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New weed control tool comes with an asterisk

Farmers can manage resistant weeds with isoxaflutole—if they can keep it out of the water

by Melody M. Bomgardner , Britt E. Erickson
June 6, 2020 | A version of this story appeared in Volume 98, Issue 22


This photo shows rows of soybeans where isoxaflutole and other herbicides have prevented weed growth.
Credit: Peter Sikkema/University of Guelph
A University of Guelph field trial shows the weed control capabilities of isoxaflutole on herbicide-tolerant soybeans. Two rows received an early treatment of isoxaflutole and another pre-emergent herbicide followed by a later application of glyphosate.

These days, the best way for farmers to control herbicide-resistant weeds is to kill them when they are young and helpless. The problem is, they don’t stay that way for long.

“It’s almost like you can stand there and watch them grow,” says Kentucky farmer Caleb Ragland, referring to pigweed species that have evolved resistance to common herbicides like glyphosate. Once weeds get over about 10 centimeters tall, “spraying them with chemicals they’re becoming resistant to just seems to make them tougher,” Ragland says.

So it’s no surprise that farmers are looking forward to a new tool that keeps weeds from getting an early roothold in the field. In April, the US Environmental Protection Agency approved the early season use of the herbicide isoxaflutole on new varieties of soybeans engineered to withstand the chemical. The soybean and herbicide combination will be available starting next spring, expanding use of a chemical that is presently only applied on corn.

This image shows isoxaflutole and its degradation products isoxaflutole diketonitrile and isoxaflutole benzoic acid.
Isoxaflutole is the main ingredient in the BASF herbicide Alite 27. When taken up by a weed or activated by rain, it quickly breaks down to isoxaflutole diketonitrile, a chemical with herbicidal activity. After weeks or months it further degrades to isoxaflutole benzoic acid. The two breakdown products can migrate to, and persist in, surface water and groundwater.

Farmers say they need isoxaflutole to fight resistant weeds. And BASF, the herbicide’s maker, says the EPA used extremely conservative guidelines in approving isoxaflutole for soybeans. But environmental organizations are raising red flags about the chemical, which they say can degrade water quality and harm other plants in regions that already bear a high burden of pollution from agricultural chemicals.

All involved acknowledge that many growers will not be able to use this new tool. Isoxaflutole and its breakdown products migrate into surface water and groundwater, where they persist and accumulate. The two biggest soybean-growing states, Iowa and Illinois, have soil types and groundwater heights that kept regulators from approving the herbicide.

In the 25 states where isoxaflutole is allowed, it is only registered for use in counties without endangered plants that might be growing near fields that could be treated. What’s more, BASF says it does not plan to pursue registration in Minnesota and Wisconsin, states that monitor how much isoxaflutole gets into water sources.

In addition to their concerns about the herbicide itself, environmental and health advocates are alarmed that the EPA did not inform the public through its usual Federal Register notification when it opened the comment period on its proposal to approve use of isoxaflutole on soybeans.

“We were not aware of any comment period,” says Nathan Donley, senior scientist at the environmental group Center for Biological Diversity. “It is worrisome to us from a transparency standpoint, because if you don’t let the public know that a comment period is open, then you aren’t getting the full range of opinions that should influence the agency’s decision.”

The EPA considers isoxaflutole a probable carcinogen, Donley points out. “That means that EPA has acknowledged that some dose can cause cancer in people,” he says.

The agency did not find a cancer risk to humans in its assessment of isoxaflutole use on soybeans because exposure levels would be too low. But that risk assessment is “fraught with uncertainty,” Donley contends. In his view, there likely is a cancer risk to people. In addition, animal studies have shown that exposure to isoxaflutole in utero can result in developmental defects, he notes.

Because of the lack of notification, no environmental groups commented on the EPA’s proposal to approve isoxaflutole for soybeans. Several farm groups did, and all their comments were positive. Yet “isoxaflutole is really a bad actor. We would really have appreciated an opportunity to comment to EPA,” says Bill Freese, science policy analyst at the Center for Food Safety, an environmental group.

