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A mixture of Iprodione and Vinclozolin delays the onset of puberty in the male rat in a cumulative manner.
Citation:
BLYSTONE, C., C. R. LAMBRIGHT, J. R. FURR, C. V. RIDER, V. S. WILSON, AND L. E. GRAY. A mixture of Iprodione and Vinclozolin delays the onset of puberty in the male rat in a cumulative manner. Presented at 2009 SOT Annual Meeting, Baltimore, MD, March 15 - 19, 2009.
Impact/Purpose:
These data demonstrate that the two fungicides share a common mode of action and interact in a cumulative manner to delay puberty. This is important to the vinclozolin risk assessment.
Description:
Vinclozolin and iprodione are dicarboximide fungicides that display anti-androgenic effects in the male rat, which suggests co-exposure to these fungicides would lead to cumulative effects on androgen-sensitive endpoints. In order to test for cumulative effects by iprodione and vinclozolin, we examined the effects of a mixture of these fungicides on pubertal development in the male rat. The mixture combined a dose of iprodione that does not significantly affect androgen-dependent morphological endpoints, with vinclozolin (a 5x2 factorial design). Sprague-Dawley rats were dosed by gavage with effective vinclozolin doses (0, 10, 30, 60, and 100 mg/kg/day) with and without 50 mg iprodione/kg/d from postnatal day (PND) 23 to 55-57 (n = 8/group). Onset of puberty (progression of preputial separation (PPS)) was measured starting on PND 37. Organ weights, serum hormones, and ex vivo testis steroid hormone production under stimulated (+human chorionic gonadotropin (hCG)) and unstimulated (-hCG) conditions were measured at necropsy. Vinclozolin alone delayed pubertal progression, reduced androgen sensitive organ weights, and increased serum testosterone levels as previously reported. The addition of 50 mg/kg/day iprodione enhanced the vinclozolin-induced delay in PPS (PND 47.5 vs 49.1; 2-way ANOVA: iprodione main effect p = 0.0002) and reduction of several reproductive organ weights. Furthermore, the increase in serum testosterone by vinclozolin, due to its AR antagonism, was reduced by the addition of iprodione (a steroidogenic inhibitor) in vivo, but not ex vivo. These results demonstrate these fungicides interact when co-administered to delay pubertal development (i.e. PPS) in the male rat in a cumulative, antiandrogenic manner. CRB and CVR were supported through the USEPA/NCSU Cooperative Training Agreement. This abstract does not necessarily reflect US EPA policy.