Environmental Science and Pollution Research

, Volume 25, Issue 5, pp 4051–4065 | Cite as

A hierarchical testing strategy for micropollutants in drinking water regarding their potential endocrine-disrupting effects—towards health-related indicator values

  • Jochen KuckelkornEmail author
  • Regine Redelstein
  • Timon Heide
  • Jennifer Kunze
  • Sibylle Maletz
  • Petra Waldmann
  • Tamara Grummt
  • Thomas-Benjamin Seiler
  • Henner HollertEmail author
Effect-related evaluation of anthropogenic trace substances, -concepts for genotoxicity, neurotoxicity and, endocrine effects


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−1) 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.


Endocrine effects Risk assessment Drinking water Testing strategy Bioassays 


Funding information

The project Tox-Box was supported by the German Federal Ministry of Education and Research (BMBF): funding number 02WRS1282I. Tox-Box is a constitutive part of the BMBF action plan “Sustainable water management (NaWaM)” and is integrated in the BMBF frame program “Research for sustainable development FONA”. It is part of the funding scheme “Risk Management of Emerging Compounds and Pathogens in the Water Cycle (RiSKWa)” introduced to the public by Huckele and Track.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.RWTH Aachen University, Inst. for Environmental Research, Department of Ecosystem AnalysisAachenGermany
  2. 2.German Environment AgencyBad ElsterGermany
  3. 3.University of GoettingenGoettingenGermany
  4. 4.Kinderwunschzentrum HeidelbergHeidelbergGermany
  5. 5.Hochschule DarmstadtDarmstadtGermany

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