Article taken from the CPM, written by Ted Fleetwood
Frequently with chemical innovations, the clever bit is being able to bring two components together in one can without them fighting against each other.
Occasionally you manage to achieve this and end up with a product that actually works better than the sum of its two components. With Kyleo, perhaps the really remarkable bit is that this was achieved with two well established and very popular actives.
Glyphosate is renowned as the world’s most widely used herbicide. But even this farming mainstay has its limits. “There are a number of weeds where glyphosate struggles,” notes Mark Hemmant of Agrovista.
“There’s cranesbill, nettle and notably volunteer oilseed rape. One of the key areas is grassland destruction – control of perennials such as docks and thistles can be slow and variable.
Illegal tank-mix
What you really want to do is add something like 2, 4-D to the mix, but the trouble is, you can’t. “Firstly it’s illegal to do so in the UK, and also they don’t mix well together in the spray tank – they work against each other and you can end up with a treatment that’s less effective than glyphosate on its own,” he says.
With both of these actives in its product portfolio one company that’s been keen to bring them together in one can is Nufarm. “It’s been a key priority for the European market for some time,” confirms head of formulation Guillaume Duchamp.
“The trouble is they’re two very different chemicals. Glyphosate is an isopropylamine salt, which 2,4-D is a dimethyl-amine salt. When you mix the two, the amine salt of the glyphosate tends to neutralise the 2,4-D, and there is the risk of flocculation, where fine particles clump together. What we needed was some form of salt or surfactant that would prevent this happening.”
Then in 2007 there was something of a breakthrough. “I was attending an international symposium on adjuvants for agrochemicals in the US, and our American colleagues revealed they already had a product in the US that combined glyphosate and 2,4-D. It wasn’t a very advanced formulation, however – it would be unlikely to be approved in the EU and it wasn’t very concentrated.”
But further discussions at the same seminar brought forward an adjuvant company that claimed it had a surfactant that would do the job. “We set up a meeting, came to an agreement, and before long we were trying out new formulations in the lab,” recalls Guillaume Duchamp.
“The combination of salt and surfactant gives Kyleo quite a sweet smell. It’s highly concentrated but easy to pour out, even when cold. One effect it has is that there’s no volatility – this can be an issue with certain formulations of 2,4-D. But what we really wanted to know is what would happen when we brought it together with glyphosate.”
Sure enough, it worked, even at the higher concentrations Nufarm had planned for the EU market. “But we discovered something remarkable – far from the two actives working against each other, there was a synergy that actually boosted the activity of the glyphosate.”
Further refinements ensured a product that was stable across a wide temperature range. But the real challenges were yet to come. “It was one thing putting together 1kg of product in the lab. It was quite another process 5000kg batches in the manufacturing plant. There’s a very precise step-by-step process that has to be followed,” notes Guillaume Duchamp.
This is where the expertise of Steve Heaton comes in, Nufarm’s European technical manager based at the company’s manufacturing plant in Wyke, near Bradford, Yorks. But there was a job to do to get Kyleo past registration, before production could be ramped up, he recalls.
“The German regulatory authorities couldn’t believe we had a glyphosate-based product that didn’t contain tallow amines – the traditional surfactant usually found in formulations. A team from Wyke had to go out and prove this was the case.”
But it’s on the phenoxy-herbicide side that Wyke holds its true heritage. This family of chemistry includes MCPA, 2,4-D, mecoprop and dichloprop. The company is the world’s number one manufacturer of the products, selling 80% of phenoxy herbicides used across Europe.
The plant itself converted to chemicals from coal mining in 1917, manufacturing DNBP. “This offered weed control in peas and stained everything yellow,” notes Steve Heaton.
“The company, known then as AH Marks, started to develop synthetic auxins in the 1940s. Over the next 40 years, as it developed its portfolio, it bought in the component parts of these chemicals. But then in the 1970s, it started to back-integrate, buying in the raw materials and processing them on site.”
This was a significant step, not just for the company, but the whole group of chemistry, he points out. “The team at Wyke completely transformed the way phenoxy herbicides are formed from the ground up. We developed the ability to chlorinate our own phenol. Then in 2002, we made the herbicides optically active.”
