Figure 6 - uploaded by Anthony Samsel
Content may be subject to copyright.
Plots of glyphosate usage on corn and soy crops (blue), and hospital discharge diagnoses of inlammatory bowel disease (Crohn's andulcerative colitis) in the US, over time. (Figure courtesy of Dr. Nancy Swanson) 

Plots of glyphosate usage on corn and soy crops (blue), and hospital discharge diagnoses of inlammatory bowel disease (Crohn's andulcerative colitis) in the US, over time. (Figure courtesy of Dr. Nancy Swanson) 

Source publication
Article
Full-text available
Manganese (Mn) is an often overlooked but important nutrient, required in small amounts for multiple essential functions in the body. A recent study on cows fed genetically modified Roundup®‐Ready feed revealed a severe depletion of serum Mn. Glyphosate, the active ingredient in Roundup®, has also been shown to severely deplete Mn levels in plants....

Context in source publication

Context 1
... At least two other studies have shown bile stagnation in fish exposed to glyphosate. [80,135] Inflammatory bowel disease (colitis and Crohn's disease) has been increasing in frequency in the US over the past 20 years, in step with glyphosate usage on corn and soy crops, as shown in [ Figure 6]. According to analyses by Cappello et al. in a hospital-based survey, [53] cholestasis is a common feature of inflammatory bowel disease. ...

Similar publications

Article
Full-text available
Manganese (Mn) is an often overlooked but important nutrient, required in small amounts for multiple essential functions in the body. A recent study on cows fed genetically modified Roundup-Ready feed revealed a severe depletion of serum Mn. Glyphosate, the active ingredient in Roundup , has also been shown to severely deplete Mn levels in plants....

Citations

... Glyphosate was also shown to be absorbed by humans and excreted in feces and urine, where its concentration was shown to vary between 1 and 10 µg/L [4]. Supporters of the broad use of GBH claim it is innocuous to humans, since it is an inhibitor of the shikimate pathway, which is absent in human cells [5,6]. However, the safety and toxicity of GBH are a matter of extensive debate in the scientific community [5][6][7]. ...
... Supporters of the broad use of GBH claim it is innocuous to humans, since it is an inhibitor of the shikimate pathway, which is absent in human cells [5,6]. However, the safety and toxicity of GBH are a matter of extensive debate in the scientific community [5][6][7]. ...
Article
Full-text available
RoundUp® (RUp) is a comercial formulation containing glyphosate (N-(phosphono-methyl) glycine), and is the world’s leading wide-spectrum herbicide used in agriculture. Supporters of the broad use of glyphosate-based herbicides (GBH) claim they are innocuous to humans, since the active compound acts on the inhibition of enzymes which are absent in human cells. However, the neurotoxic effects of GBH have already been shown in many animal models. Further, these formulations were shown to disrupt the microbiome of different species. Here, we investigated the effects of a lifelong exposure to low doses of the GBH-RUp on the gut environment, including morphological and microbiome changes. We also aimed to determine whether exposure to GBH-RUp could harm the developing brain and lead to behavioral changes in adult mice. To this end, animals were exposed to GBH-RUp in drinking water from pregnancy to adulthood. GBH-RUp-exposed mice had no changes in cognitive function, but developed impaired social behavior and increased repetitive behavior. GBH-Rup-exposed mice also showed an activation of phagocytic cells (Iba-1–positive) in the cortical brain tissue. GBH-RUp exposure caused increased mucus production and the infiltration of plama cells (CD138-positive), with a reduction in phagocytic cells. Long-term exposure to GBH-RUp also induced changes in intestinal integrity, as demonstrated by the altered expression of tight junction effector proteins (ZO-1 and ZO-2) and a change in the distribution of syndecan-1 proteoglycan. The herbicide also led to changes in the gut microbiome composition, which is also crucial for the establishment of the intestinal barrier. Altogether, our findings suggest that long-term GBH-RUp exposure leads to morphological and functional changes in the gut, which correlate with behavioral changes that are similar to those observed in patients with neurodevelopmental disorders.
... Likewise, glyphosate, a broad-spectrum herbicide of the organophosphorus group, is most widely used in current agriculture (Baylis, 2000;Campbell et al., 1999), toxicity caused by this pesticide leads to extreme disruptions in the shikimate pathway, found in bacteria and plants as well as in the human gut microbes, thereby affecting the supply of essential amino acids in human (Samsel and Seneff, 2015). Additionally, glyphosate reduces the stomatal conductivity and carbon exchange in plants, thus lowering the CO 2 assimilation capability (Kostopoulou et al., 2020). ...
