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  1. Article ; Online: Comparison of transcriptome alterations induced by pendimethalin or its commercial formulation Stomp Aqua in human MCF-7, MCF-10 A and MCF-12 A mammary epithelial cells

    Robin Mesnage / Helin Omriouate / Michael N Antoniou

    BMC Research Notes, Vol 16, Iss 1, Pp 1-

    2023  Volume 7

    Abstract: Abstract Objective The toxicology of herbicides, which are currently in use is under-explored. One highly used but under investigated herbicide is pendimethalin. Here we mined high-throughput data from the US National Toxicology Program (NTP) to identify ...

    Abstract Abstract Objective The toxicology of herbicides, which are currently in use is under-explored. One highly used but under investigated herbicide is pendimethalin. Here we mined high-throughput data from the US National Toxicology Program (NTP) to identify whether pendimethalin possesses an estrogenic capability in human cells. We also evaluated effects of pendimethalin and its reference commercial formulated herbicide Stomp Aqua on the transcriptome profile of three human mammary epithelial cell lines, cancerous MCF-7 and non-cancerous MCF-10 A and MCF-12 A to see whether this compound could have endocrine disrupting effects and if co-formulants present in the commercial formulation could amplify its toxicity. Results The data mined from the US NTP database suggests that pendimethalin activates estrogen receptors at a concentration of approximately 10?M. MCF-7, MCF-10A and MCF-12A cells were exposed to 10 ?M pendimethalin and Stomp Aqua at an equivalent concentration. Transcriptome analysis showed changes in gene expression patterns implying that pendimethalin affected ubiquitin-mediated proteolysis and the function of the spliceosome. The formulated pendimethalin product Stomp Aqua gave comparable effects suggesting pendimethalin was responsible for the observed transcriptome alterations. Given the lack of information on the exposure to this pesticide, our study prompts the need for biomonitoring studies, especially under occupational use scenarios, to understand if low level exposure to pendimethalin could have endocrine disrupting effects on populations exposed to this compound. A deeper understanding of the exposure and mechanisms of action of this endocrine-disrupting pesticide is needed.
    Keywords Herbicides ; Pendimethalin ; Breast cancer ; Endocrine disruptor ; Transcriptome ; Medicine ; R ; Biology (General) ; QH301-705.5 ; Science (General) ; Q1-390
    Subject code 500
    Language English
    Publishing date 2023-04-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: No impacts of glyphosate or Crithidia bombi, or their combination, on the bumblebee microbiome

    Edward A. Straw / Robin Mesnage / Mark J. F. Brown / Michael N. Antoniou

    Scientific Reports, Vol 13, Iss 1, Pp 1-

    2023  Volume 8

    Abstract: Abstract Pesticides are recognised as a key threat to pollinators, impacting their health in many ways. One route through which pesticides can affect pollinators like bumblebees is through the gut microbiome, with knock-on effects on their immune system ... ...

    Abstract Abstract Pesticides are recognised as a key threat to pollinators, impacting their health in many ways. One route through which pesticides can affect pollinators like bumblebees is through the gut microbiome, with knock-on effects on their immune system and parasite resistance. We tested the impacts of a high acute oral dose of glyphosate on the gut microbiome of the buff tailed bumblebee (Bombus terrestris), and glyphosate’s interaction with the gut parasite (Crithidia bombi). We used a fully crossed design measuring bee mortality, parasite intensity and the bacterial composition in the gut microbiome estimated from the relative abundance of 16S rRNA amplicons. We found no impact of either glyphosate, C. bombi, or their combination on any metric, including bacterial composition. This result differs from studies on honeybees, which have consistently found an impact of glyphosate on gut bacterial composition. This is potentially explained by the use of an acute exposure, rather than a chronic exposure, and the difference in test species. Since A. mellifera is used as a model species to represent pollinators more broadly in risk assessment, our results highlight that caution is needed in extrapolating gut microbiome results from A. mellifera to other bee species.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Ignoring Adjuvant Toxicity Falsifies the Safety Profile of Commercial Pesticides

    Robin Mesnage / Michael N. Antoniou

    Frontiers in Public Health, Vol

    2018  Volume 5

    Abstract: Commercial formulations of pesticides are invariably not single ingredients. Instead they are cocktails of chemicals, composed of a designated pesticidal “active principle” and “other ingredients,” with the latter collectively also known as “adjuvants.” ... ...

