Next Article in Journal
Analysis of Competitiveness in Agri-Supply Chain Logistics Outsourcing: A B2B Contractual Framework
Previous Article in Journal
More Is More? The Inquiry of Reducing Greenhouse Gas Emissions in the Upstream Petroleum Fields of Indonesia
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Overview of Environmental and Health Effects Related to Glyphosate Usage

by
Tomas Rivas-Garcia
1,*,
Alejandro Espinosa-Calderón
2,
Benjamin Hernández-Vázquez
1 and
Rita Schwentesius-Rindermann
3,*
1
Rural Sociology Department, CONACYT-Chapingo Autonomous University, Texcoco 56230, Mexico
2
Experimental Site Mexico’s Valley-National Institute of Agricultural and Livestock Research (INIFAP), Texcoco 56230, Mexico
3
Interdisciplinary Research Center for Integral Rural (CIIDRI), Chapingo Autonomous University, Texcoco 56230, Mexico
*
Authors to whom correspondence should be addressed.
Sustainability 2022, 14(11), 6868; https://doi.org/10.3390/su14116868
Submission received: 20 April 2022 / Revised: 31 May 2022 / Accepted: 2 June 2022 / Published: 4 June 2022

Abstract

:
Since the introduction of glyphosate (N-(phosphomethyl) glycine) in 1974, it has been the most used nonselective and broad-spectrum herbicide around the world. The widespread use of glyphosate and glyphosate-based herbicides is due to their low-cost efficiency in killing weeds, their rapid absorption by plants, and the general mistaken perception of their low toxicity to the environment and living organisms. As a consequence of the intensive use and accumulation of glyphosate and its derivatives on environmental sources, major concerns about the harmful side effects of glyphosate and its metabolites on human, plant, and animal health, and for water and soil quality, are emerging. Glyphosate can reach water bodies by soil leaching, runoff, and sometimes by the direct application of some approved formulations. Moreover, glyphosate can reach nontarget plants by different mechanisms, such as spray application, release through the tissue of treated plants, and dead tissue from weeds. As a consequence of this nontarget exposure, glyphosate residues are being detected in the food chains of diverse products, such as bread, cereal products, wheat, vegetable oil, fruit juice, beer, wine, honey, eggs, and others. The World Health Organization reclassified glyphosate as probably carcinogenic to humans in 2015 by the IARC. Thus, many review articles concerning different glyphosate-related aspects have been published recently. The risks, disagreements, and concerns regarding glyphosate usage have led to a general controversy about whether glyphosate should be banned, restricted, or promoted. Thus, this review article makes an overview of the basis for scientists, regulatory agencies, and the public in general, with consideration to the facts on and recommendations for the future of glyphosate usage.

1. Introduction

Since its introduction in 1974, glyphosate (N-(phosphonomethyl) glycine)—the active ingredient in the commercial Roundup® and RangerPro® products—has been the most used nonselective and broad-spectrum herbicide around the world [1]. Chemically, it is formulated as ammonium, di-ammonium, dimethyl ammonium, potassium, and iso-propylamine salts [2]. The glyphosate-based herbicides (GBHs) are also formulated with adjuvants (such as the polyoxyethylene amine (POEA), alkyl polyglycolide, polyethylene alkyl ether phosphates, and quaternary ammonium compounds) as surfactants to promote the uptake and translocation of the active ingredient in plants [3,4]. It is an organophosphate molecule that contains –PO3H2, –COOH, and –NH2 as the functional groups [5].
Glyphosate acts by inhibiting the enzyme 5-enol-pyruvyl-shikimate-3-phosphate synthase (EPSPS) (EC. 2.5.1.19) with the interruption of aromatic amino acid biosynthesis in the shikimate pathway [6]. These inhibited amino acids are essential for protein and secondary-metabolite biosynthesis, such as that of flavonoids, lignin, and phytoalexins [7]. Moreover, the shikimate-pathway interruption affects the carbon flow and fixation to produce energy, and the whole metabolism function [8]. Because the shikimate pathway is not present in mammals, it could be a desirable herbicide. Unfortunately, this pathway is also present in some fungi and bacteria that are present in diverse microbiota (i.e., gut, soil, and plant-surface microbiota) [9,10].
GBHs are traditionally applied at high concentrations (6.7–8.9 kg ha−1) and low concentrations (0.53–1.0 kg ha−1), respectively, before and after the establishment of conventional crops [11]. They have also been used to control invasive vegetation in forestry [12], algae proliferation in aquaculture [13], and invading weeds around perennial trees [14]. They have been used too for weed control in home gardens, parks, and across urban areas [15]. The global use of glyphosate and GBHs rose from 56, 296 tons in 1994 to 825, 804 tons in 2014, with an estimation of 740–920 thousand tons in 2025 [16].
The widespread use of glyphosate and GBHs in agricultural fields and home gardens is due to their low-cost efficiency in killing weeds, their rapid absorption by plants, and the general erroneous perception of their low toxicity and slow generation of herbicide resistance [6]. The commercialization of the first glyphosate-resistant soybean (Glycine max) variety (Roundup Ready) in 1996, and subsequent resistant-tolerant varieties of maize (Zea mays), canola (Brassica napus), and cotton (Gossypium hirsutum), have resulted in the increased commercialization and dose administration of GBHs [17]. Currently, the use of glyphosate and GBHs is widespread around the world in developed and developing countries [18]. Next-generation resistant varieties to glyphosate are encoded to produce a glyphosate oxidase enzyme to convert glyphosate into aminomethyl phosphonic acid (AMPA) and glyoxylate [19]. Despite this, the residue persistence of glyphosate and AMPA are determined by factors such as the soil properties and environmental conditions [20]. Moreover, after 46 years of glyphosate-based product application, approximately 38 different glyphosate-resistant (GR) weed species have been reported [21]. Several studies show that the half-lives of glyphosate and AMPA range between 0.8 and 151 and 10 and 98 days, respectively [1].
As a consequence of the intensive use and accumulation of glyphosate and GBHs on environmental sources and food [22], major concerns about the harmful side effects of glyphosate and AMPA on human, plant, and animal health, and on water and soil quality, are emerging [6]. Moreover, the glyphosate residues in the effluents are too difficult to purify, and, thus, they have a long-term life in water and soils [23]. Exposure to glyphosate and AMPA has been shown to induce antibiotic resistance in Salmonella spp. and Escherichia coli, and in soil bacteria in general [24]. Toxicity to honeybees, birds, amphibians, fishes, and others, has also been documented [25,26,27,28]. Moreover, reports indicate that exposure to GBHs, even at below the indicated concentrations, causes tumorigenic, carcinogenic, teratogenic, hepatorenal, and endocrine disruption effects, in addition to oxidative stress [29].
Since the World Health Organization reclassified glyphosate as probably carcinogenic (Group 2A) to humans in 2015 by the IARC [30,31,32], many review articles concerning different glyphosate-related aspects and its controversy have been published [16,33,34,35,36]. Recently, the use of GBHs has been restricted or banned in many countries, including Germany, Italy, France, the Netherlands, Belgium, the Czech Republic, Denmark, the United Arab Emirates, Bermuda, Qatar, Costa Rica, and Mexico [34,37,38]. By contrast, regulatory authorities, such as the European Commission, the United States Environmental Protection Agency (U.S. EPA), and the Canadian Pest Management Regulatory Agency, reviewed the matter and concluded that glyphosate and GBHs are safe and do not pose adverse effects to human health [38,39]. These disparities have led to a general controversy and different regulatory laws around the world, ranging from complete bans to unrestricted policies [40].
The risks, disagreements, and concerns regarding glyphosate usage have generated controversy about whether glyphosate, the most used nonselective and broad-spectrum herbicide around the world, should be banned, restricted, or promoted. There is a need for an overview with a risk assessment for scientists, regulatory agencies, and the public in general that considers the facts and recommendations about the future of glyphosate usage. Therefore, in this review article, two topics are summarized: (1) the environmental impact of glyphosate; and (2) the health effects of glyphosate.