This is the ‘-P’ component of mecoprop-P and dichlorprop-P, for example. “We stripped out the undesirable, inactive elements. It we hadn’t, we wouldn’t have been able to re-register the products.”
So although it’s based on old chemistry, it’s a somewhat refined 2,4-D you’ll find partnered with the glyphosate in Kyleo, and that’s what brings the product its benefits in the field, reckons UK technical manager Dick Dyason.
“Glyphosate’s a good grass killer, but it’s not as effective against broadleaf weeds, notably annual nettle and certain others that tend to be selected out and can become a problem,” he says.
Glyphosate acts on the EPSP synthase enzyme that plays a key role in all plant metabolism. The key to its efficacy is that it’s translocated to the growing point in the plant where the enzyme is active. 2,4-D (or 2,4-dichlorophenoxyacetic acid) was one of the first selective herbicides every used and acts only on dicots, or broadleaf weeds. It’s a synthetic auxin, similar to plant hormones that naturally occur and regulate plant growth. But 2,4-D, once applied, can’t be regulated by the plant, so it grows uncontrollably and dies.
“So Kyleo is useful in situations where nettles can be a problem, such as within rotations that have hand-picked crops, like onions. It’s also a no-brainer where you have OSR volunteers in the stubble and need a quick knockdown to destroy the green bridge and ensure there’s no canopy shading blackgrass form control.”
There’s also a resistance angle to persistent glyphosate use that growers should bear in mind, believes Dick Dyason. “There have been no cases of glyphosate resistance recorded in the UK, but it exists elsewhere, especially where GM crops are grown in no-till rotations. There’s a suggestion that only two glyphosate applications should be made to the stubble.”
But it’s not just the actives in Kyleo doing the work, he maintains – the surfactant actually enhances the level of weed control. “Glyphosate and 2,4-D formulations are normally water soluble and therefore lack rainfastness. The surfactant system in Kyleo makes the product much more lipophillic which means it’s more readily taken up by waxy leaf cuticles, and that gives it considerably more rainfastness. What’s more, being less soluble, it remains in the upper layers of the soil, reducing the risk of ground-water contamination.”
Tests have shown there’s a 98% uptake of Kyleo by plants – nearly 13% more than of high quality glyphosate formulations, he points out. Further tests tracing radio-labelled glyphosate have shown better distribution through the plant and translocation to the roots.
“It’s also more rainfast than most premium glyphosate formulations – the Kyleo label states it’s rainfast within three hours, while in practice, this is just one hour under normal circumstances.”
The result shown in trials against leading brands of glyphosate is a more effective control of broadleaf weeds, and a faster action, he points out, with plants beginning to wither just six days after application. “We’ve also seen much better uptake and sytemicity on grassweeds, such as relatively large plants and high populations of brome.”
2,4-D has some residual activity, so replanting intervals should be borne in mid, notes Dick Dyason. “For cereals, that‘s around five days, or 14 days for maize. You should delay beans, peas and OSR by 28days, while there’s a 60=day interval for sugar beet and potatoes. But we have trials underway looking at shortening these intervals and we’re confident they’ll come down.”
Mark Hemmant doesn’t see this as too much of a problem, however. “The popular alternative before sugar beet is to mix glyphosate with carfentrazone, which has a similar planting interval,” he points out.
Arable rotations
While 2,4-D is a common herbicide in grassland, it’s not used much in arable rotations these days, he notes. “It has quite a tight application window in winter cereals, while more modern alternatives such as sulfonylureas are more effective across a wider range of timings. It has its particular strengths – on mare’s tail and coltsfoot for example.
“But one of the key reasons Kyleo is a significant development is the very fact that it contains old chemistry – in the current regulatory environment with few new actives coming to market, increasingly we’re having to look at old chemistry in a new light. Putting glyphosate with a hormone in a smart new formulation is a real innovation that has real benefits for growers.”
And Guillaume Duchamp suggests there’s more in the pipeline. “We’re currently looking at the next generation of Kyleo, which may perhaps contain a third active ingredient. We’re also looking at taking two selective actives that aren’t usually in the same can and combining them in a novel way. I think it’s a noble approach that brings innovation to older chemistry,” he says.
Innovation Insight
CPM would like to thank Nufarm for kindly sponsoring this article, and for providing privileged access to staff and material used to help put the article together.
