Tech Tuesday

Purdue Study Raises Questions about Atrazine

A cutting edge toxicology study looks at how the crop protection product impacts specific genes in an aquatic environment.

The most-researched crop production product in use today is subject of another study that raises questions about the safe levels of the product in drinking water. Atrazine, a widely used herbicide, has been on the market for more than 50 years, and has been subject to thousands of studies.

This latest toxicology study from Purdue University reports to have found that atrazine "alters reproductive and neuroendocrine genes during embryonic development in fish." Digging into the study isn’t for the non-tech faint of heart; this is a look at a genetic response to the herbicide on 42 genes out of more than 35,000 in the genome of a fish - the zebrafish.

Freeman tells Farm Progress that researchers evaluated all the genes in the zebrafish genome for changes in response to exposure at 0.3 parts per billion, 3 ppb and 30 ppb. She reports that 21 genes changed at 0.3 ppb, 62 genes changed at 3 ppb and 64 genes changed at 30 ppb adding that "42 is the number o genes that were changed in both the 3 and 30 ppb treatments.

Farmers should care about any study related to atrazine for a number of reasons, first of which is that the U.S. Environmental Protection Agency has reopened review of the herbicide - again. Any study that calls safety of the product into question will get plenty of scrutiny.

The study, partially funded by the National Institutes of Health and published by Toxicological Sciences journal, focused on exact gene changes.

Why a zebrafish? Researchers report that the zebrafish model the researchers used allowed them to focus on the 72-hour embryonic development time, which mirrors human prenatal development; and the impact of atrazine on these embryos a key finding.

In looking at more than 35,000 genes in the genome, they found two genes were changed at three levels of atrazine exposure - 0.3 parts per billion, 3 parts per billion (the current federally approved safe level) and 30 parts per billion. One gene - CYP17A1 plays a role in biosynthesis of steroid hormones and the conversion of androgens to estrogen. Another - SAMHD1 controls immune function. Both were changed at all three exposure levels. The researchers say there is also a concern that 42 of the genes were affected at the 30 ppb level as well as at the approved 3 ppb level.

"Identification is just the beginning," says Jennifer Freeman, an assistant professor of toxicology in the School of Health Sciences, Purdue. "The goal is to understand the genetic pathways and how they are altered to see what's happening in the big picture."

The Purdue study also found an increase in head length for zebrafish exposed to the herbicide. "This was a subtle change for the fish larva at all exposure levels that we were able to see with finer measurements but not with the eye alone," Freeman says. "This morphological change in the zebafish indicates that low levels of atrazine can stimulate development and alter the physiology of exposed individuals."

Researchers at Purdue are also looking at the long-term effects of the fish exposed to these three atrazine levels as they grow and reproduce to link the development gene changes observed to potential adverse health outcomes.

Syngenta, lead maker of atrazine, is reviewing the Purdue study and Tim Pastoor, principal scientist, tells Farm Progress that "this is a good study, they did everything by the book and it has been published in a very reputable journal," he notes. "It's not the conduct of the study, but interpretation of the results that is important."

He notes that in reviewing the study the dose-response issue will be important. That essentially says that there should be a correlation between the level of herbicide exposure and the response in the zebrafish.

Press announcement issues

The company is still reviewing the research and Pastoor wasn't comfortable delving into the details early on, he was however, willing to talk about the press release that announced the study. He took issue with two key assertions made by the release writer in announcing the study. The release says "the herbicide is considered an endocrine disrupting chemical and potential carcinogen."

"Number one, there is absolutely no consistent evidence that atrazine is associated with any form of cancer," Pastoor asserts. "EPA's own proclamation is that atrazine is 'not likely' to cause cancer which is the agency's best category."

He also points to National Institute of Health's Agricultural Health Study ongoing since 1993, which has found no observable relationship between cancer and exposure to atrazine among farmers and farm workers and their families. "EPA, in its 2011 Scientific Advisory Panel meeting on epidemiology noted that this was among the strongest evidence that atrazine is not related to any form of cancer," Pastoor says.

The Purdue release quotes the EPA website where the comment by the agency's Federal Insecticide, Fungicide and Rodenticide Act Scientific Advisory Panel continues to evaluate the potential link. The site quotes the panel:  "Even though the panel agreed with EPA that the epidemiologic evidence does not strongly suggest a link between atrazine and cancer, the panel did not agree that a lack of strong evidence justifies a conclusion that atrazine is not likely to be a human carcinogen."

Detractors of atrazine have long played the "endocrine-disruptor" card in talking about the product. An endocrine disruptor is a chemical that can interfere with the endocrine - or hormone - system in animals and humans. Those products have been linked to a range of health disorders.

As for the endocrine-disrupting claim, Pastoor notes that this is also not accurate. "Let me tell you why atrazine is not an endocrine disrupter. To get that kind of impact would be at exposure levels far beyond any that a human would, or could, experience. Those studies and claims were done with atrazine at concentrations higher than you can dissolve it in water," he claims. "The only way you can get enough in water to cause that kind of impact is to solubilize atrazine with other agents to get it into a rat at high doses." Syngenta claims that, at common exposure levels, atrazine cannot be considered an endocrine disrupter.

Freeman's research at Purdue is the start of a new genetic conversation in toxicology. It's an area that's getting greater attention as researchers look at how exposure to specific compounds impacts genetics. "In our study, a number of gene changes were associated with cancer pathways, too, and while related gene pathways for cancer are involved, we are not saying atrazine causes cancer," she says. "We know these genes are changing in some way, and we need to do further targeted mechanistic studies to determine if there is a connection."

Gene-based toxicology is an important new topic and could change the shape of the dialogue for crop protection products. We'll watch how that plays out as more work is done in this area and keep you posted.

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