” in humans is noted. Researchers at EPA are currently consistent with the observation of reduced studying hormonal and behavioral changes pup weight in animal toxicology studies, in rats exposed to atrazine in utero, in the Christensen pointed out. hope of elucidating some of those windows. In addition to effects on the mammary ALTHOUGH EPA has decided to rely on gland, EPA is particularly interested in animal toxicology studies, it is unclear understanding the role of atrazine in suphow the agency plans to extrapolate repressing the luteinizing hormone. This sults from rats to humans. In addition, the hormone is produced by the pituitary gland results from one animal study often do and triggers ovulation in females. Some not agree with the results from another studies indicate that atrazine exposure study. The agency has already examined suppresses the luteinizing hormone, but hundreds of animal toxicology studies on others do not. atrazine, including several that were pubSo far, EPA has identified changes to the lished this year. Some of the papers show neuroendocrine system that lead to reproreproductive or developmental effects in ductive toxicity as the most biologically rats, but others do not. plausible effects of atrazine exposure. The For example, one study showed delayed agency has identified some studies showmammary gland development in animals ing atrazine effects on the nervous and exposed to extremely high doses of atraimmune systems, but these effects were WWW.CEN-ONLINE.ORG
32
OCTOBER 11, 2010
GOVERNMENT & POLICY
“EPA will continue to rely on animal toxicology data.” observed only at doses higher than those found to elicit reproductive or developmental effects. Meanwhile, Syngenta has been conducting its own experiments on the safety of atrazine. The company came to EPA’s advisory panel meeting last month armed with a suite of new research findings, all of which suggest that atrazine is safe. Syngenta scientists claimed that they have not been able to demonstrate a link between atrazine exposure and a delay in mammary gland development, and they provided evidence that atrazine does not appear to target the pituitary gland or suppress the luteinizing hormone. In addition, the company presented results from a study showing that a distributed dose of atrazine given to a rat over time produces no effects on reproductive hormones. Even when extremely high doses of atrazine—up to 500 ppm—were given to rats in a distributed way over time, no effects were observed, stressed Tim Pastoor, principal scientist at Syngenta. “This highest dose was tens of thousands of times higher than the current EPA water standards for atrazine. People would never be exposed to this level in the environment,” he noted. “Yet even at this extreme dose, atrazine had no effect.”
In contrast, when rats were given a large, single dose of atrazine, hormonal effects were observed. Syngenta claims that a distributed dose of atrazine more closely replicates real-world exposure than a single, large dose. THE PROSPECT of a revised risk assess-
ment for atrazine and possible new restrictions on the herbicide has Syngenta, as well as many agriculture groups, worried. Such groups argue that there are no cost-effective alternatives to atrazine, particularly for corn. A ban on atrazine would lead to $100 million in increased costs annually to Missouri corn growers, Gary Marshall, chief executive officer of the Missouri Corn Growers Association, stressed at last month’s advisory panel meeting. He estimated that in total U.S. corn growers would take a $2.5 billion hit. “Consumers will ultimately pay the higher price,” he said. The groups are especially concerned about the timing of EPA’s review. They point out that if EPA had followed its normal schedule, atrazine would not have been reviewed until 2013. “We find ourselves in this very unusual, unplanned re-review of atrazine that deviates considerably from EPA’s long-standing regulatory process,” said Rod Snyder,
WWW.CEN-ONLINE.ORG
33
OCTOBER 11, 2010
director of public policy at the National Corn Growers Association. “EPA and the [scientific advisory panel] have already repudiated the very studies EPA relied upon to justify this re-review of atrazine, noting that ‘their overall quality was relatively poor, thus limiting their applicability.’ ” Just months before EPA launched its reevaluation of atrazine, the environmental group Natural Resources Defense Council released a report showing spikes in atrazine concentrations in drinking water that were well above EPA’s safe level. However, the spikes were seasonal, and the average concentration of atrazine in the drinking water did not exceed legal limits (C&EN, Aug. 31, 2009, page 21). Atrazine levels in drinking water are monitored weekly from April to August, and the values are averaged over a 90-day period. EPA is concerned that spikes of short duration will be missed by weekly sampling and has asked its pesticide advisory panel for input on selecting the critical duration of exposure. The agency is also proposing more frequent water monitoring and possibly the revision of its exposure calculations to be more protective of infants and children. EPA plans to follow up the September meeting with another pesticide advisory panel meeting in 2011 to evaluate studies on the potential of atrazine to cause cancer. This should complete the agency’s reevaluation of the herbicide and allow it to make a decision on whether additional restrictions are needed. ■
