Moche Hélène, Chentouf Aouatif, Neves Sergio, Corpart Jean-Marc, Nesslany Fabrice
Institut Pasteur De Lille, 59019 Lille Cedex, France.
ROQUETTE Company, 62136 Lestrem, France.
J Toxicol. 2021 Feb 9;2021:8815202. doi: 10.1155/2021/8815202. eCollection 2021.
Because of the deleterious effects of phthalates, regulations have been taken to decrease their use, and the needs for alternatives are increasing. Due to the concerns about the endocrine-disrupting properties of phthalates, it was deemed necessary to particularly investigate these effects for potential substitutes. In this study, we compared the endocrine activity of several already used potential alternative plasticizers (DEHT, DINCH, and TOTM) or new substitutes (POLYSORB® isosorbide and POLYSORB® ID 46) to one of 2 phthalates, DEHP and DINP. Effects of these chemicals on 3 common mechanisms of endocrine disruption, i.e., interaction with estrogen receptors (ER), androgen receptors (AR), or steroidogenesis, were studied using extensively used methods. In the E-Screen assay, only DEHP moderately induced MCF-7 cell proliferation; none of the other tested substances were estrogenic or antiestrogenic. No androgenic or antiandrogenic activity in MDA-kb2 cells was shown for any of the tested phthalates or alternatives. On the other hand, both DEHP and DINP, as well as DEHT, DINCH, and TOTM, disrupted steroidogenesis in the H295R assay, mainly by inducing an increase in estradiol synthesis; no such effect was observed for POLYSORB® isosorbide and POLYSORB® ID 46.
由于邻苯二甲酸盐具有有害影响，已采取相关规定来减少其使用，并且对替代品的需求也在增加。鉴于对邻苯二甲酸盐内分泌干扰特性的担忧，有必要特别研究这些潜在替代品的此类影响。在本研究中，我们将几种已使用的潜在替代增塑剂（DEHT、DINCH和TOTM）或新替代品（聚山梨醇酯®异山梨醇和聚山梨醇酯®ID 46）的内分泌活性与两种邻苯二甲酸盐（DEHP和DINP）之一进行了比较。使用广泛应用的方法研究了这些化学物质对3种常见内分泌干扰机制的影响，即与雌激素受体（ER）、雄激素受体（AR）的相互作用或类固醇生成。在E-Screen试验中，只有DEHP适度诱导MCF-7细胞增殖；其他测试物质均无雌激素活性或抗雌激素活性。在所测试的任何邻苯二甲酸盐或替代品中，MDA-kb2细胞均未显示出雄激素活性或抗雄激素活性。另一方面，在H295R试验中，DEHP、DINP以及DEHT、DINCH和TOTM均干扰了类固醇生成，主要是通过诱导雌二醇合成增加；聚山梨醇酯®异山梨醇和聚山梨醇酯®ID 46未观察到此类影响。
