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Killing Weeds — Killing Frogs?
Herbicides, Toxicity, and Biological Effects

by Maryann Donovan, MPH, PhD, Director, CEO of UPCI

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Dr. Tyrone Hayes, Professor of Integrative Biology at Berkeley, has studied frogs since he was a little boy. In February 2007, he visited the Center for Environmental Oncology of UPCI to speak about his studies of the effects of pesticides on frogs, specifically the pesticides that act like hormones, also called “disruptors.” Run-off from pesticide application can lead to contamination of water sources including small puddles, lakes, streams, and groundwater. Amphibians, such as frogs, live in and near water making them vulnerable to contaminants. In a recent paper, Dr. Hayes discussed the effect on frog development when larvae or adults were exposed to herbicides (atrazine, metolachlor, alachlor, nicosulfuron), insecticides (cyfluthrin, cyhalothrin, tebupirimphos), and fungicides (metalaxyl, propiconizole) either individually or in combination (Hayes, T.B. et al. Pesticide mixtures, endocrine disruption, and amphibian declines: are we underestimating the impact? Environmental Health Perspectives 114: supplement 1, 2006). He chose these pesticides because they represented the actual pesticide mixture that was being applied to cornfields in the Midwest. Compared with the individual pesticides, the mixtures had much more significant effects. Exposure of frog larvae to mixtures of the chemicals caused a significant delay in the initiation of metamorphosis and retarded growth resulting in smaller animals. Seventy percent of the animals exposed to the nine-compound mixture were unable to sit upright. Certainly, at least in part, endocrine disrupting chemicals in the environment may be contributing to the decline in amphibians being reported globally.

One of the chemicals included in Dr. Hayes’ study was atrazine, the most commonly used herbicide in the United States and probably the world. Because of concerns about toxicity, atrazine is banned in Europe. In the United States, by contrast, the EPA estimates that 65-70 million pounds of atrazine is applied mostly to corn, sorghum, and sugarcane fields. Dr. Hayes has spent almost 10 years studying the effects of atrazine, an endocrine disruptor, on frog development. In his laboratory studies, he exposed Rana pipiens, the leopard frog, larvae to different concentration of atrazine ranging from 0, 0.1, or 25 parts per billion (ppb). The animals were exposed from just after hatching until tail resorption was complete. Only exposed males developed eggs in the testes (testicular oocytes) and other gonadal abnormalities. You might wonder if this was just a laboratory phenomenon and so did Dr. Hayes. To address that question, Dr. Hayes and his research team went out into the field to evaluate frogs from 8 different sites located between Iowa and Utah. They used records of atrazine sales, locally, to identify potentially contaminated sites. For controls, they evaluated frogs from non-agricultural regions in Iowa, Utah, Wisconsin, and Nebraska that reported low atrazine sales. Levels of atrazine were measured in the water taken from each site and only one site had levels too low to be measured and this was the only site where testicular oocytes were not observed in the local population of frogs (Hayes, T. et al. Feminization of male frogs in the wild. Nature 419: 895-96,2002).

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Is there evidence that contamination of food, air and water with atrazine may have health effects for humans? The answer is yes, there is some evidence. But, like many studies of chemicals, the data are not always clear and absolute. In 2006, the California EPA published a risk assessment for atrazine use in California (Gammon D., et al. Pest Manag. Sci 61:331-355, 2006). Near the end of this comprehensive report (p. 351-352) comments about endocrine (hormone) effects of atrazine and cancer studies in humans and animals are mentioned. The authors summarize published evidence showing that atrazine delays onset of puberty in male rats, inhibits estrogen binding in vitro and in vivo, and causes a premature termination of reproduction and an increase in breast tumors in female rats. In other reports, atrazine caused cells in culture to increase expression of aromatase, and this mechanism might explain the reduced testosterone and increased estrogen measured in the blood of male rats. All of the effects observed in these laboratory and animal studies are consistent with atrazine acting like a hormone directly or indirectly by changing the enzymes involved in hormone metabolism. This same report also alludes to several studies suggesting that occupational exposure to atrazine, either through manufacturing or farming, may increase the risk of prostate cancer although not all studies show this effect.

Hormones are very important for human biology and the timing, amounts, and types of hormones present are tightly regulated in humans. Like frogs, in addition to our own hormones, we are being exposed to “endocrine disrupting” chemicals in our air, food, and water. We know that humans harbor measurable levels of potentially toxic environmental pollutants in their tissues. The relationship between body-burden levels of these chemicals and chronic disease and cancer is actively being studied by many scientists including researchers at the University of Pittsburgh Cancer Institute. We look forward to sharing the results from these research studies as we get clues about the role that these chemicals may play in cancer progression.