2. Environmental Impact of Glyphosate

2.1. Behavior and Fate of Glyphosate

After its administration, glyphosate can biotransform in soil by mineralization, immobilization, or leaching; however, it cannot be significantly volatilized because of its high vapor pressure (Figure 1) [38]. Mineralization is the principal mechanism of degradation, involving biotic and abiotic pathways, with AMPA as the major metabolite, as well as other products, such as methyl phosphonic acid [CH3P(OH)2], sarcosine (C3H7NO2), glycine, phosphate (PO43−), carbon dioxide (CO2), and ammonia (NH3) [41,42]. The microbial activity that promotes glyphosate mineralization depends on factors such as the soil physicochemical characteristics, temperature, pH, and organic-matter content [43]. Thus, high levels of organic C and organic matter tend to be beneficial to the environment by delaying leaching and promoting their slow degradation and release in soil [44]. Nonetheless, excessive glyphosate depositions could saturate the soil capacity to delay leaching and its gradual mineralization [45]. Some metals in the soil, such as manganese oxide (MnO2), promote the abiotic degradation of glyphosate [46].
Glyphosate and AMPA mineralization are related to many soil physicochemical factors, and they too can be variable in short periods under certain specific circumstances [47]. After revision, Bai and Ogbourne [1] concluded that the half-lives of glyphosate and AMPA residues vary between 0.8 and 151 and 10 and 98 days, respectively. The degradation of glyphosate through mineralization is directly affected by the physicochemical properties of soil (organic-matter content, pH, and texture), climatic conditions (temperature and humidity), and biological properties (microbial diversity and activity) [20,48]. Thus, glyphosate and AMPA exhibit from low to very high persistence in soil (Table 1).
As mentioned before, glyphosate may biotransform in soil by immobilization and leaching. Glyphosate immobilization occurs naturally rapidly, and it is affected by the organic matter, mineral availability, clay, and phosphate concentration [54]. Thus, glyphosate will accumulate for a long time in soils with high organic matter, phosphate, clay content, Al and Fe concentrations, and low pH, and it is easily leached under the opposite conditions [55]. The phosphonic acid structure of glyphosate binds with the cations contained in clay structures and organic matter in soil [54]. Soil minerals such as Al and Fe in the oxide state have strong chemical affinities with the phosphonate, amino, and carboxyl groups of glyphosate, while inorganic phosphorus binds competitively to its sorption sites [56]. Glyphosate acts as a polyprotic acid that binds anions and cations at 4–8 pH in soils [57]. The immobilization in the soil is not a permanent process, and it decreases after a certain period [58].
Despite glyphosate being immobilized by high soil affinity, factors such as the concentration, prevalence, and mineralization rate are determinants for its leaching [55,59]. Rainfall and the soil structure are determinants for leaching too [60]. Glyphosate can reach the water sediment or water surface either in dissolved or particle form [38]. Leaching is a growing concern because it contaminates the water [16]. Glyphosate is also introduced to water bodies by runoff, but rarely by its direct application (i.e., unwanted seaweed control) [61]. Because AMPA is more mobile, it is found in higher concentrations by leaching [62]. AMPA is also a degradation product of the sweetener acesulfame; nonetheless, the leached AMPA in water bodies is related to glyphosate residues [63].

2.2. Glyphosate Residuality

Glyphosate and GBH application has been rising considerably since the late 1970s because of the false belief in their low toxicity and mobility in the environment, and after the introduction of genetically modified corn, soybean, and cotton [64]. Glyphosate is the most used (>100 crops) and sealed (>130 countries) herbicide around the world [16]. A consequence of the intensive use of glyphosate and AMPA is being detected in the residuality of soil, water, and nontarget plants [1].
Glyphosate and AMPA can appear residually at the cropping site and around it [22]. The principal effects of their residuality are the toxicity to soil microbial communities and the reduction in nutrient availability [65]. Microbial communities have essential functions, such as improving the soil structure and making nutrients available to plants [66]. Nonetheless, their activity is regulated by nematodes that feed them [67]. Because of such importance, microbial communities and nematodes are proposed as indicators of soil quality and health [68]. In a coffee plantation with 22 years of glyphosate application, the soil nematode population was lower than that in a plantation with 7 years of no-glyphosate application [69]. However, glyphosate has not yet been conclusively implicated in the repercussions to nematodes per the current extent of the research [70,71,72]. The residuality of glyphosate antagonizes some enzymes in the soil, such as acid phosphomonoesterase (EC. 3.1.3.2), urease (EC. 3.5.1.5), β-glucosidase (EC. 3.2.1.21), and alcohol-dehydrogenase (EC. 1.1.1.1) [73].
As mentioned before, glyphosate and AMPA can reach water bodies by soil leaching, runoff, and sometimes by the direct application of some approved formulations [74]. AMPA could be present in water as the degradation product of detergents; nonetheless, AMPA detection by detergents always corresponds to specific sites, such as plant treatment effluents and stormwater discharge [75]. Glyphosate has been detected in many water bodies, ranging from 2 to 430 μg L−1 [22]. In sediment samples from the United States, the glyphosate concentrations ranged from 397 to 476 μg L−1 [76]. According to Wang et al. [77], the microbial degradation of glyphosate in water sediments is slower than in soil environments. Some aquatic species, such as fish and amphibians, could be affected by glyphosate concentrations over 400 μg L−1 [78]. The free fish species could be exposed via gills and dietary routes [79]. Amphibians are susceptible to glyphosate residues because of their dual life cycle (aquatic/terrestrial) [74]. Despite the studies that argue that glyphosate is not toxic to aquatic species [80,81], the growing evidence suggests the potential impact on aquatic environment species and human health [82,83,84]. It is important to consider that this can be mixture effects in the soil and water that are not usually taken into account by single-substance dosage studies.
Glyphosate can reach nontarget plants by different mechanisms [36]. Spray application is the primary route, with more than a 10% application rate to nontarget crops after application in crops such as soybean and cotton [85,86]. This spray drift caused distorted fruit in tomatoes, even at minor doses of lethal concentrations [36]. Another mechanism is the release of glyphosate through the tissues of treated plants, such as weeds [87]. Decaying plant matter from weeds is decomposed and absorbed by the soil, and, thus, some traces of glyphosate, available for both target and nontarget plants, are reincorporated by root absorption [36]. Moreover, glyphosate inactivates the EPSPS enzyme, which plays a key role in the synthesis of phenolic compounds that have a function in the plant defense mechanisms [88]. The pathogen’s colonization rate was increased in wheat and barley roots when glyphosate was administrated before planting [89]. Nontarget plants are affected indirectly by the alterations in the soil characteristics and their microbial communities, which affect nutrient availability and thus alter the plant defense physiology [36]. Other potential side effects on nontarget plants are root disruption and increasing fruit drop [90]. As a consequence of this nontarget exposure, glyphosate and AMPA residues are being detected in the food chains of diverse products, such as bread, cereal products, wheat, vegetable oil, fruit juice, beer, wine, honey, eggs, and others, at concentrations that range between 2.948 and 0.0005 mg kg−1 (Table 2) [91].

3. Health Effects of Glyphosate

After the EPSP inhibition by glyphosate application, the target plants suffer alterations in their physiology and die after 7–21 days [92]. Since the shikimic acid pathway is present in plants, fungi, and some microorganisms, but absent in animals such as mammals, this is the parameter that states that glyphosate is not toxic for animals, even after evidence of exposition and toxicology effects [38]. In mammals, glyphosate and AMPA are considered nontoxic because of their limited tissue and gastrointestinal absorption [39]. Nonetheless, GBHs have demonstrated their toxic effects on nontarget aquatic and terrestrial organisms [26,93,94]. Moreover, a considerable portion of the toxicity of GBHs is attributed to the surfactant POEA [4,93,95].

3.1. Human Health Effects

The increasing global use of GBHs has led to a concern about their residuality on water sources, nontarget plants such as food, and the environment. This human exposure promotes the absorption of residues through ingestion, inhalation, and dermal contact [96]. Residues of glyphosate and AMPA were detected in the urine of the general public from the United States (60–80% of sampled) and Europe (44% of sampled), with 2–3 and <1 µg L−1 means, respectively, and 233 and 5 µg L−1 maximum concentrations, respectively [97,98]. The human health effects of glyphosate and GBHs have been studied and documented (Figure 2) [29,99,100]. Nonetheless, there is a general lack of accord as to glyphosate and GBH health effects.
There are many laboratory-based studies that report the negative effects of glyphosate and GBHs on human cells. Generally, the variation in the results relies on many variables, such as the methodology, dose and exposure time, GBH formulation, and cell type (Table 3) [29]. Despite the inconclusive and sometimes contradictory results on human health, the summarized results are a base statement for future decisions about glyphosate and GBH toxicological effects.
Despite the recognized residuality of glyphosate and AMPA (0.8–151 and 10–98 days, respectively) in the environment [125], it is difficult to predict the significance and the impact of these residues when there are not enough long-term and independent data related to their safety, health, and toxicity. Nonetheless, some epidemiological studies with concluding correlations between glyphosate and/or GBH exposure and health problems, such as cancer, respiratory disease, neurological and congenital effects, and others, have been reported.
In terms of epidemiological cancer studies, Leon et al. [126] conclude that there exists a moderate correlation between glyphosate exposure and β-cell cancer lymphoma. Besides direct exposition and ingestion, glyphosate could be inhaled from the air environment [1]. It is important to mention that the air exposure that was evaluated by Leon et al. [126] was about five times less than the acceptable daily intake proposed by the EFSA [39]. The results by Hoppin et al. [127] show a connection between glyphosate exposure and allergic and nonallergic wheeze in male farmers. Recently, some studies have evaluated the neurological effects of glyphosate exposure [128,129]. Caballero et al. [128] found a 33% higher risk of Parkinson’s disease mortality after glyphosate exposure. Von Ehrenstein et al. [129] conclude that there is a correlation between glyphosate prenatal exposure and autism spectrum disorder. During pregnancy, the fetus could be exposed indirectly to glyphosate; thus, Parvez et al. [130] used urine samples and concluded that >90% had glyphosate-detectable levels that were correlated with shortened pregnancy.
The toxicity of glyphosate and GBHs to different human cells has been demonstrated. However, most epidemiological studies lack glyphosate-administrated doses to directly confirm its effect. On the basis of the in vitro and epidemiological results, it is difficult to directly infer that glyphosate and GBHs pose a risk to human health and safety.

