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DEVELOPMENTAL TOXICITY OF ATRAZINE METABOLITES IN FISCHER 344 RATS
Citation:
Best, D S., M G. Narotsky, AND R L. Cooper. DEVELOPMENTAL TOXICITY OF ATRAZINE METABOLITES IN FISCHER 344 RATS. Presented at RTB-AALAS at CIIT, RTP, NC, February 2-8, 2000.
Description:
Previously we have shown that atrazine, a commonly used herbicide, causes full-litter resorption (FLR) in Fischer 344 rats at 50 mg/kg. In this study, we tested four atrazine metabolites for their potential to cause FLR and developmental toxicity. Desethylatrazine (DEA), desisopropylatrazine (DIA), hydroxyatrazine (OHA), and diaminochlorotriazine (DACT) were administered in 1% methyl cellulose by gavage at 87, 80, 275, and 92 mg/kg/day, or 0.46, 0.46, 1.39, and 0.63 mmol/kg, respectively, on gestation days (GD) 6-10. These respective dosages were equimolar to 100, 100, 300, and 136 mg atrazine/kg. Dams were weighed daily and allowed to deliver. Litters were examined on postnatal days 1 and 6. Apparently nongravid uteri were stained with 10% ammonium sulfide to detect/confirm resorption sites. DEA, DIA, and DACT caused maternal weight loss after the first dose, whereas mean body weights in the OHA group showed reduced weight gain after four doses and weight loss after the fifth dose. DIA-exposed litters showed no signs of developmental toxicity; however, FLR was seen in 33% (3/9), 19% (3/16), and 78% (7/9) of dams treated with DEA, OHA, and DACT, respectively. All cases of FLR were evident prior to ammonium sulfide staining; however, based on clinical and necropsy findings, two of the DEA-exposed litters appeared to resorb somewhat later than the other cases. Surviving litters appeared normal in the DEA and OHA groups, but DACT-exposed litters had increased prenatal mortality resulting in reduced litter sizes. In addition, the DACT-exposed litters had increased postnatal mortality and reduced pup weights. These data indicate that some of the chlorotriazine metabolites (DEA, OHA, and DACT) can disrupt pregnancy maintenance. There was no clear evidence of teratogenicity at the doses tested; however, DACT adversely affected growth and viability in the surviving litters.