Dataset Information

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

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 continuous exposure to ATZ at the chronic point of departure (POD = 1.8?mg/kg/day) was 360.6??g/L.

SUBMITTER: Campbell JL

PROVIDER: S-EPMC4809456 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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

Campbell Jerry L JL Andersen Melvin E ME Hinderliter Paul M PM Yi Kun Don KD Pastoor Timothy P TP Breckenridge Charles B CB Clewell Harvey J HJ

Toxicological sciences : an official journal of the Society of Toxicology 20160121 2

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 methylc ...[more]

PMID: 26794140

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Dataset Information

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

Publications

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

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