3.2. Health Effects on Other Organisms

Glyphosate and GBHs are perceived as a group of chemicals that are well regulated in their environmental risks and health effects on nontarget organisms [131]. Moreover, some research states that glyphosate is nontoxic or slightly toxic to different organisms [132,133,134,135]. However, numerous studies have demonstrated the toxicological effects of glyphosate and GBHs on a wide range of nontarget organisms. Glyphosate showed an adverse effect on unicellular organisms, such as Euglenia gracilis, where glyphosate at 3 × 10−3 M reduced the chlorophyll, photosynthesis, and respiration [136]. In rhizobium bacteria, glyphosate applied to glyphosate-resistant crops, such as soybean and corn, decreased the proliferation of Acidobacteria, which are implicated in biogeochemical processes related to nutrient acquisition [137]. In poultry microbiota, exposure to glyphosate affects the availability of some beneficial bacteria, such as Lactobacillus spp., Enterococcus faecium, Bifidobacterium adolescentis, and Bacillus badius [10].
Glyphosate also demonstrated negative effects on multicellular organisms found in soil and water. The population and radial growth of some mycorrhiza fungi, such as Cenococcum geophilum and Hebeloma longicaudum, were reduced after glyphosate exposure at concentrations of >5000 ppm [138]. Kittle and McDermid [139] conclude that glyphosate decreased the macroalgae chlorophyll content. As mentioned, nematodes are important for maintaining a healthy ecosystem in the soil. Dominguez et al. [135] demonstrated that AMPA decreased the bodyweight of juvenile nematodes. Zaller et al. [131] analyzed the effect of GBHs on the correlation between Lumbricus terrestris and mycorrhizal fungi. Arthropods are 90% of the animal kingdom, and they have an important function in the ecological balance and in human nutrition [140]. In the research, Daphnia magna and D. spinulata were treated with glyphosate and, after 48 h at 150 mg L−1, the organisms were immobilized [141]. The effect of glyphosate and POEA on crayfish (Cherax quadricarinatus) was evaluated after 50 days of exposure, and the results show a reduction in somatic-cell growth and a reduction in the muscle glycogen and lipid reserves [142].
Insects are invertebrates from the Arthropoda phylum, and they have also been affected by the use of glyphosate and GBHs. Three different concentrations of glyphosate (2.5, 5.0, and 10 mg L−1) were mixed in a sucrose solution, and the results show that glyphosate damaged the cognitive functions of bees (Apis mellifera) [143]. GBH was harmful to the larvae eggs of Trichogramma pretiosum [144]. The negative effects of glyphosate and GBHs have also been demonstrated in molluscs, such as aquatic snails (Pseudosuccinea columella) [145] and terrestrial snails (Helix aspersa) [146]. Glyphosate was also toxic to fish [147], amphibians [148], and birds [149].

4. Conclusions

Glyphosate is the most used nonselective and broad-spectrum herbicide around the world. Glyphosate and GBH application has been increasing considerably since the late 1970s because of the false belief in their low toxicity and mobility in the environment. As a consequence of their overuse, glyphosate and AMPA are being detected residually on soil, water, and nontarget plants, causing considerable negative side effects to the environment and to the health of humans and other organisms. This review article presents the state of the art on the environmental and health effects of GBHs, glyphosate, and its principal residue, AMPA. It can be concluded that the indiscriminate use of glyphosate and GBHs has led to documented effects on nontarget organisms. As a consequence of all the recent controversy, glyphosate and GBHs have been either restricted or banned. Nonetheless, further studies are needed on the side effects of glyphosate and GBHs on the environment, human health, and nontarget organisms to fill in the gaps in the knowledge. This general overview provides a risk assessment for scientists, regulatory agencies, and the public in general, with consideration to the facts on the glyphosate-usage risks.

Author Contributions

Conceptualization, T.R.-G.; investigation, T.R.-G. and B.H.-V.; resources, R.S.-R.; writing—original draft preparation, T.R.-G.; writing—review and editing, T.R.-G., B.H.-V., and R.S.-R.; supervision, A.E.-C. and R.S.-R.; funding acquisition, A.E.-C. and R.S.-R. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by Universidad Autonoma Chapingo (UACh), and Consejo Nacional de Ciencia y Tecnologia, grant number 319021.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Acknowledgments

