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Mejuto, J. Glyphosate-Resistant Weeds. Encyclopedia. Available online: (accessed on 20 April 2024).
Mejuto J. Glyphosate-Resistant Weeds. Encyclopedia. Available at: Accessed April 20, 2024.
Mejuto, Juan. "Glyphosate-Resistant Weeds" Encyclopedia, (accessed April 20, 2024).
Mejuto, J. (2021, March 02). Glyphosate-Resistant Weeds. In Encyclopedia.
Mejuto, Juan. "Glyphosate-Resistant Weeds." Encyclopedia. Web. 02 March, 2021.
Glyphosate-Resistant Weeds

Agro-industries should adopt effective strategies to use agrochemicals such as glyphosate herbicides cautiously in order to protect public health. This entails careful testing and risk assessment of available choices, and also educating farmers and users with mitigation strategies in ecosystem protection and sustainable development.

glyphosate use resistant weeds AMPA cancer risks herbicide research

1. Introduction

Glyphosate (N-phosphonomethylglycine; Figure 1a) is an aminophosphonate. This compound is typically used as a broad-spectrum herbicide and is absorbed by plant leaves. Glyphosate, discovered in the 1970s, was registered in more than 130 countries [1], and the use of glyphosate-based herbicides increased 100 times since then [2]. Genetically engineered herbicide-tolerant (GEHT) crops have considerably facilitated weed management in cotton, soybean, and maize [3][4][5]. However, they have also caused the emergence of glyphosate-resistant weed phenotypes [3][4][5][6][7][8]. The incorporation of additional herbicides into spraying programs [6][7] has caused herbicide per hectare on crops with GEHT varieties to escalate in this century [5][8][9]. This upward trend is expected to result in heavier environmental loads and increased human exposure to herbicides, including glyphosate and its main metabolite, aminomethylphosphonic acid (AMPA; Figure 1b), and to the adjuvants contained in its formulations. Weed management should face resistance before it happens [10]. It is key to promote changing crops or crop rotations against herbicide resistant (HR) weeds with effective herbicides [11]. Non-herbicidal alternatives (natural products, selective herbicides, mechanical controls, etc.) need to be added to satisfy the reduced efficacy of herbicides [12].

Figure 1c shows the degradation pathway for glyphosate in soil [13]. Although leaching of glyphosate is very unlikely due to its high soil sorption, depending on the type of soil, it can move to ground and surface waters through leaching and runoff [14]. Human exposure to urban sources of glyphosate should be considered too. Although some nonselective (broad spectrum) herbicides for both urban and home use in emerging countries contain glyphosate at low levels—and pose little risk of acute toxic exposure as a result [15]—those used in developing countries contain higher levels of this compound, or are mixed without official control. Dietary exposure in areas lacking residue information can be assessed from data for areas where glyphosate use and residues have been accurately determined [16].

Figure 1. Structural formula of glyphosate (a) and AMPA –(aminomethyl)phosphonic acid– (b), together with degradation pathway for glyphosate in soil (c).

The glyphosate mechanism as herbicidal involves inhibition of 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), which interferes with phenylalanine, tyrosine, and tryptophan synthesis. Unlike plants and some microorganisms, mammals have no EPSPS, which is in principle an advantage safety-wise [17]. However, glyphosate herbicides are highly controversial in toxicological and environmental terms. This review, therefore, diagnoses on the use of glyphosate and the associated development of glyphosate-resistant weeds. It also deals with the risk assessment on human health of glyphosate formulations through environment and dietary exposures based on the impact of glyphosate and its metabolite AMPA on water and food. All this to setup further conclusions and recommendations on the regulated use of glyphosate and how to mitigate the adverse effects in the below selected sections.

2. Glyphosate-Resistant Weeds

The international database on herbicide resistance [18] contains more than 510 studies. The best resistance mainframe is based on prevention and on detection with regular appraisal of herbicides-treated fields [19]. There are various methods to detect resistance with tests in the field and with bioassays in greenhouses and laboratories [20]; for example, hybridization between A. palmeri and A. spinosus occurred with frequencies in the field studies ranging from <0.01% to 0.4%, and 1.4% in greenhouse crosses [21]. Non-target-site resistance (NTSR) to herbicides in weeds can be conferred as a result of the alteration of one or more physiological processes, including herbicide absorption, translocation, sequestration, and metabolism. The mechanisms of NTSR are generally more complex to decipher than target-site resistance (TSR) and can impart cross-resistance to herbicides with different modes of action. Metabolism-based NTSR has been reported in many agriculturally important weeds, although reduced translocation and sequestration of herbicides has also been found in some weeds [22][23]. Crossed resistance is when the plant developed resistance to an herbicide, which permits to resist herbicides with the same action mode [24]. Multiple resistance is when a plant has one or several mechanisms of resistance to herbicides with distinct action modes. The selection pressure of an herbicide is then capable to select resistant plant biotypes depending on the herbicide treatment type, its formulation, application frequency, and the biological characteristics of the weed and the crop [25][26][27][28]. Examples of glyphosate-resistant weeds and their locations can be found in Table 1.

Table 1. Example of glyphosate-resistant weeds and their locations, extended from reference [29].