    Abstract Commercial formulations of pesticides are invariably not single ingredients. Instead they are cocktails of chemicals, composed of a designated pesticidal “active principle” and “other ingredients,” with the latter collectively also known as “adjuvants.” These include surfactants, antifoaming agents, dyes, etc. Some adjuvants are added to influence the absorption and stability of the active principle and thus promote its pesticidal action. Currently, the health risk assessment of pesticides in the European Union and in the United States focuses almost exclusively on the stated active principle. Nonetheless, adjuvants can also be toxic in their own right with numerous negative health effects having been reported in humans and on the environment. Despite the known toxicity of adjuvants, they are regulated differently from active principles, with their toxic effects being generally ignored. Adjuvants are not subject to an acceptable daily intake, and they are not included in the health risk assessment of dietary exposures to pesticide residues. Here, we illustrate this gap in risk assessment by reference to glyphosate, the most used pesticide active ingredient. We also investigate the case of neonicotinoid insecticides, which are strongly suspected to be involved in bee and bumblebee colony collapse disorder. Authors of studies sometimes use the name of the active principle (for example glyphosate) when they are testing a commercial formulation containing multiple (active principle plus adjuvant) ingredients. This results in confusion in the scientific literature and within regulatory circles and leads to a misrepresentation of the safety profile of commercial pesticides. Urgent action is needed to lift the veil on the presence of adjuvants in food and human bodily fluids, as well as in the environment (such as in air, water, and soil) and to characterize their toxicological properties. This must be accompanied by regulatory precautionary measures to protect the environment and general human population from some ...
    Keywords pesticides ; adjuvants ; toxicity tests ; risk assessment ; endocrine disruptors ; surfactants ; Public aspects of medicine ; RA1-1270
    Language English
    Publishing date 2018-01-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Facts and Fallacies in the Debate on Glyphosate Toxicity

    Robin Mesnage / Michael N. Antoniou

    Frontiers in Public Health, Vol

    2017  Volume 5

    Abstract: The safety profile of the herbicide glyphosate and its commercial formulations is controversial. Reviews have been published by individuals who are consultants and employees of companies commercializing glyphosate-based herbicides in support of ... ...

    Abstract The safety profile of the herbicide glyphosate and its commercial formulations is controversial. Reviews have been published by individuals who are consultants and employees of companies commercializing glyphosate-based herbicides in support of glyphosate’s reapproval by regulatory agencies. These authors conclude that glyphosate is safe at levels below regulatory permissible limits. In contrast, reviews conducted by academic scientists independent of industry report toxic effects below regulatory limits, as well as shortcomings of the current regulatory evaluation of risks associated with glyphosate exposures. Two authors in particular (Samsel and Seneff) have published a series of commentaries proposing that long-term exposure to glyphosate is responsible for many chronic diseases (including cancers, diabetes, neuropathies, obesity, asthma, infections, osteoporosis, infertility, and birth defects). The aim of this review is to examine the evidential basis for these claimed negative health effects and the mechanisms that are alleged to be at their basis. We found that these authors inappropriately employ a deductive reasoning approach based on syllogism. We found that their conclusions are not supported by the available scientific evidence. Thus, the mechanisms and vast range of conditions proposed to result from glyphosate toxicity presented by Samsel and Seneff in their commentaries are at best unsubstantiated theories, speculations, or simply incorrect. This misrepresentation of glyphosate’s toxicity misleads the public, the scientific community, and regulators. Although evidence exists that glyphosate-based herbicides are toxic below regulatory set safety limits, the arguments of Samsel and Seneff largely serve to distract rather than to give a rational direction to much needed future research investigating the toxicity of these pesticides, especially at levels of ingestion that are typical for human populations.
    Keywords glyphosate ; chronic disease ; pesticides ; toxicity ; glycine ; gluten sensitivity ; Public aspects of medicine ; RA1-1270
    Subject code 333
    Language English
    Publishing date 2017-11-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Terrestrial ecotoxicity of glyphosate, its formulations, and co-formulants

