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Ethoxylated adjuvants of glyphosate-based herbicides are active principles of human cell toxicity
Abstract
Pesticides are always used in formulations as mixtures of an active principle with adjuvants. Glyphosate, the active ingredient of the major pesticide in the world, is an herbicide supposed to be specific on plant metabolism. Its adjuvants are generally considered as inert diluents. Since side effects for all these compounds have been claimed, we studied potential active principles for toxicity on human cells for 9 glyphosate-based formulations. For this we detailed their compositions and toxicities, and as controls we used a major adjuvant (the polyethoxylated tallowamine POE-15), glyphosate alone, and a total formulation without glyphosate. This was performed after 24h exposures on hepatic (HepG2), embryonic (HEK293) and placental (JEG3) cell lines. We measured mitochondrial activities, membrane degradations, and caspases 3/7 activities. The compositions in adjuvants were analyzed by mass spectrometry. Here we demonstrate that all formulations are more toxic than glyphosate, and we separated experimentally three groups of formulations differentially toxic according to their concentrations in ethoxylated adjuvants. Among them, POE-15 clearly appears to be the most toxic principle against human cells, even if others are not excluded. It begins to be active with negative dose-dependent effects on cellular respiration and membrane integrity between 1 and 3ppm, at environmental/occupational doses. We demonstrate in addition that POE-15 induces necrosis when its first micellization process occurs, by contrast to glyphosate which is known to promote endocrine disrupting effects after entering cells. Altogether, these results challenge the establishment of guidance values such as the acceptable daily intake of glyphosate, when these are mostly based on a long term in vivo test of glyphosate alone. Since pesticides are always used with adjuvants that could change their toxicity, the necessity to assess their whole formulations as mixtures becomes obvious. This challenges the concept of active principle of pesticides for non-target species.
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“Even if G has shown to interact directly with the active site of aromatase at high levels [19], at low contaminating levels, adjuvants may be better candidates than G to explain the toxicity or endocrine disruptive side effects of R on human cells [8,20] and also in vivo for acute toxicity [21].”
From Republished study: long-term toxicity of a Roundup herbicide and a Roundup-tolerantgenetically modified maize (2014) · cites this paper as [20]
Citations
Cites
Bradford, M. M. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90527-3 · Cited by 255,302
Mosmann, T. (1983) · Journal of Immunological Methods · doi:10.1016/0022-1759(83)90303-4 · Cited by 56,104
Developmental Effects of Endocrine-Disrupting Chemicals in Wildlife and Humans
Colborn, T., Saal, F. S. V., & Soto, A. M. (1993) · Environmental Health Perspectives · doi:10.1289/ehp.93101378 · Cited by 3,570
Global Status of Commercialized biotech/GM crops
James, C. L. R. (2006) · Cited by 1,708
The use of ATP bioluminescence as a measure of cell proliferation and cytotoxicity
