Comparative cyto- and genotoxicity assessment of glyphosate and glyphosate-based herbicides in human peripheral white blood cells

Károly Nagy; Roba Argaw Tessema; Lygia Therese Budnik; Balázs Ádám

doi:10.1016/j.envres.2019.108851

Comparative cyto- and genotoxicity assessment of glyphosate and glyphosate-based herbicides in human peripheral white blood cells

Environ Res. 2019 Dec;179(Pt B):108851. doi: 10.1016/j.envres.2019.108851. Epub 2019 Oct 21.

Authors

Károly Nagy¹, Roba Argaw Tessema², Lygia Therese Budnik³, Balázs Ádám²

Affiliations

¹ Division of Occupational Health, Department of Preventive Medicine, Faculty of Public Health, University of Debrecen, Debrecen, Hungary. Electronic address: nagy.karoly@sph.unideb.hu.
² Division of Occupational Health, Department of Preventive Medicine, Faculty of Public Health, University of Debrecen, Debrecen, Hungary.
³ Translational Toxicology and Immunology Unit, Institute for Occupational and Maritime Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

PMID: 31678731
DOI: 10.1016/j.envres.2019.108851

Abstract

Glyphosate is the most heavily applied active compound of agricultural pesticides. It is solely used in more than 750 different glyphosate-based herbicide formulations (GBHs) that also contain other substances, mostly presumed as inert by regulatory agencies. The toxicity of formulations is currently assessed substance by substance, neglecting possible combined effects in mixtures and many of the findings regarding the toxic effects of glyphosate and GBHs to human cells are inconsistent. This is the first study to investigate and compare the cyto- and genotoxic potential of the active ingredient glyphosate and GBHs in human mononuclear white blood (HMWB) cells. HMWB cells were treated for 4 h at 37 °C with increasing concentrations (1-1000 μM) of glyphosate alone and in three GBHs (Roundup Mega, Fozat 480 and Glyfos) to test cytotoxic effect with fluorescent colabelling and genotoxic effect with comet assay. In addition, each concentration was tested with and without metabolic activation using human liver S9 fraction. We found that glyphosate alone does not induce significant cytotoxicity and genotoxicity over the tested concentration range. Contrarily, GBHs induced statistically significant cell death from 250 μM (Roundup Mega and Glyfos) and 500 μM (Fozat 480), as well as statistically significant increase of DNA damage from 500 μM (Roundup Mega and Glyfos) and 750 μM (Fozat 480); however, the latter observation may not be explained by direct DNA injuries, rather due to the high level of cell death (>70%) exerted by the formulations. Metabolic activation significantly increased the DNA damage levels induced by Glyfos, but not of the other GBHs and of glyphosate. The differences observed in the toxic pattern of formulations and the active principle may be attributed to the higher cytotoxic activity of other ingredients in the formulations or to the interaction of them with the active ingredient glyphosate. Hence, further investigation of formulations is crucial for assessing the true health risks of occupational and environmental exposures.

Keywords: Comet assay; Cytotoxicity; Formulation; Genotoxicity; Glyphosate.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

DNA Damage
Glycine / analogs & derivatives*
Glycine / toxicity
Glyphosate
Herbicides / toxicity*
Humans
Leukocytes
Toxicity Tests*

Substances

Herbicides
Glycine