Bibliography Tag: glyphosate

Gorga et al., 2021

Gorga, A., Rindone, G. M., Centola, C. L., Sobarzo, C. M., Pellizzari, E. H., Camberos, M. D. C., Marin-Briggiler, C. I., Cohen, D. J., Riera, M. F., Galardo, M. N., & Meroni, S. B.; “Low Doses of Glyphosate/Roundup Alter Blood-Testis Barrier Integrity in Juvenile Rats;” Frontiers in Endocrinology, 2021, 12, 615678; DOI: 10.3389/fendo.2021.615678.


It has been postulated that glyphosate (G) or its commercial formulation Roundup (R) might lead to male fertility impairment. In this study, we investigated the possible effects of G or R treatment of juvenile male rats on blood-testis barrier function and on adult male sperm production. Pups were randomly assigned to the following groups: control group (C), receiving water; G2 and G50 groups, receiving 2 and 50 mg/kg/day G respectively; and R2 and R50 groups receiving 2 and 50 mg/kg/day R respectively. Treatments were performed orally from postnatal day (PND) 14 to 30, period of life that is essential to complete a functional blood-testis barrier. Evaluation was done on PND 31. No differences in body and testis weight were observed between groups. Testis histological analysis showed disorganized seminiferous epithelium, with apparent low cellular adhesion in treated animals. Blood-testis barrier permeability to a biotin tracer was examined. A significant increase in permeable tubules was observed in treated groups. To evaluate possible mechanisms that could explain the effects on blood-testis barrier permeability, intratesticular testosterone levels, androgen receptor expression, thiobarbituric acid reactive substances (TBARS) and the expression of intercellular junction proteins (claudin11, occludin, ZO-1, connexin43, 46, and 50 which are components of the blood-testis barrier) were examined. No modifications in the above-mentioned parameters were detected. To evaluate whether juvenile exposure to G and R could have consequences during adulthood, a set of animals of the R50 group was allowed to grow up until PND 90. Histological analysis showed that control and R50 groups had normal cellular associations and complete spermatogenesis. Also, blood-testis barrier function was recovered and testicular weight, daily sperm production, and epididymal sperm motility and morphology did not seem to be modified by juvenile treatment. In conclusion, the results presented herein show that continuous exposure to low doses of G or R alters blood-testis barrier permeability in juvenile rats. However, considering that adult animals treated during the juvenile stage showed no differences in daily sperm production compared with control animals, it is feasible to think that blood-testis barrier impairment is a reversible phenomenon. More studies are needed to determine possible damage in the reproductive function of human juvenile populations exposed to low doses of G or R. FULL TEXT

Rueda-Ruzafa et al., 2019

Rueda-Ruzafa, L., Cruz, F., Roman, P., & Cardona, D.; “Gut microbiota and neurological effects of glyphosate;” NeuroToxicology, 2019, 75, 1-8; DOI: 10.1016/j.neuro.2019.08.006.


There are currently various concerns regarding certain environmental toxins and the possible impact they can have on developmental diseases. Glyphosate (Gly) is the most utilised herbicide in agriculture, although its widespread use is generating controversy in the scientific world because of its probable carcinogenic effect on human cells. Gly performs as an inhibitor of 5-enolpyruvylshikimate-3-phospate synthase (EPSP synthase), not only in plants, but also in bacteria. An inhibiting effect on EPSP synthase from intestinal microbiota has been reported, affecting mainly beneficial bacteria. To the contrary, Clostridium spp. and Salmonella strains are shown to be resistant to Gly. Consequently, researchers have suggested that Gly can cause dysbiosis, a phenomenon which is characterised by an imbalance between beneficial and pathogenic microorganisms. The overgrowth of bacteria such as clostridia generates high levels of noxious metabolites in the brain, which can contribute to the development of neurological deviations. This work reviews the impact of Gly-induced intestinal dysbiosis on the central nervous system, focusing on emotional, neurological and neurodegenerative disorders. A wide variety of factors were investigated in relation to brain-related changes, including highlighting genetic abnormalities, pregnancy-associated problems, diet, infections, vaccines and heavy metals. However, more studies are required to determine the implication of the most internationally used herbicide, Gly, in behavioural disorders. FULL TEXT

