Aniline Is Rapidly Converted Into Paracetamol Impairing Male Reproductive Development

• DOI: 10.1093/toxsci/kfv179
• Publication Date: 2015-08-11T01:59:26Z
• Authors: Jacob Bak Holm; Clementine Chalmey; Hendrik Modick; Lars Skovgaard Je...; Georg Dierkes; Tobias Weiss; Benjamin Andersch...; Mette Marie Nørre...; Kamil Borkowski; Bjarne Styrishave; Holger Martin Koch; Severine Mazaud-G...; Bernard Jegou; Karsten Kristiansen; David Møbjerg Kri...
• Keywords: Acetaminophen; Aniline Compounds

Industrial use of aniline is increasing worldwide with production estimated to surpass 5.6 million metric tons in 2016. Exposure occurs via air, diet, and water augmenting the risk exposing a large number individuals. Early observations suggest that metabolized paracetamol/acetaminophen, likely explaining omnipresence low concentrations paracetamol European populations. This concern as recent studies implicate disrupter reproduction. Here, we show through steroidogenic profiling exposure led increased levels Δ4 steroids, suggesting activity CYP21 was decreased. By contrast, decreased androgens inhibition CYP17A1 activity. We confirm vivo rapidly converted by liver. Intrauterine environmental pharmaceutical relevant doses resulted shortening anogenital distance mice, sensitive marker fetal androgen humans associated reproductive malformations later life disorders. In conclusion, our results provide evidence for scenario where aniline, its conversion into antiandrogenic paracetamol, impairs male development.