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ATRAZINE DISPOSITION IN PREGNANT AND LACTATING LONG-EVANS RATS
Citation:
RAYNER, J., E. P. HINES, R. R. BARBEE, J. V. NGUYEN, P. PANUWET, D. B. BARR, R. D. WHITEHEAD, AND S. E. FENTON. ATRAZINE DISPOSITION IN PREGNANT AND LACTATING LONG-EVANS RATS. Presented at Society of Toxicology, San Diego, CA, March 05 - 09, 2006.
Description:
Atrazine (ATR) is a widely used herbicide shown to delay early mammary development in female offspring of gestationally exposed rats. The effects of ATR can be induced by in utero exposure and/or suckling from a dam exposed during late pregnancy, but ATR is reported to have a half-life of less than 1 day in adult non-pregnant rats. We hypothesized that ATR disposition in the pregnant and lactating rat may differ from that in the adult non-pregnant rat resulting in transference to pups transplacentally and via milk. To test this hypothesis, rat dams (N=24/group) were gavage dosed on gestation days (GD)13-19 with 100 mg ATR/kg or GD13-19 with vehicle (control, C). Urine and other body fluids were collected on GD19, 20, 21, postnatal day (PND)1, 4, and 11. Urine samples from C and GD13-19 ATR-dosed dams were analyzed by isotope dilution high performance liquid chromatography tandem mass spectrometry for the presence of hydroxyl-, dealkyl- and mercapturate ATR metabolites. ATR metabolites were detected at levels substantially above the limits of detection from GD20 until at least 5 days later, PND 4. The highest total urinary levels of metabolites were found 1-4 days post dosing, which differs from results in non-pregnant/lactating rats. The percent recovered ATR metabolites in urine throughout the course of study were 89-99% diaminochlorotriazine and 4-0.4%, 4-0.8%, 13-0.07%, and 0.7-0.002% of desisopropyl ATR, desethyl ATR, hydroxy ATR, and ATR mercapturate, respectively. The parent compound, ATR, was detected in trace amounts. These results suggest that even though exposure to the pregnant dam ended on GD19, ATR metabolites may be available to the developing offspring until at least PND4 when abnormal mammary gland development has been detected in female pups. Studies evaluating ATR metabolite levels in milk from these animals are warranted. (This abstract does not necessarily reflect EPA policy; Supported by NHEERL-DESE, EPA CT826513)