Cell Toxicology Team, National Food Institute, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.
Research group for Analytical Food Chemistry, National Food Institute, Technical University of Denmark, 2800 Kgs, Lyngby, Denmark.
Chemosphere. 2024 Feb;349:140773. doi: 10.1016/j.chemosphere.2023.140773. Epub 2023 Nov 22.
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 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 of 6.7 μM compared to IC 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.
尽管除草剂利谷隆由于其生殖和发育毒性已在欧盟被禁止使用，但在欧盟内外随机抽样的食物中仍能发现它的存在。目前尚不清楚利谷隆的代谢物是否会对接触母体化合物后的内分泌干扰效应产生影响。为了解决这一差距，我们分析了利谷隆及其代谢物 1-(3,4-二氯苯基)脲（DCU）、3,4-二氯苯胺（DCA）和 1-(3,4-二氯苯基)-3-甲氧基脲（DCXU）对雄激素受体（AR）活性和类固醇生成的影响。通常，利谷隆和代谢物表现出定性相似的抗雄激素特征，但效力有所不同。所有化合物均为 AR 拮抗剂，其中利谷隆的效力最高（IC 为 2.8 μM）。对类固醇生成的总体影响表明，利谷隆和代谢物增加了雌激素和皮质类固醇的水平，而雄激素的合成则受到抑制。代谢物 DCU 是迄今为止最有效的抑制睾丸激素合成的化合物（IC 为 6.7 μM，而利谷隆的 IC 为 51.1 μM）。我们认为，代谢物很可能会在体内对利谷隆的抗雄激素作用产生影响，特别是通过抑制睾丸激素的合成。
