Oral absorption and oxidative metabolism of atrazine in rats evaluated by physiological modeling approaches.
Toxicology
; 240(1-2): 1-14, 2007 Oct 30.
Article
en En
| MEDLINE
| ID: mdl-17767989
ABSTRACT
Atrazine (ATRA) is metabolized by cytochrome P450s to the chlorinated metabolites, 2-chloro-4-ethylamino-6-amino-1,3,5-triazine (ETHYL), 2-chloro-4-amino-6-isopropylamino-1, 3, 5-triazine (ISO), and diaminochlorotriazine (DACT). Here, we develop a set of physiologically based pharmacokinetic (PBPK) models that describe the influence of oral absorption and oxidative metabolism on the blood time course curves of individual chlorotriazines (Cl-TRIs) in rat after oral dosing of ATRA. These models first incorporated in vitro metabolic parameters to describe time course plasma concentrations of DACT, ETHYL, and ISO after dosing with each compound. Parameters from each individual model were linked together into a final composite model in order to describe the time course of all 4 Cl-TRIs after ATRA dosing. Oral administration of ISO, ETHYL and ATRA produced double peaks of the compounds in plasma time courses that were described by multiple absorption phases from gut. An adequate description of the uptake and bioavailability of absorbed ATRA also required inclusion of additional oxidative metabolic clearance of ATRA to the mono-dealkylated metabolites occurring in GI a tract compartment. These complex processes regulating tissue dosimetry of atrazine and its chlorinated metabolites likely reflect limited compound solubility in the gut from dosing with an emulsion, and sequential absorption and metabolism along the GI tract at these high oral doses.
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Bases de datos:
MEDLINE
Asunto principal:
Atrazina
/
Herbicidas
/
Modelos Biológicos
/
Mucosa Bucal
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Toxicology
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos