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Cited by 342Pesticide Exposure and ToxicityAgricultural safety and regulationsPesticide and Herbicide Environmental Studies

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Major Pesticides Are More Toxic to Human Cells Than Their Declared Active Principles

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Mesnage, Robin, Defarge, Nicolas, Spiroux de Vendômois, Joël, Séralini, Gilles-Eric·2014·BioMed Research International
DOI 10.1155/2014/179691PMC PMC3955666
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Abstract

Pesticides are used throughout the world as mixtures called formulations. They contain adjuvants, which are often kept confidential and are called inerts by the manufacturing companies, plus a declared active principle, which is usually tested alone. We tested the toxicity of 9 pesticides, comparing active principles and their formulations, on three human cell lines (HepG2, HEK293, and JEG3). Glyphosate, isoproturon, fluroxypyr, pirimicarb, imidacloprid, acetamiprid, tebuconazole, epoxiconazole, and prochloraz constitute, respectively, the active principles of 3 major herbicides, 3 insecticides, and 3 fungicides. We measured mitochondrial activities, membrane degradations, and caspases 3/7 activities. Fungicides were the most toxic from concentrations 300–600 times lower than agricultural dilutions, followed by herbicides and then insecticides, with very similar profiles in all cell types. Despite its relatively benign reputation, Roundup was among the most toxic herbicides and insecticides tested. Most importantly, 8 formulations out of 9 were up to one thousand times more toxic than their active principles. Our results challenge the relevance of the acceptable daily intake for pesticides because this norm is calculated from the toxicity of the active principle alone. Chronic tests on pesticides may not reflect relevant environmental exposures if only one ingredient of these mixtures is tested alone.

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Figures

Figure 1 Differential cytotoxic effects between formulations of herbicides and their active principles (APs) on HepG2, HEK293, and JEG3 human cell lines. Effects on the mitochondrial succinate dehydrogenase (SD) activity, reflecting cell respiration inhibition, were measured in percentage of control in serum-free medium after 24 h of exposure. The concentrations in ppm are dilutions of each AP (dotted line) and their equivalent in formulation with adjuvants (solid line). All formulations are more toxic than their APs, except for isoproturon. SEMs are shown in all instances (n = 9).
Figure 1 Differential cytotoxic effects between formulations of herbicides and their active principles (APs) on HepG2, HEK293, and JEG3 human cell lines. Effects on the mitochondrial succinate dehydrogenase (SD) activity, reflecting cell respiration inhibition, were measured in percentage of control in serum-free medium after 24 h of exposure. The concentrations in ppm are dilutions of each AP (dotted line) and their equivalent in formulation with adjuvants (solid line). All formulations are more toxic than their APs, except for isoproturon. SEMs are shown in all instances (n = 9).CC BY · PubMed Central
Figure 2 Differential cytotoxic effects between formulations of insecticides and their APs on HepG2, HEK293, and JEG3 human cell lines. The three described human cell lines were used in the conditions of Figure 1 and the results were almost identical. All formulations (solid line) are more toxic than their APs (dotted line); APs are slightly cytotoxic. SEMs are shown in all instances (n = 9).
Figure 2 Differential cytotoxic effects between formulations of insecticides and their APs on HepG2, HEK293, and JEG3 human cell lines. The three described human cell lines were used in the conditions of Figure 1 and the results were almost identical. All formulations (solid line) are more toxic than their APs (dotted line); APs are slightly cytotoxic. SEMs are shown in all instances (n = 9).CC BY · PubMed Central
Figure 3 Differential cytotoxic effects between formulations of fungicides and their APs on HepG2, HEK293, and JEG3 human cell lines. The three described human cell lines were used in the culture conditions of Figure 1, and the results were almost identical. All formulations (solid line) are more cytotoxic than their APs (dotted line). Maronee is the most toxic compound tested from 1 ppm in JEG3. SEMs are shown in all instances (n = 9).
Figure 3 Differential cytotoxic effects between formulations of fungicides and their APs on HepG2, HEK293, and JEG3 human cell lines. The three described human cell lines were used in the culture conditions of Figure 1, and the results were almost identical. All formulations (solid line) are more cytotoxic than their APs (dotted line). Maronee is the most toxic compound tested from 1 ppm in JEG3. SEMs are shown in all instances (n = 9).CC BY · PubMed Central
Figure 4 Differential necrotic effects between formulations and their APs. The three described human cell lines were used in the culture conditions of Figure 1. We have chosen the doses at the first differential effects measured by MTT assay. Formulations (stripped columns, expressed in ppm of the AP) are generally more cytotoxic than their APs (dashed columns) due to a necrotic effect of adjuvants. SEMs are shown in all instances (n = 9). For the comparison of each AP or formulation to the control (white column), *P < 0.05, **P < 0.01, and ***P < 0.001 in a nonparametric Mann-Whitney test. # symbol is used similarly for comparisons between APs and their formulations.
Figure 4 Differential necrotic effects between formulations and their APs. The three described human cell lines were used in the culture conditions of Figure 1. We have chosen the doses at the first differential effects measured by MTT assay. Formulations (stripped columns, expressed in ppm of the AP) are generally more cytotoxic than their APs (dashed columns) due to a necrotic effect of adjuvants. SEMs are shown in all instances (n = 9). For the comparison of each AP or formulation to the control (white column), *P < 0.05, **P < 0.01, and ***P < 0.001 in a nonparametric Mann-Whitney test. # symbol is used similarly for comparisons between APs and their formulations.CC BY · PubMed Central
Figure 5 Differential apoptotic effects between formulations and their APs. The three described human cell lines were used in the culture conditions of Figure 1. We have chosen the doses at the first differential effects measured by MTT assay. SEMs are shown in all instances (n = 9). For the comparison of each AP or formulation to the control (white column), *P < 0.05, **P < 0.01, and ***P < 0.001 in a nonparametric Mann-Whitney test. # symbol is used similarly for comparisons between APs and their formulations.
Figure 5 Differential apoptotic effects between formulations and their APs. The three described human cell lines were used in the culture conditions of Figure 1. We have chosen the doses at the first differential effects measured by MTT assay. SEMs are shown in all instances (n = 9). For the comparison of each AP or formulation to the control (white column), *P < 0.05, **P < 0.01, and ***P < 0.001 in a nonparametric Mann-Whitney test. # symbol is used similarly for comparisons between APs and their formulations.CC BY · PubMed Central

