Subacute oral glyphosate induces dose-dependent renal injury in male mice (Mus musculus).

Abstract

Glyphosate is the most heavily applied herbicide worldwide and human exposure is now near-ubiquitous, yet its renal toxicity at near-threshold doses remains incompletely characterized. We tested whether subacute oral glyphosate produces integrated, dose-dependent renal injury in male mice (Mus musculus). Adult male mice (n = 10/group) received vehicle or technical-grade glyphosate at 10, 50 or 100 mg/kg/day by oral gavage for 28 days, with 50 mg/kg anchored near the chronic NOAEL. Serum renal-function markers, renal oxidative-stress markers (MDA, GSH, SOD, CAT) and hematoxylin-eosin histopathology were assessed in the same 40 animals. Glyphosate produced coherent, dose-dependent renal injury. At 100 mg/kg, serum urea, creatinine and uric acid rose by 63.5%, 46.9% and 84.7%, with hyponatraemia, hypochloraemia and hyperkalaemia; renal MDA increased 2.1-fold while GSH, SOD and CAT fell by 46-51%, and the composite lesion score rose from 0 to 9.5 (median). No endpoint differed from control at 10 mg/kg under the prespecified analysis (one heteroscedastic sensitivity test detected a low-dose MDA increase), whereas significant effects were present at 50 mg/kg. A monotone dose trend was confirmed for every endpoint tested (Jonckheere-Terpstra, FDR-adjusted p < 0.001), and exploratory benchmark doses lay below the 50 mg/kg anchor. These findings indicate dose-dependent renal injury under subacute conditions and warrant duration-matched, both-sex confirmation. The doses studied lie far above realistic human intakes and characterize hazard rather than risk.