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Human biomonitoring (HBM) studies have highlighted widespread daily exposure to environmental chemicals. Some of these are suspected to contribute to adverse health outcomes such as reproductive, neurological, and metabolic disorders, among other developmental and chronic impairments. One of the objectives of the H2020 European Human Biomonitoring Initiative (HBM4EU) was the development of informative effect biomarkers for application in a more systematic and harmonized way in large-scale European HBM studies. The inclusion of effect biomarkers would complement exposure data with mechanistically-based information on early and late adverse effects. For this purpose, a stepwise strategy was developed to identify and implement a panel of validated effect biomarkers in European HBM studies. This work offers an overview of the complete procedure followed, from comprehensive literature search strategies, selection of criteria for effect biomarkers and their classification and prioritization, based on toxicological data and adverse outcomes, to pilot studies for their analytical, physiological, and epidemiological validation. We present the example of one study that demonstrated the mediating role of the effect biomarker status of brain-derived neurotrophic factor BDNF in the longitudinal association between infant bisphenol A (BPA) exposure and behavioral function in adolescence. A panel of effect biomarkers has been implemented in the HBM4EU Aligned Studies as main outcomes, including traditional oxidative stress, reproductive, and thyroid hormone biomarkers. Novel biomarkers of effect, such as DNA methylation status of BDNF and kisspeptin (KISS) genes were also evaluated as molecular markers of neurological and reproductive health, respectively. A panel of effect biomarkers has also been applied in HBM4EU occupational studies, such as micronucleus analysis in lymphocytes and reticulocytes, whole blood comet assay, and malondialdehyde, 8-oxo-2′-deoxygua

There is public and scientific concern about air, soil and water contamination and possible adverse environmental and human health effects as a result of hydraulic fracturing activities. The use of greener chemicals in fracturing fluid aims to mitigate these effects. This study compares fracturing fluids marketed as either ‘conventional’ or ‘green’, as assessed by their chemical composition and their toxicity in bioassays. Chemical composition was analysed via non-target screening using liquid chromatography - high resolution mass spectrometry, while toxicity was evaluated by the Ames fluctuation test to assess mutagenicity and CALUX reporter gene assays to determine specific toxicity. Overall, the results do not indicate that the ‘green’ fluids are less harmful than the ‘conventional’ ones. First, there is no clear indication that the selected green fluids contain chemicals present at lower concentrations than the selected conventional fluids. Second, the predicted environmental fate of the identified compounds does not seem to be clearly distinct between the ‘green’ and ‘conventional’ fluids, based on the available data for the top five chemicals based on signal intensity that were tentatively identified. Furthermore, Ames fluctuation test results indicate that the green fluids have a similar genotoxic potential than the conventional fluids. Results of the CALUX reporter gene assays add to the evidence that there is no clear difference between the green and conventional fluids. These results do not support the claim that currently available and tested green-labeled fracturing fluids are environmentally more friendly alternatives to conventional fracturing fluids.

Arsenic (As) is a highly toxic element which naturally occurs in drinking water. In spite of substantial evidence on the association between many illnesses and chronic consumption of As, there is still a considerable uncertainty about the health risks due to low As concentrations in drinking water. In the Netherlands, drinking water companies aim to supply water with As concentration of <1 μg/L – a water quality goal which is tenfold more stringent than the current WHO guideline. This paper provides (i) an account on the assessed lung cancer risk for the Dutch population due to pertinent low-level As in drinking water and cost-comparison between health care provision and As removal from water, (ii) an overview of As occurrence and mobility in drinking water sources and water treatment systems in the Netherlands and (iii) insights into As removal methods that have been employed or under investigation to achieve As reduction to <1 µg/L at Dutch water treatment plants. Lowering of the average As concentration to <1μg/L in the Netherlands is shown to result in an annual benefit of 7.2–14 M€. This study has a global significance for setting drinking water As limits and provision of safe drinking water.