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  1. 2013, Food and Chemical Toxicology, 53, 461
  2. 1997, Veterinary and Human Toxicology, 39, 147

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Metadata

Authors
Mesnage, R., Defarge, N., Spiroux de Vendômois, J., & Séralini, G.-E.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • CRIIGEN, 40 rue Monceau, 75008 Paris, France
  • University of Caen, Institute of Biology, CRIIGEN and Network on Risks, Quality and Sustainable Environment MRSH-CNRS, Esplanade de la Paix, 14032 Caen Cedex, France
ORCID
Venue
BioMed Research International
Publisher
Wiley
Published
2014
Volume
2014
Pages
1-8
ISSN
  • 1110-7243 (ISSN-L)
  • 2314-6133
  • 2314-6141
DOI
10.1155/2014/179691
PMC
PMC3955666
OpenAlex
W2022206707
Cited by
342
References
36
Citations by year
2026: 13 · 2025: 19 · 2024: 18 · 2023: 27 · 2022: 35 · 2021: 39 · 2020: 41 · 2019: 45 · 2018: 33 · 2017: 22 · 2016: 19 · 2015: 22 · 2014: 9
FWCI
27.87
Type
journal article
Language
en
Open access
Licence
Locations
  • BioMed Research International (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pesticide Exposure and Toxicity
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Agricultural safety and regulations
  • Physical Sciences › Environmental Science › Pollution › Pesticide and Herbicide Environmental Studies
Keywords
pesticide formulations, pesticide mixtures, active ingredients, adjuvants, herbicides, insecticides, fungicides, glyphosate, Roundup, isoproturon, fluroxypyr, pirimicarb, imidacloprid, acetamiprid, tebuconazole, epoxiconazole, prochloraz, cytotoxicity, mitochondrial activity, membrane degradation, caspase 3/7, acceptable daily intake, human cell lines, environmental exposure
MeSH terms
Cell Membrane, Dose-Response Relationship, Drug, Environmental Exposure, Humans, Mitochondria, Pesticides, Caspases, Hep G2 Cells, HEK293 Cells

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