Tetrahydrofurandiols (THF-diols), leukotoxindiols (LTX-diols), and endocrine disruption in rats

Barry M. Markaverich, Mary Alejandro, Trellis Thompson, Shaila Mani, Andrea Reyna, Wendy Portillo, John Sharp, John Turk, Jan R. Crowley

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Background: Ground corncob animal bedding and corn food products contain substances that disrupt endocrine function in rats. The disruptors were identified as isomeric mixtures of tetrahydrofurandiols (THF-diols; 9,12,oxy-10,13-dihydroxyoctadecanoic acid and 10,13-oxy,9,12-dihydroxyoctadecanoic acid) and leukotoxindiols (LTX-diols; 9,10-dihydroxy-12-octadecenoic acid and 12,13-dihydroxy-9-octadecenoic acid). The authentic compounds blocked sexual behavior in male rats and estrous cyclicity in female rats at oral doses of 2 ppm. Objectives: To define the lowest observed adverse effect level (LOAEL) for the THF-diols and LTX-diols, in rats, we examined the nature of their interaction (additive or synergistic) and quantified the concentration of THF-diols in rat tissues. Methods: Adult male and female rats were provided drinking solutions containing various doses of THF-diols and/or LTX-diols, and we evaluated their effects on male sexual behavior and female estrous cyclicity. Tissues were collected for THF-diol determination by gas chromatograph-mass spectrometry. Results: The LOAEL for THF-diols and LTX-diols for blocking estrous cyclicity was 0.5-1.0 ppm and 0.2-0.5 ppm, respectively. Higher concentrations (1-2 ppm) of THF-diols were required to block male sexual behavior, Combination studies with subthreshold doses of 0.05 ppm, THF-diols plus 0.05 ppm LTX-diols revealed that their effects on estrous cyclicity were not synergistic. We were unable to detect THF-diols in tissues from rats treated with 10 ppm of the compounds, suggesting that metabolism may be involved. Discussion: THF-diols, LTX-diols, and/or their metabolites likely act additively to disrupt endocrine function in male and female rats at concentrations (0.5-1 ppm) that are 200-fold lower than those of classical phytoestrogen endocrine disruptors.

Original languageEnglish
Pages (from-to)702-708
Number of pages7
JournalEnvironmental Health Perspectives
Issue number5
StatePublished - May 2007


  • Corncob bedding
  • Endocrine disruptors
  • LTX-diols
  • THF-diols

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    Markaverich, B. M., Alejandro, M., Thompson, T., Mani, S., Reyna, A., Portillo, W., Sharp, J., Turk, J., & Crowley, J. R. (2007). Tetrahydrofurandiols (THF-diols), leukotoxindiols (LTX-diols), and endocrine disruption in rats. Environmental Health Perspectives, 115(5), 702-708. https://doi.org/10.1289/ehp.9311