The numbers of potential neurotoxicants in the environment are raising and pose a great risk for humans and the environment. Currently neurotoxicity assessment is mostly performed to predict and prevent harm to human populations. Despite all the efforts invested in the last years in developing novel in vitro or in silico test systems, in vivo tests with rodents are still the only accepted test for neurotoxicity risk assessment in Europe. Despite an increasing number of reports of species showing altered behaviour, neurotoxicity assessment for species in the environment is not required and therefore mostly not performed. Considering the increasing numbers of environmental contaminants with potential neurotoxic potential, eco-neurotoxicity should be also considered in risk assessment. In order to do so novel test systems are needed that can cope with species differences within ecosystems. In the field, online-biomonitoring systems using behavioural information could be used to detect neurotoxic effects and effect-directed analyses could be applied to identify the neurotoxicants causing the effect. Additionally, toxic pressure calculations in combination with mixture modelling could use environmental chemical monitoring data to predict adverse effects and prioritize pollutants for laboratory testing. Cheminformatics based on computational toxicological data from in vitro and in vivo studies could help to identify potential neurotoxicants. An array of in vitro assays covering different modes of action could be applied to screen compounds for neurotoxicity. The selection of in vitro assays could be guided by AOPs relevant for eco-neurotoxicity. In order to be able to perform risk assessment for eco-neurotoxicity, methods need to focus on the most sensitive species in an ecosystem. A test battery using species from different trophic levels might be the best approach. To implement eco-neurotoxicity assessment into European risk assessment, cheminformatics and in vitro screening tests could be used as first approach to identify eco-neurotoxic pollutants. In a second step, a small species test battery could be applied to assess the risks of ecosystems.

Freshwater is a precious resource, and shortages can lead to water stress, impacting agriculture, industry, and other sectors. Wastewater reuse is increasingly considered as an opportunity to meet the freshwater demand. Legislative frameworks are under development to support the responsible reuse of wastewater, i.e., to balance benefits and risks. In an evaluation of the proposed European regulation for water reuse, we concluded that the proposed regulation is not practically feasible, as the water provider alone is responsible for the risk assessment and management, even beyond their span of control. The required knowledge and resources are extensive. Therefore, without clear guidance for implementation, the regulation would hinder implementation of reuse programs. As a consequence, the current practice of uncontrolled, unintentional, and indirect reuse continues, including related risks and inefficiency. Therefore, we provide an outline of the interdisciplinary approach required to design and achieve safe, responsible water reuse. Responsible water reuse requires knowledge of water demand and availability, quality and health, technology, and governance for the various types of application. Through this paper we want to provide a starting point for an interdisciplinary agenda to compile and generate knowledge (databases), approaches, guidelines, case examples, codes of practice, and legislation to help bring responsible water reuse into practice.

Stand-alone reverse osmosis (RO) has been proposed to produce high-quality drinking water from raw riverbank filtrate impacted by anthropogenic activities. To evaluate RO efficacy in removing organic micropollutants, biological analyses were combined with non-target screening using high-resolution mass spectrometry and open cheminformatics tools. The bank filtrate induced xenobiotic metabolism mediated by the aryl hydrocarbon receptor AhR, adaptive stress response mediated by the transcription factor Nrf2 and genotoxicity in the Ames-fluctuation test. These effects were absent in the RO permeate (product water), indicating the removal of bioactive micropollutants by RO membranes. In the water samples, 49 potentially toxic compounds were tentatively identified with the in silico fragmentation tool MetFrag using the US Environmental Protection Agency CompTox Chemicals Dashboard database. 5 compounds were confirmed with reference standards and 16 were tentatively identified with high confidence based on similarities to accurate mass spectra in open libraries. The bioactivity data of the confirmed chemicals indicated that 2,6-dichlorobenzamide and bentazone in water samples can contribute to the activation of AhR and oxidative stress response, respectively. The bioactivity data of 7 compounds tentatively identified with high confidence indicated that these structures can contribute to the induction of such effects. This study showed that riverbank filtration followed by RO could produce drinking water free of the investigated toxic effects.

Xanthates, derivatives of xanthic acid, are widely utilized across industries such as agrochemicals, rubber processing, pharmaceuticals, metallurgical, paper and mining to help separate metals from ore. Despite their prevalent use, many registered xanthates lack comprehensive information on potential risks to human health and the environment. The mining sector, a significant consumer of xanthates, drives demand. However, emissions into the environment remain poorly understood, especially concerning water quality. A recent EU parliamentary voting on water legislation highlights the urgency to address water pollution and the potential toxicity of xanthates. While limited data exist on xanthate presence in the environment, existing studies indicate their toxicity and contribution to environmental pollution, primarily due to carbon disulfide, a decomposition product. Concerns are mounting over the release of xanthates and carbon disulfide, particularly in mining areas near populated regions and river tributaries, raising questions about downstream impacts and public health risks. Proposed expansions of xanthate-reliant mining activities in Europe, heighten concerns about emissions and water quality impacts. Current databases lack xanthate-related monitoring data, hindering environmental and health risk assessments. Addressing this gap requires water sampling and chemical analysis and investigations into the use, occurrence, and potential impacts of xanthates from industrial activities on water bodies, including those used for drinking water production is imperative.

The increasing production and use of chemicals leads to a higher number of contaminants in (drinking) water sources, which poses significant challenges to those responsible for water quality. An important task for water companies and regulators is to ensure that (drinking) water quality does not compromise public health and confidence in water safety. A key component of this effort is toxicological risk assessment, which evaluates the safety of chemicals that may be present in water systems. Although there has been considerable progress in risk assessment methods, there is currently a lack of a clear approach to the risk assessment of chemicals in (drinking) water for which concentrations vary over time. In the current study, methods for the assessment of less than lifetime exposure (LTL) are presented that are particularly applicable for substances with time-varying concentrations in (drinking) water. The presented framework is a decision tree that helps experts to decide whether a measured or predicted LTL exposure to a chemical can lead to adverse health effects. To develop these methods, we used existing knowledge and incorporated new developments in toxicological risk assessment. A case study illustrates the application of the proposed approaches in a realistic scenario. The method can be used by risk assessors as a tool to improve the understanding of human exposure to contaminants in (drinking) water and to inform risk-based monitoring. In addition, it enables customised investigations and responses that lead to a more nuanced view of water quality and its impact on public health.

Chemical water quality monitoring is increasingly complemented with bioassays. The performance of drinking water treatment technologies was evaluated with bioassays. CALUX bioassays and the Ames fluctuation bioassay for mutagenicity were used to analyze the responses of raw feed water with and without a spiking mixture of organic contaminants in different pilot-scale water treatment trains applying advanced oxidation processes, reverse osmosis and filtration with activated carbon for the preparation of drinking water. In general, CALUX responses in the spiked feed water were in the same range as in the unspiked feed water, indicating that spiking did not significantly elevate the activity measured in the feed water. This observation was in line with a calculation of the combined additive behavior of the spiking mixture using bioactivities of the spiked chemicals in analog bioassays from ToxCast. This calculation gave no indication of a measurable response in the bioassays to be expected by the spiking, except for oxidative stress. Responses in the Ames fluctuation assay in most feed water were in some cases increased by advanced oxidation processes (AOPs) and mostly removed by active concentrations. The bioassay responses demonstrate the removal of emerging chemicals with different mechanisms of action by different water treatment technologies.