The group did submit comments to the US Department of Agriculture in 2013 in opposition to soybeans genetically engineered to tolerate isoxaflutole.

Isoxaflutole is really a bad actor. We would really have appreciated an opportunity to comment to EPA.
Bill Freese, science policy analyst, Center for Food Safety

Isoxaflutole has been used on corn since 1999. Although the herbicide is applied on less than 10% of corn grown in the US, it has left a large environmental footprint because of its persistence in the environment and ability to leach into groundwater.

In 2004, scientists at the US Geological Survey monitored 10 major rivers in Iowa that drain into the Missouri and Mississippi Rivers for the presence of isoxaflutole and its diketonitrile and benzoic acid degradation products. “They were surprised to find it so frequently, given how little used it is,” Freese says. “It has atrazine-like properties.” Atrazine is a widely used herbicide that is notorious for contaminating groundwater.

Where farmers are allowed to use isoxaflutole, many probably will, agriculture experts say. Controlling weeds is an existential battle for farmers of row crops, including corn and soybeans. If weeds are allowed to grow, the average soybean yield shrinks by 52% as weeds steal nutrients, water, and sunlight (Weed Technol. 2019, DOI: 10.1017/wet.2019.21). Since the late 1990s growers in the US have fought this war with combinations of herbicides and seeds engineered to withstand their use.

This year’s popular soybean varieties can be sprayed with three chemicals: glyphosate, also known as Roundup; glufosinate, called Liberty; and either dicamba or 2,4-dichlorophenoxyacetic acid, known as 2,4-D. But using multiple modes of action is no longer a guarantee that some weeds won’t survive and disperse seeds for a new, harder to kill generation.

Farmers’ likelihood of success increases, weed scientists say, if they also use herbicides like isoxaflutole that are applied on the field at or near planting time to take down weeds right after they germinate.

Chemicals like isoxaflutole are commonly known as bleaching herbicides. They rob plants of their ability to make antioxidants that protect delicate chloroplasts, the engines of photosynthesis, from the oxidative stress of sunlight.

Isoxaflutole is one of a class of chemicals called HPPD inhibitors that block the production of the enzyme 4-hydroxyphenylpyruvate dioxygenase, which plants use to break down the amino acid tyrosine into homogentisic acid. Weeds use homogentisic acid as a raw material to synthesize the yellow and orange carotenoids and tocopherols they use as sunscreen. Without that protection, green-pigmented chlorophyll in a plant’s chloroplasts quickly degrades in sunlight. The result is a bleached—and soon dead—weed.

What’s unusual about this herbicidal mechanism of action is that mammals also break down tyrosine using the same HPPD enzyme. In humans, that enzyme is located mostly in the liver, so isoxaflutole has the potential to cause liver toxicity. Animal studies have shown it can also be toxic to other organs, Freese says. In contrast, most herbicides on the market typically work on biological mechanisms present only in plants.

BASF says it does not yet know how much Alite 27, as it calls its isoxaflutole formulation, will be used on soybeans. The first indication will be how many acres of the company’s isoxaflutole-tolerant LibertyLink GT27 soybeans are planted in spring of 2021, says Kate Greif, the company’s spokesperson for Alite 27.

Compared to herbicides like glyphosate or dicamba, isoxaflutole will not be a blockbuster product, predicts Mark Loux, a professor and weed scientist at the Ohio State University’s department of horticulture and crop science. Instead, it will be one more chemical a farmer can mix in the spray tank for the first pass of weed control. “It’s OK for what it does,” Loux says.

The main complication for farmers who wish to use Alite 27, Loux says, is they will have to read and understand the label and its advisories on keeping it out of groundwater and surface water. “You can use it in Ohio, but users have to know what that advisory on the label means. Do they all the time? Probably not,” he says.

This photo shows a bleached and dying weed.
Credit: BASF
Isoxaflutole kills weeds by preventing them from synthesizing compounds that protect them from sun damage.