The authors’ thanks to Luis Enrique Vazquez Robles and Guadalupe Godinez Bazán for their technical assistance.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Bai, S.H.; Ogbourne, S.M. Glyphosate: Environmental contamination, toxicity and potential risks to human health via food contamination. Environ. Sci. Pollut. Res. 2016, 23, 18988–19001. [Google Scholar] [CrossRef]
  2. Benbrook, C.M. Trends in glyphosate herbicide use in the United States and globally. Environ. Sci. Eur. 2016, 28, 3. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  3. Duke, S.O.; Powles, S.B. Glyphosate: A once-in-a-century herbicide. Pest Manag. Sci. 2008, 64, 319–325. [Google Scholar] [CrossRef] [PubMed]
  4. Mesnage, R.; Benbrook, C.; Antoniou, M.N. Insight into the confusion over surfactant co-formulants in glyphosate-based herbicides. Food Chem. Toxicol. 2019, 128, 137–145. [Google Scholar] [CrossRef]
  5. Ren, Z.; Dong, Y.; Liu, Y. Enhanced glyphosate removal by montmorillonite in the presence of Fe(III). Ind. Eng. Chem. Res. 2014, 53, 14485–14492. [Google Scholar] [CrossRef]
  6. Martinez, D.A.; Loening, U.E.; Graham, M.C. Impacts of glyphosate-based herbicides on disease resistance and health of crops: A review. Environ. Sci. Eur. 2018, 30, 2. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  7. Zabalza, A.; Orcaray, L.; Fernández-Escalada, M.; Zulet-González, A.; Royuela, M. The pattern of shikimate pathway and phenylpropanoids after inhibition by glyphosate or quinate feeding in pea roots. Pestic. Biochem. Physiol. 2017, 141, 96–102. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  8. Shaner, D.L.; Lindenmeyer, R.B.; Ostlie, M.H. What have the mechanisms of resistance to glyphosate taught us? Pest Manag. Sci. 2012, 68, 3–9. [Google Scholar] [CrossRef] [PubMed]
  9. Duke, S.O.; Lydon, J.; Koskinen, W.C.; Moorman, T.B.; Chaney, R.L.; Hammerschmidt, R. Glyphosate effects on plant mineral nutrition, crop rhizosphere microbiota, and plant disease in glyphosate-resistant crops. J. Agric. Food Chem. 2012, 60, 10375–10397. [Google Scholar] [CrossRef]
  10. Shehata, A.A.; Schrödl, W.; Aldin, A.A.; Hafez, H.M.; Krüger, M. The effect of glyphosate on potential pathogens and beneficial members of poultry microbiota in vitro. Curr. Microbiol. 2013, 66, 350–358. [Google Scholar] [CrossRef]
  11. Villamar-Ayala, C.A.; Carrera-Cevallos, J.V.; Vasquez-Medrano, R.; Espinoza-Montero, P.J. Fate, eco-toxicological characteristics, and treatment processes applied to water polluted with glyphosate: A critical review. Crit. Rev. Environ. Sci. Technol. 2019. [Google Scholar] [CrossRef]
  12. Rolando, C.; Baillie, B.; Thompson, D.; Little, K. The Risks Associated with Glyphosate-Based Herbicide Use in Planted Forests. Forests 2017, 8, 208. [Google Scholar] [CrossRef] [Green Version]
  13. Clements, D.; Dugdale, T.M.; Butler, K.L.; Florentine, S.K.; Sillitoe, J. Herbicide efficacy for aquatic Alternanthera philoxeroides management in an early stage of invasion: Integrating above-ground biomass, below-ground biomass and viable stem fragmentation. Weed Res. 2017, 57, 257–266. [Google Scholar] [CrossRef]
  14. Maqueda, C.; Undabeytia, T.; Villaverde, J.; Morillo, E. Behaviour of glyphosate in a reservoir and the surrounding agricultural soils. Sci. Total Environ. 2017, 593–594, 787–795. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  15. Okada, E.; Allinson, M.; Barral, M.P.; Clarke, B.; Allinson, G. Glyphosate and aminomethylphosphonic acid (AMPA) are commonly found in urban streams and wetlands of Melbourne, Australia. Water Res. 2020, 168, 115139. [Google Scholar] [CrossRef]
  16. Matozzo, V.; Fabrello, J.; Marin, M.G. The effects of glyphosate and its commercial formulations to marine invertebrates: A review. J. Mar. Sci. Eng. 2020, 8, 399. [Google Scholar] [CrossRef]
  17. Green, J.M. The rise and future of glyphosate and glyphosate-resistant crops. Pest Manag. Sci. 2018, 74, 1035–1039. [Google Scholar] [CrossRef] [PubMed]
  18. Brookes, G.; Taheripour, F.; Tyner, W.E. The contribution of glyphosate to agriculture and potential impact of restrictions on use at the global level. GM Crop. Food 2017, 8, 216–228. [Google Scholar] [CrossRef] [Green Version]
  19. Hearon, S.E.; Wang, M.; McDonald, T.J.; Phillips, T.D. Decreased bioavailability of aminomethylphosphonic acid (AMPA) in genetically modified corn with activated carbon or calcium montmorillonite clay inclusion in soil. J. Environ. Sci. 2021, 100, 131–143. [Google Scholar] [CrossRef] [PubMed]
  20. Bergström, L.; Börjesson, E.; Stenström, J. Laboratory and Lysimeter Studies of Glyphosate and Aminomethylphosphonic Acid in a Sand and a Clay Soil. J. Environ. Qual. 2011, 40, 98–108. [Google Scholar] [CrossRef] [Green Version]
  21. Heap, I.; Duke, S.O. Overview of glyphosate-resistant weeds worldwide. Pest Manag. Sci. 2018, 74, 1040–1049. [Google Scholar] [CrossRef]
  22. Van Bruggen, A.H.C.; He, M.M.; Shin, K.; Mai, V.; Jeong, K.C.; Finckh, M.R.; Morris, J.G. Environmental and health effects of the herbicide glyphosate. Sci. Total Environ. 2018, 616–617, 255–268. [Google Scholar] [CrossRef] [PubMed]
  23. Sun, M.; Li, H.; Jaisi, D.P. Degradation of glyphosate and bioavailability of phosphorus derived from glyphosate in a soil-water system. Water Res. 2019, 163, 114840. [Google Scholar] [CrossRef] [PubMed]
  24. Rainio, M.J.; Ruuskanen, S.; Helander, M.; Saikkonen, K.; Saloniemi, I.; Puigbò, P. Adaptation of bacteria to glyphosate: A microevolutionary perspective of the enzyme 5-enolpyruvylshikimate-3-phosphate synthase. Environ. Microbiol. Rep. 2021, 13, 309–316. [Google Scholar] [CrossRef] [PubMed]
  25. Delkash-Roudsari, S.; Chicas-Mosier, A.M.; Goldansaz, S.H.; Talebi-Jahromi, K.; Ashouri, A.; Abramson, C.I. Assessment of lethal and sublethal effects of imidacloprid, ethion, and glyphosate on aversive conditioning, motility, and lifespan in honey bees (Apis mellifera L.). Ecotoxicol. Environ. Saf. 2020, 204, 111108. [Google Scholar] [CrossRef]
  26. Gill, J.P.K.; Sethi, N.; Mohan, A.; Datta, S.; Girdhar, M. Glyphosate toxicity for animals. Environ. Chem. Lett. 2018, 16, 401–426. [Google Scholar] [CrossRef]
  27. Herek, J.S.; Vargas, L.; Trindade, S.A.R.; Rutkoski, C.F.; Macagnan, N.; Hartmann, P.A.; Hartmann, M.T. Can environmental concentrations of glyphosate affect survival and cause malformation in amphibians? Effects from a glyphosate-based herbicide on Physalaemus cuvieri and P. gracilis (Anura: Leptodactylidae). Environ. Sci. Pollut. Res. 2020, 27, 22619–22630. [Google Scholar] [CrossRef]
  28. Faria, M.; Bedrossiantz, J.; Ramírez, J.R.R.; Mayol, M.; García, G.H.; Bellot, M.; Prats, E.; Garcia-Reyero, N.; Gómez-Canela, C.; Gómez-Oliván, L.M.; et al. Glyphosate targets fish monoaminergic systems leading to oxidative stress and anxiety. Environ. Int. 2021, 146, 106253. [Google Scholar] [CrossRef]
  29. Agostini, L.P.; Dettogni, R.S.; dos Reis, R.S.; Stur, E.; dos Santos, E.V.W.; Ventorim, D.P.; Garcia, F.M.; Cardoso, R.C.; Graceli, J.B.; Louro, I.D. Effects of glyphosate exposure on human health: Insights from epidemiological and in vitro studies. Sci. Total Environ. 2020, 705, 135808. [Google Scholar] [CrossRef] [PubMed]
  30. European Food Safety Autthority (EFSA). Conclusion on the peer review of the pesticide risk assessment of the active substance glyphosate. EFSA J. 2015, 13, 107. [Google Scholar] [CrossRef]
  31. Guyton, K.Z.; Loomis, D.; Grosse, Y.; El Ghissassi, F.; Benbrahim-Tallaa, L.; Guha, N.; Scoccianti, C.; Mattock, H.; Straif, K.; Blair, A.; et al. Carcinogenicity of tetrachlorvinphos, parathion, malathion, diazinon, and glyphosate. Lancet Oncol. 2015, 16, 490–491. [Google Scholar] [CrossRef]
  32. International Agency for Research on Cancer (IARC). Evaluation of Five Organophosphate Insecticides and Herbicides. IARC Monographs Volume 112. Available online: https://www.iarc.who.int/news-events/iarc-monographs-volume-112-evaluation-of-five-organophosphate-insecticides-and-herbicides/ (accessed on 8 January 2021).
