title: Co-Formulants in Glyphosate-Based Herbicides Disrupt Aromatase Activity in Human Cells below Toxic Levels.
abstract: Pesticide formulations contain declared active ingredients and co-formulants presented as inert and confidential compounds. We tested the endocrine disruption of co-formulants in six glyphosate-based herbicides (GBH), the most used pesticides worldwide. All co-formulants and formulations were comparably cytotoxic well below the agricultural dilution of 1% (18-2000 times for co-formulants, 8-141 times for formulations), and not the declared active ingredient glyphosate (G) alone. The endocrine-disrupting effects of all these compounds were measured on aromatase activity, a key enzyme in the balance of sex hormones, below the toxicity threshold. Aromatase activity was decreased both by the co-formulants alone (polyethoxylated tallow amine-POEA and alkyl polyglucoside-APG) and by the formulations, from concentrations 800 times lower than the agricultural dilutions; while G exerted an effect only at 1/3 of the agricultural dilution. It was demonstrated for the first time that endocrine disruption by GBH could not only be due to the declared active ingredient but also to co-formulants. These results could explain numerous in vivo results with GBHs not seen with G alone; moreover, they challenge the relevance of the acceptable daily intake (ADI) value for GBHs exposures, currently calculated from toxicity tests of the declared active ingredient alone.
authors.affiliation: Institute of Biology, University of Caen Normandy, EA2608 and Network on Risks, Quality and Sustainable Environment MRSH, Esplanade de la Paix, CS 14032, Caen Cedex 5, France. nicolas.defarge@gmail.com.|CRIIGEN, 81 rue Monceau, 75008 Paris, France. nicolas.defarge@gmail.com.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Defarge
authors.affiliation: Agro-Environmental Research Institute, National Agricultural Research and Innovation Centre, H-1022, Herman Ottó u. 15, Budapest, Hungary. e.takacs@cfri.hu.
authors.forename: Eszter
authors.initials: E
authors.lastname: Takács
authors.affiliation: Institute of Biology, University of Caen Normandy, EA2608 and Network on Risks, Quality and Sustainable Environment MRSH, Esplanade de la Paix, CS 14032, Caen Cedex 5, France. veritol77@gmail.com.
authors.forename: Verónica Laura
authors.initials: VL
authors.lastname: Lozano
authors.affiliation: Institute of Biology, University of Caen Normandy, EA2608 and Network on Risks, Quality and Sustainable Environment MRSH, Esplanade de la Paix, CS 14032, Caen Cedex 5, France. robinmes@gmail.com.|CRIIGEN, 81 rue Monceau, 75008 Paris, France. robinmes@gmail.com.
authors.forename: Robin
authors.initials: R
authors.lastname: Mesnage
authors.affiliation: CRIIGEN, 81 rue Monceau, 75008 Paris, France. jmspiroux@wanadoo.fr.
authors.forename: Joël
authors.initials: J
authors.lastname: Spiroux de Vendômois
authors.affiliation: Institute of Biology, University of Caen Normandy, EA2608 and Network on Risks, Quality and Sustainable Environment MRSH, Esplanade de la Paix, CS 14032, Caen Cedex 5, France. gilles-eric.seralini@unicaen.fr.|CRIIGEN, 81 rue Monceau, 75008 Paris, France. gilles-eric.seralini@unicaen.fr.
authors.forename: Gilles-Eric
authors.initials: GE
authors.lastname: Séralini
authors.affiliation: Agro-Environmental Research Institute, National Agricultural Research and Innovation Centre, H-1022, Herman Ottó u. 15, Budapest, Hungary. a.szekacs@cfri.hu.
authors.forename: András
authors.initials: A
authors.lastname: Székács
mesh_terms: D000014:Abnormalities, Drug-Induced; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D004781:Environmental Exposure / Q000009:adverse effects* / Q000032:analysis; D005998:Glycine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D006540:Herbicides / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D006801:Humans; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000633:toxicity*; D018675:Toxicity Tests; D000097797:Glyphosate
chemical_list: D052244:Endocrine Disruptors; D005998:Glycine; D006540:Herbicides; D009943:Organophosphorus Compounds; D000097797:Glyphosate
keywords: JEG3 cells; aromatase; co-formulant; endocrine disruption; glyphosate-based herbicide; pesticide