Tetrahydrofurandiols (THF-diols), leukotoxindiols (LTX-diols), and endocrine disruption in rats.
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.
Markaverich
Barry M
BM
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA. barrym@bcm.tmc.edu
Alejandro
Mary
M
Thompson
Trellis
T
Mani
Shaila
S
Reyna
Andrea
A
Portillo
Wendy
W
Sharp
John
J
Turk
John
J
Crowley
Jan R
JR
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*
D052244:Endocrine Disruptors; D005663:Furans; D008041:Linoleic Acids; D013229:Stearic Acids; C018674:tetrahydrofuran; C051208:9,10-epoxy-12-octadecenoic acid