Bioassays for neuroactive substances in water

Astrid Reus, Milou Dingemans PhD

  • Start date
    01 Nov 2019
  • Principal
    Joint Research Programme
  • collaborating partners
    Vrije Universiteit, Universiteit Utrecht, RIVM

More and more substances are being found worldwide in surface water that may have adverse effects on the nervous system. Because about forty percent[1] of Dutch drinking water is made from infiltrated surface water, knowledge about the presence and possible adverse effects of neuroactive substances in the aquatic environment is essential[2]. The brains of people and animals are particularly sensitive to these substances during the early stages of development. Given the need to determine the presence of the substances and interpret possible adverse health effects, there are many developments relating to bioassays, test methods using human or animal nerve cells and model organisms.

Interpreting possibly adverse health effects

Neurotoxicity is a complex toxicological endpoint that is difficult to estimate with a single simple bioassay. A tiered testing strategy combining different bioassays is needed to identify possible adverse effects on the nervous system. A distinction can be made here between bio-analytical tools (such as bioassays for estimating exposure) and bioassays for integral risk assessment (for example the estimation of adverse health effects on humans).

Bio-analytical tools have to be relatively simple models that can be used cost-effectively and quickly (in screening), such as bioassays using animal or human cells and cell lines. For the purposes of screening, measurement methods should also be cost-effective and fast.

Bioassays for integral risk assessment can also be more advanced models used for further research after prioritisation on the basis of the results of the bio-analytical tools, examples being embryonic stem cells and zebrafish. In the near future, more complex and costly techniques, such as functional genomics, may also be used as measurement methods, although simple techniques and cost-effective techniques with an advanced model may also be adequate.

Neurotoxicity tests for the water sector

Exploratory research based on national research and literature relating to different bioassays for neuroactive substances shows that neurotoxicity tests in vitro or in alternative organisms can be used in the water sector[3]. Further investigation is needed to determine which models and techniques are the most suitable and cost-effective.

To estimate the probability of adverse health effects, it may be helpful to use a tiered testing strategy that combines different methods. Many developments in legislation and regulations are under way to allow this in the chemical, pharmaceutical and food industries, but also specifically for testing water quality. The ongoing monitoring of these developments, as well as those relating to the development of models and techniques, is advisable so that contributions can be made to the development of a strategy and the implementation of neurotoxicity tests in water quality monitoring.


[2] Legradi JB, Di Paolo C, Kraak MHS, van der Geest HG, Schymanski EL, Williams AJ, Dingemans MML, Massei R, Brack W, Cousin X, Begout ML, van der Oost R, Carion A, Suarez-Ulloa V, Silvestre F, Escher BI, Engwall M, Nilén G, Keiter SH, Pollet D, Waldmann P, Kienle C, Werner I, Haigis AC, Knapen D, Vergauwen L, Spehr M, Schulz W, Busch W, Leuthold D, Scholz S, Vom Berg CM, Basu N, Murphy CA, Lampert A, Kuckelkorn J, Grummt T, Hollert H. An ecotoxicological view on neurotoxicity assessment. Environ Sci Eur. 2018;30(1):46. doi: 10.1186/s12302-018-0173-x.

[3] BTO report Bioassays voor neuroactieve stoffen in water, in preparation