    Szandra Klátyik / Gergely Simon / Marianna Oláh / Robin Mesnage / Michael N. Antoniou / Johann G. Zaller / András Székács

    Environmental Sciences Europe, Vol 35, Iss 1, Pp 1-

    evidence from 2010–2023

    2023  Volume 29

    Abstract: Abstract Glyphosate (GLY), the most widely used herbicide in the world, is frequently detected in various environmental matrices, including soil, the foundation of agriculture. In practice, more than 2000 GLY-based herbicide (GBH) products are used, ... ...

    Abstract Abstract Glyphosate (GLY), the most widely used herbicide in the world, is frequently detected in various environmental matrices, including soil, the foundation of agriculture. In practice, more than 2000 GLY-based herbicide (GBH) products are used, consisting of one or more active ingredients (AIs) and so-called “inert” co-formulants that increase the efficacy of the AIs. However, the focus of ecotoxicological assessments is mainly on AIs, while organisms are exposed to complex pesticide formulations under real-world conditions. Overall, the effects on non-target organisms indicate a broad range of biochemical and physiological modes of action, which contrasts with the general assumption that herbicides are specific and act only on target plants. Both GLY alone and GBHs have unintended side-effects on many terrestrial organisms, including non-target plants, microorganisms, insects, spiders, or earthworms, as well as vertebrates such as amphibians, reptiles, or mammals. One of the triggering mechanisms for these effects is oxidative stress with consequences on biochemical parameters and DNA damage. In addition, disruptions of various physiological, behavioral and ecological processes have been reported. Most studies have examined the short-term effects of a single application of GLY/GBH to a single species. However, the agricultural practice of applying GBHs two to three times during a cultivation season over an extended period of time, the interactions with other pesticides and agrochemicals applied to the same field, and effects on ecological interactions within the field and landscape are rarely considered. In the vast majority of cases, the toxicity of GBHs exceeds the toxicity of GLY, demonstrating that supposedly inert co-formulants are either toxic in their own right or interact and add to the toxicity of AIs. The chemical diversity of different GBHs and the non-disclosure of the co-formulants make it difficult to attribute effects to specific chemical substances within a GBH. Moreover, impurities in GBHs ...
    Keywords Glyphosate ; Chemical weed control ; AMPA ; POEA ; Roundup ; Co-formulants ; Environmental sciences ; GE1-350 ; Environmental law ; K3581-3598
    Subject code 333
    Language English
    Publishing date 2023-07-01T00:00:00Z
    Publisher SpringerOpen
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Impacts of a glyphosate-based herbicide on the gut microbiome of three earthworm species (Alma millsoni, Eudrilus eugeniae and Libyodrilus violaceus)

    Folarin Owagboriaye / Robin Mesnage / Gabriel Dedeke / Taofeek Adegboyega / Adeyinka Aladesida / Mistura Adeleke / Stephen Owa / Michael N. Antoniou

    Toxicology Reports, Vol 8, Iss , Pp 753-

    A pilot study

    2021  Volume 758

    Abstract: While the impact of glyphosate-based herbicides (GBHs) on earthworms has been studied, little is known about their effects on the earthworm gut microbiome. This study investigated the impact of a GBH on the gut microbial communities of three earthworm ... ...