  33. Beckie, H.J.; Flower, K.C.; Ashworth, M.B. Farming without Glyphosate? Plants 2020, 9, 96. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  34. Kudsk, P.; Mathiassen, S.K. Pesticide regulation in the European Union and the glyphosate controversy. Weed Sci. 2020, 68, 214–222. [Google Scholar] [CrossRef]
  35. Antier, C.; Kudsk, P.; Reboud, X.; Ulber, L.; Baret, P.V.; Messéan, A. Glyphosate Use in the European Agricultural Sector and a Framework for Its Further Monitoring. Sustainability 2020, 12, 5682. [Google Scholar] [CrossRef]
  36. Kanissery, R.; Gairhe, B.; Kadyampakeni, D.; Batuman, O.; Alferez, F. Glyphosate: Its Environmental Persistence and Impact on Crop Health and Nutrition. Plants 2019, 8, 499. [Google Scholar] [CrossRef] [Green Version]
  37. Alcántara-de la Cruz, R.; Cruz-Hipolito, H.E.; Domínguez-Valenzuela, J.A.; De Prado, R. Glyphosate ban in Mexico: Potential impacts on agriculture and weed management. Pest Manag. Sci. 2021, 77, 3820–3831. [Google Scholar] [CrossRef]
  38. Meftaul, I.M.; Venkateswarlu, K.; Dharmarajan, R.; Annamalai, P.; Asaduzzaman, M.; Parven, A.; Megharaj, M. Controversies over human health and ecological impacts of glyphosate: Is it to be banned in modern agriculture? Environ. Pollut. 2020, 263, 114372. [Google Scholar] [CrossRef] [PubMed]
  39. Williams, G.M.; Aardema, M.; Acquavella, J.; Berry, S.C.; Brusick, D.; Burns, M.M.; de Camargo, J.L.V.; Garabrant, D.; Greim, H.A.; Kier, L.D.; et al. A review of the carcinogenic potential of glyphosate by four independent expert panels and comparison to the IARC assessment. Crit. Rev. Toxicol. 2016, 46, 3–20. [Google Scholar] [CrossRef] [Green Version]
  40. Klingelhöfer, D.; Braun, M.; Brüggmann, D.; Groneberg, D.A. Glyphosate: How do ongoing controversies, market characteristics, and funding influence the global research landscape? Sci. Total Environ. 2021, 765, 144271. [Google Scholar] [CrossRef]
  41. la Cecilia, D.; Maggi, F. Analysis of glyphosate degradation in a soil microcosm. Environ. Pollut. 2018, 233, 201–207. [Google Scholar] [CrossRef] [PubMed]
  42. Al-Rajab, A.J.; Hakami, O.M. Behavior of the non-selective herbicide glyphosate in agricultural soil. Am. J. Environ. Sci. 2014, 10, 94–101. [Google Scholar] [CrossRef]
  43. Zhang, C.; Hu, X.; Luo, J.; Wu, Z.; Wang, L.; Li, B.; Wang, Y.; Sun, G. Degradation dynamics of glyphosate in different types of citrus orchard soils in China. Molecules 2015, 20, 1161–1175. [Google Scholar] [CrossRef] [Green Version]
  44. Mamy, L.; Barriuso, E.; Gabrielle, B. Environmental fate of herbicides trifluralin, metazachlor, metamitron and sulcotrione compared with that of glyphosate, a substitute broad spectrum herbicide for different glyphosate-resistant crops. Pest Manag. Sci. 2005, 61, 905–916. [Google Scholar] [CrossRef] [PubMed]
  45. Lancaster, S.H.; Hollister, E.B.; Senseman, S.A.; Gentry, T.J. Effects of repeated glyphosate applications on soil microbial community composition and the mineralization of glyphosate. Pest Manag. Sci. 2010, 66, 59–64. [Google Scholar] [CrossRef] [PubMed]
  46. Ololade, I.A.; Oladoja, N.A.; Oloye, F.F.; Alomaja, F.; Akerele, D.D.; Iwaye, J.; Aikpokpodion, P. Sorption of Glyphosate on Soil Components: The Roles of Metal Oxides and Organic Materials. Soil Sediment Contam. 2014, 23, 571–585. [Google Scholar] [CrossRef]
  47. Nguyen, N.K.; Dörfler, U.; Welzl, G.; Munch, J.C.; Schroll, R.; Suhadolc, M. Large variation in glyphosate mineralization in 21 different agricultural soils explained by soil properties. Sci. Total Environ. 2018, 627, 544–552. [Google Scholar] [CrossRef]
  48. Muskus, A.M.; Krauss, M.; Miltner, A.; Hamer, U.; Nowak, K.M. Effect of temperature, pH and total organic carbon variations on microbial turnover of 13C315N-glyphosate in agricultural soil. Sci. Total Environ. 2019, 658, 697–707. [Google Scholar] [CrossRef]
  49. Laitinen, P.; Rämö, S.; Nikunen, U.; Jauhiainen, L.; Siimes, K.; Turtola, E. Glyphosate and phosphorus leaching and residues in boreal sandy soil. Plant Soil 2009, 323, 267–283. [Google Scholar] [CrossRef]
  50. Okada, E.; Costa, J.L.; Bedmar, F. Glyphosate Dissipation in Different Soils Under No-Till and Conventional Tillage. Pedosphere 2019, 29, 773–783. [Google Scholar] [CrossRef] [Green Version]
  51. Simonsen, L.; Fomsgaard, I.S.; Svensmark, B.; Spliid, N.H. Fate and availability of glyphosate and AMPA in agricultural soil. J. Environ. Sci. Health Part B 2008, 43, 365–375. [Google Scholar] [CrossRef]
  52. Carretta, L.; Cardinali, A.; Onofri, A.; Masin, R.; Zanin, G. Dynamics of Glyphosate and Aminomethylphosphonic Acid in Soil Under Conventional and Conservation Tillage. Int. J. Environ. Res. 2021, 15, 1037–1055. [Google Scholar] [CrossRef]
  53. Veiga, F.; Zapata, J.M.; Fernandez Marcos, M.L.; Alvarez, E. Dynamics of glyphosate and aminomethylphosphonic acid in a forest soil in Galicia, north-west Spain. Sci. Total Environ. 2001, 271, 135–144. [Google Scholar] [CrossRef]
  54. Gómez Ortiz, A.M.; Okada, E.; Bedmar, F.; Costa, J.L. Sorption and desorption of glyphosate in Mollisols and Ultisols soils of Argentina. Environ. Toxicol. Chem. 2017, 36, 2587–2592. [Google Scholar] [CrossRef]
  55. Sidoli, P.; Baran, N.; Angulo-Jaramillo, R. Glyphosate and AMPA adsorption in soils: Laboratory experiments and pedotransfer rules. Environ. Sci. Pollut. Res. 2016, 23, 5733–5742. [Google Scholar] [CrossRef]
  56. Padilla, J.T.; Selim, H.M. Interactions among Glyphosate and Phosphate in Soils: Laboratory Retention and Transport Studies. J. Environ. Qual. 2019, 48, 156–163. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  57. Shushkova, T.V.; Vasilieva, G.K.; Ermakova, I.T.; Leontievsky, A.A. Sorption and microbial degradation of glyphosate in soil suspensions. Appl. Biochem. Microbiol. 2009, 45, 599–603. [Google Scholar] [CrossRef]
  58. Piccolo, A.; Celano, G.; Conte, P. Adsorption of Glyphosate by Humic Substances. J. Agric. Food Chem. 1996, 44, 2442–2446. [Google Scholar] [CrossRef]
  59. Grandcoin, A.; Piel, S.; Baurès, E. Amino Methyl Phosphonic acid (AMPA) in natural waters: Its sources, behavior and environmental fate. Water Res. 2017, 117, 187–197. [Google Scholar] [CrossRef] [PubMed]
  60. Norgaard, T.; Moldrup, P.; Ferré, T.P.A.; Olsen, P.; Rosenbom, A.E.; de Jonge, L.W. Leaching of Glyphosate and Aminomethylphosphonic Acid from an Agricultural Field over a Twelve-Year Period. Vadose Zo. J. 2014, 13, 1–18. [Google Scholar] [CrossRef]
  61. Borggaard, O.K.; Gimsing, A.L. Fate of glyphosate in soil and the possibility of leaching to ground and surface waters: A review. Pest Manag. Sci. 2008, 64, 441–456. [Google Scholar] [CrossRef]
  62. Skeff, W.; Neumann, C.; Schulz-Bull, D.E. Glyphosate and AMPA in the estuaries of the Baltic Sea method optimization and field study. Mar. Pollut. Bull. 2015, 100, 577–585. [Google Scholar] [CrossRef]
  63. Van Stempvoort, D.R.; Roy, J.W.; Brown, S.J.; Bickerton, G. Residues of the herbicide glyphosate in riparian groundwater in urban catchments. Chemosphere 2014, 95, 455–463. [Google Scholar] [CrossRef]
  64. Myers, J.P.; Antoniou, M.N.; Blumberg, B.; Carroll, L.; Colborn, T.; Everett, L.G.; Hansen, M.; Landrigan, P.J.; Lanphear, B.P.; Mesnage, R.; et al. Concerns over use of glyphosate-based herbicides and risks associated with exposures: A consensus statement. Environ. Heal. 2016, 15, 19. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  65. Hagner, M.; Mikola, J.; Saloniemi, I.; Saikkonen, K.; Helander, M. Effects of a glyphosate-based herbicide on soil animal trophic groups and associated ecosystem functioning in a northern agricultural field. Sci. Rep. 2019, 9, 8540. [Google Scholar] [CrossRef] [PubMed]
  66. Gonze, D.; Coyte, K.Z.; Lahti, L.; Faust, K. Microbial communities as dynamical systems. Curr. Opin. Microbiol. 2018, 44, 41–49. [Google Scholar] [CrossRef] [PubMed]
  67. Ingham, R.E.; Trofymow, J.A.; Ingham, E.R.; Coleman, D.C. Interactions of Bacteria, Fungi, and their Nematode Grazers: Effects on Nutrient Cycling and Plant Growth. Ecol. Monogr. 1985, 55, 119–140. [Google Scholar] [CrossRef]
  68. Pulleman, M.; Creamer, R.; Hamer, U.; Helder, J.; Pelosi, C.; Pérès, G.; Rutgers, M. Soil biodiversity, biological indicators and soil ecosystem services-an overview of European approaches. Curr. Opin. Environ. Sustain. 2012, 4, 529–538. [Google Scholar] [CrossRef]
