In vitro antiandrogenic effects of the herbicide linuron and its metabolites.

Although the herbicide linuron is banned for use in the EU due to its reproductive and developmental toxicity, it can still be found in randomly sampled foods grown in and outside the EU. It is not clear if metabolites of linuron can contribute to the endocrine disrupting effects following exposure to the parent compound. To address this gap, we analysed linuron and the metabolites 1-(3,4-dichlorophenyl) urea (DCU), 3,4-dichloroaniline (DCA) and 1-(3,4-dichlorophenyl)-3-methoxyurea (DCXU) for androgen receptor (AR) activities and effects on steroidogenesis. Generally, linuron and the metabolites showed qualitatively similar antiandrogenic profiles, but potencies varied. All compounds were AR antagonists, with linuron showing highest potency (IC 50 of 2.8 μM). The overall picture of effects on steroidogenesis showed that linuron and metabolites increased the levels of estrogens and corticosteroids, whereas the synthesis of androgens was inhibited. The metabolite DCU was by far the most potent inhibitor of testosterone synthesis (IC 50 of 6.7 μM compared to IC 50 of 51.1 μM for linuron). We suggest that it is likely that the metabolites contribute to the antiandrogenic effects of linuron in vivo , especially by inhibiting testosterone synthesis. [Display omitted] • Potency ranking for hAR antagonism: Linuron > DCXU > DCA > DCU. • Metabolite DCU is the most potent testosterone synthesis inhibitor in vitro. • The metabolites may contribute to linuron-induced male reproductive toxicity. [ABSTRACT FROM AUTHOR]