Article
The overuse of pesticides for augmenting agriculture productivity always comes at the cost of environment, biodiversity, and human health and has put the land, water, and environmental footprints under severe threat throughout the globe. Underpinning and maximizing the microbiome functions in pesticide-contaminated environments has become a prerequisite for a sustainable environment and resilient agriculture. It is imperative to elucidate the metabolic network of the microbial communities and environmental variables at the contaminated site to predict the best strategy for remediation and soil microbe-pesticide interactions. High throughput next-generation sequencing and in silico analysis allow us to identify and discern the members and characteristics of core microbiomes at the contaminated site. Integration of modern high throughput multi-omics investigations and informatics pipelines provide novel approaches and pathways to capitalize on the core microbiomes for enhancing environmental functioning and mitigation. The role of eco-genomics tools in visualising the microbial network, taxonomy, functional potential, and environmental variables in contaminated habitats is discussed in this review. The integrated role of the potential microbe identification as individual or consortia, mechanistic approach for pesticide degradation, identification of responsible enzymes/genes, and in silico approach is emphasized for the prospects of the area.
... Investigation of potential toxicity of Roundup (Samsel and Seneff, 2015) and its major active substance glyphosate on various model organisms may help to elucidate the role of defense mechanisms in its toxic effects. Evaluation of the impact of Roundup and its components on metabolism, cell signaling, apoptosis and aging with particular attention to mitochondria in order to understand interference with bioenergetic functions is very important from theoretical and practical points of view. ...
Article
Full-text available
The effects of pesticides on the health of non-target living organisms in agricultural areas are critically important aspects for their safe use. Their release into the environment is an inevitable aspect for predicting and evaluation of the risk of their application. Roundup, a glyphosate-based herbicide, has been designed as an effective pesticide against weeds and now is the most widely used agrochemicals around the world due to its highly specific action of the biosynthesis of certain amino acids in plants. Despite it is claimed to be low toxic for not-target organisms, due to its broad application Roundup and products of its degradation were detected in organisms of diverse animals and humans. In this review, we describe animal and human studies of general adverse effects of Roundup and its principal substance glyphosate with focus on endocrine disruption, oxidative stress and behavioral disorders. At mechanistic level, we focus on the potential toxicity of the herbicide Roundup and glyphosate as effectors of bioenergetic functions of mitochondria. Their effects on mitochondrial membrane potential and oxidative phosphorylation are among described to date critical components responsible for its toxicity. Finally, we discuss general molecular mechanisms potentially involved in the interaction between glyphosate and mitochondria which to some extent are associated with generation of reactive oxygen species.
... Furthermore, glyphosate based herbicides affect the supply of essential amino acids in human body by disrupting different biochemical pathways such as shikimate pathway found in the human gut bacteria. (Samsel & Seneff, 2015). A well-known pesticide "Roundup," causes endocrine disruption and DNA damage in human cell lines (Gasnier et al., 2009) Several metabolic, cellular, reproductive and mitochondrial disorders have been associated with fewer carbamate pesticides, such as ziram, aldicarb and carbofuran (Goad, Goad, Atieh, & Gupta, 2004;Mnif et al., 2011). ...
Chapter
Full-text available
Environment protection is a critical issue for the sustainability of life. The level of pollutants from anthropogenic activities is a constant threat to the environment. Among these pollutants, pesticides are the important entities owing to their application in crop protection. Pesticides are available to combat herbs, insects, fungi, and bacteria. Pesticides can have mild to extreme toxicity, ranging from extremely hazardous to severe or chronic. There is an utmost need to monitor the concentration of pesticides in soil. Several conventional techniques available for pesticide detection, such as liquid chromatography-tandem mass spectroscopic techniques, nuclear magnetic resonance spectroscopy, and UV–Visible spectroscopy. These techniques require highly specialized instrumentation and expert personnel for their operation. Nanomaterials and nanosensors are the mainstream instruments these days since they have become an important detection tool for environmental toxins. Nanosensors exhibit exceptional properties like robustness, sensitivity, selectivity, cost-effectiveness within a miniaturized setup. In this chapter, various classes of pesticides, their associated hazards, conventional methods for their quantification, along with nanomaterials and nanotechnology-based approaches to monitor pesticide concentration in soil are discussed in detail. This chapter will help better understanding of the fate and behavior of nanomaterials in the soil, distribution among plants, uptake, and their impact on soil microbial communities, along with their interactions with other pollutants.
... Studies are emerging of adverse effects of both G alone and GBH, and correlation with several diseases is rising following its use in agriculture. Within these conditions, there are inflammatory bowel disease, thyroid dysfunction, and infertility (Samsel and Seneff, 2015). The association between a greater GBHs application and immune-endocrine-mediated diseases strengthens the hypothesis that G or better GBHs can alter these systems. ...