    Abstract While the impact of glyphosate-based herbicides (GBHs) on earthworms has been studied, little is known about their effects on the earthworm gut microbiome. This study investigated the impact of a GBH on the gut microbial communities of three earthworm species (Alma millsoni, Eudrilus eugeniae and Libyodrilus violaceus). Earthworm species accommodated in soil were sprayed with 115.49 mL/m² of Roundup® Alphée or water. Gut microbiome composition was analysed using 16S rRNA Bacterial Tag–Encoded FLX Amplicon Pyrosequencing (bTEFAP) at the 8th week post-herbicide application. A profound shift in bacterial populationswas observed in all exposed earthworms with Proteobacteria becoming the dominant phylum. Affected bacteria were mostly from the genus Enterobacter, Pantoea and Pseudomonas, which together represented approximately 80 % of the total abundance assigned at the genus level in exposed earthworms, while they were present at a minor abundance (∼1%) in unexposed earthworms. Although consistent results were observed between the three groups of worm species, it is not possible to generalize these outcomes due to a lack of biological replicates, which does not allow for inferential statistical analysis. Nevertheless, our study is the first to report the effects of a GBH on the earthworm gut microbiome and paves the way for future more comprehensive investigations.
    Keywords Microbiome ; Glyphosate ; Roundup ; Soil contamination ; 16S rRNA sequencing ; Agriculture ; Toxicology. Poisons ; RA1190-1270
    Subject code 590
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Relative and Absolute Quantification of Aberrant and Normal Splice Variants in HBB IVSI −1 10 (G > A) β-Thalassemia

    Petros Patsali / Panayiota Papasavva / Soteroulla Christou / Maria Sitarou / Michael N. Antoniou / Carsten W. Lederer / Marina Kleanthous

    International Journal of Molecular Sciences, Vol 21, Iss 6671, p

    2020  Volume 6671

    Abstract: The β-thalassemias are an increasing challenge to health systems worldwide, caused by absent or reduced β-globin (HBB) production. Of particular frequency in many Western countries is HBB IVSI−110(G > A) β-thalassemia (HGVS name: HBB:c.93-21G > A). Its ... ...

    Abstract The β-thalassemias are an increasing challenge to health systems worldwide, caused by absent or reduced β-globin (HBB) production. Of particular frequency in many Western countries is HBB IVSI−110(G > A) β-thalassemia (HGVS name: HBB:c.93-21G > A). Its underlying mutation creates an abnormal splice acceptor site in the HBB gene, and while partially retaining normal splicing of HBB , it severely reduces HBB protein expression from the mutant locus and HBB loci in trans. For the assessment of the underlying mechanisms and of therapies targeting β-thalassemia, accurate quantification of aberrant and normal HBB mRNA is essential, but to date, has only been performed by approximate methods. To address this shortcoming, we have developed an accurate, duplex reverse-transcription quantitative PCR assay for the assessment of the ratio and absolute quantities of normal and aberrant mRNA species as a tool for basic and translational research of HBB IVSI−110(G > A) β-thalassemia. The method was employed here to determine mRNA ratios and quantities in blood and primary cell culture samples and correlate them with HBB protein levels. Moreover, with its immediate utility for β-thalassemia and the mutation in hand, the approach can readily be adopted for analysis of alternative splicing or for quantitative assays of any disease-causing mutation that interferes with normal splicing.
    Keywords β-thalassemia ; splice defect ; duplex quantitative PCR ; absolute quantification ; transcript variants ; splicing ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 333
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Author Correction

    Robin Mesnage / George Renney / Gilles-Eric Séralini / Malcolm Ward / Michael N. Antoniou

    Scientific Reports, Vol 8, Iss 1, Pp 1-

    Multiomics reveal non-alcoholic fatty liver disease in rats following chronic exposure to an ultra-low dose of Roundup herbicide

    2018  Volume 2

    Abstract: A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper. ...

    Abstract A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2018-08-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Glyphosate does not substitute for glycine in proteins of actively dividing mammalian cells

    Michael N. Antoniou / Armel Nicolas / Robin Mesnage / Martina Biserni / Francesco V. Rao / Cristina Vazquez Martin

    BMC Research Notes, Vol 12, Iss 1, Pp 1-

    2019  Volume 7

    Abstract: Abstract Objectives Glyphosate (N-phosphonomethyl glycine) and its commercial herbicide formulations have been shown to exert toxicity via various mechanisms. It has been asserted that glyphosate substitutes for glycine in polypeptide chains leading to ... ...