Amaranthus palmeri

United States

Amaranthus tuberculatus

United States

Ambrosia artemissifolia

United States

Ambrosia trifida

United States

Conyza bonariensis

United States, Brazil,


Conyza canadensis

United States

Euphorbia heterophylla


Lolium perenne

United States,



Sorghum halepense

United States,


The problem is compounded by non-target site multiple resistances in grasses, as is the case of Lolium rigidum and Alopecurus myosuroides [12][26]. In addition, the growing expansion of multiple resistance to broadleaf weeds is bound to worsen things in the future. Managing non-target site resistance is difficult owing to the many unpredictable resistance patterns against which rotating herbicide sites of action may be ineffective. Herbicides are the main means for weed control in developed countries, but they should be used more sustainably [30]. This entails not only using improved herbicide mixtures and rotations, but still adopting intensive integrated weed management programs including effective mechanical and cultural strategies [31]. A pressing need therefore exists for economic incentives to the search for new, safer, and more effective herbicides [4].

Developing herbicide-resistance crop traits may grant the use of old herbicides in new ways through tailored mixtures efficiently avoiding multiple resistance [32][33]. Indeed, the use of different genetic engineering techniques as RNA interference (RNAi) [3][32][34][35][36][37][38], chimeric RNA/DNA oligonucleotides [39], and gene-editing techniques (GM), such as CRISPR/Cas9 or CRISPR/Cpf1 [40][41][42][43][44][45][46][47][48] technology, might be useful for this purpose. The best approach to prevent resistant weeds is to use a combined weed management, and herbicides will likely be partly replaced with new technologies such as, among others, research on crop allelopathy [49][50][51][52][53][54][55][56] and engineering of microbial control agents [57][58][59][60][61]. Progress in these technologies is expected to allow methods for weed control to be used in an integrated manner with the aim of maximizing diversity in weed control and minimizing resistance. Applying evolutionary principles to agricultural settings is essential to properly understand the system-wide effects of herbicide selection intensity [62]. Although the main driver of herbicide resistance is the selection pressure of management, further knowledge of the scientific bases of herbicide resistance at the genetic and cellular levels needs to be developed [63][64][65][66][67]. The causes and dynamics of resistance expansion might be elucidated by assessing the flexibility of certain alleles involved in herbicide resistance [68]. The capability of resistant weeds to prevail, replicate, and selectively infest habitats depends on the degree of vigour of the particular resistant gene [69]. The effects of the environment on resistant plants in cropping conditions could thus reduce the heritability and frequencies of resistance alleles with time [70].

Research in this field should also address the effects of climate change on the expansion of herbicide resistance. According to Renton [71], spatially computational models could be of help in this context by providing powerful indicators on how genetics, plant biology, population structure, environmental conditions, and management strategies connect to shape weed resistance dynamics. The use of scarcely diverse practices drove to a fast increment in multiple-resistance weeds with upgraded abilities for herbicide metabolism worldwide [72]. Elucidating herbicide metabolic pathways could help re-classify and re-rank the risks of herbicide resistance and hence enable the adoption of more effective herbicide rotations, such as those based on both site of action and metabolic pathway. Processes associated with climatic changes, such as elevated temperatures, can strongly affect weed control efficiency. For example, responses of several grass weed populations to herbicides that inhibit acetyl-CoA carboxylase (ACCase) were examined under different temperature regimes [73].

Mitigation Strategies

Weed resistance management has three planks: rotate modes of action to reduce selection pressure, incorporate non-chemical practices and control weed seed set, together with asexual reproduction (rhizomes, stolons, etc.). Effective weed control needs to discern weeds biology, prevents with weed seed production, plant into weed-free fields, grow weed-free seed, and inspect lands regularly. There is also a need to adopt numerous herbicide action mechanisms active versus damaging weeds, spread herbicide estimate at selected weed extents, and highlight growing conditions that put an end to weeds by crop competition. Further, it is useful to practice mechanical and biological executive strategies, avoid field-to-field and within-field migration of weed vegetative propagules, regulate weed seed to avoid a reinforcement of the weed seed-stock, and preclude an invasion of weeds into land by controlling ground boundaries. All these diverse approaches to managing herbicide resistance need to be incorporated into weed management [74][75][76][77][78].

This will be beneficial in managing resistance in the long term, together with mathematical simulations proving that mixtures magnify herbicide efficacy, choice array of soil-applied herbicides, and postpone herbicide resistance growth in weeds. It shows than extension efforts rotating herbicide mixtures give vision to guide the progression of weed resistance [69]. Multiple modes of action (MOAs) for weed control are important for managing herbicide resistance and enabling no-till farming practices that help to sequester greenhouse gases, but discovering new herbicide MOAs has been a challenge for the industry [76].

According to the International Assessment of Agricultural Knowledge, Science and Technology for Development [79] (IAASTD, 2008), agricultural development has focused on increasing farm-level yield, more than on consolidating effects on biodiversity and the liaison of agriculture with climate change. Increased attention needs to be directed to build up soil fertility and to sustain agricultural production, with a focus also on protection of biodiversity. Agro-ecology refers to treating agricultural ecosystems as ecosystems, and can enable a successful transition to more sustainable farming and food systems [80].

Moreover, in recent decades, studies were performed looking for alternatives to glyphosate. There is a rise in efficacy tests using different natural (or even modified) allelo-chemicals obtained from essential oils for pest-control [81][82][83][84][85][86][87][88][89][90][91][92][93][94][95][96], as well as in their use as herbicides [97][98][99][100][101][102][103][104][105][106][107][108][109][110][111][112].


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