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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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 and also in vivo for acute toxicity.
“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]
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- 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 · 2012: 3
- 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 › Agricultural and Biological Sciences › Plant Science › 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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