**3. Glyphosate: sales in Brazil and worldwide, origin and mode of action**

Currently, the most efficient method used for weed control is the use of herbicides, mainly in large areas of cultivation, for which its rapid action added more viable costs. Among the herbicides used, glyphosate is the most marketed worldwide in more than 119 countries with about 150 trademarks for this product [14]. **Figure 9** presents the commercialized quantities of glyphosate and its channels in Brazil.

According to the ABRASCO [16], 110 products with glyphosate alone have been sold in Brazil, in 29 different companies, and 173,150.75 tons sold in 2017, the amount being 3 times more than the second most commercialized herbicide, the 2,4-D. This considerable increase in sales was due to the production of corn and cotton after the development of transgenic soybeans, from 40,000 tons of products marketed to 300,000 per year in Brazil. In 2013, Asian countries, especially China and India, were the ones that consumed glyphosate-based products the most. At the same time, the United States accounted for more than 25% of all glyphosates marketed. The estimate is that in 2020, the demand for this herbicide is worldwide, which exceeds one ton [17].

The discovery of glyphosate occurred in 1950, and this acid was an interesting complexion agent, a pH reducer, a detergent, and several other applications [18]. The glyphosate molecule was invented by the Cilag/Ciba industry in Switzerland, during the process of selection of chelating compounds for paints. In the mid-1960s, some scientists at Stauffer discovered other chelating properties of glyphosate. However, only in the early 1970s did Monsanto scientists discover the herbicide properties of glyphosate. Two decades after it began to be marketed, there were

*Multifunctionality and Impacts of Organic and Conventional Agriculture*

*Commercialization of classes of pesticides used in Brazil. Source: SINDIVEG [13].*

(**Figure 8**). The consumption of pesticides in the Midwest increased in the 1970s and 1980s due to the occupation of the Cerrados and the cultivation of soybean, cotton, corn, and sugarcane continues to increase in this region. The South region represents

Empty pesticide packaging, unlike any plastic packaging, cannot be reused for domestic uses. This is because the products are aggressive, i.e., harmful to human and animal health, and can cause contamination if reused. And due to the toxicity of pesticides, their handling requires extreme care, attention, and personal protective equipment, and empty containers cannot be disposed in the dumping ground due to the aforementioned eminent risks. Therefore, all pesticides that are marketed

26% of pesticide consumption, while in the Northeast region, it is only 9%.

in Brazil have empty packaging collected by the National Institute for Empty Packaging Processing (inpEV), which is responsible for the final destination of this

*Commercialization of pesticides used by crops in Brazil. Non-food crops: reforestation, pasture, floriculture, and tobacco. Fruits: citrus, apple, grape, melon and watermelon, banana, and others. Vegetables: potatoes, tomatoes, onions, garlic, and others. Grains: wheat, oats, rye, barley, and peanuts. Others: stored grains and* 

**8**

**Figure 7.**

*others. Source: SINDIVEG [13].*

material.

**Figure 6.**

#### **Figure 9.**

*Annual distribution of the quantity, in tons, of glyphosate in Brazil, from 2014 to 2017. Source: IBAMA [15].*

more than 90 commercial products with this active equivalent [19]. Today, glyphosate is widely used and has become the most marketed herbicide in the world.

Due to its lack of selectivity, the use of glyphosate was initially limited to preplanting, directed jet, pre-harvest, and postemergence of weeds. With the introduction of glyphosate-resistant crops in the mid-1990s, it is now used for weed control in resistant crops without concerns about crop damage. Currently, glyphosate-resistant crops are grown in several countries, with great adoption in the United States, Canada, Argentina, and Brazil. The wide adoption of glyphosateresistant crops has caused changes in weed species in these crops and resulted in the evolution of resistant weeds [20].

Glyphosate is a nonselective herbicide (affecting all "natural" or non-transgenic plants), which has a broad spectrum, is systemic, and is applied in postemergence, belonging to the glycine-derived chemical group that has been widely used in the world in the last four decades [20].

