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Investigations of putative reproductive toxicity of low-dose exposures to vinclozolin in Wistar rats

  • Reproductive Toxicology
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Abstract

The current investigation examines whether the fungicide vinclozolin, which has an anti-androgenic mode of action, is capable of disrupting endocrine homeostasis at very low doses. The data generated clarify whether a non-monotonic dose–response relationship exists to enhance the current debate about the regulation of endocrine disruptors. Moreover, it is part of a series of investigations assessing the dose–response relationship of single and combined administration of anti-androgenic substances. A pre-postnatal in vivo study design was chosen which was compliant with regulatory testing protocols. The test design was improved by additional endpoints addressing hormone levels, morphology and histopathological examinations. Doses were chosen to represent an effect level (20 mg/kg bw/d), the current NOAEL (4 mg/kg bw/d), and a dose close to the “ADI” (0.005 mg/kg bw/d) for the detection of a possible non-monotonic dose–response curve. Anti-androgenic changes were observable at the effect level but not at lower exposures. Nipple/areola counts appeared to be the most sensitive measure of effect, followed by male sex organ weights at sexual maturation, and finally gross and histopathological findings. The results indicate the absence of evidence for effects at low or very low dose levels. A non-monotonic dose–response relationship was not evident.

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Acknowledgments

The study was (partly) sponsored by CEFIC LRI, 1160 Brussels, Belgium.

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Authors and Affiliations

  1. Experimental Toxicology and Ecology, BASF SE, 67056, Ludwigshafen, Germany

    Burkhard Flick, Steffen Schneider, Sibylle Gröters, Roland Buesen, Volker Strauss & Bennard van Ravenzwaay

  2. Product Safety, Regulations, Toxicology and Ecology, BASF SE, Ludwigshafen, Germany

    Stephanie Melching-Kollmuss

  3. Chemical Food Safety, Nestlé, Lausanne, Switzerland

    Karma C. Fussell

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  1. Burkhard Flick
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  2. Steffen Schneider
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  3. Stephanie Melching-Kollmuss
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  4. Karma C. Fussell
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  6. Roland Buesen
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  8. Bennard van Ravenzwaay
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Correspondence to Bennard van Ravenzwaay.

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This study was co-sponsored by BASF SE, Ludwigshafen, Germany. BASF is producer of vinclozolin.

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Flick, B., Schneider, S., Melching-Kollmuss, S. et al. Investigations of putative reproductive toxicity of low-dose exposures to vinclozolin in Wistar rats. Arch Toxicol 91, 1941–1956 (2017). https://doi.org/10.1007/s00204-016-1811-y

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