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IN VITRO CONAZOLE EXPOSURE INHIBITS TESTOSTERONE PRODUCTION IN ADULT AND NEONATAL RAT TESTIS
Citation:
BLYSTONE, C., D. J. DIX, AND J. C. ROCKETT. IN VITRO CONAZOLE EXPOSURE INHIBITS TESTOSTERONE PRODUCTION IN ADULT AND NEONATAL RAT TESTIS. Presented at NCSU Department of Toxicology Student Poster Symposium, Research Triangle Park, NC, February 21, 2004.
Description:
IN VITRO CONAZOLE EXPOSURE INHIBITS TESTOSTERONE PRODUCTION IN THE ADULT AND NEONATAL TESTIS
Chad R. Blystone1, 2, David J. Dix2, and John C. Rockett2
1Department of Environmental and Molecular Toxicology, Box 7633, NC State University, Raleigh, NC 27695, USA and 2U.S. Environmental Protection Agency, Office of Research and Development, Reproductive Toxicology Division, RTP, NC, 27709, USA.
Abstract
Identifying endocrine disrupting chemicals and understanding their mechanism of action is important for human and ecological risk assessment. Inhibition of testosterone production in the male can result in abnormal sexual development and decreased fecundity in the adult. We hypothesized that two agricultural conazole fungicides, myclobutanil and triadimefon, are endocrine disrupting compounds that inhibit testosterone production in the adult and neonatal testis. To test this hypothesis, sliced adult orwhole neonatal testis were incubated in medium (M199, with10% FBS and 100mU hCG) containing 1, 10, or 100 ?M of myclobutanilor triadimefon. At selected time points (0.5, 1.5 & 2.5h), testosterone (T), progesterone (P), and lactate dehydrogenase (LDH), a marker of cytotoxicity, were measured in the media. In the adult and neonatal testis, both chemicals inhibited T production at the highest dose at the 1.5 and 2.5 hr timepoints. T was also inhibited at the 10 ?M dose at the 1.5 timepoint in the neonatal testis. Neither chemical affected LDH levels, indicating that these compounds inhibit T by modulating synthesis through a non-lethal mechanism. Both chemicals increased levels of P in the adult testis (neonatal data pending), indicating that the activity of CYP17 or 17-bHSD, or both, was the target of their action. These data provide evidence that myclobutanil and triadimefon are endocrine disrupting chemicals and can affect testosterone production in early and late developmental stages. Further workin vitro and in vivo must be conducted to elucidate the extent of their reproductive toxicity and specific mechanism of action. This abstract does not necessarily reflect EPA policy.