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REPRODUCTIVE TOXICITY OF EXPOSURE TO CONAZOLE FUNGICIDES IN THE FEMALE RAT
Citation:
Rockett, J C., M G. Narotsky, I. THILLAINADARAJAH, C. BLYSTONE, A. GOETZ, H. REN, D. S. BEST, R. MURRELL, H. P. NICHOLS, J. E. SCHMID, K. E. THOMPSON, AND D. J. DIX. REPRODUCTIVE TOXICITY OF EXPOSURE TO CONAZOLE FUNGICIDES IN THE FEMALE RAT. Presented at Society of Toxicology, New Orleans, LA, March 6-10, 2005.
Description:
Conazole fungicides are used extensively in pharmaceutical and agricultural applications. Although some conazoles have been investigated extensively for toxicological effects, there is little published information on the reproductive toxicity of many of the agriculturally important conazoles. In this study, three agricultural conazoles were evaluated for effects on female reproductive development. Wistar-Han rats were exposed via feed to vehicle control, propiconazole(P) (100, 500, or 2500ppm), myclobutanil (M) (100, 500, or 2000ppm), ortriadimefon(T) (100, 500, or1800ppm) from gestation day 6 to the first proestrous after post natal day (PND) 98. Body weight (BW) and anogenital distance (AGD) at PND0,age and BW at vaginal opening (VO), and BW and organ weight at termination were measured. Histological examination of ovaries was conducted. Female pup weights at PND0 were unaffected by treatment. AGDat PND0 was increased byM2000. Age of puberty (VO) was delayed byT1800 independent of BW. At PND99 there was a decrease in BW by T1800, an increase in relative liver weight byP2500 and T1800, and an increase in relative ovarian weight by M2000 and T1800. All ovaries contained follicles at all stages of development and had normal appearing corpora lutea. We conclude that exposure to the high concentrations of M and T adversely impacted female reproductive development. The observed changes suggest a mechanism involving inhibition of estrogenic synthesis or function. Ongoing analysis of estrous cyclicity, serum hormone levels, and ovarian pathology will serve to further characterize the effects of these exposures and help clarify mechanism.