The mechanism of action of glyphosate is the inhibition of the enzyme EPSPS and, consequently, the biosynthesis of aromatic amino acids, tryptophan, phenylalanine, and tyrosine [18, 20], and precursors of compounds such as lignins, flavonoids, and benzoic acids [21]. This leads to several metabolic disorders, inhibiting the biosynthesis of proteins and secondary products and generating a significant increase in the concentration of shikimate, a common precursor in the metabolic route of the three amino acids (**Figure 10**) [22]. Glyphosate inhibits the enzyme EPSPS by competing with the phosphoenolpyruvate (PEP) substrate, preventing shikimate from being transformed into chorismate. The synthesis of the enzyme EPSPS occurs in the cytoplasm, which is transported to the chloroplast where it operates; glyphosate binds to it by glutamic acid carboxylic (glutamine) at position 418 of the amino acid sequence. The final action of the herbicide is not explained by the reduction of amino acids and the accumulation of shikimate. It is believed that the deregulation of the shikimic acid route causes the loss of carbons available for other cellular reactions in the plant, once 20% of plant carbon is used in this metabolic route, because tryptophan, phenylalanine, and tyrosine are forerunners of most aromatic compounds in plants. Glyphosate causes the reduction of phytoalexin synthesis. There is an increased concentration in toxic levels of nitrate, ethylene, kinetic acid, and other compounds that accelerate plant death [22].

**11**

**Figure 11.**

*Chemical structure of glyphosate.*

*Current Approaches to Pesticide Use and Glyphosate-Resistant Weeds in Brazilian Agriculture*

The dose of glyphosate used depends on the species that will be controlled

*Glyphosate acts by inhibiting the enzyme 5-enolpyruvylshikimate-3-phosphate synthase in the shikimate pathway, blocking the production of tryptophan, phenylalanine, or tyrosine. Source: Adapted from Helander* 

a period of 4–6 h without rain is necessary to increase the efficiency. After being treated with this herbicide, the plants die between 7 and 14 days. For absorption to be facilitated, it should be used in low flow and larger drops. The yellowing of meristems is a symptom in plants that can lead to necrosis and then to death in days

Glyphosate presents the molecular formula C3H8NO5P (molecular weight = 169.1

replaced glycine. The glyphosate structure is presented in **Figure 11**.

) [24]. This herbicide can be formulated as isopropylamine salt, ammonium salt, or trimethylsulfonic salt [25] (sulfate) [19]. The chemical glyphosate group is a

. After application of this herbicide,

*DOI: http://dx.doi.org/10.5772/intechopen.91872*

and can range from 0.18 to 2.16 kg a.e. ha<sup>−</sup><sup>1</sup>

**4. Physicochemical properties of glyphosate**

or weeks [21].

**Figure 10.**

*et al. [23].*

g mol<sup>−</sup><sup>1</sup>

*Current Approaches to Pesticide Use and Glyphosate-Resistant Weeds in Brazilian Agriculture DOI: http://dx.doi.org/10.5772/intechopen.91872*

#### **Figure 10.**

*Multifunctionality and Impacts of Organic and Conventional Agriculture*

more than 90 commercial products with this active equivalent [19]. Today, glyphosate is widely used and has become the most marketed herbicide in the world. Due to its lack of selectivity, the use of glyphosate was initially limited to preplanting, directed jet, pre-harvest, and postemergence of weeds. With the introduction of glyphosate-resistant crops in the mid-1990s, it is now used for weed control in resistant crops without concerns about crop damage. Currently, glyphosate-resistant crops are grown in several countries, with great adoption in the United States, Canada, Argentina, and Brazil. The wide adoption of glyphosateresistant crops has caused changes in weed species in these crops and resulted in the

*Annual distribution of the quantity, in tons, of glyphosate in Brazil, from 2014 to 2017. Source: IBAMA [15].*

Glyphosate is a nonselective herbicide (affecting all "natural" or non-transgenic plants), which has a broad spectrum, is systemic, and is applied in postemergence, belonging to the glycine-derived chemical group that has been widely used in the

