RWTH Aachen University, Inst. for Environmental Research, Department of Ecosystem Analysis, Worringerweg 1, 52074, Aachen, Germany.
German Environment Agency, Heinrich-Heine-Str. 12, 08645, Bad Elster, Germany.
Environ Sci Pollut Res Int. 2018 Feb;25(5):4051-4065. doi: 10.1007/s11356-017-0155-3. Epub 2017 Sep 21.
In Germany, micropollutants that (may) occur in drinking water are assessed by means of the health-related indicator value (HRIV concept), developed by the German Federal Environment Agency. This concept offers five threshold values (≤ 0.01 to ≤ 3 μg l) depending on availability and completeness of data regarding genotoxicity, neurotoxicity, and germ cell-damaging potential. However, the HRIV concept is yet lacking integration of endocrine disruptors as one of the most prominent toxicological concerns in water bodies, including drinking water. Thresholds and proposed bioassays hence urgently need to be defined. Since endocrine disruption of ubiquitary chemicals as pharmaceuticals, industrial by-products, or pesticides is a big issue in current ecotoxicology, the aim of this study was to explore endocrine effects, i.e., estrogenic and androgenic effects, as an important, additional toxicological mode of action for the HRIV concept using a hierarchical set of well-known but improved bioassays. Results indicate that all of the 13 tested substances, industrial chemicals and combustion products (5), pharmaceuticals and medical agents (4), and pesticides and metabolites (4), have no affinity to the estrogen and androgen receptor in human U2OS cells without metabolic activation, even when dosed at their water solubility limit, while in contrast some of these substances showed estrogenic effects in the RYES assay, as predicted in pre-test QSAR analysis. Using a specifically developed S9-mix with the U2OS cells, those micropollutants, i.e., Benzo[a]pyrene, 2,4-Dichlorophenol, 3,3-Dichlorbenzidin, 3,4-Dichloranilin, and diclofenac, they show estrogenic effects at the same concentration range as for the yeast cells. Three of the drinking water-relevant chemicals, i.e., atrazine, tributyltin oxide, and diclofenac, caused effects on hormone production in the H295R assay, which can be correlated with changes in the expression of steroidogenic genes. One chemical, 17α-Ethinylestradiol, caused an estrogenic or anti-androgenic effect in the reproduction test with Potamopyrgus antipodarum. Considering these results, a proposal for a test strategy for micropollutants in drinking water regarding potential endocrine effects (hormonal effects on reproduction and sexual development) will be presented to enhance the existing HRIV concept.
在德国，通过德国联邦环境署开发的与健康相关的指标值 (HRIV 概念) 来评估饮用水中可能存在的微量污染物。该概念提供了五个阈值 (≤0.01 至 ≤3μg l)，具体取决于有关遗传毒性、神经毒性和生殖细胞损伤潜力的可用性和完整性的数据。然而，HRIV 概念尚未将内分泌干扰物作为水体(包括饮用水)中最突出的毒理学问题之一进行整合。因此，阈值和拟议的生物测定方法急需定义。由于作为药品、工业副产品或农药的普遍存在的化学物质的内分泌干扰是当前生态毒理学中的一个大问题，因此本研究的目的是使用一组已知但经过改进的生物测定方法，探索内分泌效应，即雌激素和雄激素效应，作为 HRIV 概念的另一种重要的毒理学作用模式。结果表明，在没有代谢激活的情况下，所有 13 种测试物质，即工业化学品和燃烧产物 (5 种)、药品和医疗制剂 (4 种) 和农药和代谢物 (4 种)，都没有与人类 U2OS 细胞中的雌激素和雄激素受体结合，即使在其水溶性极限剂量下也是如此，而相反，这些物质中的一些在 RYES 测定中显示出雌激素效应，正如预测试 QSAR 分析所预测的那样。使用专门开发的含有 U2OS 细胞的 S9 混合物，那些微量污染物，即苯并[a]芘、2,4-二氯苯酚、3,3-二氯联苯胺、3,4-二氯苯胺和双氯芬酸，在与酵母细胞相同的浓度范围内表现出雌激素效应。三种与饮用水相关的化学物质，即莠去津、三丁基锡氧化物和双氯芬酸，在 H295R 测定中引起了激素产生的影响，这可以与类固醇生成基因表达的变化相关联。一种化学物质，17α-乙炔基雌二醇，在与 Potamopyrgus antipodarum 的生殖测试中引起了雌激素或抗雄激素作用。考虑到这些结果，将提出一种针对饮用水中微量污染物的测试策略，以评估其潜在的内分泌效应(对生殖和性发育的激素影响)，以增强现有的 HRIV 概念。