Frequently with chemical innovations, the clever bit is being able to bring two components together in one can without them fighting against each other.
Occasionally you manage to achieve this and end up with a product that actually works better than the sum of its two components. With Kyleo, perhaps the really remarkable bit is that this was achieved with two well established and very popular actives.
Glyphosate is renowned as the world’s most widely used herbicide. But even this farming mainstay has its limits. “There are a number of weeds where glyphosate struggles,” notes Mark Hemmant of Agrovista.
“There’s cranesbill, nettle and notably volunteer oilseed rape. One of the key areas is grassland destruction – control of perennials such as docks and thistles can be slow and variable.
Illegal tank-mix
What you really want to do is add something like 2, 4-D to the mix, but the trouble is, you can’t. “Firstly it’s illegal to do so in the UK, and also they don’t mix well together in the spray tank – they work against each other and you can end up with a treatment that’s less effective than glyphosate on its own,” he says.
With both of these actives in its product portfolio one company that’s been keen to bring them together in one can is Nufarm. “It’s been a key priority for the European market for some time,” confirms head of formulation Guillaume Duchamp.
“The trouble is they’re two very different chemicals. Glyphosate is an isopropylamine salt, which 2,4-D is a dimethyl-amine salt. When you mix the two, the amine salt of the glyphosate tends to neutralise the 2,4-D, and there is the risk of flocculation, where fine particles clump together. What we needed was some form of salt or surfactant that would prevent this happening.”
Then in 2007 there was something of a breakthrough. “I was attending an international symposium on adjuvants for agrochemicals in the US, and our American colleagues revealed they already had a product in the US that combined glyphosate and 2,4-D. It wasn’t a very advanced formulation, however – it would be unlikely to be approved in the EU and it wasn’t very concentrated.”
But further discussions at the same seminar brought forward an adjuvant company that claimed it had a surfactant that would do the job. “We set up a meeting, came to an agreement, and before long we were trying out new formulations in the lab,” recalls Guillaume Duchamp.
“The combination of salt and surfactant gives Kyleo quite a sweet smell. It’s highly concentrated but easy to pour out, even when cold. One effect it has is that there’s no volatility – this can be an issue with certain formulations of 2,4-D. But what we really wanted to know is what would happen when we brought it together with glyphosate.”
Sure enough, it worked, even at the higher concentrations Nufarm had planned for the EU market. “But we discovered something remarkable – far from the two actives working against each other, there was a synergy that actually boosted the activity of the glyphosate.”
Further refinements ensured a product that was stable across a wide temperature range. But the real challenges were yet to come. “It was one thing putting together 1kg of product in the lab. It was quite another process 5000kg batches in the manufacturing plant. There’s a very precise step-by-step process that has to be followed,” notes Guillaume Duchamp.
This is where the expertise of Steve Heaton comes in, Nufarm’s European technical manager based at the company’s manufacturing plant in Wyke, near Bradford, Yorks. But there was a job to do to get Kyleo past registration, before production could be ramped up, he recalls.
“The German regulatory authorities couldn’t believe we had a glyphosate-based product that didn’t contain tallow amines – the traditional surfactant usually found in formulations. A team from Wyke had to go out and prove this was the case.”
But it’s on the phenoxy-herbicide side that Wyke holds its true heritage. This family of chemistry includes MCPA, 2,4-D, mecoprop and dichloprop. The company is the world’s number one manufacturer of the products, selling 80% of phenoxy herbicides used across Europe.
The plant itself converted to chemicals from coal mining in 1917, manufacturing DNBP. “This offered weed control in peas and stained everything yellow,” notes Steve Heaton.
“The company, known then as AH Marks, started to develop synthetic auxins in the 1940s. Over the next 40 years, as it developed its portfolio, it bought in the component parts of these chemicals. But then in the 1970s, it started to back-integrate, buying in the raw materials and processing them on site.”
This was a significant step, not just for the company, but the whole group of chemistry, he points out. “The team at Wyke completely transformed the way phenoxy herbicides are formed from the ground up. We developed the ability to chlorinate our own phenol. Then in 2002, we made the herbicides optically active.”