Article
Glyphosate (G) is the active ingredient of the most widely used herbicide products. It targets the enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), which lacks in humans, suggesting to confer a low mammalian toxicity to G-based herbicides (GBHs). Despite this, the use of G is currently under intense debate. Many studies indicating its hazard and toxicity on non-target organisms are emerging, and associations between GBHs and immune-endocrine disturbances have been described. This review aims to investigate, based on recent epidemiological studies and studies performed in vitro and in vivo in animals, the possible association between GBHs and immune-endocrine alterations. Published data suggest that GBHs have endocrine disrupting potentiality targeting sex and thyroid hormones, although its relevance for humans will require further investigations. Evidence of immunotoxicity are limited compared to those on endocrine effects, but overall highlight possible noxious effects, including lung inflammation and rhinitis. An attractive hypothesis could be the one that connects microbiota dysbiosis with possible immune-endocrine outcomes. Indeed, several intestinal microorganisms express the enzyme EPSPS and, studies are emerging that highlight a possible G-induced dysbiosis. Considering the wide use of GBHs in agriculture, further studies investigating their noxious effects at levels relevant for human exposure should be performed. A critical analysis of emerging evidence of G toxicity is required to better characterize its safety profile. In addition, attention should be paid to the differences between G alone and its formulations, which, containing substances able to increase G absorption, may present a different toxicity profile.
... We have not noted this pH adjustment in other toxicity studies, but the pH has been shown to influence toxicity in aquatic organisms (Mann and Bidwell 1999;Tsui and Chu 2003). The chelation of cations by glyphosate has been discussed in relation interference with micronutrients required in plants (Mertens et al. 2018) and has been suggested to promote adverse effects in mammals by interfering with availability of manganese, an essential mineral, from the gut (Samsel and Seneff 2015). The evidence for this at small realistic dietary exposures to glyphosate is weak (Mesnage and Antoniou 2017) but at the heroic doses of glyphosate that are given to mammals in some toxicity tests, this may be responsible for the observed effects in the animals as well as on the microbiota of the gut. ...
Article
The chemical and biological properties of glyphosate are key to understanding its fate in the environment and potential risks to non-target organisms. Glyphosate is polar and water soluble and therefore does not bioaccumulate, biomagnify, or accumulate to high levels in the environment. It sorbs strongly to particles in soil and sediments and this reduces bioavailability so that exposures to non-target organisms in the environment are acute and decrease with half-lives in the order of hours to a few days. The target site for glyphosate is not known to be expressed in animals, which reduces the probability of toxicity and small risks. Technical glyphosate (acid or salts) is of low to moderate toxicity; however, when mixed with some formulants such as polyoxyethylene amines (POEAs), toxicity to aquatic animals increases about 15-fold on average. However, glyphosate and the formulants have different fates in the environment and they do not necessarily co-occur. Therefore, toxicity tests on formulated products in scenarios where they would not be used are unrealistic and of limited use for assessment of risk. Concentrations of glyphosate in surface water are generally low with minimal risk to aquatic organisms, including plants. Toxicity and risks to non-target terrestrial organisms other than plants treated directly are low and risks to terrestrial invertebrates and microbial processes in soil are very small. Formulations containing POEAs are not labeled for use over water but, because POEA rapidly partitions into sediment, risks to aquatic organisms from accidental over-sprays are reduced in shallow water bodies. We conclude that use of formulations of glyphosate under good agricultural practices presents a de minimis risk of direct and indirect adverse effects in non-target organisms.
... We have not noted this pH adjustment in other toxicity studies, but the pH has been shown to influence toxicity in aquatic organisms (Mann and Bidwell 1999;Tsui and Chu 2003). The chelation of cations by glyphosate has been discussed in relation interference with micronutrients required in plants (Mertens et al. 2018) and has been suggested to promote adverse effects in mammals by interfering with availability of manganese, an essential mineral, from the gut (Samsel and Seneff 2015). The evidence for this at small realistic dietary exposures to glyphosate is weak (Mesnage and Antoniou 2017) but at the heroic doses of glyphosate that are given to mammals in some toxicity tests, this may be responsible for the observed effects in the animals as well as on the microbiota of the gut. ...
