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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...

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Detalles Bibliográficos
Autores principales: Markaverich, Barry M., Alejandro, Mary, Thompson, Trellis, Mani, Shaila, Reyna, Andrea, Portillo, Wendy, Sharp, John, Turk, John, Crowley, Jan R.
Formato: Texto
Lenguaje:English
Publicado: National Institute of Environmental Health Sciences 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1868002/
https://www.ncbi.nlm.nih.gov/pubmed/17520056
http://dx.doi.org/10.1289/ehp.9311
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author Markaverich, Barry M.
Alejandro, Mary
Thompson, Trellis
Mani, Shaila
Reyna, Andrea
Portillo, Wendy
Sharp, John
Turk, John
Crowley, Jan R.
author_facet Markaverich, Barry M.
Alejandro, Mary
Thompson, Trellis
Mani, Shaila
Reyna, Andrea
Portillo, Wendy
Sharp, John
Turk, John
Crowley, Jan R.
author_sort Markaverich, Barry M.
collection PubMed
description 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 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. 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.
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spelling pubmed-18680022007-06-07 Tetrahydrofurandiols (THF-diols), Leukotoxindiols (LTX-diols), and Endocrine Disruption in Rats Markaverich, Barry M. Alejandro, Mary Thompson, Trellis Mani, Shaila Reyna, Andrea Portillo, Wendy Sharp, John Turk, John Crowley, Jan R. Environ Health Perspect Research 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 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. 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. National Institute of Environmental Health Sciences 2007-05 2007-01-29 /pmc/articles/PMC1868002/ /pubmed/17520056 http://dx.doi.org/10.1289/ehp.9311 Text en http://creativecommons.org/publicdomain/mark/1.0/ Publication of EHP lies in the public domain and is therefore without copyright. All text from EHP may be reprinted freely. Use of materials published in EHP should be acknowledged (for example, ?Reproduced with permission from Environmental Health Perspectives?); pertinent reference information should be provided for the article from which the material was reproduced. Articles from EHP, especially the News section, may contain photographs or illustrations copyrighted by other commercial organizations or individuals that may not be used without obtaining prior approval from the holder of the copyright.
spellingShingle Research
Markaverich, Barry M.
Alejandro, Mary
Thompson, Trellis
Mani, Shaila
Reyna, Andrea
Portillo, Wendy
Sharp, John
Turk, John
Crowley, Jan R.
Tetrahydrofurandiols (THF-diols), Leukotoxindiols (LTX-diols), and Endocrine Disruption in Rats
title Tetrahydrofurandiols (THF-diols), Leukotoxindiols (LTX-diols), and Endocrine Disruption in Rats
title_full Tetrahydrofurandiols (THF-diols), Leukotoxindiols (LTX-diols), and Endocrine Disruption in Rats
title_fullStr Tetrahydrofurandiols (THF-diols), Leukotoxindiols (LTX-diols), and Endocrine Disruption in Rats
title_full_unstemmed Tetrahydrofurandiols (THF-diols), Leukotoxindiols (LTX-diols), and Endocrine Disruption in Rats
title_short Tetrahydrofurandiols (THF-diols), Leukotoxindiols (LTX-diols), and Endocrine Disruption in Rats
title_sort tetrahydrofurandiols (thf-diols), leukotoxindiols (ltx-diols), and endocrine disruption in rats
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1868002/
https://www.ncbi.nlm.nih.gov/pubmed/17520056
http://dx.doi.org/10.1289/ehp.9311
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