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      Effect of a Glyphosate-Containing Herbicide on Escherichia coli and Salmonella Ser. Typhimurium in an In Vitro Rumen Simulation System

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          Abstract

          Glyphosate ( N-(phosphonomethyl)glycine) is the most-used herbicide worldwide. Many studies in the past have shown that residues of the herbicide can be found in many cultivated plants, including those used as livestock feed. Sensitivity to glyphosate varies with bacteria, particularly those residing in the intestine, where microbiota is exposed to glyphosate residues. Therefore, less susceptible pathogenic isolates could have a distinct advantage compared to more sensitive commensal isolates, probably leading to dysbiosis.

          To determine whether the ruminal growth and survival of pathogenic Escherichia coli or Salmonella serovar Typhimurium are higher when glyphosate residues are present in the feed, an in vitro fermentation trial with a “Rumen Simulation System” (RUSITEC) and a glyphosate-containing commercial formulation was performed.

          Colony forming units of E. coli and Salmonella ser. Typhimurium decreased steadily in all fermenters, regardless of the herbicide application. Minimum inhibitory concentrations of the studied Salmonella and E. coli strains did not change, and antibiotic susceptibility varied only slightly but independent of the glyphosate application.

          Overall, application of the glyphosate-containing formulation in a worst-case concentration of 10 mg/L neither increased the abundance for the tested E. coli and Salmonella strain in the in vitro fermentation system, nor promoted resistance to glyphosate or antibiotics.

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          Most cited references 53

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          THE SHIKIMATE PATHWAY.

          The shikimate pathway links metabolism of carbohydrates to biosynthesis of aromatic compounds. In a sequence of seven metabolic steps, phosphoenolpyruvate and erythrose 4-phosphate are converted to chorismate, the precursor of the aromatic amino acids and many aromatic secondary metabolites. All pathway intermediates can also be considered branch point compounds that may serve as substrates for other metabolic pathways. The shikimate pathway is found only in microorganisms and plants, never in animals. All enzymes of this pathway have been obtained in pure form from prokaryotic and eukaryotic sources and their respective DNAs have been characterized from several organisms. The cDNAs of higher plants encode proteins with amino terminal signal sequences for plastid import, suggesting that plastids are the exclusive locale for chorismate biosynthesis. In microorganisms, the shikimate pathway is regulated by feedback inhibition and by repression of the first enzyme. In higher plants, no physiological feedback inhibitor has been identified, suggesting that pathway regulation may occur exclusively at the genetic level. This difference between microorganisms and plants is reflected in the unusually large variation in the primary structures of the respective first enzymes. Several of the pathway enzymes occur in isoenzymic forms whose expression varies with changing environmental conditions and, within the plant, from organ to organ. The penultimate enzyme of the pathway is the sole target for the herbicide glyphosate. Glyphosate-tolerant transgenic plants are at the core of novel weed control systems for several crop plants.
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            Safety evaluation and risk assessment of the herbicide Roundup and its active ingredient, glyphosate, for humans.

