Endocrine activities of phthalate alternatives; assessing the safety profile of furan dicarboxylic acid esters using a panel of human cell based reporter gene assays,Green Chemistry

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Endocrine activities of phthalate alternatives; assessing the safety profile of furan dicarboxylic acid esters using a panel of human cell based reporter gene assays
Green Chemistry ( IF 9.3 ) Pub Date : 2020/02/27 , DOI: 10.1039/c9gc04348a
Barbara M. A. van Vugt-Lussenburg _{1,

2,

3,

4} , Daan S. van Es _{4,

5,

6} , Matthijs Naderman _{1,

2,

3,

4} , Jerome le Notre _{4,

5,

6} , Frits van der Klis _{4,

5,

6} , Abraham Brouwer _{1,

2,

3,

4,

7} , Bart van der Burg _{4,

5,

6}

Affiliation

FDCA esters are highly relevant biobased alternatives for currently used benzene dicarboxylic acid esters. Despite all the developments on 2,5-FDCA applications, to the best of our knowledge thus far no toxicological data were available for 2,5-FDCA esters. In the present study we aimed to fill this gap, by using an in vitro reporter gene assay approach to compare the activity profile of commonly used phthalates to that of their furan-based counterparts. The assay selection was aimed at the detection of endocrine activity, since several phthalates are heavily scrutinised for their endocrine disrupting properties. However, to avoid missing other relevant toxicological endpoints, several assays able to detect various forms of cellular stress were also included in the panel. The results showed that the (ortho)benzene dicarboxylic acid esters were predominantly active on several of the endocrine assays. In comparison, six of the seven furan dicarboxylic acid based diesters tested here showed no activity in any of the 13 assays used. Only the isobutyl derivative DIBF showed moderate estrogenic activity on one assay, compared to much more pronounced activities on four assays for the ortho-phthalate analogue. Overall, the results presented in this paper are a strong indication that 2,5-FDCA based diesters in general are not only technically viable alternatives to phthalates, but also offer significant toxicological benefits, which supports a non-regrettable substitution.

中文翻译：

邻苯二甲酸酯替代品的内分泌活性；使用一组基于人类细胞的报告基因试验评估呋喃二羧酸酯的安全性

FDCA酯是目前使用的苯二羧酸酯的高度相关的生物基替代品。尽管在2，5-FDCA的应用方面已取得了所有进展，但据我们所知，到目前为止，尚无2，5-FDCA酯的毒理学数据。在本研究中，我们旨在通过使用体外报告基因检测方法来比较常用邻苯二甲酸酯与呋喃基邻苯二甲酸酯的活性谱，以填补这一空白。该方法的选择旨在检测内分泌活性，因为对几种邻苯二甲酸酯的内分泌干扰特性进行了严格审查。但是，为避免遗漏其他相关的毒理学终点，面板中还包括几种能够检测各种形式的细胞应激的测定法。结果显示（邻苯二羧酸二酯主要在几种内分泌测定中具有活性。相比之下，此处测试的七种基于呋喃二羧酸的二酯中的六种在所用的13种测定中均未显示活性。与邻苯二甲酸酯类似物的四种测定相比，只有异丁基衍生物DIBF在一种测定中显示出中等的雌激素活性。总体而言，本文提出的结果有力地表明，一般而言，基于2，5-FDCA的二酯不仅是邻苯二甲酸酯在技术上可行的替代品，而且还具有明显的毒理学优势，支持不可替代的替代。

更新日期：2020-03-24

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