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EFFECT OF SIMAZINE ON MALE REPRODUCTIVE DEVELOPMENT IN THE RAT
STOKER, T. E., A. R. BUCKALEW, J. M. FERRELL, AND R. L. COOPER. EFFECT OF SIMAZINE ON MALE REPRODUCTIVE DEVELOPMENT IN THE RAT. Presented at Society for the Study of Reproduction, Quebec, QC, CANADA, July 24 - 27, 2005.
The chlorotriazine herbicides, such as atrazine, are used extensively in the United States each year. Chlorotriazine metabolites, as well as the parent compounds, have been detected in surface and ground water in areas of major usage. Previously, we found that atrazine delayed puberty in juvenile male and female rats. The mode of action appears to be a disruption of the hypothalamic control of pituitary function, resulting in decreased secretion of luteinizing hormone and prolactin from the pituitary. The primary metabolites of atrazine were equally potent in inducing alterations in reproductive development. These findings underscore the need to consider these metabolites and other parent compounds in the cumulative risk assessment of chlorotriazine herbicides. For these reasons, we hypothesized that simazine, like atrazine, would delay pubertal progression in the male rat. In this study, we exposed male rats in the male pubertal protocol that the Endocrine Disruptor Screening Program (EDSP) is considering for a Tier 1 screening assay. Male Wistar rats were administered simazine (0, 6.25, 25, 75, 150 and 300 mg/kg) by oral gavage from postnatal day (PND) 23 to 53. Males were monitored for preputial separation (PPS) as an indicator of puberty and then necropsied on PND 53. A non-monotonic dose response was found for the onset of puberty, with an advancement at the low doses (6.25 mg/kg by 1.3 days and 25 mg/kg by 2.5 days) and a non-significant rise at the three highest doses. Consistent with the low dose advancement of PPS, mean serum testosterone (T) and androstenedione (A) were also significantly increased at 6.25 and 25 mg/kg dose of simazine (Controls, 1.89 +/- 0.29 and 0.305+/- 0.06; 6.25 mg/kg, 5.06 +/- 0.97 and 1.19 +/- 0.29; 25 mg/kg, 4.92 +/- 1.2 and 1.076 +/- 0.29, respectively for T and A in ng/ml +/- SEM). There was also a dose-related decrease in the absolute seminal vesicle and prostate weights at the three highest doses (75 to 300 mg/kg). In conclusion, simazine appears to have a bimodal effect on puberty in the male rat, with an increase in androgens and corresponding advancement in puberty at the low doses and a delay in reproductive tract development at higher doses. Further studies are planned to elucidate the mechanisms of these effects on male development. This abstract does not necessarily reflect EPA policy.