12
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      A comprehensive analysis of the animal carcinogenicity data for glyphosate from chronic exposure rodent carcinogenicity studies

      review-article
      1 , 2 , 3 ,
      Environmental Health
      BioMed Central
      Glyphosate, Cancer, Animal carcinogenicity studies, Trend test, Historical controls

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Since the introduction of glyphosate-tolerant genetically-modified plants, the global use of glyphosate has increased dramatically making it the most widely used pesticide on the planet. There is considerable controversy concerning the carcinogenicity of glyphosate with scientists and regulatory authorities involved in the review of glyphosate having markedly different opinions. One key aspect of these opinions is the degree to which glyphosate causes cancer in laboratory animals after lifetime exposure. In this review, twenty-one chronic exposure animal carcinogenicity studies of glyphosate are identified from regulatory documents and reviews; 13 studies are of sufficient quality and detail to be reanalyzed in this review using trend tests, historical control tests and pooled analyses. The analyses identify 37 significant tumor findings in these studies and demonstrate consistency across studies in the same sex/species/strain for many of these tumors. Considering analyses of the individual studies, the consistency of the data across studies, the pooled analyses, the historical control data, non-neoplastic lesions, mechanistic evidence and the associated scientific literature, the tumor increases seen in this review are categorized as to the strength of the evidence that glyphosate causes these cancers. The strongest evidence shows that glyphosate causes hemangiosarcomas, kidney tumors and malignant lymphomas in male CD-1 mice, hemangiomas and malignant lymphomas in female CD-1 mice, hemangiomas in female Swiss albino mice, kidney adenomas, liver adenomas, skin keratoacanthomas and skin basal cell tumors in male Sprague-Dawley rats, adrenal cortical carcinomas in female Sprague-Dawley rats and hepatocellular adenomas and skin keratocanthomas in male Wistar rats.

          Related collections

          Most cited references57

          • Record: found
          • Abstract: found
          • Article: not found

          Glyphosate-based herbicides are toxic and endocrine disruptors in human cell lines.

          Glyphosate-based herbicides are the most widely used across the world; they are commercialized in different formulations. Their residues are frequent pollutants in the environment. In addition, these herbicides are spread on most eaten transgenic plants, modified to tolerate high levels of these compounds in their cells. Up to 400 ppm of their residues are accepted in some feed. We exposed human liver HepG2 cells, a well-known model to study xenobiotic toxicity, to four different formulations and to glyphosate, which is usually tested alone in chronic in vivo regulatory studies. We measured cytotoxicity with three assays (Alamar Blue, MTT, ToxiLight), plus genotoxicity (comet assay), anti-estrogenic (on ERalpha, ERbeta) and anti-androgenic effects (on AR) using gene reporter tests. We also checked androgen to estrogen conversion by aromatase activity and mRNA. All parameters were disrupted at sub-agricultural doses with all formulations within 24h. These effects were more dependent on the formulation than on the glyphosate concentration. First, we observed a human cell endocrine disruption from 0.5 ppm on the androgen receptor in MDA-MB453-kb2 cells for the most active formulation (R400), then from 2 ppm the transcriptional activities on both estrogen receptors were also inhibited on HepG2. Aromatase transcription and activity were disrupted from 10 ppm. Cytotoxic effects started at 10 ppm with Alamar Blue assay (the most sensitive), and DNA damages at 5 ppm. A real cell impact of glyphosate-based herbicides residues in food, feed or in the environment has thus to be considered, and their classifications as carcinogens/mutagens/reprotoxics is discussed.
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Conclusion on the peer review of the pesticide risk assessment of the active substance glyphosate

            (2015)
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Glyphosate induces human breast cancer cells growth via estrogen receptors.

              Glyphosate is an active ingredient of the most widely used herbicide and it is believed to be less toxic than other pesticides. However, several recent studies showed its potential adverse health effects to humans as it may be an endocrine disruptor. This study focuses on the effects of pure glyphosate on estrogen receptors (ERs) mediated transcriptional activity and their expressions. Glyphosate exerted proliferative effects only in human hormone-dependent breast cancer, T47D cells, but not in hormone-independent breast cancer, MDA-MB231 cells, at 10⁻¹² to 10⁻⁶M in estrogen withdrawal condition. The proliferative concentrations of glyphosate that induced the activation of estrogen response element (ERE) transcription activity were 5-13 fold of control in T47D-KBluc cells and this activation was inhibited by an estrogen antagonist, ICI 182780, indicating that the estrogenic activity of glyphosate was mediated via ERs. Furthermore, glyphosate also altered both ERα and β expression. These results indicated that low and environmentally relevant concentrations of glyphosate possessed estrogenic activity. Glyphosate-based herbicides are widely used for soybean cultivation, and our results also found that there was an additive estrogenic effect between glyphosate and genistein, a phytoestrogen in soybeans. However, these additive effects of glyphosate contamination in soybeans need further animal study. Copyright © 2013 Elsevier Ltd. All rights reserved.
                Bookmark

                Author and article information

                Contributors
                cportier@mac.com
                Journal
                Environ Health
                Environ Health
                Environmental Health
                BioMed Central (London )
                1476-069X
                12 February 2020
                12 February 2020
                2020
                : 19
                : 18
                Affiliations
                [1 ]GRID grid.189967.8, ISNI 0000 0001 0941 6502, Rollins School of Public Health, , Emory University, ; Atlanta, GA USA
                [2 ]GRID grid.5012.6, ISNI 0000 0001 0481 6099, Department of Toxicogenomics, , Maastricht University, ; Maastricht, Netherlands
                [3 ]CJP Consulting, Seattle, Washington USA
                Author information
                http://orcid.org/0000-0002-0954-0279
                Article
                574
                10.1186/s12940-020-00574-1
                7014589
                32050978
                c2aeced3-e2e1-47a7-9557-3af0120dfb7f
                © The Author(s) 2020

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 10 December 2019
                : 6 February 2020
                Categories
                Review
                Custom metadata
                © The Author(s) 2020

                Public health
                glyphosate,cancer,animal carcinogenicity studies,trend test,historical controls
                Public health
                glyphosate, cancer, animal carcinogenicity studies, trend test, historical controls

                Comments

                Comment on this article