Metabolism of Glyphosate in Sprague-Dawley Rats: Tissue Distribution, Identification, and Quantitation of Glyphosate-Derived Materials following a Single Oral Dose

Five groups of male Sprague-Dawley rats were orally administered a mixture of [14C]- and [12C]-glyphosate (N-phosphonomethylglycine) at a dose level of 10 mg/kg body weight. The majority of radioactivity 2 hr after administration was associated with the gastrointestinal contents and small intestinal tissue. Approximately 35–40% of the administered dose was absorbed from the gastrointestinal tract, and urine and feces were equally important routes of elimination. The total body burden 7 days after administration was approximately 1% of the administered dose and was primarily associated with the bone. Total recovery for this study ranged from 95 to 102% of the administered dose. Metabolic profiles of tissues containing greater than 1% of the administered dose at various times after administration indicated that nearly 100% of the body burden of radioactivity was present as unmetabolized parent glyphosate. A minor component constituting <0.1% of the administered dose (<0.4 ppm) was observed in colon tissue from animals 2 hr after the administration of glyphosate and was also present in the GI contents of one animal 28 hr after administration of the radiolabel. The retention time for this metabolite was similar, but not identical, to the retention time for AMPA (aminomethylphosphonic acid), the major bacterial metabolite of glyphosate found in soil. Tissue extraction efficiency was always greater than 90% and stability assays indicated no significant effect of storage on either parent glyphosate or AMPA. The results from this study indicate that virtually no toxic metabolites of glyphosate were produced since there was little evidence of metabolism and essentially 100% of the body burden was parent compound with no significant persistence of material.