  69. García-Pérez, J.A.; Alarcón-Gutiérrez, E.; Perroni, Y.; Barois, I. Earthworm communities and soil properties in shaded coffee plantations with and without application of glyphosate. Appl. Soil Ecol. 2014, 83, 230–237. [Google Scholar] [CrossRef]
  70. Wolmarans, K.; Swart, W.J. Influence of glyphosate, other herbicides and genetically modified herbicide-resistant crops on soil microbiota: A review. S. Afr. J. Plant Soil 2014, 31, 177–186. [Google Scholar] [CrossRef]
  71. Allegrini, M.; Zabaloy, M.C.; Gómez, E. del V. Ecotoxicological assessment of soil microbial community tolerance to glyphosate. Sci. Total Environ. 2015, 533, 60–68. [Google Scholar] [CrossRef] [PubMed]
  72. Druille, M.; Cabello, M.N.; García Parisi, P.A.; Golluscio, R.A.; Omacini, M. Glyphosate vulnerability explains changes in root-symbionts propagules viability in pampean grasslands. Agric. Ecosyst. Environ. 2015, 202, 48–55. [Google Scholar] [CrossRef] [Green Version]
  73. Riah, W.; Laval, K.; Laroche-Ajzenberg, E.; Mougin, C.; Latour, X.; Trinsoutrot-Gattin, I. Effects of pesticides on soil enzymes: A review. Environ. Chem. Lett. 2014, 12, 257–273. [Google Scholar] [CrossRef]
  74. Annett, R.; Habibi, H.R.; Hontela, A. Impact of glyphosate and glyphosate-based herbicides on the freshwater environment. J. Appl. Toxicol. 2014, 34, 458–479. [Google Scholar] [CrossRef] [PubMed]
  75. Botta, F.; Lavison, G.; Couturier, G.; Alliot, F.; Moreau-Guigon, E.; Fauchon, N.; Guery, B.; Chevreuil, M.; Blanchoud, H. Transfer of glyphosate and its degradate AMPA to surface waters through urban sewerage systems. Chemosphere 2009, 77, 133–139. [Google Scholar] [CrossRef]
  76. Battaglin, W.A.; Meyer, M.T.; Kuivila, K.M.; Dietze, J.E. Glyphosate and its degradation product AMPA occur frequently and widely in U.S. soils, surface water, groundwater, and precipitation. J. Am. Water Resour. Assoc. 2014, 50, 275–290. [Google Scholar] [CrossRef]
  77. Wang, S.; Seiwert, B.; Kästner, M.; Miltner, A.; Schäffer, A.; Reemtsma, T.; Yang, Q.; Nowak, K.M. (Bio)degradation of glyphosate in water-sediment microcosms—A stable isotope co-labeling approach. Water Res. 2016, 99, 91–100. [Google Scholar] [CrossRef]
  78. Braz-Mota, S.; Sadauskas-Henrique, H.; Duarte, R.M.; Val, A.L.; Almeida-Val, V.M.F. Roundup® exposure promotes gills and liver impairments, DNA damage and inhibition of brain cholinergic activity in the Amazon teleost fish Colossoma macropomum. Chemosphere 2015, 135, 53–60. [Google Scholar] [CrossRef] [PubMed]
  79. Hued, A.C.; Oberhofer, S.; De Los Ángeles Bistoni, M. Exposure to a commercial glyphosate formulation (Roundup®) alters normal gill and liver histology and affects male sexual activity of Jenynsia multidentata (Anablepidae, cyprinodontiformes). Arch. Environ. Contam. Toxicol. 2012, 62, 107–117. [Google Scholar] [CrossRef] [PubMed]
  80. Levine, S.L.; von Mérey, G.; Minderhout, T.; Manson, P.; Sutton, P. Aminomethylphosphonic acid has low chronic toxicity to Daphnia magna and Pimephales promelas. Environ. Toxicol. Chem. 2015, 34, 1382–1389. [Google Scholar] [CrossRef]
  81. Struger, J.; Thompson, D.; Staznik, B.; Martin, P.; McDaniel, T.; Marvin, C. Occurrence of glyphosate in surface waters of southern Ontario. Bull. Environ. Contam. Toxicol. 2008, 80, 378–384. [Google Scholar] [CrossRef] [PubMed]
  82. Rendón-Von Osten, J.; Dzul-Caamal, R. Glyphosate residues in groundwater, drinking water and urine of subsistence farmers from intensive agriculture localities: A survey in Hopelchén, Campeche, Mexico. Int. J. Environ. Res. Public Health 2017, 14, 595. [Google Scholar] [CrossRef] [PubMed]
  83. Gomes, M.P.; Rocha, D.C.; Moreira de Brito, J.C.; Tavares, D.S.; Marques, R.Z.; Soffiatti, P.; Sant’Anna-Santos, B.F. Emerging contaminants in water used for maize irrigation: Economic and food safety losses associated with ciprofloxacin and glyphosate. Ecotoxicol. Environ. Saf. 2020, 196, 110549. [Google Scholar] [CrossRef]
  84. Gunarathna, S.; Gunawardana, B.; Jayaweera, M.; Manatunge, J.; Zoysa, K. Glyphosate and AMPA of agricultural soil, surface water, groundwater and sediments in areas prevalent with chronic kidney disease of unknown etiology, Sri Lanka. J. Environ. Sci. Heal. Part B Pestic. Food Contam. Agric. Wastes 2018, 53, 729–737. [Google Scholar] [CrossRef] [PubMed]
  85. Al-Khatib, K.; Peterson, D. Soybean (Glycine max) Response to Simulated Drift from Selected Sulfonylurea Herbicides, Dicamba, Glyphosate, and Glufosinate. Weed Technol. 1999, 13, 264–270. [Google Scholar] [CrossRef]
  86. Kolberg, R.; Wiles, L. Effect of Steam Application on Cropland Weeds1. Weed Technol. 2002, 16, 43–49. [Google Scholar] [CrossRef]
  87. Reddy, K.N.; Rimando, A.M.; Duke, S.O. Aminomethylphosphonic acid, a metabolite of glyphosate, causes injury in glyphosate-treated, glyphosate-resistant soybean. J. Agric. Food Chem. 2004, 52, 5139–5143. [Google Scholar] [CrossRef]
  88. Fernandez, M.R.; Zentner, R.P.; Basnyat, P.; Gehl, D.; Selles, F.; Huber, D. Glyphosate associations with cereal diseases caused by Fusarium spp. in the Canadian Prairies. Eur. J. Agron. 2009, 31, 133–143. [Google Scholar] [CrossRef]
  89. Fernandez, M.R.; Zentner, R.P.; DePauw, R.M.; Gehl, D.; Stevenson, F.C. Impacts of crop production factors on common root rot of barley in Eastern Saskatchewan. Crop Sci. 2007, 47, 1585–1595. [Google Scholar] [CrossRef]
  90. Kanissery, R.; Alferez, F.; Batuman, O. Glyphosate related fruit drop in citrus. EDIS 2018, 2018. [Google Scholar]
  91. Zoller, O.; Rhyn, P.; Rupp, H.; Zarn, J.A.; Geiser, C. Glyphosate residues in Swiss market foods: Monitoring and risk evaluation. Food Addit. Contam. Part B Surveill. 2018, 11, 83–91. [Google Scholar] [CrossRef]
  92. Saunders, L.E.; Pezeshki, R. Glyphosate in runoffwaters and in the root-zone: A review. Toxics 2015, 3, 462–480. [Google Scholar] [CrossRef] [Green Version]
  93. Defarge, N.; Spiroux de Vendômois, J.; Séralini, G.E. Toxicity of formulants and heavy metals in glyphosate-based herbicides and other pesticides. Toxicol. Rep. 2018, 5, 156–163. [Google Scholar] [CrossRef]
  94. Sesin, V.; Davy, C.M.; Stevens, K.J.; Hamp, R.; Freeland, J.R. Glyphosate Toxicity to Native Nontarget Macrophytes Following Three Different Routes of Incidental Exposure. Integr. Environ. Assess. Manag. 2021, 17, 597–613. [Google Scholar] [CrossRef] [PubMed]
  95. de Brito Rodrigues, L.; Gonçalves Costa, G.; Lundgren Thá, E.; da Silva, L.R.; de Oliveira, R.; Morais Leme, D.; Cestari, M.M.; Koppe Grisolia, C.; Campos Valadares, M.; de Oliveira, G.A.R. Impact of the glyphosate-based commercial herbicide, its components and its metabolite AMPA on non-target aquatic organisms. Mutat. Res. Genet. Toxicol. Environ. Mutagen. 2019, 842, 94–101. [Google Scholar] [CrossRef] [PubMed]
  96. Soukup, S.T.; Merz, B.; Bub, A.; Hoffmann, I.; Watzl, B.; Steinberg, P.; Kulling, S.E. Glyphosate and AMPA levels in human urine samples and their correlation with food consumption: Results of the cross-sectional KarMeN study in Germany. Arch. Toxicol. 2020, 94, 1575–1584. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  97. Krüger, M.; Schledorn, P.; Schrödl, W.; Hoppe, H.-W.; Lutz, W.; Shehata, A.A. Detection of Glyphosate Residues in Animals and Humans. J Env. Anal Toxicol 2014, 4, 2. [Google Scholar] [CrossRef]
  98. Niemann, L.; Sieke, C.; Pfeil, R.; Solecki, R. A critical review of glyphosate findings in human urine samples and comparison with the exposure of operators and consumers. J. Verbraucherschutz Leb. 2015, 10, 3–12. [Google Scholar] [CrossRef] [Green Version]
  99. Torretta, V.; Katsoyiannis, I.A.; Viotti, P.; Rada, E.C. Critical review of the effects of glyphosate exposure to the environment and humans through the food supply chain. Sustainability 2018, 10, 950. [Google Scholar] [CrossRef] [Green Version]
  100. Gillezeau, C.; Van Gerwen, M.; Shaffer, R.M.; Rana, I.; Zhang, L.; Sheppard, L.; Taioli, E. The evidence of human exposure to glyphosate: A review. Environ. Health A Glob. Access Sci. Source 2019, 18, 2. [Google Scholar] [CrossRef] [Green Version]