This is the ‘-P’ component of mecoprop-P and dichlorprop-P, for example. “We stripped out the undesirable, inactive elements. It we hadn’t, we wouldn’t have been able to re-register the products.”
So although it’s based on old chemistry, it’s a somewhat refined 2,4-D you’ll find partnered with the glyphosate in Kyleo, and that’s what brings the product its benefits in the field, reckons UK technical manager Dick Dyason.
“Glyphosate’s a good grass killer, but it’s not as effective against broadleaf weeds, notably annual nettle and certain others that tend to be selected out and can become a problem,” he says.
Glyphosate acts on the EPSP synthase enzyme that plays a key role in all plant metabolism. The key to its efficacy is that it’s translocated to the growing point in the plant where the enzyme is active. 2,4-D (or 2,4-dichlorophenoxyacetic acid) was one of the first selective herbicides every used and acts only on dicots, or broadleaf weeds. It’s a synthetic auxin, similar to plant hormones that naturally occur and regulate plant growth. But 2,4-D, once applied, can’t be regulated by the plant, so it grows uncontrollably and dies.
“So Kyleo is useful in situations where nettles can be a problem, such as within rotations that have hand-picked crops, like onions. It’s also a no-brainer where you have OSR volunteers in the stubble and need a quick knockdown to destroy the green bridge and ensure there’s no canopy shading blackgrass form control.”
There’s also a resistance angle to persistent glyphosate use that growers should bear in mind, believes Dick Dyason. “There have been no cases of glyphosate resistance recorded in the UK, but it exists elsewhere, especially where GM crops are grown in no-till rotations. There’s a suggestion that only two glyphosate applications should be made to the stubble.”
But it’s not just the actives in Kyleo doing the work, he maintains – the surfactant actually enhances the level of weed control. “Glyphosate and 2,4-D formulations are normally water soluble and therefore lack rainfastness. The surfactant system in Kyleo makes the product much more lipophillic which means it’s more readily taken up by waxy leaf cuticles, and that gives it considerably more rainfastness. What’s more, being less soluble, it remains in the upper layers of the soil, reducing the risk of ground-water contamination.”
Tests have shown there’s a 98% uptake of Kyleo by plants – nearly 13% more than of high quality glyphosate formulations, he points out. Further tests tracing radio-labelled glyphosate have shown better distribution through the plant and translocation to the roots.
“It’s also more rainfast than most premium glyphosate formulations – the Kyleo label states it’s rainfast within three hours, while in practice, this is just one hour under normal circumstances.”
The result shown in trials against leading brands of glyphosate is a more effective control of broadleaf weeds, and a faster action, he points out, with plants beginning to wither just six days after application. “We’ve also seen much better uptake and sytemicity on grassweeds, such as relatively large plants and high populations of brome.”
2,4-D has some residual activity, so replanting intervals should be borne in mid, notes Dick Dyason. “For cereals, that‘s around five days, or 14 days for maize. You should delay beans, peas and OSR by 28days, while there’s a 60=day interval for sugar beet and potatoes. But we have trials underway looking at shortening these intervals and we’re confident they’ll come down.”
Mark Hemmant doesn’t see this as too much of a problem, however. “The popular alternative before sugar beet is to mix glyphosate with carfentrazone, which has a similar planting interval,” he points out.
Arable rotations
While 2,4-D is a common herbicide in grassland, it’s not used much in arable rotations these days, he notes. “It has quite a tight application window in winter cereals, while more modern alternatives such as sulfonylureas are more effective across a wider range of timings. It has its particular strengths – on mare’s tail and coltsfoot for example.
“But one of the key reasons Kyleo is a significant development is the very fact that it contains old chemistry – in the current regulatory environment with few new actives coming to market, increasingly we’re having to look at old chemistry in a new light. Putting glyphosate with a hormone in a smart new formulation is a real innovation that has real benefits for growers.”
And Guillaume Duchamp suggests there’s more in the pipeline. “We’re currently looking at the next generation of Kyleo, which may perhaps contain a third active ingredient. We’re also looking at taking two selective actives that aren’t usually in the same can and combining them in a novel way. I think it’s a noble approach that brings innovation to older chemistry,” he says.
Innovation Insight
CPM would like to thank Nufarm for kindly sponsoring this article, and for providing privileged access to staff and material used to help put the article together.