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PUBERTAL DEVELOPMENT IN FEMALE WISTAR RATS FOLLOWING EXPOSURE TO PROPAZINE AND ATRAZINE METABOLITES, DIAMINO-S-CHLOROTRIAZINE AND HYDROXYATRAZINE
Citation:
Laws, S C., J M. Ferrell, T E. Stoker, AND R L. Cooper. PUBERTAL DEVELOPMENT IN FEMALE WISTAR RATS FOLLOWING EXPOSURE TO PROPAZINE AND ATRAZINE METABOLITES, DIAMINO-S-CHLOROTRIAZINE AND HYDROXYATRAZINE. Presented at Society of Toxicology, Nashville, TN, March 17-21, 2002.
Description:
PUBERTAL DEVELOPMENT IN FEMALE WISTAR RATS FOLLOWING EXPOSURE TO PROPAZINE AND ATRAZINE METABOLITES, DIAMINO-S-CHLOROTRIAZINE AND HYDROXYATRAZINE. S C Laws, J M Ferrell, T E Stoker, and R L Cooper. Endocrinology Branch, RTD, NHEERL, ORD, USEPA, RTP, NC, USA. Sponser: R J Kavlock.
We have shown that the chorotriazine herbicide, atrazine (ATR), delays the onset of pubertal development in female wistar rats. ATR and its by-products of microbial degradation are present in soil and groundwater. Since current maximum contaminant levels are set for ATR, but not its metabolites, it is important to determine whether or not the metabolites of ATR can also alter pubertal development and possibly pose a cummulative exposure risk. In the studies, we evaluated the effects of two atrazine metabolites, diamino-s-chlorotriazine (DACT) and hydroxatrazine (OH-ATR), and a structurally similar herbicide, propazine, on female pubertal development. Using the Protocol for the Assessment of Pubertal Development and Thyroid Function in Juvenile Female Rats, female rats were dosed by oral gavage from postnatal day (PND) 22 through PND 41 with DACT (16.5, 33.7, 67.5, 135 mg/kg/d), OH-ATR (22.8, 45.7, 91.4, 183 mg/kg), or propazine (53, 107, 213 mg/kg/d). The dose range for each chemical was selected as the molar equivalents of ATR that was reported to alter the onset of females puberty (25, 50, 100, 200 mg/kg/d). Females were monitored daily for vaginal opening (VO) and killed on PND 41. DACT significantly delayed vaginal opening by 3.1, 4.5, and 7.1 days as compared to the controls (32.7 ? 1.8 days of age) following exposure to 33.7, 67.5 and 135 mg/kg, respectively. The NOAEL (no adverse effect level) for DACT (16.5 mg/kg) was identical to the molar equilvalent dose observed as the NOAEL for ATR (25 mg/kg). At necropsy, body weight (BW) was reduced only by the high dose of DACT (7.1 % reduction in BW) indicating that growth was not associated with the delayed VO. Also, the BW on the day of VO was significantly increased by 33.7, 67.5 and 135 mg/kg DACT. Proprazine, (107 and 213 mg/kg) delayed VO by 4 days. BW at necropsy was not altered by any dose of propazine, but BW on the day of VO was significantly increased by 107 and 213 mg/kg. In contrast, the de-chlorinated metabolite, OH-ATR, did not significantly delay the age at VO. These data suggest that the presence of the chlorine group may be necessary for the delay in the onset of puberty observed following exposure to ATR, propazine or DACT. Together, these data demonstrate that propazine and DACT can modify the onset of puberty in the female rat at doses equimolar to that of ATR, and suggest that they could pose a cumulative hazard. This abstract does not refect U.S. EPA policy.