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MAMMARY GLAND DEVELOPMENT AS A SENSITIVE END-POINT FOLLOWING ACUTE PERNATAL EXPOSURE TO A LOW DOSE ATRAZINE METABOLITE MIXTURE IN FEMALE LONG EVANS RATS
Citation:
ENOCH, R., J. STANKO, S. GREINER, G. YOUNGBLOOD, J. RAYNER, AND S. E. FENTON. MAMMARY GLAND DEVELOPMENT AS A SENSITIVE END-POINT FOLLOWING ACUTE PERNATAL EXPOSURE TO A LOW DOSE ATRAZINE METABOLITE MIXTURE IN FEMALE LONG EVANS RATS. ENVIRONMENTAL HEALTH PERSPECTIVES. National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, 115(4):541-547, (2007).
Impact/Purpose:
To characterize the potential developmental effects of atrazine (ATR) metabolites at low doses
Description:
In order to characterize the potential developmental effects of atrazine (ATR) metabolites at low doses, an environmentally-based mixture (EBM) of ATR and its metabolites hydroxyatrazine, diaminochlorotriazine, deethylatrazine, and deisopropylatrazine was formulated based on surveys of ground and surface contamination of ATR and metabolite concentrations in the literature. Two blocks of pregnant Long Evans rats (n > 6/treatment) were gavaged with 0, 0.09, 0.87, 8.73 mg EBM/kg body weight (BW)/d, or 100 mg ATR/kg BW/d as a positive control, on gestation days (GD) 15-19. Female offspring were evaluated for standard physiological indicators of puberty and mammary glands were collected on postnatal day (PND) 4, PND25, PND33, PND40, and PND60. At the PND60 necropsy, offspring were weighed and pituitary, ovary, uterus, mammary gland, and serum were collected. EBM-exposed dams gained body weight during the dosing period at the same rate as controls, while their female offspring weighed 7-8% more than control pups on PND4. Day of vaginal opening was not significantly delayed by the EBM, but an increased body weight at vaginal opening was observed in the 0.87 mg EBM/kg BW-treated animals. Pituitary prolactin levels were also increased in 0.87 mg EBM/kg BW and ATR-treated animals. Delayed mammary gland development, evaluated by whole mount analysis, was detected as early as PND4 in all treatment groups. Our data suggest that acute exposure to EBM at levels as low as 0.09 mg/kg BW during late pregnancy cause persistent alterations in female offspring mammary gland development, and that these effects do not appear to be related to BW or associated with pubertal timing.