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Toxicol Lett. 2009 Oct 8;190(1):91-5. doi: 10.1016/j.toxlet.2009.07.008. Epub 2009 Jul 14.

Toxicokinetics of glyphosate and its metabolite aminomethyl phosphonic acid in rats.

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  • 1Department of Toxicology and Pharmacology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain.


The toxicokinetics of glyphosate after single 100 mgkg(-1) intravenous (i.v.) and 400 mgkg(-1) oral doses were studied in rats. Serial blood samples were obtained after i.v. and oral administration. Plasma concentrations of glyphosate and its metabolite amiomethyl phosphonic acid (AMPA) were determined by HPLC method. After i.v. and oral administration, plasma concentration-time curves were best described by a two-compartment open model. For glyphosate, the elimination half-lives (T(1/2beta)) from plasma were 9.99 h after i.v. and 14.38 h after oral administration. The total plasma clearance was not influenced by dose concentration or route and reached a value of 0.995 l h(-1)kg(-1). After i.v. administration, the apparent volume of distribution in the second compartment (V(2)) and volume of distribution at steady state (V(ss)) were 2.39 and 2.99 l kg(-1), respectively, suggesting a considerable diffusion of the herbicide into tissues. After oral administration, glyphosate was partially and slowly absorbed with a T(max) of 5.16 h. The oral bioavailability of glyphosate was found to be 23.21%. Glyphosate was converted to AMPA. The metabolite AMPA represented 6.49% of the parent drug plasma concentrations. The maximum plasma concentrations of glyphosate and AMPA were 4.62 and 0.416 microg ml(-1), respectively. The maximum plasma concentration of AMPA was achieved at 2.42 h. For AMPA, the elimination half-life (T(1/2beta)) was 15.08 h after oral administration of glyphosate parent compound.

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