The mechanism of action of glyphosate is the inhibition of the enzyme EPSPS and, consequently, the biosynthesis of aromatic amino acids, tryptophan, phenylalanine, and tyrosine [18, 20], and precursors of compounds such as lignins, flavonoids, and benzoic acids [21]. This leads to several metabolic disorders, inhibiting the biosynthesis of proteins and secondary products and generating a significant increase in the concentration of shikimate, a common precursor in the metabolic route of the three amino acids (**Figure 10**) [22]. Glyphosate inhibits the enzyme EPSPS by competing with the phosphoenolpyruvate (PEP) substrate, preventing shikimate from being transformed into chorismate. The synthesis of the enzyme EPSPS occurs in the cytoplasm, which is transported to the chloroplast where it operates; glyphosate binds to it by glutamic acid carboxylic (glutamine) at position 418 of the amino acid sequence. The final action of the herbicide is not explained by the reduction of amino acids and the accumulation of shikimate. It is believed that the deregulation of the shikimic acid route causes the loss of carbons available for other cellular reactions in the plant, once 20% of plant carbon is used in this metabolic route, because tryptophan, phenylalanine, and tyrosine are forerunners of most aromatic compounds in plants. Glyphosate causes the reduction of phytoalexin synthesis. There is an increased concentration in toxic levels of nitrate, ethylene, kinetic acid, and other compounds that accelerate plant death [22].

evolution of resistant weeds [20].

**Figure 9.**

world in the last four decades [20].

**10**

*Glyphosate acts by inhibiting the enzyme 5-enolpyruvylshikimate-3-phosphate synthase in the shikimate pathway, blocking the production of tryptophan, phenylalanine, or tyrosine. Source: Adapted from Helander et al. [23].*

The dose of glyphosate used depends on the species that will be controlled and can range from 0.18 to 2.16 kg a.e. ha<sup>−</sup><sup>1</sup> . After application of this herbicide, a period of 4–6 h without rain is necessary to increase the efficiency. After being treated with this herbicide, the plants die between 7 and 14 days. For absorption to be facilitated, it should be used in low flow and larger drops. The yellowing of meristems is a symptom in plants that can lead to necrosis and then to death in days or weeks [21].

## **4. Physicochemical properties of glyphosate**

Glyphosate presents the molecular formula C3H8NO5P (molecular weight = 169.1 g mol<sup>−</sup><sup>1</sup> ) [24]. This herbicide can be formulated as isopropylamine salt, ammonium salt, or trimethylsulfonic salt [25] (sulfate) [19]. The chemical glyphosate group is a replaced glycine. The glyphosate structure is presented in **Figure 11**.

**Figure 11.** *Chemical structure of glyphosate.*

Under environmental conditions, both glyphosate and its salts are crystalline solids, which have high solubility in water (12 g L<sup>−</sup><sup>1</sup> to 25°C, for glyphosate) and are practically insoluble in common organic solvents such as acetone and ethanol. Glyphosate melts at 189.5°C and has an apparent density of 0.5 g cm<sup>−</sup><sup>3</sup> and presents significant water solubility in the presence of light, including at temperatures above 60°C [24]. **Table 1** shows the physicochemical properties of glyphosate.

As shown in **Table 1**, glyphosate has high Sw and pKa values with acid character and a low Kow value, indicating that glyphosate has a great hydrophilic tendency, which decreases soil sorption. However, glyphosate quickly binds to positive soil charges (mainly in clays) such as in soils abundant in iron and aluminum oxides. This indicates high values of sorption coefficient normalized by soil organic carbon (OC) (Koc) than other herbicides, limiting their leaching in the soil profile [27].

The pKa values found in the literature for glyphosate are pKa1, 0.8; pKa2, 2.16; pKa3, 5.46; and pKa4, 10.14. These dissociation constants indicate the degree of dissociation of the herbicide as a function of pH [24]. This shows the relationship between the amount of matter that exists after a certain reagent has been consumed and the amount of material that exists initially.

At pH values below 0.8, most glyphosate is found in a protonation on the amine site. In a pH of 0.8, being the value of the first constant, 50% of the molecules present this protonation and the other 50% with a dissociation in the phosphate group. From this value up to pH of 2.2, the molecular formula is predominant, with a dissociation (▬PO2H▬) and a protonation (▬NH2 + ▬), and in a pH of 2.2, 50% of the compound will have dissociation despite maintaining protonation in the amine group. Among the pH values of 2.2 and 5.4, the predominant form of the herbicide


**13**

*Current Approaches to Pesticide Use and Glyphosate-Resistant Weeds in Brazilian Agriculture*

of glyphosate. Above pH = 11, the glyphosate is fully dissociated [24].