    Abstract Abstract Objectives Glyphosate (N-phosphonomethyl glycine) and its commercial herbicide formulations have been shown to exert toxicity via various mechanisms. It has been asserted that glyphosate substitutes for glycine in polypeptide chains leading to protein misfolding and toxicity. However, as no direct evidence exists for glycine to glyphosate substitution in proteins, including in mammalian organisms, we tested this claim by conducting a proteomics analysis of MDA-MB-231 human breast cancer cells grown in the presence of 100 mg/L glyphosate for 6 days. Protein extracts from three treated and three untreated cell cultures were analysed as one TMT-6plex labelled sample, to highlight a specific pattern (+/+/+/−/−/−) of reporter intensities for peptides bearing true glyphosate treatment induced-post translational modifications as well as allowing an investigation of the total proteome. Results Comparative statistical analysis of global proteome changes between glyphosate treated and non-treated samples did not show significant differences. Crucially, filtering of data to focus analysis on peptides potentially bearing glycine for glyphosate replacement revealed that the TMT reporter intensity pattern of all candidates showed conclusively that they are all false discoveries, with none displaying the expected TMT pattern for such a substitution. Thus, the assertion that glyphosate substitutes for glycine in protein polypeptide chains is incorrect.
    Keywords Glyphosate ; Glycine ; Proteome ; Medicine ; R ; Biology (General) ; QH301-705.5 ; Science (General) ; Q1-390
    Subject code 616
    Language English
    Publishing date 2019-08-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Commentary

    Charles Benbrook / Melissa J. Perry / Fiorella Belpoggi / Philip J. Landrigan / Michelle Perro / Daniele Mandrioli / Michael N. Antoniou / Paul Winchester / Robin Mesnage

    Environmental Health, Vol 20, Iss 1, Pp 1-

    Novel strategies and new tools to curtail the health effects of pesticides

    2021  Volume 13

    Abstract: Abstract Background Flaws in the science supporting pesticide risk assessment and regulation stand in the way of progress in mitigating the human health impacts of pesticides. Critical problems include the scope of regulatory testing protocols, the near- ... ...

    Abstract Abstract Background Flaws in the science supporting pesticide risk assessment and regulation stand in the way of progress in mitigating the human health impacts of pesticides. Critical problems include the scope of regulatory testing protocols, the near-total focus on pure active ingredients rather than formulated products, lack of publicly accessible information on co-formulants, excessive reliance on industry-supported studies coupled with reticence to incorporate published results in the risk assessment process, and failure to take advantage of new scientific opportunities and advances, e.g. biomonitoring and “omics” technologies. Recommended Actions Problems in pesticide risk assessment are identified and linked to study design, data, and methodological shortcomings. Steps and strategies are presented that have potential to deepen scientific knowledge of pesticide toxicity, exposures, and risks. We propose four solutions: (1) End near-sole reliance in regulatory decision-making on industry-supported studies by supporting and relying more heavily on independent science, especially for core toxicology studies. The cost of conducting core toxicology studies at labs not affiliated with or funded directly by pesticide registrants should be covered via fees paid by manufacturers to public agencies. (2) Regulators should place more weight on mechanistic data and low-dose studies within the range of contemporary exposures. (3) Regulators, public health agencies, and funders should increase the share of exposure-assessment resources that produce direct measures of concentrations in bodily fluids and tissues. Human biomonitoring is vital in order to quickly identify rising exposures among vulnerable populations including applicators, pregnant women, and children. (4) Scientific tools across disciplines can accelerate progress in risk assessments if integrated more effectively. New genetic and metabolomic markers of adverse health impacts and heritable epigenetic impacts are emerging and should be included more ...
    Keywords Industrial medicine. Industrial hygiene ; RC963-969 ; Public aspects of medicine ; RA1-1270
    Subject code 910 ; 170
    Language English
    Publishing date 2021-08-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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