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PREGNANCY LOSS AND DELAYED PARTURITION CAUSED BY ATRAZINE AND ITS METABOLITES IN F344 RATS
Narotsky, M G., D S. Best, S. R. Bielmeier, S. A. Spangler, AND R L. Cooper. PREGNANCY LOSS AND DELAYED PARTURITION CAUSED BY ATRAZINE AND ITS METABOLITES IN F344 RATS. Presented at Society for the Study of Reproduction, Baltimore, MD, July 28-31, 2002.
Previously we reported that atrazine (ATR), a widely used herbicide, caused pregnancy loss (i.e., full-litter resorption) and, in surviving litters, delayed parturition in the rat. In this study we compared the dose-response relationships for ATR and four metabolites. Hydroxyatrazine (OHA) is a dechlorinated metabolite of plants that is found in food. Deethylatrazine (DEA), deisopropylatrazine (DIA), and diaminochlorotriazine (DACT), are dealkylated mammalian and microbial metabolites, with DACT being predominant; these metabolites are also found in the environment. The chemicals were administered in 1% methylcellulose to F344 rats by gavage on gestation days (GD) 6-10 (plug day = GD 0). There were 7-16 animals per treatment group. ATR and DACT were administered at 0, 0.12, 0.23, and 0.46 mmol/kg (equimolar to 0, 25, 50, and 100 mg ATR/kg); DEA and DIA were administered at 0, 0.23, 0.46, and 0.69 mmol/kg (equimolar to 0, 50, 100, and 150 mg ATR/kg); and OHA was administered at 0, 0.46, 1.39, and 2.32 mmol/kg (equimolar to 0, 100, 300, and 500 mg ATR/kg). Dams were allowed to deliver and their litters were examined postnatally. Apparently nongravid uteri were stained with 10% ammonium sulfide to detect/confirm resorption sites. Maternally, the highest dose of OHA caused significant weight loss after the 4th and 5th doses. For the four other chemicals, the two highest dosages (ATR and DACT) or all dosages (DIA and DEA) caused significant weight loss after the 1st or 2nd dose. All five chemicals disrupted pregnancy maintenance. Pregnancy loss was observed following treatment with ATR at 0.23 and 0.46 mmol/kg (36% and 74%, respectively); DEA at 0.69 mmol/kg (38%); DIA at 0.46 and 0.69 mmol/kg (19% and 29%, respectively); DACT at 0.46 mmol/kg (40%); and OHA at 0.46 and 2.32 mmol/kg (14% and 36%, respectively). Overall, only one (3%) control dam had pregnancy loss. For surviving litters, parturition was slightly, but significantly, delayed for dams exposed to ATR (0.46 mmol/kg), DEA (0.23 and 0.69 mmol/kg), DIA (0.46 and 0.69 mmol/kg), and DACT (0.23 and 0.46 mmol/kg). Thus, the potency ranking for causing pregnancy loss was ATR > DACT > DIA DEA OHA. For delayed parturition, DACT and possibly DEA appeared to be the most potent, whereas OHA had no apparent effect on parturition.
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB
REPRODUCTIVE TOXICOLOGY DIVISION