  101. Vigfusson, N.V.; Vyse, E.R. The effect of the pesticides, dexon, captan and roundup, on sister-chromatid exchanges in human lymphocytes in vitro. Mutat. Res. Genet. Toxicol. 1980, 79, 53–57. [Google Scholar] [CrossRef]
  102. Alvarez-Moya, C.; Silva, M.R.; Valdez Ramírez, C.; Gallardo, D.G.; León Sánchez, R.; Aguirre, A.C.; Velasco, A.F. Comparison of the in vivo and in vitro genotoxicity of glyphosate isopropylamine salt in three different organisms. Genet. Mol. Biol. 2014, 37, 105–110. [Google Scholar] [CrossRef] [PubMed]
  103. Santovito, A.; Ruberto, S.; Gendusa, C.; Cervella, P. In vitro evaluation of genomic damage induced by glyphosate on human lymphocytes. Environ. Sci. Pollut. Res. 2018, 25, 34693–34700. [Google Scholar] [CrossRef]
  104. Martínez, A.; Reyes, I.; Reyes, N. Citotoxicidad del glifosato en células mononucleares de sangre periférica humana. Biomédica 2007, 27, 594. [Google Scholar] [CrossRef] [Green Version]
  105. Woźniak, E.; Sicińska, P.; Michałowicz, J.; Woźniak, K.; Reszka, E.; Huras, B.; Zakrzewski, J.; Bukowska, B. The mechanism of DNA damage induced by Roundup 360 PLUS, glyphosate and AMPA in human peripheral blood mononuclear cells—genotoxic risk assessement. Food Chem. Toxicol. 2018, 120, 510–522. [Google Scholar] [CrossRef] [PubMed]
  106. Kwiatkowska, M.; Huras, B.; Bukowska, B. The effect of metabolites and impurities of glyphosate on human erythrocytes (in vitro). Pestic. Biochem. Physiol. 2014, 109, 34–43. [Google Scholar] [CrossRef]
  107. Kwiatkowska, M.; Nowacka-Krukowska, H.; Bukowska, B. The effect of glyphosate, its metabolites and impurities on erythrocyte acetylcholinesterase activity. Environ. Toxicol. Pharmacol. 2014, 37, 1101–1108. [Google Scholar] [CrossRef]
  108. Kwiatkowska, M.; Jarosiewicz, P.; Michałowicz, J.; Koter-Michalak, M.; Huras, B.; Bukowska, B. The impact of glyphosate, its metabolites and impurities on viability, ATP level and morphological changes in human peripheral blood mononuclear cells. PLoS ONE 2016, 11, e0156946. [Google Scholar] [CrossRef]
  109. Kwiatkowska, M.; Reszka, E.; Woźniak, K.; Jabłońska, E.; Michałowicz, J.; Bukowska, B. DNA damage and methylation induced by glyphosate in human peripheral blood mononuclear cells (in vitro study). Food Chem. Toxicol. 2017, 105, 93–98. [Google Scholar] [CrossRef] [PubMed]
  110. Elie-Caille, C.; Heu, C.; Guyon, C.; Nicod, L. Morphological damages of a glyphosate-treated human keratinocyte cell line revealed by a micro-to nanoscale microscopic investigation. Cell Biol. Toxicol. 2010, 26, 331–339. [Google Scholar] [CrossRef]
  111. Heu, C.; Berquand, A.; Elie-Caille, C.; Nicod, L. Glyphosate-induced stiffening of HaCaT keratinocytes, a Peak Force Tapping study on living cells. J. Struct. Biol. 2012, 178, 1–7. [Google Scholar] [CrossRef]
  112. Mañas, F.; Peralta, L.; Raviolo, J.; Ovando, H.G.; Weyers, A.; Ugnia, L.; Cid, M.G.; Larripa, I.; Gorla, N. Genotoxicity of glyphosate assessed by the comet assay and cytogenetic tests. Environ. Toxicol. Pharmacol. 2009, 28, 37–41. [Google Scholar] [CrossRef]
  113. Mesnage, R.; Bernay, B.; Séralini, G.E. Ethoxylated adjuvants of glyphosate-based herbicides are active principles of human cell toxicity. Toxicology 2013, 313, 122–128. [Google Scholar] [CrossRef]
  114. Benachour, N.; Séralini, G.E. Glyphosate formulations induce apoptosis and necrosis in human umbilical, embryonic, and placental cells. Chem. Res. Toxicol. 2009, 22, 97–105. [Google Scholar] [CrossRef]
  115. Benachour, N.; Sipahutar, H.; Moslemi, S.; Gasnier, C.; Travert, C.; Séralini, G.E. Time- and dose-dependent effects of roundup on human embryonic and placental cells. Arch. Environ. Contam. Toxicol. 2007, 53, 126–133. [Google Scholar] [CrossRef] [PubMed]
  116. Martinez, A.; Al-Ahmad, A.J. Effects of glyphosate and aminomethylphosphonic acid on an isogeneic model of the human blood-brain barrier. Toxicol. Lett. 2019, 304, 39–49. [Google Scholar] [CrossRef]
  117. Gao, H.; Chen, J.; Ding, F.; Chou, X.; Zhang, X.; Wan, Y.; Hu, J.; Wu, Q. Activation of the N-methyl-d-aspartate receptor is involved in glyphosate-induced renal proximal tubule cell apoptosis. J. Appl. Toxicol. 2019, 39, 1096–1107. [Google Scholar] [CrossRef] [PubMed]
  118. Mesnage, R.; Biserni, M.; Wozniak, E.; Xenakis, T.; Mein, C.A.; Antoniou, M.N. Comparison of transcriptome responses to glyphosate, isoxaflutole, quizalofop-p-ethyl and mesotrione in the HepaRG cell line. Toxicol. Rep. 2018, 5, 819–826. [Google Scholar] [CrossRef]
  119. Hao, Y.; Zhang, Y.; Ni, H.; Gao, J.; Yang, Y.; Xu, W.; Tao, L. Evaluation of the cytotoxic effects of glyphosate herbicides in human liver, lung, and nerve. J. Environ. Sci. Heal. Part B Pestic. Food Contam. Agric. Wastes 2019, 54, 737–744. [Google Scholar] [CrossRef]
  120. Kašuba, V.; Milić, M.; Rozgaj, R.; Kopjar, N.; Mladinić, M.; Žunec, S.; Vrdoljak, A.L.; Pavičić, I.; Čermak, A.M.M.; Pizent, A.; et al. Effects of low doses of glyphosate on DNA damage, cell proliferation and oxidative stress in the HepG2 cell line. Environ. Sci. Pollut. Res. 2017, 24, 19267–19281. [Google Scholar] [CrossRef]
  121. Stur, E.; Aristizabal-Pachon, A.F.; Peronni, K.C.; Agostini, L.P.; Waigel, S.; Chariker, J.; Miller, D.M.; Thomas, S.D.; Rezzoug, F.; Detogni, R.S.; et al. Glyphosate-based herbicides at low doses affect canonical pathways in estrogen positive and negative breast cancer cell lines. PLoS ONE 2019, 14, e0219610. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  122. Mesnage, R.; Phedonos, A.; Biserni, M.; Arno, M.; Balu, S.; Corton, J.C.; Ugarte, R.; Antoniou, M.N. Evaluation of estrogen receptor alpha activation by glyphosate-based herbicide constituents. Food Chem. Toxicol. 2017, 108, 30–42. [Google Scholar] [CrossRef] [Green Version]
  123. Li, Q.; Lambrechts, M.J.; Zhang, Q.; Liu, S.; Ge, D.; Yin, R.; Xi, M.; You, Z. Glyphosate and AMPA inhibit cancer cell growth through inhibiting intracellular glycine synthesis. Drug Des. Devel. Ther. 2013, 7, 635–643. [Google Scholar] [CrossRef] [Green Version]
  124. Anifandis, G.; Katsanaki, K.; Lagodonti, G.; Messini, C.; Simopoulou, M.; Dafopoulos, K.; Daponte, A. The effect of glyphosate on human sperm motility and sperm DNA fragmentation. Int. J. Environ. Res. Public Health 2018, 15, 1117. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  125. Landrigan, P.J.; Belpoggi, F. The need for independent research on the health effects of glyphosate-based herbicides. Environ. Health A Glob. Access Sci. Source 2018, 17, 51. [Google Scholar] [CrossRef]
  126. Leon, M.E.; Schinasi, L.H.; Lebailly, P.; Beane Freeman, L.E.; Nordby, K.C.; Ferro, G.; Monnereau, A.; Brouwer, M.; Tual, S.; Baldi, I.; et al. Pesticide use and risk of non-Hodgkin lymphoid malignancies in agricultural cohorts from France, Norway and the USA: A pooled analysis from the AGRICOH consortium. Int. J. Epidemiol. 2019, 48, 1519–1535. [Google Scholar] [CrossRef]
  127. Hoppin, J.A.; Umbach, D.M.; Long, S.; London, S.J.; Henneberger, P.K.; Blair, A.; Alavanja, M.; Freeman Beane, L.E.; Sandler, D.P. Pesticides are associated with allergic and non-allergic wheeze among male farmers. Environ. Health Perspect. 2017, 125, 535–543. [Google Scholar] [CrossRef] [PubMed]
  128. Caballero, M.; Amiri, S.; Denney, J.T.; Monsivais, P.; Hystad, P.; Amram, O. Estimated residential exposure to agricultural chemicals and premature mortality by Parkinson’s disease in Washington state. Int. J. Environ. Res. Public Health 2018, 15, 2885. [Google Scholar] [CrossRef] [Green Version]
  129. Von Ehrenstein, O.S.; Ling, C.; Cui, X.; Cockburn, M.; Park, A.S.; Yu, F.; Wu, J.; Ritz, B. Prenatal and infant exposure to ambient pesticides and autism spectrum disorder in children: Population based case-control study. BMJ 2019, 364, 962. [Google Scholar] [CrossRef] [Green Version]
  130. Parvez, S.; Gerona, R.R.; Proctor, C.; Friesen, M.; Ashby, J.L.; Reiter, J.L.; Lui, Z.; Winchester, P.D. Glyphosate exposure in pregnancy and shortened gestational length: A prospective Indiana birth cohort study. Environ. Health A Glob. Access Sci. Source 2018, 17, 23. [Google Scholar] [CrossRef] [PubMed]
