For 40 years, glyphosate has been widely used as an active chemical component of more than 750 commercial herbicides under the assumption that its side effects were minimal [11,27]. However, this compound’s intensive and large-scale use in industrialized and developing countries motivated the scientific community to evaluate the risks associated with the possible accumulation of its residues in various environmental systems and its effects on environmental and human health [28]. In this sense, recent evidence shows that herbicides containing glyphosate can contaminate the soils around the treated areas, glyphosate is adsorbed to clays and organic matter, slowing down its degradation by the action of microorganisms, leading to an accumulation in soils over time [29,30,31], the persistence of glyphosate in high clay content soil reaches more than a year [31,32].

Glyphosate has a great capacity for adsorption in the clay and organic matter present in soils, being considered as a low mobility compound, so that it is assumed that it does not represent a significant risk for the contamination of the water sources [33,34,35]. However, the scientific literature has reported the presence of this compound dissolved in groundwater [36,37], the transport of soil particles with glyphosate in surface water [21,37,38], as well as its adsorption in the sediments of water bodies [35]. Moreover, the glyphosate deposited in the first centimeters of the superficial soil layer is susceptible to wind erosion and atmospheric transport [39,40], consequently, glyphosate has been detected in the air, rain, and water from melting snow [21,41]. Finally, glyphosate has also been reported in seawater, where it is very persistent [42] and in drinking water [43].

Resulting from its accumulation and persistence in the soil, glyphosate can affect exposed organisms in this environmental compartment [44]. For example, it has been reported that glyphosate can affect the activity of soil microorganisms that are involved in biogeochemical cycles, the mineralization of organic remains, the immobilization and solubilization of minerals, and the degradation of other xenobiotics [45,46,47]. Likewise, a reduction in the reproduction rate, biomass, and DNA damage in earthworms has been reported [48,49,50], as well as adverse effects in other small size organisms, such as nematodes, distributed in soils [51]. Moreover, in plant species, the direct effects of their exposure to glyphosate are related to the inhibition of the activity of antioxidant enzymes and the induction of reactive oxygen species (ROS), which promote cell damage and physiological alterations in processes such as photosynthesis and the production of secondary metabolites [52]. Furthermore, traces of this compound can be detected in plant tissues of temperate zone species up to more than 12 years after the treatment [4]. Glyphosate indirectly changes the rhizosphere microbiome, which affects plant health [28,53].

In water bodies, the negative impacts of glyphosate have been observed in organisms such as protozoa, mussels, crustaceans, frogs, and fish [28]. Similar to that reported in terrestrial ecosystems, the presence of glyphosate in fish produces metabolism alterations, leading to the overproduction of reactive oxygen species and oxidative stress resulting in kidney damage [54]. Likewise, other studies have linked glyphosate exposure to DNA damage and chromosomal alterations in fish [55,56]. The presence of glyphosate not only has effects at the level of individual organisms, but alterations in the interactions between species have also been documented. As an example, an increase in the levels of susceptibility of fish to its parasites has been documented [57,58]. Similarly, unwanted effects of glyphosate exposure have been reported in bee species that provide valuable ecosystem services such as pollination [59]. Finally, glyphosate has been detected in animal feed, animal meat, and urine, as well as in the food intended for human consumption, which is why the presence of this herbicide has been detected in samples of breast milk and urine [5]. Another additional environmental risk associated with the presence of glyphosate, which has not been adequately considered, is that it is a potent mineral chelator [18] whose application can lead to the reduction of macro and micronutrients that are essential cofactors in many biological processes of glyphosate-treated plants and potentially also for the organisms that feed on them. Consequently, a reduced supply of nutrients in the treated plants can compromise their resistance to diseases. In the case of humans and other animals that consume food obtained from plants treated with glyphosate, the residues of this herbicide and the reduced levels of nutrients can also have an impact on their health [18,60]. Therefore, to minimize its environmental and human health impacts, monitoring and detection of its presence in different environments, as well as the evaluation of exposure to this herbicide in humans, is of utmost importance.

Humans have been exposed to glyphosate directly through occupational exposure or indirectly through various sources [61]. Occupational exposure includes agricultural workers, farmers, gardeners, and people who work in plants that process glyphosate [62]. These people can be exposed to glyphosate through inhalation, dermal and ocular contact. In contrast, the indirect exposure includes the consumption of water or food contaminated with glyphosate residues [63] or the environmental exposure to residues or products of its transformation, such as aminomethyl phosphonic acid (AMPA) in environmental matrixes such as air, water, or soil [61,62].

The mode of action of glyphosate consists of the inhibition of the enzyme EPSPS involved in the biosynthesis of the aromatic amino acids tyrosine, tryptophan, and phenylalanine through the shikimate pathway in plants [64]. Therefore, glyphosate was proposed as a low toxicity compound for non-target organisms and was considered relatively safe for humans, according to the results of different exposure studies carried out in rodents, chickens, and amphibians [12,13,65,66].

More recently, it was determined that the toxicity of commercial herbicides based on glyphosate is exacerbated by the presence of surfactant compounds in the formulation, being polyoxyethyleneamine (POEA) the most common [5,61]. This compound uncouples elements of phosphorylation oxidative stress, causing oxidative stress and cardiotoxicity [67]. Thus, in 2015, the World Health Organization reclassified glyphosate as a possible human carcinogen [11,68,69]. Glyphosate reclassification into the group 2A of the International Agency for Research on Cancer (IARC) was based on the review of the accumulated evidence provided by experts in cancer and toxicology, which has contributed to a better understanding of the toxicity of the compound for all kinds of exposed organisms in natural areas, and in experimental animals, and its mechanisms of action [70].

Among the most relevant information on the effects caused by glyphosate exposure in humans are the studies by Samsel and Seneff (2013b) [71], which indicated that exposure to the herbicide represented the main factor causing gluten intolerance and gastrointestinal disorders, as well as interference in the assimilation of micronutrients such as iron, cobalt, molybdenum, copper, and amino acids such as tryptophan, tyrosine, methionine, and selenomethionine. Subsequently, Samsel and Seneff (2013a) [60] and Schinasi and Leon (2014) [72] evidenced an association between non-Hodgkin’s lymphoma and agrochemical exposure. In particular, the latest work showed that occupational exposure to glyphosate increases the relative risk of developing this disease and the development of B-cell lymphoma. Other reports of chronic exposure to the herbicide in human populations show the association with conditions such as allergies, and asthma [73], cardiovascular diseases [74], autism, and chronic degenerative diseases such as multiple myeloma [75]. Cytotoxic damage has also been reported in chorioplacental cells of humans, which triggers inhibition in the synthesis of progesterone as a secondary effect [76]. Recent reviews suggest that glyphosate and glyphosate-based herbicides promote cytotoxic and genotoxic effects, a significant increase in oxidative stress, disruption of the estrogen pathway, adverse effects on various cognitive processes, and an association with the development of certain cancers [77,78]. The studies mentioned above compile evidence of the high glyphosate toxicity and establish this compound as a menace to the health of the agricultural population that has a history of direct exposure and for whom the exposure has been indirect through the consumption of food or water with residues of glyphosate. Human individuals exposed to this compound have presented multiple organ toxicity, nephrotoxicity, hepatotoxicity, gastrointestinal, cardiovascular, and respiratory effects [62,79].