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The distribution of atrazine (ATR) and ATR metabolites in the Wistar rat following gestational/lactational exposures
Citation:
STOKER, T. E., A. Kamel, Y. Qian, L. Podhorniak, R. L. COOPER, L. M. Zorrilla, AND L. Strader. The distribution of atrazine (ATR) and ATR metabolites in the Wistar rat following gestational/lactational exposures. Presented at Society of Toxicology (SOT) Annual Meeting, Washington, DC, March 06 - 10, 2011.
Impact/Purpose:
In the current study, the distribution of atrazine and certain metabolites were determined in the dam, fetus and neonate following gavage exposure.
Description:
Gestational/lactational exposure to ATR is reported to alter reproductive/developmental function, yet our understanding of the transfer of ATR and/or its metabolites from the dam to the fetus/offspring is limited. Previously we examined the lactational transfer of CI4-ATR, but specific ATR metabolites were not determined. In the current study, the distribution of atrazine and certain metabolites were determined in the dam, fetus and neonate following gavage exposure. Groups of dams were exposed to 0, 5 and 25 mg/kg ATR from (1) gestation day (GD) 18-20, (2) GD 14-20 or (3) GD 14-postnatal day (PND) 10. Two hours after the last dose, blood was drawn by cardiac puncture and the dam perfused with saline. GD20 fetuses were collected, along with the plasma, brain, adrenal glands and mammary glands of the dam. On PND 10 pups were separated from the dam for 2.5 h and then allowed to nurse 30 minutes before plasma, brain, adrenal and milk samples were collected. We measured ATR, desethyl ATR (DEA), desisopropyl ATR (DlA), diaminochlorotriazine (DACT), and hydroxyl ATR (OH-ATR) using LCIMS/MS. In the dams DACT accounted for the highest concentration in plasma and tissues, followed by DIA and DEA, with similar amounts present after both the 3 and 7 day exposure. ATR was present in very low amounts. OH-ATR was not detected in the majority of the samples. There was transfer of ATR from the dam to the fetus on GD 20 following both exposures and doses. Although all analytes were present in the GD20 fetus, DACT contributed to over 75% ofthe total. In the PNDlO pups DACT accounted for 99% ofthe analytes which correlated well with the 91% of DACT found in the milk. This study demonstrates that DACT was the primary metabolite found in the dam and fetus/neonate at 2 h after the last dose and that ATR crossed both the placental and blood-brain barrier of the dam/neonate. This study does not reflect EPA policy.