  131. Zaller, J.G.; Brühl, C.A. Editorial: Non-target Effects of Pesticides on Organisms Inhabiting Agroecosystems. Front. Environ. Sci. 2019, 7, 75. [Google Scholar] [CrossRef] [Green Version]
  132. Giesy, J.P.; Dobson, S.; Solomon, K.R. Ecotoxicological risk assessment for Roundup® herbicide. Rev. Environ. Contam. Toxicol. 2000, 167, 35–120. [Google Scholar] [CrossRef]
  133. Howe, C.M.; Berrill, M.; Pauli, B.D.; Helbing, C.C.; Werry, K.; Veldhoen, N. Toxicity of glyphosate-based pesticides to four North American frog species. Environ. Toxicol. Chem. 2004, 23, 1928–1938. [Google Scholar] [CrossRef] [PubMed]
  134. Moore, L.J.; Fuentes, L.; Rodgers, J.H.; Bowerman, W.W.; Yarrow, G.K.; Chao, W.Y.; Bridges, W.C. Relative toxicity of the components of the original formulation of Roundup® to five North American anurans. Ecotoxicol. Environ. Saf. 2012, 78, 128–133. [Google Scholar] [CrossRef] [PubMed]
  135. Domínguez, A.; Brown, G.G.; Sautter, K.D.; De Oliveira, C.M.R.; De Vasconcelos, E.C.; Niva, C.C.; Bartz, M.L.C.; Bedano, J.C. Toxicity of AMPA to the earthworm Eisenia andrei Bouché, 1972 in tropical artificial soil. Sci. Rep. 2016, 6, 19731. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  136. Richardson, J.T.; Frans, R.E.; Talbet, R.E. Reactions of Euglena gracilis to fluometuron, MSMA, metribuzin, and glyphosate. Weed Sci. 1979, 619–624. [Google Scholar] [CrossRef]
  137. Newman, M.M.; Hoilett, N.; Lorenz, N.; Dick, R.P.; Liles, M.R.; Ramsier, C.; Kloepper, J.W. Glyphosate effects on soil rhizosphere-associated bacterial communities. Sci. Total Environ. 2016, 543, 155–160. [Google Scholar] [CrossRef] [Green Version]
  138. Estok, D.; Freedman, B.; Boyle, D. Effects of the herbicides 2,4-D, glyphosate, hexazinone, and triclopyr on the growth of three species of ectomycorrhizal fungi. Bull. Environ. Contam. Toxicol. 1989, 42, 835–839. [Google Scholar] [CrossRef] [PubMed]
  139. Paul Kittle, R.; McDermid, K.J. Glyphosate herbicide toxicity to native Hawaiian macroalgal and seagrass species. J. Appl. Phycol. 2016, 28, 2597–2604. [Google Scholar] [CrossRef]
  140. Whiles, M.R.; Charlton, R.E. The ecological significance of tallgrass prairie arthropods. Annu. Rev. Entomol. 2006, 51, 387–412. [Google Scholar] [CrossRef] [Green Version]
  141. Alberdi, J.L.; Sàenz, M.E.; Di Marzio, W.D.; Tortorelli, M.C. Comparative acute toxicity of two herbicides, paraquat and glyphosate, to Daphnia magna and D. spinulata. Bull. Environ. Contam. Toxicol. 1996, 57, 229–235. [Google Scholar] [CrossRef]
  142. Frontera, J.L.; Vatnick, I.; Chaulet, A.; Rodríguez, E.M. Effects of glyphosate and polyoxyethylenamine on growth and energetic reserves in the freshwater crayfish Cherax quadricarinatus (Decapoda, Parastacidae). Arch. Environ. Contam. Toxicol. 2011, 61, 590–598. [Google Scholar] [CrossRef]
  143. Balbuena, M.S.; Tison, L.; Hahn, M.L.; Greggers, U.; Menzel, R.; Farina, W.M. Effects of sublethal doses of glyphosate on honeybee navigation. J. Exp. Biol. 2015, 218, 2799–2805. [Google Scholar] [CrossRef] [Green Version]
  144. Bueno, A. de F.; Bueno, R.C.O. de F.; Parra, J.R.P.; Vieira, S.S. Efeitos dos agroquimicos utilizados na cultura da soja ao parasitoide de ovos Trichogramma pretiosum. Cienc. Rural 2008, 38, 1495–1504. [Google Scholar] [CrossRef] [Green Version]
  145. Tate, T.M.; Spurlock, J.O.; Christian, F.A. Effect of glyphosate on the development of Pseudosuccinea columella snails. Arch. Environ. Contam. Toxicol. 1997, 33, 286–289. [Google Scholar] [CrossRef]
  146. Druart, C.; Millet, M.; Scheifler, R.; Delhomme, O.; de Vaufleury, A. Glyphosate and glufosinate-based herbicides: Fate in soil, transfer to, and effects on land snails. J. Soils Sediments 2011, 11, 1373–1384. [Google Scholar] [CrossRef]
  147. Murussi, C.R.; Costa, M.D.; Leitemperger, J.W.; Guerra, L.; Rodrigues, C.C.R.; Menezes, C.C.; Severo, E.S.; Flores-Lopes, F.; Salbego, J.; Loro, V.L. Exposure to different glyphosate formulations on the oxidative and histological status of Rhamdia quelen. Fish Physiol. Biochem. 2016, 42, 445–455. [Google Scholar] [CrossRef] [PubMed]
  148. Bach, N.C.; Natale, G.S.; Somoza, G.M.; Ronco, A.E. Effect on the growth and development and induction of abnormalities by a glyphosate commercial formulation and its active ingredient during two developmental stages of the South-American Creole frog, Leptodactylus latrans. Environ. Sci. Pollut. Res. 2016, 23, 23959–23971. [Google Scholar] [CrossRef]
  149. Ruuskanen, S.; Rainio, M.J.; Uusitalo, M.; Saikkonen, K.; Helander, M. Effects of parental exposure to glyphosate-based herbicides on embryonic development and oxidative status: A long-term experiment in a bird model. Sci. Rep. 2020, 10, 6349. [Google Scholar] [CrossRef] [Green Version]
Figure 1. Behavior and fate of glyphosate in the environment.
Figure 1. Behavior and fate of glyphosate in the environment.
Sustainability 14 06868 g001
Figure 2. Human health effects after water, food, direct contact, and environmental exposure, and, consequently, absorption.
Figure 2. Human health effects after water, food, direct contact, and environmental exposure, and, consequently, absorption.
Sustainability 14 06868 g002
Table 1. Glyphosate and AMPA persistence in soil.
Table 1. Glyphosate and AMPA persistence in soil.
Glyphosate Dose (kg ha−1)Half-Life (d)Soil PropertiesLocationReference
1.5498 (Gly), 51 (AMPA)Clay and sandySweden[20]
542 (Gly)LoamyChina[43]
1613 (Gly and AMPA)Boreal sandyFinland[49]
2.160 (Gly and AMPA)Silty loamArgentina[50]
0.259 (Gly) and 32 (AMPA)SandyDenmark[51]
1.818 (Gly) and 250 (AMPA)SandyItaly[52]
831 (Gly and AMPA)Sandy loamSpain[53]
Table 2. Residual concentrations of Glyphosate and AMPA from different food sources.
Table 2. Residual concentrations of Glyphosate and AMPA from different food sources.
Food SourceGlyphosate (mg kg−1)AMPA (mg kg−1)
Beer<0.0005<0.001
Wine0.0031<0.0007
Mineral water<0.0006<0.0005
Milk<0.0006<0.0025
Fruit juice0.0016<0.0006
Baby food<0.001<0.0025
Potatoes and vegetables<0.001<0.0025
Honey0.0030<0.0025
Eggs<0.001<0.0025
Meat and fish<0.001<0.0025
Pulses0.0012<0.0025
Oilseeds and vegetable oil<0.001<0.0025
Pseudo cereals<0.001<0.0025
Breakfast cereals0.0036<0.0025
Durum wheat0.1390.0107
Pastry and snacks <0.001<0.0025
Bread0.0019<0.0025
Flour and baking mixtures<0.001<0.0025
Other cereal products<0.001<0.0025
Source: Zoller et al. [91].
Table 3. Effects of glyphosate and GBHs on human in vitro cell cultures.
Table 3. Effects of glyphosate and GBHs on human in vitro cell cultures.
Human Cell TypeDose of Glyphosate (µg mL−1)Exposure Time (h)Evaluated EffectsReferences
Blood0.50052Mutagenicity, Cytotoxicity,
DNA damage, Hemolysis, Acetyl cholinesterase activity
[101,102,103,104,105,106,107,108,109]
Epithelial0.30018Oxidative stress, Cell damage, Genotoxicity[110,111,112]
Embryonic0.45024Cell damage, Toxicity, Endocrine disruption[113,114,115]
Pluripotent stem0.10048Blood–brain barrier[116]
Renal0.60024Cell viability, Apoptosis, Cell viability[117]
Hepatic0.54024Transcriptomic changes, Genotoxicity, Oxidative stress, DNA damage, [112,118,119,120]
Breast0.10048Endocrine disruption, Toxicity, DNA damage, [121,122]
Ovarian0.50072Abnormal growth,[123]
Pulmonary0.54024Cell viability[119]
Neuronal0.54024Toxicity, DNA damage[119]
Sperm0.361Cell viability, DNA fragmentation[124]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Rivas-Garcia, T.; Espinosa-Calderón, A.; Hernández-Vázquez, B.; Schwentesius-Rindermann, R. Overview of Environmental and Health Effects Related to Glyphosate Usage. Sustainability 2022, 14, 6868. https://doi.org/10.3390/su14116868

AMA Style

Rivas-Garcia T, Espinosa-Calderón A, Hernández-Vázquez B, Schwentesius-Rindermann R. Overview of Environmental and Health Effects Related to Glyphosate Usage. Sustainability. 2022; 14(11):6868. https://doi.org/10.3390/su14116868

Chicago/Turabian Style

Rivas-Garcia, Tomas, Alejandro Espinosa-Calderón, Benjamin Hernández-Vázquez, and Rita Schwentesius-Rindermann. 2022. "Overview of Environmental and Health Effects Related to Glyphosate Usage" Sustainability 14, no. 11: 6868. https://doi.org/10.3390/su14116868

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop