TETRAHYDROFURAN-DIOLS AND ENDOCRINE DISRUPTION IN ADULT RATS

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 THF-二醇（9，12-氧-10，13-二羟基十八烷酸和10，13-氧-9，12-二羟基十八烷酸）或LTX-二醇（9，10-二羟基-12-十八碳烯酸和12，13-二羟基-9-十八碳烯酸）的异构体混合物在口服剂量为<$2 ppm时完全阻断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对其毒理学性质进行的进一步评价表明，THF-二醇（0.5-1.0 ppm）或LTX-二醇（0.2-0.5 ppm）影响雌性大鼠发情周期的最低有效口服浓度小于2 ppm。 在饮用溶液中需要更高浓度（1-2 ppm）的THF-二醇来阻止男性性行为。亚阈值剂量的THF-二醇（0.05 ppm）和LTX-二醇（0.05 ppm）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，而不是协同的。 通过GC-MS方法，在从用高得多的水平（10 ppm）的化合物处理的大鼠收集的任何组织中，不能检测到< 0.2 ppm的THF-二醇，这表明THF-二醇的活性形式可能是代谢物。

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).