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<title lang=en>Aniline is rapidly converted into paracetamol impairing male reproductive development</title>
<creator>Holm, Jacob Bak</creator>
<creator>Chalmey, Clémentine</creator>
<creator>Modick, Hendrik</creator>
<creator>Jensen, Lars Skovgaard</creator>
<creator>Dierkes, Georg</creator>
<creator>Weiss, Tobias</creator>
<creator>Jensen, Benjamin</creator>
<creator>Nørregård, Mette Marie</creator>
<creator>Borkowski, Kamil</creator>
<creator>Styrishave, Bjarne</creator>
<creator>Koch, Holger Martin</creator>
<creator>Mazaud-Guittot, Séverine</creator>
<creator>Jégou, Bernard</creator>
<creator>Kristiansen, Karsten</creator>
<creator>Kristensen, David Møbjerg</creator>
<contributor>Institut de recherche, santé, environnement et travail [Rennes] (Irset) ; Université d'Angers (UA) - Université des Antilles et de la Guyane (UAG) - Université de Rennes 1 (UR1) - École des Hautes Études en Santé Publique [EHESP] (EHESP) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )</contributor>
<contributor>University of Copenhagen (KU)</contributor>
<contributor>École des Hautes Études en Santé Publique [EHESP] (EHESP)</contributor>
<description>International audience</description>
<source>Toxicological Sciences: An Official Journal of the Society of Toxicology</source>
<identifier>hal-01187305</identifier>
<identifier>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01187305</identifier>
<source>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01187305</source>
<source>Toxicological Sciences: An Official Journal of the Society of Toxicology, 2015, 148 (1), pp.288-298. 〈10.1093/toxsci/kfv179〉</source>
<identifier>DOI : 10.1093/toxsci/kfv179</identifier>
<relation>info:eu-repo/semantics/altIdentifier/doi/10.1093/toxsci/kfv179</relation>
<identifier>PUBMED : 26259604</identifier>
<relation>info:eu-repo/semantics/altIdentifier/pmid/26259604</relation>
<language>en</language>
<subject>[SDV] Life Sciences [q-bio]</subject>
<type>info:eu-repo/semantics/article</type>
<type>Journal articles</type>
<description lang=en>Industrial use of aniline is increasing worldwide with production estimated to surpass 5.6 million metric tons in 2016. Exposure to aniline occurs via air, diet and water augmenting the risk of exposing a large number of individuals. Early observations suggest that aniline is metabolised to paracetamol/acetaminophen, likely explaining the omnipresence of low concentrations of paracetamol in European populations. This is of concern as recent studies implicate paracetamol as a disrupter of reproduction. Here we show through steroidogenic profiling that exposure to aniline led to increased levels of the Δ4 steroids, suggesting that the activity of CYP21 was decreased. By contrast, paracetamol decreased levels of androgens likely through inhibition of CYP17A1 activity. We confirm that aniline in vivo is rapidly converted to paracetamol by the liver. Intrauterine exposure to aniline and paracetamol in environmental and pharmaceutical relevant doses resulted in shortening of the anogenital distance in mice, a sensitive marker of fetal androgen levels that in humans is associated with reproductive malformations and later life reproductive disorders. In conclusion, our results provide evidence for a scenario where aniline, through its conversion into anti-androgenic paracetamol, impairs male reproductive development</description>
<date>2015</date>
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