TETRAHYDROFURAN-DIOLS AND ENDOCRINE DISRUPTION IN ADULT RATS

Washington University, Saint Louis MO

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Abstract

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 [unreadable]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).