            Reviews on the safety of glyphosate and Roundup herbicide that have been conducted by several regulatory agencies and scientific institutions worldwide have concluded that there is no indication of any human health concern. Nevertheless, questions regarding their safety are periodically raised. This review was undertaken to produce a current and comprehensive safety evaluation and risk assessment for humans. It includes assessments of glyphosate, its major breakdown product [aminomethylphosphonic acid (AMPA)], its Roundup formulations, and the predominant surfactant [polyethoxylated tallow amine (POEA)] used in Roundup formulations worldwide. The studies evaluated in this review included those performed for regulatory purposes as well as published research reports. The oral absorption of glyphosate and AMPA is low, and both materials are eliminated essentially unmetabolized. Dermal penetration studies with Roundup showed very low absorption. Experimental evidence has shown that neither glyphosate nor AMPA bioaccumulates in any animal tissue. No significant toxicity occurred in acute, subchronic, and chronic studies. Direct ocular exposure to the concentrated Roundup formulation can result in transient irritation, while normal spray dilutions cause, at most, only minimal effects. The genotoxicity data for glyphosate and Roundup were assessed using a weight-of-evidence approach and standard evaluation criteria. There was no convincing evidence for direct DNA damage in vitro or in vivo, and it was concluded that Roundup and its components do not pose a risk for the production of heritable/somatic mutations in humans. Multiple lifetime feeding studies have failed to demonstrate any tumorigenic potential for glyphosate. Accordingly, it was concluded that glyphosate is noncarcinogenic. Glyphosate, AMPA, and POEA were not teratogenic or developmentally toxic. There were no effects on fertility or reproductive parameters in two multigeneration reproduction studies with glyphosate. Likewise there were no adverse effects in reproductive tissues from animals treated with glyphosate, AMPA, or POEA in chronic and/or subchronic studies. Results from standard studies with these materials also failed to show any effects indicative of endocrine modulation. Therefore, it is concluded that the use of Roundup herbicide does not result in adverse effects on development, reproduction, or endocrine systems in humans and other mammals. For purposes of risk assessment, no-observed-adverse-effect levels (NOAELs) were identified for all subchronic, chronic, developmental, and reproduction studies with glyphosate, AMPA, and POEA. Margins-of-exposure for chronic risk were calculated for each compound by dividing the lowest applicable NOAEL by worst-case estimates of chronic exposure. Acute risks were assessed by comparison of oral LD50 values to estimated maximum acute human exposure. It was concluded that, under present and expected conditions of use, Roundup herbicide does not pose a health risk to humans.
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              Potential toxic effects of glyphosate and its commercial formulations below regulatory limits.

              Glyphosate-based herbicides (GlyBH), including Roundup, are the most widely used pesticides worldwide. Their uses have increased exponentially since their introduction on the market. Residue levels in food or water, as well as human exposures, are escalating. We have reviewed the toxic effects of GlyBH measured below regulatory limits by evaluating the published literature and regulatory reports. We reveal a coherent body of evidence indicating that GlyBH could be toxic below the regulatory lowest observed adverse effect level for chronic toxic effects. It includes teratogenic, tumorigenic and hepatorenal effects. They could be explained by endocrine disruption and oxidative stress, causing metabolic alterations, depending on dose and exposure time. Some effects were detected in the range of the recommended acceptable daily intake. Toxic effects of commercial formulations can also be explained by GlyBH adjuvants, which have their own toxicity, but also enhance glyphosate toxicity. These challenge the assumption of safety of GlyBH at the levels at which they contaminate food and the environment, albeit these levels may fall below regulatory thresholds. Neurodevelopmental, reproductive, and transgenerational effects of GlyBH must be revisited, since a growing body of knowledge suggests the predominance of endocrine disrupting mechanisms caused by environmentally relevant levels of exposure.
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                Author and article information

                Journal
                Eur J Microbiol Immunol (Bp)
                Eur J Microbiol Immunol (Bp)
                EUJMI
                European Journal of Microbiology & Immunology
                Akadémiai Kiadó (Budapest )
                2062-509X
                2062-8633
                27 June 2019
                03 October 2019
                : 9
                : 3
                : 94-99
                Affiliations
                [1 ]Institute for Animal Hygiene and Environmental Health, Freie Universität Berlin , Berlin, Germany
                [2 ]Institute for Physiology and Cell Biology, University of Veterinary Medicine , Hannover, Germany
                Author notes
                *Author for correspondence: Institute for Animal Hygiene and Environmental Health, Robert-von-Ostertag-St. 7–13, 14163, Berlin, Germany; E-mail: Katrin.Bote@ 123456fu-berlin.de and E-mail: tierhygiene@ 123456vetmed.fu-berlin.de ; Phone: +49 30 838 51845; Fax: +49 30 838 451863.
                Article
                10.1556/1886.2019.00010
                © 2019, The Author(s)

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and reproduction in any medium for non-commercial purposes, provided the original author and source are credited, a link to the CC License is provided, and changes - if any – are indicated.

                Page count
                Figures: 2, Tables: 5, Equations: 0, References: 52, Pages: 6
                Categories
                Original Research Paper

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