Chapter
Glyphosate is the most used herbicide globally. It is a unique non-selective herbicide with a mode of action that is ideal for vegetation management in both agricultural and non-agricultural settings. Its use was more than doubled by the introduction of transgenic, glyphosate-resistant (GR) crops. All of its phytotoxic effects are the result of inhibition of only 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), but inhibition of this single enzyme of the shikimate pathway results in multiple phytotoxicity effects, both upstream and downstream from EPSPS, including loss of plant defenses against pathogens. Degradation of glyphosate in plants and microbes is predominantly by a glyphosate oxidoreductase to produce aminomethylphosphonic acid and glyoxylate and to a lesser extent by a C-P lyase to produce sarcosine and phosphate. Its effects on non-target plant species are generally less than that of many other herbicides, as it is not volatile and is generally sprayed in larger droplet sizes with a relatively low propensity to drift and is inactivated by tight binding to most soils. Some microbes, including fungal plant pathogens, have glyphosate-sensitive EPSPS. Thus, glyphosate can benefit GR crops by its activity on some plant pathogens. On the other hand, glyphosate can adversely affect some microbes that are beneficial to agriculture, such as Bradyrhizobium species, although GR crop yield data indicate that such an effect has been minor. Effects of glyphosate on microbes of agricultural soils are generally minor and transient, with other agricultural practices having much stronger effects.
... Glyphosate is released into the environment mostly due to reckless mixing, application, and cleaning of sprayers [3]; resulting in contaminated food and water that serve as the main routes of uptake in humans [4]. Glyphosate exposure may contribute to the development of a wide variety of chronic diseases such as developmental disorders (autism), allergies, gastrointestinal diseases, endocrine dysfunction, cardiovascular diseases, Alzheimer's disease, Parkinson's disease, cancer and infertility [5][6][7][8]. Paraquat (1, 1 dimethyl-4, 4 -bipyridium dichloride) is a non-selective contact bipyridilium herbicide in frequent use since the 1980s [9]. Farmers are often exposed by occupational, homicidal, or accidental exposure [10][11][12][13][14]. Paraquat may enter the human body through various routes such as oral, nasal, ocular and dermal routes [15][16][17][18]. ...
Article
Full-text available
Extensive use of herbicides is common among rural agricultural workers in Sri Lanka. Recent studies have postulated their role in the development of chronic kidney disease of unknown etiology (CKDu). Paraquat and glyphosate are leading herbicides used by sugarcane farmers (SF), hence occupational exposure is inevitable. This study examined the expression of urinary paraquat, glyphosate and biomarkers among residential SF in CKDu emerging regions, Warunagama (WA) and Rahathangama (RH), in the Uva Province with non-endemic Matara (MA) in the Southern Province of Sri Lanka. Urinary glyphosate, Paraquat, Kidney injury molecule -1 (KIM-I), Neutrophil gelatinase-associated lipocalin (NGAL) andβ2-microglobulin (B2M) were determined using enzyme-linked immunosorbent assays (ELISA). Urinary creatinine, microalbumin, serum creatinine (SCr), serum cystatin C, estimated glomerular filtration rate (eGFR), and albumin creatinine ratio (ACR) were also assessed. Generally, herbicide residues and kidney injury biomarkers were higher in SF compared to the non-endemic MA. Creatinine-adjusted urinary glyphosate and paraquat levels were significantly higher in WA compared to MA. ACR in RH (median 14.9; IQR 5.4–393.1 mg/g) and WA (23.7; 11.5–64.6) was significantly higher than MA (4.3; 2.2–6.7). This study reports 39 individuals with impaired kidney function among SF in Sri Lanka for the first time. Urinary NGAL levels were significantly higher in both WA (median 2.14; IQR 1.28–6.15 ng/mg Cr) and RH (3.09; 1.15–9.09) compared to MA (1.28; 0.56–2.81). However, urinary KIM-I levels in RH (3.2; 1.29–106.1 ng/g Cr) and WA (3.6; 1.94–115.1) were not significantly higher in MA (1.74; 0.76–116.9). Urinary NGAL (r = 0.493), eGFR (r = −0.147) and ACR (r = 0.171) significantly correlated with urinary glyphosate, but not with urinary paraquat levels. Urinary KIM-1 levels did not correlate with either urinary glyphosate or paraquat, while urinary B2M and serum cystatin C levels showed significant correlation with urinary glyphosate levels. The current study reports higher urinary herbicide levels among sugarcane farmers in WA and RH, and that is potentially linked to the subsequent decline in kidney function, as indicated by ACR, eGFR, and NGAL. We posit that these indicators may serve as markers to detect renal injury among herbicide-exposed SF in Rural Sri Lanka.
