Format

Send to

Choose Destination
Toxicol Sci. 2015 Nov;148(1):288-98. doi: 10.1093/toxsci/kfv179. Epub 2015 Aug 10.

Aniline Is Rapidly Converted Into Paracetamol Impairing Male Reproductive Development.

Author information

1
*Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, DK-2100 Copenhagen, Denmark;
2
Institut National de la Santé et de la Recherche Médicale (Inserm) U1085-IRSET, Université de Rennes 1, Structure Fédérative Recherche Biosit, Campus de Beaulieu, F-35042 Rennes, France;
3
Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-Universität Bochum (IPA), 44789 Bochum, Germany;
4
Toxicology Laboratory, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; and.
5
Institut National de la Santé et de la Recherche Médicale (Inserm) U1085-IRSET, Université de Rennes 1, Structure Fédérative Recherche Biosit, Campus de Beaulieu, F-35042 Rennes, France; EHESP - School of Public Health, Avenue du Professeur Léon Bernard, F-35043 Rennes, France.
6
*Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, DK-2100 Copenhagen, Denmark; Institut National de la Santé et de la Recherche Médicale (Inserm) U1085-IRSET, Université de Rennes 1, Structure Fédérative Recherche Biosit, Campus de Beaulieu, F-35042 Rennes, France; david@moebjerg.com.

Abstract

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 metabolized 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 antiandrogenic paracetamol, impairs male reproductive development.

KEYWORDS:

acetaminophen; aniline; endocrine disruptors; paracetamol; reproduction; testosterone

PMID:
26259604
DOI:
10.1093/toxsci/kfv179
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center