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EFFECTS OF CONAZOLE FUNGICIDES ON DEVELOPMENT AND PARTURITION IN THE RAT
Citation:
Narotsky, M G., J C. Rockett, C. BLYSTONE, A. GOETZ, H. REN, D. S. BEST, H. P. NICHOLS, J. E. SCHMID, AND D. J. DIX. EFFECTS OF CONAZOLE FUNGICIDES ON DEVELOPMENT AND PARTURITION IN THE RAT. Presented at Society of Toxicology, New Orleans, LA, March 6-10, 2005.
Description:
Conazoles are fungicides used extensively in agriculture and as pharmaceuticals. As part of an effort to evaluate the changes in gene expression corresponding to reproductive toxicity, we examined the effects of three conazoles on pregnancy and neonates. Wistar Han rats were exposed via feed from gestation day 6 to the weaning of their litters to propiconazole (P) at 100, 500, or 2500 ppm; myclobutanil (M) at 100, 500, or 2000 ppm; triadimefon (T) at 100, 500, or 1800 ppm; or vehicle control. Litters were examined on postnatal days 0 and 8. The highest concentration of each of the three chemicals caused delayed parturition. T1800 had particularly severe effects, with 19% of the dams unable to successfully deliver live pups; in some cases dystocia led to maternal death. Increased pre- and postnatal mortality at M2000 and T1800 were attributed to effects on parturition. In addition, prenatal loss at P2500 was marginally increased. Pup weights were increased at M100 on day 0. Marginal increases in pup weight were noted on day 0 at M2000 and P2500, and on day 8 at M500 and P500. In contrast, T1800 pup weights were decreased on days 0 and 8. Anogenital distance (on day 0), analyzed with pup weight as a covariate, was increased in females at M2000, and in males at M2000, P2500, and T1800. We conclude that exposure to the highest concentrations of M, P, and T adversely affected parturition and consequently impacted perinatal survival. The effects on parturition and anogenital distance may be related to aromatase inhibition, a known property of conazole compounds.