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Modifications to the Current EPA Endocrine Disruptor Screening Program's Tier 1 Female Pubertal Protocol: A Study on the Effects of the Chlorotriazine Simazine
Citation:
Zorrilla, L. M., J. C. Childress, E. K. GIBSON, AND T. E. STOKER. Modifications to the Current EPA Endocrine Disruptor Screening Program's Tier 1 Female Pubertal Protocol: A Study on the Effects of the Chlorotriazine Simazine. Presented at Triangle Consortium for Reproductive Biology, RTP, NC, January 31, 2009.
Impact/Purpose:
To be presented at TCRB 2009 Meeting
Description:
Currently the US EPA is implementing a screening program for environmental endocrine disruptors. One of the in vivo assays in the Tier 1 Screen of the Endocrine Disruptors Screening Program (EDSP) is a female pubertal assay. In this study we examined the chlorotriazine simazine, a widely used herbicide, on female pubertal progression using the pubertal assay. Studies with similar chlorotriazines (atrazine and its metabolites) have demonstrated a delay in vaginal opening (VO, a marker of pubertal onset) and a disruption in estrous cyclicity. These changes were shown to be due to a suppression of the ovulatory surge of luteinizing hormone (LH) through a hypothalamic insult. However, the effects of simazine in the female pubertal rat have not been studied. We used the current female pubertal protocol and also continued dosing for another 20-23 days to determine if these changes would provide a more valid evaluation of the chemical tested. In the first study, Wistar rats were exposed to 0, 12.5, 25, 50, or 100 mg/kg of simazine by oral gavage from postnatal day (PND) 22 to 42. VO was examined beginning on PND 27, and vaginal smears were obtained from the day of VO until necropsy. Rats were necropsied on PND 42 and reproductive tissue and organ weights were recorded. Serum was collected at necropsy for hormonal analysis of estradiol (E2), serum and pituitary LH, progesterone (P), serum and pituitary prolactin (PRL) and thyroxine (T4). VO was significantly delayed at 25 and 100 mg/kg of simazine. Pituitary weights were significantly decreased at 100 mg/kg and adrenals were dose-dependantly decreased with 50 and 100 mg/kg of simazine. Days in estrous and number of cycles were significantly decreased in the 25 and 100 mg/kg groups. In the second and third studies, Wistar rats were exposed to 0, 12.5, 25, 50, 100, or 200 mg/kg of simazine by oral gavage from PND 23 until the first day of estrous after day 62. VO was examined beginning on PND 27, and vaginal smears were obtained from the day of VO until necropsy. The same terminal endpoints and hormonal analyses were performed. In block 2 VO was delayed only at 100 mg/kg, whereas VO was delayed at 25 mg/kg and higher. Days in estrous and number of cycles were decreased at 25, 100 and 200 mg/kg. Pituitary weights were also significantly decreased at 100 and 200 mg/kg. Therefore simazine does appear to delay onset of puberty in the female rat, which is similar to the effects observed previously in our lab following atrazine exposure. The extended protocol allowed for a more comprehensive evaluation of estrous cyclicity following vaginal opening. This abstract does not necessarily reflect U.S. EPA policy.