Leino et al., 2020

Leino, L., Tall, T., Helander, M., Saloniemi, I., Saikkonen, K., Ruuskanen, S., & Puigbo, P.; “Classification of the glyphosate target enzyme (5-enolpyruvylshikimate-3-phosphate synthase) for assessing sensitivity of organisms to the herbicide;” Journal of Hazardous Materials, 2020, 124556; DOI: 10.1016/j.jhazmat.2020.124556.


Glyphosate is the most common broad-spectrum herbicide. It targets the key enzyme of the shikimate pathway, 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), which synthesizes three essential aromatic amino acids (phenylalanine, tyrosine and tryptophan) in plants. Because the shikimate pathway is also found in many prokaryotes and fungi, the widespread use of glyphosate may have unsuspected impacts on the diversity and composition of microbial communities, including the human gut microbiome. Here, we introduce the first bioinformatics method to assess the potential sensitivity of organisms to glyphosate based on the type of EPSPS enzyme. We have precomputed a dataset of EPSPS sequences from thousands of species that will be an invaluable resource to advancing the research field. This novel methodology can classify sequences from nearly 90% of eukaryotes and >80% of prokaryotes. A conservative estimate from our results shows that 54% of species in the core human gut microbiome are sensitive to glyphosate. FULL TEXT

Mesnage et al., 2021

Mesnage, R, Teixeira, M, Mandrioli, D., Falcioni, L., Ducarmon, QR, Zwittink, RD, Mazzacuva, F, Caldwell, A, Halket, J, Amiel, C., Panoff, J. , Belpoggi, F., & Antoniou, MN; “Use of shotgun metagenomics and metabolomics to evaluate the impact of glyphosate or Roundup MON 52276 on the gut microbiota and serum metabolome of Sprague-Dawley rats;” Environmental Health Perspectives, 2021 (in press); DOI: 10.1289/EHP6990.


BACKGROUND: There is intense debate on whether glyphosate can inhibit the shikimate pathway of gastrointestinal microorganisms, with potential health implications.

OBJECTIVES: We tested whether glyphosate or its representative EU herbicide formulation Roundup MON 52276 affects the rat gut microbiome.

METHODS: We combined cecal microbiome shotgun metagenomics with serum and cecum metabolomics to assess the effects of glyphosate [0.5, 50, 175 mg=kg body weight (BW) per day] or MON 52276 at the same glyphosate-equivalent doses, in a 90-d toxicity test in rats.

RESULTS: Glyphosate and MON 52276 treatment resulted in ceca accumulation of shikimic acid and 3-dehydroshikimic acid, suggesting inhibition of 5-enolpyruvylshikimate-3-phosphate synthase of the shikimate pathway in the gut microbiome. Cysteinylglycine, γ-glutamylglutamine, and valylglycine levels were elevated in the cecal microbiome following glyphosate and MON 52276 treatments. Altered cecum metabolites were not differentially expressed in serum, suggesting that the glyphosate and MON 52276 impact on gut microbial metabolism had limited consequences on physiological biochemistry. Serum metabolites differentially expressed with glyphosate treatment were associated with nicotinamide, branched-chain amino acid, methionine, cysteine, and taurine metabolism, indicative of a response to oxidative stress. MON 52276 had similar, but more pronounced, effects than glyphosate on the serum metabolome. Shotgun metagenomics of the cecum showed that treatment with glyphosate and MON 52276 resulted in higher levels of Eggerthella spp., Shinella zoogleoides, Acinetobacter johnsonii, and Akkermansia muciniphila. Shinella zoogleoides was higher only with MON 52276 exposure. In vitro culture assays with Lacticaseibacillus rhamnosus strains showed that Roundup GT plus inhibited growth at concentrations at which MON 52276 and glyphosate had no effect.

