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

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

Content Provider	Springer Nature Link
Author	Flick, Burkhard Schneider, Steffen Melching Kollmuss, Stephanie Fussell, Karma C. Gröters, Sibylle Buesen, Roland Strauss, Volker Ravenzwaay, Bennard
Copyright Year	2016
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.
Starting Page	1941
Ending Page	1956
Page Count	16
File Format	PDF
ISSN	03405761
Journal	Archives of Toxicology
Volume Number	91
Issue Number	4
e-ISSN	14320738
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2016-09-09
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Vinclozolin Low dose Non-monotonic dose response Anti-androgenic Endocrine disruptor Experimental test guidelines Pharmacology/Toxicology Occupational Medicine/Industrial Medicine Environmental Health Biomedicine
Content Type	Text
Resource Type	Article
Subject	Health, Toxicology and Mutagenesis Medicine Toxicology

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