title: Tetrahydrofurandiols (THF-diols), leukotoxindiols (LTX-diols), and endocrine disruption in rats.
abstract: 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.
  
  
  OBJECTIVE
  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 chromatography-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA. barrym@bcm.tmc.edu
authors.forename: Barry M
authors.initials: BM
authors.lastname: Markaverich
authors.forename: Mary
authors.initials: M
authors.lastname: Alejandro
authors.forename: Trellis
authors.initials: T
authors.lastname: Thompson
authors.forename: Shaila
authors.initials: S
authors.lastname: Mani
authors.forename: Andrea
authors.initials: A
authors.lastname: Reyna
authors.forename: Wendy
authors.initials: W
authors.lastname: Portillo
authors.forename: John
authors.initials: J
authors.lastname: Sharp
authors.forename: John
authors.initials: J
authors.lastname: Turk
authors.forename: Jan R
authors.initials: JR
authors.lastname: Crowley
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000737:chemistry / Q000633:toxicity*; D030762:Estrous Cycle / Q000187:drug effects*; D005260:Female; D005663:Furans; D008401:Gas Chromatography-Mass Spectrometry; D008041:Linoleic Acids; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D051381:Rats; D012726:Sexual Behavior, Animal / Q000187:drug effects*; D013229:Stearic Acids / Q000737:chemistry / Q000633:toxicity*; D003313:Zea mays / Q000737:chemistry*
chemical_list: D052244:Endocrine Disruptors; D005663:Furans; D008041:Linoleic Acids; D013229:Stearic Acids; C018674:tetrahydrofuran; C051208:9,10-epoxy-12-octadecenoic acid