DISCUSSION: Our study highlights the power of multi-omics approaches to investigate the toxic effects of pesticides. Multi-omics revealed that glyphosate and MON 52276 inhibited the shikimate pathway in the rat gut microbiome. Our findings could be used to develop biomarkers for epidemiological studies aimed at evaluating the effects of glyphosate herbicides on humans FULL TEXT.

Zhang et al., 2021

Zhang, H., Liu, J., Wang, L., & Zhai, Z.; “Glyphosate escalates horizontal transfer of conjugative plasmid harboring antibiotic resistance genes;” Bioengineered, 2021, 12(1), 63-69; DOI: 10.1080/21655979.2020.1862995.


Glyphosate has been frequently detected in water environments because of the wide use for controlling weed in farm lands and urban areas. Presently, the focus of the majority of studies is placed on the toxicity of glyphosate on humans and animals. However, the effects of glyphosate on horizontal transfer of conjugative plasmid carrying antibiotic resistance gene (ARG) are largely unknown. Here, we explored the ability and potential mechanism of glyphosate for accelerating horizontal transfer of conjugative plasmid-mediated ARG. The results showed that glyphosate can effectively boost horizontal transfer rate of conjugative plasmid carrying ARG. The possible mechanism analysis demonstrated that over-production of reactive oxygen species and reactive nitrogen species effectively regulated expression levels of bacterial outer membrane protein and conjugative transfer-related genes, thereby resulting into elevated horizontal transfer rate of plasmid-mediated ARG. In conclusion, this study casts new understanding into the biological effects of glyphosate on ARG. FULL TEXT

Suppa et al., 2020

Suppa, A., Kvist, J., Li, X., Dhandapani, V., Almulla, H., Tian, A. Y., Kissane, S., Zhou, J., Perotti, A., Mangelson, H., Langford, K., Rossi, V., Brown, J. B., & Orsini, L.; “Roundup causes embryonic development failure and alters metabolic pathways and gut microbiota functionality in non-target species;” Microbiome, 2020, 8(1), 170; DOI: 10.1186/s40168-020-00943-5.


BACKGROUND: Research around the weedkiller Roundup is among the most contentious of the twenty-first century. Scientists have provided inconclusive evidence that the weedkiller causes cancer and other life-threatening diseases, while industry-paid research reports that the weedkiller has no adverse effect on humans or animals. Much of the controversial evidence on Roundup is rooted in the approach used to determine safe use of chemicals, defined by outdated toxicity tests. We apply a system biology approach to the biomedical and ecological model species Daphnia to quantify the impact of glyphosate and of its commercial formula, Roundup, on fitness, genome-wide transcription and gut microbiota, taking full advantage of clonal reproduction in Daphnia. We then apply machine learning-based statistical analysis to identify and prioritize correlations between genome-wide transcriptional and microbiota changes.

RESULTS: We demonstrate that chronic exposure to ecologically relevant concentrations of glyphosate and Roundup at the approved regulatory threshold for drinking water in the US induce embryonic developmental failure, induce significant DNA damage (genotoxicity), and interfere with signaling. Furthermore, chronic exposure to the weedkiller alters the gut microbiota functionality and composition interfering with carbon and fat metabolism, as well as homeostasis. Using the “Reactome,” we identify conserved pathways across the Tree of Life, which are potential targets for Roundup in other species, including liver metabolism, inflammation pathways, and collagen degradation, responsible for the repair of wounds and tissue remodeling.

CONCLUSIONS: Our results show that chronic exposure to concentrations of Roundup and glyphosate at the approved regulatory threshold for drinking water causes embryonic development failure and alteration of key metabolic functions via direct effect on the host molecular processes and indirect effect on the gut microbiota. The ecological model species Daphnia occupies a central position in the food web of aquatic ecosystems, being the preferred food of small vertebrates and invertebrates as well as a grazer of algae and bacteria. The impact of the weedkiller on this keystone species has cascading effects on aquatic food webs, affecting their ability to deliver critical ecosystem services. FULL TEXT

Santos et al., 2020

Santos, J. S., Pontes, M. S., Santiago, E. F., Fiorucci, A. R., & Arruda, G. J.; “An efficient and simple method using a graphite oxide electrochemical sensor for the determination of glyphosate in environmental samples;” Science of The Total Environment, 2020, 749, 142385; DOI: 10.1016/j.scitotenv.2020.142385.


