TETRAHYDROFURAN-DIOLS AND ENDOCRINE DISRUPTION IN ADULT RATS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 THF-二醇(9，12-氧基-10，13-二羟基十八酸和10，13-氧基-9，12-二羟基十八酸)或LTX-二醇(9，10-二羟基-12-十八烯酸和12，13-二羟基-9-十八烯酸)的异构体混合物在口服剂量为2ppm时，完全阻止雄性或雌性大鼠的性行为和周期性。通过更详细的剂量反应研究进一步评估它们的毒理学特性，发现四氢呋喃二醇(0.5-1.0ppm)或LTX-二醇(0.2-0.5ppm)影响雌性大鼠动情周期的最低有效口服浓度低于2ppm。饮用溶液中需要较高浓度(1-2ppm)的四氢呋喃二醇来阻止男性性行为。亚阈值剂量的四氢呋喃二醇(0.05ppm)和LTX二醇(0.05ppm)的联合研究表明，它们对雌性大鼠发情周期的影响可能是相加的，而不是协同作用的。用浓度高得多的化合物(10ppm)处理大鼠的组织，用GC-MS方法检测不到四氢呋喃二醇，提示四氢呋喃二醇的活性形式(S)可能是一种代谢物(S)。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Isomeric mixtures of THF-diols (9,12-oxy-10,13-dihydroxyoctadecanoic acid and 10,13-oxy-9,12-dihydroxyoctadecanoic acid) or LTX-diols (9,10-dihydroxy-12-octadecenoic acid and 12,13-dihydroxy-9-octadecenoic acid) completely block male or female rat sexual behavior and cyclicity at oral doses of ¿2 ppm. Further evaluation of their toxicological properties with more detailed dose response studies revealed that minimum effective oral concentration of THF-diols (0.5-1.0 ppm) or LTX-diols (0.2-0.5 ppm) to affect estrous cyclicity in female rats is less than 2 ppm. Higher concentrations (1-2 ppm) of THF-diols in drinking solutions were required to block male sexual behavior. Combination studies with sub-threshold doses of THF-diols (0.05 ppm) plus LTX-diols (0.05 ppm) revealed that their effects on the estrous cycle of female rats were likely to be additive, not synergistic. THF-diols were not detected by GC-MS methods capable of detecting < 0.2 ppm in any tissue collected from rats treated with much higher levels (10 ppm) of the compounds, suggesting the active form (s) of the THF-diols may be a metabolite(s).