Crouch, S. P. M., Kozlowski, R., Slater, K. J., & Fletcher, J. (1993) · Journal of Immunological Methods · doi:10.1016/0022-1759(93)90011-u · Cited by 926
Toxicology for the twenty-first century
Härtung, T. (2009) · Nature · doi:10.1038/460208a · Cited by 686
Glyphosate-based herbicides are toxic and endocrine disruptors in human cell lines
Gasnier, C., Dumont, C., Benachour, N., Clair, E., Chagnon, M.-C., & Séralini, G.-E. (2009) · Toxicology · doi:10.1016/j.tox.2009.06.006 · Cited by 658
Self-citationTsui, M. T., & Chu, L. M. (2003) · Chemosphere · doi:10.1016/s0045-6535(03)00306-0 · Cited by 630
Differential effects of glyphosate and roundup on human placental cells and aromatase
Richard, S., Moslemi, S., Sipahutar, H., Benachour, N., & Seralini, G.-E. (2005) · Environmental Health Perspectives · doi:10.1289/ehp.7728 · Cited by 619
Self-citationPaganelli, A. R., Gnazzo, V., Acosta, H., López, S. L., & Carrasco, A. E. (2010) · Chemical Research in Toxicology · doi:10.1021/tx1001749 · Cited by 460
Benachour, N., & Séralini, G.-E. (2009) · Chemical Research in Toxicology · doi:10.1021/tx800218n · Cited by 428
Self-citationAcquavella, J., Alexander, B. H., Mandel, J. S., Gustin, C., Baker, B. A., Chapman, P. S., & Bleeke, M. S. (2003) · Environmental Health Perspectives · doi:10.1289/ehp.6667 · Cited by 310
Kinetics of 5‐enolpyruvylshikimate‐3‐phosphate synthase inhibition by glyphosate
Boocock, M. R., & Coggins, J. R. (1983) · FEBS Letters · doi:10.1016/0014-5793(83)80888-6 · Cited by 273
Environmental properties and effects of nonionic surfactant adjuvants in pesticides: a review
Krogh, K. A., Halling‐Sørensen, B., Mogensen, B. B., & Vejrup, K. V. (2002) · Chemosphere · doi:10.1016/s0045-6535(02)00648-3 · Cited by 263
Comparative effects of the Roundup and glyphosate on mitochondrial oxidative phosphorylation
Peixoto, F. (2005) · Chemosphere · doi:10.1016/j.chemosphere.2005.03.044 · Cited by 259
Emilie Clair, A., Mesnage, R., Travert, C., & Séralini, G. (2011) · Toxicology in Vitro · doi:10.1016/j.tiv.2011.12.009 · Cited by 238
Self-citationTime- and dose-dependent effects of Roundup on human embryonic and placental cells
Benachour, N., Sipahutar, H., Moslemi, S., Gasnier, C., Travert, C., & Séralini, G. E. (2007) · Archives of Environmental Contamination and Toxicology · doi:10.1007/s00244-006-0154-8 · Cited by 226
Self-citationPre- and postnatal toxicity of the commercial glyphosate formulation in Wistar rats
Dallegrave, E., Mantese, F. D. G., de Oliveira, R. T., Martino‐Andrade, A. J., Dalsenter, P. R., & Langeloh, A. (2007) · Archives of Toxicology · doi:10.1007/s00204-006-0170-5 · Cited by 211
Male Pesticide Exposure and Pregnancy Outcome
Savitz, D. A., Arbuckle, T. E., Kaczor, D., & Curtis, K. M. (1997) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a009231 · Cited by 207
Glyphosate impairs male offspring reproductive development by disrupting gonadotropin expression
Romano, M. A., Romano, R. M., Santos, L. D., Wisniewski, P., Campos, D. A., de Souza, P. B., Viau, P., Bernardi, M. M., Nunes, M. T., & de Oliveira, C. A. (2012) · Archives of Toxicology · doi:10.1007/s00204-011-0788-9 · Cited by 196
Aris, A., & Leblanc, S. (2011) · Reproductive Toxicology · doi:10.1016/j.reprotox.2011.02.004 · Cited by 187
