PBPK Model for Atrazine and Its Chlorotriazine Metabolites in Rat and Human

Toxicological Sciences : an Official Journal of the Society of Toxicology
Jerry L CampbellHarvey J Clewell

Abstract

The previously-published physiologically based pharmacokinetic model for atrazine (ATZ), deisopropylatrazine (DIA), deethylatrazine (DEA), and diaminochlorotriazine (DACT), which collectively comprise the total chlorotriazines (TCT) as represented in this study, was modified to allow for scaling to humans. Changes included replacing the fixed dose-dependent oral uptake rates with a method that represented delayed absorption observed in rats administered ATZ as a bolus dose suspended in a methylcellulose vehicle. Rate constants for metabolism of ATZ to DIA and DEA, followed by metabolism of DIA and DEA to DACT were predicted using a compartmental model describing the metabolism of the chlorotriazines by rat and human hepatocytesin vitro Overall, the model successfully predicted both the 4-day plasma time-course data in rats administered ATZ by bolus dose (3, 10, and 50 mg/kg/day) or in the diet (30, 100, or 500 ppm). Simulated continuous daily exposure of a 55-kg adult female to ATZ at a dose of 1.0 µg/kg/day resulted in steady-state urinary concentrations of 0.6, 1.4, 2.5, and 6.0 µg/L for DEA, DIA, DACT, and TCT, respectively. The TCT (ATZ + DEA + DIA + DACT) human urinary biomonitoring equivalent concentration following conti...Continue Reading

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Citations

Jan 23, 2016·Toxicological Sciences : an Official Journal of the Society of Toxicology·Charles B BreckenridgeRobert L Sielken
Sep 9, 2017·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Arthur D ZimmermanChad D Foradori
Jul 11, 2018·Arhiv za higijenu rada i toksikologiju·Tanja Živković SemrenAlica Pizent
Mar 23, 2021·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Jie PengLi He
Aug 3, 2021·Frontiers in Endocrinology·Arthur D ZimmermanChad D Foradori

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