... Glyphosate has a variety of tumorigenic effects on biological systems, including direct DNA damage in sensitive cells, disruption of glycine homeostasis, succinate dehydrogenase inhibition, manganese chelation, modification to more carcinogenic molecules like N-nitrosoglyphosate and glyoxylate, disruption of fructose metabolism, and so on. Strong temporal links between glyphosate use on crops and a variety of malignancies that are reaching epidemic proportions, including breast cancer, pancreatic cancer, kidney cancer, thyroid cancer, liver cancer, bladder cancer, and myeloid leukaemia, are supported by epidemiological studies [13]. Increased risk of massive mammary tumours in the females, along with kidney and liver damage in the males has been observed in rats fed GM maize and/or Roundup in their water over their entire lifespan associated with the increased risk of glyphosate usage [14]. ...
... As a result, it appears to impair folic acid production in both exposed plant food sources and the human gut, resulting in deficits that promote colorectal carcinogenesis and a variety of malignancies, including colorectal, breast, ovarian, pancreatic, brain, lung, and cervix cancers [49]. Glyphosate exposure impairs tryptophan bioavailability to the human host, resulting in tumours in the lung, colon, liver, breast, and skin melanoma [13,50]. ...
Article
Full-text available
Pesticides are a vast mixture of compounds used to control pests like plants, moulds, and insects. In agriculture, non-agricultural vegetation management, and crop desiccant harvesting aid, chemicals from every major functional family of pesticides, such as insecticides, herbicides, fungicides, and fumigants, were frequently used. Herbicides are one of the most effective tools for farmers to obtain optimal crop yields when used correctly. Glyphosate (N-(phosphonomethyl) glycine) is a broad-spectrum weed killer that is used all over the world in agriculture and forestry. Glyphosate's herbicidal activity in plants is to disrupt the shikimic acid pathway's generation of branched-chain amino acids by preventing the binding of phosphoenolpyruvate (PEP) to the enzyme 5-enolpyruvylshikimate 3-phosphate synthase. This causes a deficiency in aromatic amino acid synthesis and, as a result, weeds mortality. Glyphosate exposure through food, drinking water, wind, water erosion, and other environmental pathways has been linked to human health issues as a carcinogen, mutagen, and reproductive toxicity. Glyphosate has a wide range of tumorigenic Review Article Prasad et al.; JPRI, 33(62A): 307-316, 2021; Article no.JPRI.83787 308 effects in biological systems, and epidemiological evidence suggests that glyphosate use on crops is linked to a wide range of cancers, including liver cancer, breast cancer, thyroid cancer, pancreatic cancer, kidney cancer, bladder cancer, and myeloid cancer. The shikimate pathway enzymes, intermediates, and derivative amino acids, which have been associated to genotoxicity and carcinogenicity, are thought to have a role in most cancer pathologies. This review summarises glyphosate's function in cancer pathology, including the ability of the glyphosate circuit to induce cancer and implications for future therapeutic methods.
... Herbicides related to health problems are a cause of global concern. The most controversial one being glyphosate, which has been linked to cytotoxic, endocrine disrupting, immunotoxigenic, genotoxic, and carcinogenic effects (Gigante et al. 2018) that can derive into neurodevelopmental and congenital problems, Alzheimer's disease, Parkinson's disease (Rueda-Ruzafa et al. 2019), metabolic syndrome, thyroid disease, obesity, diabetes mellitus, hypertension, nephropathy (Samsel and Seneff 2015;Seneff and Orlando, 2018), pneumopathies, and various types of cancer (Gigante et al. 2018). Genotoxicity biomarkers are considered an essential tool for the study of potentially exposed individuals to contaminants that also complements the measurement of environmental and epidemiological risk (Lock and Bonventre, 2008;Katsikantami et al. 2017). ...
Article
Full-text available
Valle del Mayo is an important agricultural area at the northwest of Mexico where up to 20,000 L of a mix composed of glyphosate and tordon is used in drains and canals. This study was carried out in order to evaluate the cellular damage caused by glyphosate, aminomethylphosphonic acid (AMPA), and picloram in agricultural workers. Biomonitoring was performed through the quantification of herbicides in urine using HPLC (high-performance liquid chromatography) to then evaluate the cellular damage in exposed people by means of an evaluation of micronuclei and cellular proliferation in lymphocyte cultures. The urine samples (n = 30) have shown a concentration of up to 10.25 μg/L of picloram and 2.23 μg/L of AMPA; no positive samples for glyphosate were reported. The calculation of the external dose reveals that agricultural workers ingest up to 146 mg/kg/day; however, this concentration does not surpass the limits that are allowed internationally. As for the results for the micronuclei test, 53% of the workers showed cellular damage, and the nuclear division index test reported that there was a significant difference (P < 0.05) between the exposed and the control population, which indicated that the exposure time to pesticides in the people of Valle del Mayo can induce alterations which can cause chronic damage.