Williams, A. L., Watson, R. E., & DeSesso, J. M. (2011) · Journal of Toxicology and Environmental Health Part B · doi:10.1080/10937404.2012.632361 · Cited by 157
Effect of the herbicide glyphosate on liver lipoperoxidation in pregnant rats and their fetuses
Beuret, C., Zirulnik, F., & Giménez, M. S. (2004) · Reproductive Toxicology · doi:10.1016/j.reprotox.2004.09.009 · Cited by 145
Brausch, J. M., & Smith, P. N. (2006) · Archives of Environmental Contamination and Toxicology · doi:10.1007/s00244-006-0151-y · Cited by 129
Effect of the Herbicide Glyphosate on Enzymatic Activity in Pregnant Rats and Their Fetuses
Daruich, J., Zirulnik, F., & Giménez, M. S. (2001) · Environmental Research · doi:10.1006/enrs.2000.4229 · Cited by 124
A role for solvents in the toxicity of agricultural organophosphorus pesticides
Eddleston, M., Street, J. M., Self, I., Thompson, A. P., King, T., Williams, N., Naredo, G., Dissanayake, K. N., Yu, L., Worek, F., et al. (2012) · Toxicology · doi:10.1016/j.tox.2012.02.005 · Cited by 122
Effect of pesticides on cell survival in liver and brain rat tissues
Astiz, M., de Alaniz, M. J. T., & Marra, C. A. (2009) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2009.05.001 · Cited by 119
Toxic effects of carbofuran and glyphosate on semen characteristics in rabbits
Yousef, M. I., Salem, M. H., Ibrahim, H. Z., Helmi, S., Seehy, M. A., & Bertheussen, K. (1995) · Journal of Environmental Science and Health Part B · doi:10.1080/03601239509372951 · Cited by 114
Hawthorne, D. J., & Dively, G. P. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026796 · Cited by 105
Effects of the herbicide Roundup on the epididymal region of drakes Anas platyrhynchos
de Oliveira, A. G., Telles, L. F., Hess, R. A., Mahecha, G. A. B., & Oliveira, C. A. (2006) · Reproductive Toxicology · doi:10.1016/j.reprotox.2006.11.004 · Cited by 86
Protective Effect of Ginkgo biloba L. Leaf Extract Against Glyphosate Toxicity in Swiss Albino Mice
Çavuşoğlu, K., Yapar, K., Oruç, E., & Yalçın, E. (2011) · Journal of Medicinal Food · doi:10.1089/jmf.2010.0202 · Cited by 71
Nobels, I., Spanoghe, P., Haesaert, G., Robbens, J., & Blust, R. (2011) · PLoS ONE · doi:10.1371/journal.pone.0024139 · Cited by 70
A glyphosate-based pesticide impinges on transcription
Marc, J., Breton, M. L., Cormier, P., Morales, J., Bellé, R., & Mulner‐Lorillon, O. (2004) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2004.07.014 · Cited by 68
Boeije, G., Cano, M. L., Marshall, S., Belanger, S. E., van Compernolle, R., Dorn, P. B., Gümbel, H., Toy, R. J., & Wind, T. (2005) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2005.08.009 · Cited by 68
Letcher, R. J., van Holsteijn, I., Drenth, H., Norstrom, R. J., Bergman, Å., Safe, S. H., Pieters, R. H. H., & van den Berg, M. (1999) · Toxicology and Applied Pharmacology · doi:10.1006/taap.1999.8746 · Cited by 66
Courtney, H. S., Simpson, W. A., & Beachey, E. H. (1986) · Infection and Immunity · doi:10.1128/iai.51.2.414-418.1986 · Cited by 62
Liu, J. J., Wang, W., Dicker, D. T., & El‐Deiry, W. S. (2005) · Cancer Biology & Therapy · doi:10.4161/cbt.4.8.2133 · Cited by 58
Human-derived cell lines to study xenobiotic metabolism
Urani, C., Doldi, M., Crippa, S., & Camatini, M. (1998) · Chemosphere · doi:10.1016/s0045-6535(98)00321-x · Cited by 55
The oral and intratracheal toxicities of ROUNDUP and its components to rats.