That difficulty concerns Freese. “The label reminds me a little bit of dicamba, with the incredibly restrictive use conditions that most farmers really can’t follow,” he says. With isoxaflutole, the licensed applicator is supposed to determine how much organic matter is in the soil, and how high the water table is beneath the field.

Still, Kentucky farmer Ragland, who's on the board of the American Soybean Association, the main advocacy group for US soybean farmers, is looking forward to using the new herbicide and soybean combo on his fields. “It is an exciting thing to have new platforms come available that we can use so we can mix up different platforms and combine them,” he notes.

I think Alite 27 will hit the market running and be embraced quickly.
Caleb Ragland, Kentucky farmer

Growers are getting the message that they need to change up their herbicide strategy from year to year to prevent resistance from emerging, Ragland says. “I think Alite 27 will hit the market running and be embraced quickly,” he says. “A licensed and trained applicator is going to do real well with it.”

Farmers who plant BASF’s LibertyLink GT27 soybeans will also be able to use glyphosate and glufosinate, which are sprayed after the soybeans are growing. That gives growers three herbicidal modes of action, Greif says.

But that trio may still not be enough to satisfy farmers’ weed-control needs, she says. The company recommends farmers include at least one additional herbicide in their mix. One option is Zidua, also made by BASF. Zidua’s active ingredient is pyroxasulfone, which inhibits a germinated weed’s ability to synthesize long-chain fatty acids.

Both Zidua and Alite 27 stick around in the soil for roughly 4–6 weeks to kill weeds as they emerge. One bonus in mixing the two herbicides, Greif says, is that growers gain about 2 weeks of added control. Alite 27 is easy to mix in, she says, because very little is needed; the application rate is about 100–200 g per hectare.

To reduce potential impact on off-target species, Greif says, BASF is raising awareness of the label’s application restrictions, engaging its sales team to educate farmers, and posting information on a website for farmers to reference.

Those measures don’t assuage environmental groups, who are concerned about ramping up use of yet another herbicide. “We are seeing so much more herbicide used with genetic engineering of these crops,” Donley says. “When you start combining herbicides, and spraying tank mixes of, like, five at a time, you are just increasing the complexity of those mixtures. How do those mixtures interact with wildlife, humans, our food? We just really don’t know, because no one does those studies.”

The EPA will review the registration for isoxaflutole used on soybeans in 5 years. The agency will evaluate potential weed resistance based on annual reports submitted by users. And it will consider reports of unreasonable adverse effects of the herbicide on the environment. The review could result in additional restrictions.

“You’re always concerned to have a tool taken out of your toolbox, but I have great confidence in the vetting process these tools go through before they are introduced into the market,” Ragland says.

Loux, the Ohio State weed scientist, is not sure that isoxaflutole will be effective for very long. He notes some populations of one common weed, waterhemp, in the Midwest are already resistant to mesotrione, an HPPD-group herbicide. If farmers use it with their corn crop and then again with their soybeans, more weeds will grow resistant to it.

As more and more weeds survive applications of three, four, or five different herbicides, farmers need to change tactics, Loux says. For example, he recommends farmers attach a device to their combines that destroys weed seeds at harvest time.

At 33, Ragland is part of a younger generation of farmers. He’s open to trying whatever works, including nonherbicidal approaches. Ragland points out that Kentucky farmers were the first to adopt no-till agriculture; he also grows winter wheat and cover crops, which smother weeds as well as protect and improve the soil on his rolling fields.

Ragland says he’s prepared to stay nimble in the battle against weeds. “I think we have a good story to tell as we’re learning to adapt and become successful despite the increasing complexity of weed resistance.”


This story was updated on June 11, 2020, to acknowledge that Caleb Ragland is on the board of the American Soybean Association, the main advocacy group for US soybean farmers.


The story was updated on June 15, 2020, to clarify that some populations of one common weed, waterhemp, have been shown to be resistant to HPPD herbicides but not to isoxaflutole specifically. Also, the resistance is known to be in the Midwest but not yet in Ohio.


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