Excessive and indiscriminate use of the herbicide glyphosate (GLY) leaves the environment susceptible to its contamination. This work describes the development of a simple, inexpensive, and efficient electroanalytical method using graphite oxide paste electrode (GrO-PE) for the direct determination of GLY traces in groundwater samples, soybean extracts, and lettuce extracts. Under optimal experimental conditions, the developed sensor exhibited a linear response of the peak current intensity vs. the concentration, in the range of 1.8 x 10(-5) to 1.2 x 10(-3) mol L(-1) for GLY. The limits of detection and quantification are 1.7 x 10(-8) mol L(-1) and 5.6 x 10(-8) mol L(-1), respectively. The methodology developed here demonstrated a strong analytical performance, with high reproducibility, repeatability, and precision. Moreover, it successfully avoided interference from other substances, showing high selectivity. The GrO-PE sensor was effectively applied to determine GLY traces in real samples with recovery rates ranging from 98% to 102%. Results showed that the GrO-PE is effective and useful for GLY detection, with the advantage of not involving laborious modifications and complicated handling, making it a promising tool for environmental analysis. FULL TEXT

Rydz et al., 2020

Rydz, C. E., Larsen, K., & Peters, C. E.; “Estimating Exposure to Three Commonly Used, Potentially Carcinogenic Pesticides (Chlorolathonil, 2,4-D, and Glyphosate) Among Agricultural Workers in Canada;” Annals of Work Exposures and Health, 2020; DOI: 10.1093/annweh/wxaa109.


OBJECTIVES: Certain pesticides have been associated with adverse health outcomes including cancer and reproductive harms. However, little is known about the prevalence of occupational pesticide exposure among agricultural workers in Canada. The purpose of this study was to estimate the prevalence and likelihood of occupational exposure to pesticides in Canada’s agricultural industry, using three commonly used, potentially carcinogenic pesticides [chlorothalonil, 2,4-dichlorophenoxyacetic acid (2,4-D), and glyphosate] as an example.

METHODS: Estimates were calculated using the Canadian Census of Population and the Census of Agriculture. The number of workers and the proportion of farms applying ‘herbicides’ or ‘fungicides’ by farm type was estimated using survey data from the Census of Agriculture. These values were multiplied to yield the potential number of workers at risk of exposure. Likelihood of exposure (i.e. exposed, probably exposed, and possibly exposed) was then qualitatively assigned using information on crop type, primary expected tasks, crop production practices, and residue transfer data. Additional agricultural workers who are at risk of exposure but not captured by the Census of Agriculture were identified using the 2016 Census of Population.

RESULTS: An estimated range of 37 700-55 800 workers (11-13% of agricultural workers) were exposed to glyphosate in Canada while 30 800-43 600 workers (9-11%) and 9000-14 100 (2.9-3.2%) were exposed to 2,4-D and chlorothalonil, respectively. Approximately 70-75% of workers at risk of exposure were considered probably or possibly exposed to any of the pesticides. Glyphosate exposure was most common among workers in oilseed (29% of oilseed farm workers exposed) and dry pea/bean farms (28%), along with those providing support activities for farms (31%). 2,4-D exposure was most common in corn (28%), other grain (28%), and soybean farms (27%), while chlorothalonil exposure was more likely among greenhouse, nursery, and floriculture workers (42%), workers on farms (28%, for occupations not captured by the Census of Agriculture, specifically), and those providing support activities for farms (20%). Regional variations broadly reflected differences in farm types by province.

CONCLUSIONS: This study estimated the prevalence of occupational exposure to three pesticides in Canada. Seasonal and temporary agricultural workers, which were captured by the Census of Agriculture, contributed to many additionally exposed workers. A large percent of the workers who were considered at risk of exposure were considered probably or possibly exposed, indicating a need for enhanced data collection and availability on pesticide use data in Canada. The study’s methods can be applied to estimate workers’ exposures to other pesticides within the agricultural industry.