Adam, A., Marzuki, A., Rahman, H. A., & Aziz, M. A. (1997) · PubMed · Cited by 49
The use of Coomassie brilliant blue for critical micelle concentration determination of detergents
Samsonoff, C., Daily, J., Almog, R., & Berns, D. S. (1986) · Journal of Colloid and Interface Science · doi:10.1016/0021-9797(86)90310-3 · Cited by 46
Separation and quantitative determination of non-ionic surfactants used as pesticide additives
Cserháti, T., & Forgács, E. (1997) · Journal of Chromatography A · doi:10.1016/s0021-9673(97)00333-6 · Cited by 35
Defined plant extracts can protect human cells against combined xenobiotic effects
Gasnier, C., Laurant, C., Decroix-Laporte, C., Mesnage, R., Clair, E., Travert, C., & Séralini, G.-E. (2011) · Journal of Occupational Medicine and Toxicology · doi:10.1186/1745-6673-6-3 · Cited by 31
Self-citationIn vitro endothelial cell susceptibility to xenobiotics: Comparison of three cell types
L'Azou, B., Fernandez, P., Bareille, R., Bénéteau, M., Bourget, C., Cambar, J., & Bordenave, L. (2005) · Cell Biology and Toxicology · doi:10.1007/s10565-005-0172-8 · Cited by 28
Corbera, M., Simonet, B. M., Salvadó, V., & Hidalgo, M. (2010) · Rapid Communications in Mass Spectrometry · doi:10.1002/rcm.4698 · Cited by 17
Chamel, A. R., & Gambonnet, B. (1997) · Chemosphere · doi:10.1016/s0045-6535(97)00033-7 · Cited by 9
Frijhoff, A. F. W., Krul, C. A. M., de Vries, A., KELDERS, M. C. J. M., Weeda, G., STEEG, H. V., & Baan, R. A. (1998) · Environmental and Molecular Mutagenesis · doi:10.1002/(sici)1098-2280(1998)31:1 · Cited by 6
Research works printed but not linked: 2
- Cox, 2004, Herbicide factsheet—glyphosate, J. Pesticide Reform, 24, 10
- Mesnage, 2010, Roundup in genetically modified plants: regulation and toxicity in mammals, Theor. Ökol., 16, 31
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Myers, J. P., Antoniou, M. N., Blumberg, B., Carroll, L., Colborn, T., Everett, L. G., Hansen, M., Landrigan, P. J., Lanphear, B. P., Mesnage, R., et al. (2016) · Environmental Health · doi:10.1186/s12940-016-0117-0 · Cited by 907
Self-citationBattaglin, W. A., Meyer, M. T., Kuivila, K. M., & Dietze, J. E. (2014) · JAWRA Journal of the American Water Resources Association · doi:10.1111/jawr.12159 · Cited by 597
Potential toxic effects of glyphosate and its commercial formulations below regulatory limits
Mesnage, R., Defarge, N., de Vendômois, J. S., & Séralini, G. (2015) · Food and Chemical Toxicology · doi:10.1016/j.fct.2015.08.012 · Cited by 536
Self-citationPesticides: formulants, distribution pathways and effects on human health – a review
Kalyabina, V. P., Esimbekova, E. N., Kopylova, K. V., & Kratasyuk, V. A. (2021) · Toxicology Reports · doi:10.1016/j.toxrep.2021.06.004 · Cited by 540
Toxicity of formulants and heavy metals in glyphosate-based herbicides and other pesticides
Defarge, N., de Vendômois, J. S., & Séralini, G. (2017) · Toxicology Reports · doi:10.1016/j.toxrep.2017.12.025 · Cited by 449
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Metadata
- Authors
- Mesnage, R., Bernay, B., & Séralini, G.-E.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Université de Caen Normandie (FR)
- Venue
- Toxicology
- Publisher
- Elsevier BV
- Published
- 2013-11
- Volume
- 313
- Issue
- 2-3
- Pages
- 122-128
- ISSN
- 0300-483X (ISSN-L)
- OpenAlex
- W1970847183
- Cited by
- 424
- References
- 48
- Citations by year
- 2026: 19 · 2025: 25 · 2024: 24 · 2023: 35 · 2022: 48 · 2021: 56 · 2020: 42 · 2019: 43 · 2018: 35 · 2017: 22 · 2016: 27 · 2015: 23 · 2014: 16 · 2013: 5
- FWCI
- 17.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pesticide Exposure and Toxicity
- Physical Sciences › Environmental Science › Environmental Chemistry › Environmental Chemistry and Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Keywords
- glyphosate, herbicide adjuvants, pesticide formulations, HepG2 cells, HEK293 cells, JEG-3 cells, mitochondrial respiration, membrane integrity, caspase 3/7, necrosis, micellization, acceptable daily intake, endocrine disruption, non-target organisms
- MeSH terms
- Glyphosate, Amines, Cell Line, Cell Survival, Dose-Response Relationship, Drug, Ethyl Ethers, Glycine, Herbicides, Humans, Polyethylene Glycols, Surface-Active Agents, Molecular Structure, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
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