Glyphosate-based herbicides induce oxidative stress: Insights from human biomarker and in vitro mutagenic studies.

Glyphosate-based herbicides (GBHs) are widely used and raise concerns about human health risks due to the detection of glyphosate (GLY) in body fluids. Their toxicity remains the subject of ongoing debate, especially regarding their carcinogenic potential, while epidemiological evidence associates GBHs exposure with increased non-Hodgkin lymphoma incidence. This study addresses key gaps by characterizing the kinetic profiles of GLY, its metabolites, and oxidative stress biomarkers in urine from 11 agricultural workers over 14 days, alongside evaluating mutagenicity using the AS52 cell model. 1H NMR metabolomic analysis identified GLY and several downstream metabolites, with formaldehyde showing the strongest associations with oxidative damage biomarkers. AS52 cells exhibited concurrent oxidative and mutagenic responses, indicating involvement of GBHs in reactive oxygen species generation, DNA damage, and apoptosis. These integrated findings demonstrate biologically relevant GLY transformation and implicate both GLY and its reactive metabolites in oxidative and genotoxic stress, advancing understanding of GBHs' toxicity in humans.