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Effect of nonpersistent pesticides on estrogen receptor, androgen receptor, and aryl hydrocarbon receptor

Authors

  • Svjetlana Medjakovic,

    1. Christian Doppler Laboratory for Receptor Biotechnology, A-1190 Vienna, Austria
    2. Department of Biotechnology, University of Natural Resources and Life Sciences Vienna, A-1190 Vienna, Austria
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    • These authors contributed equally to this work.

  • Alfred Zoechling,

    1. Christian Doppler Laboratory for Receptor Biotechnology, A-1190 Vienna, Austria
    2. Department of Biotechnology, University of Natural Resources and Life Sciences Vienna, A-1190 Vienna, Austria
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    • These authors contributed equally to this work.

  • Petra Gerster,

    1. Christian Doppler Laboratory for Receptor Biotechnology, A-1190 Vienna, Austria
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  • Margarita M. Ivanova,

    1. Department of Biochemistry and Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA
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  • Yun Teng,

    1. Department of Biochemistry and Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA
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  • Carolyn M. Klinge,

    1. Department of Biochemistry and Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA
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  • Barbara Schildberger,

    1. Federal College and Research Institute for Viticulture and Pomology, A-3400 Klosterneuburg, Austria
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  • Michael Gartner,

    1. LVA GmbH, Magdeburggasse 10, 3400 Klosterneuburg, Austria
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  • Alois Jungbauer

    Corresponding author
    1. Christian Doppler Laboratory for Receptor Biotechnology, A-1190 Vienna, Austria
    2. Department of Biotechnology, University of Natural Resources and Life Sciences Vienna, A-1190 Vienna, Austria
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Abstract

Nonpersistent pesticides are considered less harmful for the environment, but their impact as endocrine disruptors has not been fully explored. The pesticide Switch was applied to grape vines, and the maximum residue concentration of its active ingredients was quantified. The transactivation potential of the pesticides Acorit, Frupica, Steward, Reldan, Switch, Cantus, Teldor, and Scala and their active compounds (hexythiazox, mepanipyrim, indoxacarb, chlorpyrifos-methyl, cyprodinil, fludioxonil, boscalid, fenhexamid, and pyrimethanil) were tested on human estrogen receptor α (ERα), androgen receptor (AR) and arylhydrocarbon receptor (AhR) in vitro. Relative binding affinities of the pure pesticide constituents for AR and their effect on human breast cancer and prostate cancer cell lines were evaluated. Residue concentrations of Switch's ingredients were below maximum residue limits. Fludioxonil and fenhexamid were ERα agonists (EC50-values of 3.7 and 9.0 μM, respectively) and had time-dependent effects on endogenous ERα-target gene expression (cyclin D1, progesterone receptor, and nuclear respiratory factor 1) in MCF-7 human breast cancer cells. Fludioxonil, mepanipyrim, cyprodinil, pyrimethanil, and chlorpyrifos-methyl were AhR-agonists (EC50s of 0.42, 0.77, 1.4, 4.6, and 5.1 μM, respectively). Weak AR binding was shown for chlorpyrifos-methyl, cyprodinil, fenhexamid, and fludioxonil. Assuming a total uptake which does not take metabolism and clearance rates into account, our in vitro evidence suggests that pesticides could activate pathways affecting hormonal balance, even within permitted limits, thus potentially acting as endocrine disruptors. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1201–1216, 2014.

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