Masood et al., 2021

Masood, M. I., Naseem, M., Warda, S. A., Tapia-Laliena, M. A., Rehman, H. U., Nasim, M. J., & Schafer, K. H.; “Environment permissible concentrations of glyphosate in drinking water can influence the fate of neural stem cells from the subventricular zone of the postnatal mouse;” Environmental Pollution, 2021, 270, 116179; DOI: 10.1016/j.envpol.2020.116179.


The developing nervous system is highly vulnerable to environmental toxicants especially pesticides. Glyphosate pesticide induces neurotoxicity both in humans and rodents, but so far only when exposed to higher concentrations. A few studies, however, have also reported the risk of general toxicity of glyphosate at concentrations comparable to allowable limits set up by environmental protection authorities. In vitro data regarding glyphosate neurotoxicity at concentrations comparable to maximum permissible concentrations in drinking water is lacking. In the present study, we established an in vitro assay based upon neural stem cells (NSCs) from the subventricular zone of the postnatal mouse to decipher the effects of two maximum permissible concentrations of glyphosate in drinking water on the basic neurogenesis processes. Our results demonstrated that maximum permissible concentrations of glyphosate recognized by environmental protection authorities significantly reduced the cell migration and differentiation of NSCs as demonstrated by the downregulation of the expression levels of the neuronal ss-tubulin III and the astrocytic S100B genes. The expression of the cytoprotective gene CYP1A1 was downregulated whilst the expression of oxidative stresses indicator gene SOD1 was upregulated. The concentration comparable to non-toxic human plasma concentration significantly induced cytotoxicity and activated Ca(2+) signalling in the differentiated culture. Our findings demonstrated that the permissible concentrations of glyphosate in drinking water recognized by environmental protection authorities are capable of inducing neurotoxicity in the developing nervous system. FULL TEXT

Lopez-Castanos et al., 2020

Lopez-Castanos, K. A., Ortiz-Frade, L. A., Mendez, E., Quiroga-Gonzalez, E., Gonzalez-Fuentes, M. A., & Mendez-Albores, A.; “Indirect Quantification of Glyphosate by SERS Using an Incubation Process With Hemin as the Reporter Molecule: A Contribution to Signal Amplification Mechanism;” Frontiers in Chemistry, 2020, 8, 612076; DOI: 10.3389/fchem.2020.612076.


The indirect determination of the most used herbicide worldwide, glyphosate, was achieved by the SERS technique using hemin chloride as the reporter molecule. An incubation process between hemin and glyphosate solutions was required to obtain a reproducible Raman signal on SERS substrates consisting of silicon decorated with Ag nanoparticles (Si-AgNPs). At 780 nm of excitation wavelength, SERS spectra from hemin solutions do not show extra bands in the presence of glyphosate. However, the hemin bands increase in intensity as a function of glyphosate concentration. This allows the quantification of the herbicide using as marker band the signal associated with the ring breathing mode of pyridine at 745 cm-1. The linear range was from 1 × 10-10 to 1 × 10-5 M and the limit of detection (LOD) was 9.59 × 10-12 M. This methodology was successfully applied to the quantification of the herbicide in honey. From Raman experiments with and without silver nanoparticles, it was possible to state that the hemin is the species responsible for the absorption in the absence or the presence of the herbicide via vinyl groups. Likewise, when the glyphosate concentration increases, a subtle increase occurs in the planar orientation of the vinyl group at position 2 in the porphyrin ring of hemin over the silver surface, favoring the reduction of the molecule. The total Raman signal of the hemin-glyphosate incubated solutions includes a maximized electromagnetic contribution by the use of the appropriate laser excitation, and chemical contributions related to charge transfer between silver and hemin, and from resonance properties of Raman scattering of hemin. Incubation of the reporter molecule with the analyte before the conjugation with the SERS substrate has not been explored before and could be extrapolated to other reporter-analyte systems that depend on a binding equilibrium process. FULL TEXT