is with two dissociations, thus having 50% of the molecules with three pH dissociations of 5.5. In a pH ranging from 5.5 to 10.2, there are three and four dissociations

Amino acids and their derivatives present a zwitterionic behavior, that is, in its structure the carboxylic acid has a more acidic characteristics than the ammonium group. In glyphosate, phosphate and carboxylic groups have a greater acidic characteristics than the ammonium group. Cikalo et al. [28] observed the zwitterionic behavior of glyphosate when describing its dissociation. Thus, in the first dissociation of glyphosate, it would lose hydrogen linked to oxygen and only in the last

The occurrence of weed resistance to herbicides is a natural and inheritable capacity of certain biotypes within a given population to develop and reproduce after being exposed to herbicide doses that would be lethal to a normal population of the same species. This resistance is from an evolutionary process, occurring naturally at low frequency, and the selection pressure exerted by repetitive application of some herbicide or different types of herbicides that have the same mechanism of action increases the number of resistant individuals in the population. Herbicide resistance is identified when, generally, 30% of the plants are

Several weed species are inherently more resistant to glyphosate than others. A biotype of glyphosate resistance that occurred naturally was the *Convolvulus arvensis* without reporting the use of glyphosate [20]. A biotype of *Lotus corniculatus* resistant to glyphosate doses was identified by Boerboom et al. [30]. The natural resistance to this herbicide, these and other species, was not a problem until the emergence of glyphosate-resistant crops. With the adoption of these crops, many species became problematic because they occupied places where other weed species

Biotypes that have glyphosate resistance have been selected in crops such as corn, soybeans, and various orchards. In Brazil, glyphosate-resistant biotypes of *Conyza bonariensis* [31], *Conyza canadensis* [32, 33], *Conyza sumatrensis* [34], *Lolium multiflorum* [35, 36], *Digitaria insularis* [9, 37], *Chloris elata* [38], *Eleusine indica* [39], *Amaranthus palmeri* [40], and more recently *Amaranthus hybridus* [41] and

Due to the increase in the adoption of glyphosate-resistant crops, there was a great difficulty in selecting the herbicide to be used in weed populations in the past decade. The alternating herbicides that have different modes of action or herbicides mixed in tanks are recommended in resistance management programs; however, this is often ignored by farmers, because the cost to control weeds only with glypho-

It is recommended that a rotation be made between cultivating glyphosateresistant crops and nonresistant crops, so that the development of glyphosate resistance in weeds is delayed. However, the correct use of glyphosate with other herbicides, a survey of the weed population, extension of the area, and economy of producers are important factors in the management of weeds in glyphosate-

**Figure 12** shows all the species of glyphosate-resistant weeds worldwide. The first case of reported resistance was in 1996 of the species *Lolium rigidum* in Victoria, Australia. In Brazil, the first case of glyphosate-resistant weed identified was in 2003, which was the species *Lolium perenne* ssp. *multiflorum*. In 2019, four

did not inhabit and glyphosate-resistant crops were cultivated [20].

*DOI: http://dx.doi.org/10.5772/intechopen.91872*

dissociation that hydrogen linked to nitrogen.

**5. Glyphosate-resistant weeds in Brazil**

*Euphorbia heterophylla* [42] were identified.

resistant [29].

sate is much cheaper.

resistant crops [20].

#### **Table 1.** *Physicochemical properties of glyphosate.*

#### *Current Approaches to Pesticide Use and Glyphosate-Resistant Weeds in Brazilian Agriculture DOI: http://dx.doi.org/10.5772/intechopen.91872*

is with two dissociations, thus having 50% of the molecules with three pH dissociations of 5.5. In a pH ranging from 5.5 to 10.2, there are three and four dissociations of glyphosate. Above pH = 11, the glyphosate is fully dissociated [24].

Amino acids and their derivatives present a zwitterionic behavior, that is, in its structure the carboxylic acid has a more acidic characteristics than the ammonium group. In glyphosate, phosphate and carboxylic groups have a greater acidic characteristics than the ammonium group. Cikalo et al. [28] observed the zwitterionic behavior of glyphosate when describing its dissociation. Thus, in the first dissociation of glyphosate, it would lose hydrogen linked to oxygen and only in the last dissociation that hydrogen linked to nitrogen.
