The effects of simazine, a chlorotriazine herbicide, on pubertal development in the female Wistar rat

Abstract

Chlorotriazine herbicides, such as atrazine and its metabolites, have been shown to target the neuroendocrine regulation of male and female reproductive development. However, no studies have evaluated the effects of the chlorotriazine simazine on pubertal development in the female rat. Here we report the effects of a 21- and 41-day exposure to simazine on pubertal development and estrous cyclicity in the female rat using the U.S. Environmental Protection Agency's Endocrine Disruptor Screening Program, Pubertal Development and Thyroid Function in Intact/Juvenile Peripubertal Female Rats (Tier 1) protocol. In the first study, Wistar rats were exposed orally to 0, 12.5, 25, 50, or 100 mg/kg of simazine from postnatal day 22 to 42. In the second study, rats were exposed from PND 22 until the first day of estrus after PND 62 to 0, 12.5, 25, 50, 100 or 200 mg/kg of simazine. In the 21-day exposure, vaginal opening (VO) was delayed, the number of normal cycles was significantly decreased, and the day of first estrus was delayed compared to controls. In the 41-day exposure, VO and the day of first estrus was delayed, but the number of normal estrous cycles was not different than controls. In addition, both studies showed a significant decrease in serum prolactin (PRL) following simazine exposure. This data clearly demonstrates that simazine delays the onset of puberty in the female rat and decreases serum PRL similar to other chlorotriazines. The extended dosing period after VO provides a sufficient time period to monitor the effects of a toxicant on estrous cyclicity, an important measure for reproductive competence.