Co-Formulants in Glyphosate-Based Herbicides Disrupt Aromatase Activity in Human Cells below Toxic Levels

Int J Environ Res Public Health. 2016 Feb 26;13(3):264. doi: 10.3390/ijerph13030264.


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.

Keywords: JEG3 cells; aromatase; co-formulant; endocrine disruption; glyphosate-based herbicide; pesticide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Drug-Induced
  • Cell Line
  • Cell Survival / drug effects
  • DNA Damage
  • Dose-Response Relationship, Drug
  • Endocrine Disruptors / chemistry
  • Endocrine Disruptors / pharmacokinetics
  • Endocrine Disruptors / toxicity*
  • Environmental Exposure / adverse effects*
  • Environmental Exposure / analysis
  • Glycine / analogs & derivatives*
  • Glycine / chemistry
  • Glycine / pharmacokinetics
  • Glycine / toxicity
  • Herbicides / chemistry
  • Herbicides / pharmacokinetics
  • Herbicides / toxicity*
  • Humans
  • Organophosphorus Compounds / chemistry
  • Organophosphorus Compounds / toxicity*
  • Toxicity Tests


  • Endocrine Disruptors
  • Herbicides
  • Organophosphorus Compounds
  • glyphosate
  • Glycine