Arsenic (As) is a highly toxic element which naturally occurs in drinking water. In spite of substantial evidence on the association between many illnesses and chronic consumption of As, there is still a considerable uncertainty about the health risks due to low As concentrations in drinking water. In the Netherlands, drinking water companies aim to supply water with As concentration of <1 μg/L – a water quality goal which is tenfold more stringent than the current WHO guideline. This paper provides (i) an account on the assessed lung cancer risk for the Dutch population due to pertinent low-level As in drinking water and cost-comparison between health care provision and As removal from water, (ii) an overview of As occurrence and mobility in drinking water sources and water treatment systems in the Netherlands and (iii) insights into As removal methods that have been employed or under investigation to achieve As reduction to <1 µg/L at Dutch water treatment plants. Lowering of the average As concentration to <1μg/L in the Netherlands is shown to result in an annual benefit of 7.2–14 M€. This study has a global significance for setting drinking water As limits and provision of safe drinking water., Geo-engineering

Arsenic (As) is a highly toxic element which naturally occurs in drinking water. In spite of substantial evidence on the association between many illnesses and chronic consumption of As, there is still a considerable uncertainty about the health risks due to low As concentrations in drinking water. In the Netherlands, drinking water companies aim to supply water with As concentration of < 1 mu g/L - a water quality goal which is tenfold more stringent than the current WHO guideline. This paper provides (i) an account on the assessed lung cancer risk for the Dutch population due to pertinent low-level As in drinking water and cost-comparison between health care provision and As removal from water, (ii) an overview of As occurrence and mobility in drinking water sources and water treatment systems in the Netherlands and (iii) insights into As removal methods that have been employed or under investigation to achieve As reduction to < 1 mu g/L at Dutch water treatment plants. Lowering of the average As concentration to < 1 mu g/L in the Netherlands is shown to result in an annual benefit of 7.2-14 M(sic). This study has a global significance for setting drinking water As limits and provision of safe drinking water., QC 20200103

Publicly available chemical assessments of hydraulic fracturing related waters are generally based on shale gas practices in the U.S. There is a lack of information on hydraulic fracturing related gas development from EU countries and more generally on other types of extractions. This research fills this knowledge gap by presenting chemical and bioassay assessments of hydraulic fracturing related waters from a tight gas development in the Netherlands. Fracturing fluid, flowback water and groundwater from surrounding aquifers before and after the actual fracturing were analysed by means of high resolution liquid chromatography tandem mass spectrometry, the Ames test and three chemical activated luciferase gene expression bioassays aimed at determining genotoxicity, oxidative stress response and polyaromatic hydrocarbon contamination. After sample enrichment a higher number of peaks can be found in both fracturing fluid and flowback samples. No clear differences in chemical composition were shown in the groundwater samples before and after hydraulic fracturing. Preliminary environmental fate data of the tentatively identified chemicals points towards persistence in water. Clear genotoxic and oxidative stress responses were found in the fracturing fluid and flowback samples. A preliminary suspect screening resulted in 25 and 36 matches in positive and negative ionisation respectively with the 338 possible suspect candidates on the list. Extensive measures relating to the handling, transport and treatment of hydraulic fracturing related waters are currently in place within the Dutch context. The results of the present study provide a scientific justification for such measures taken to avoid adverse environmental and human health impacts.

Advancements in high-resolution mass spectrometry based methods have enabled a shift from pure target analysis to target, suspect and non-target screening analyses to detect chemicals in water samples. The multitude of suspect chemicals thereby detected needs to be prioritized for further identification, prior to health risk assessment and potential inclusion into monitoring programs. Here, we compare prioritization of chemicals in Dutch water samples based on relative intensities only to prioritization including hazard information based on high-throughput in vitro toxicity data. Over 1000 suspects detected in sewage treatment plant effluent, surface water, groundwater and drinking water samples were ranked based on their relative intensities. Toxicity data availability and density in the ToxCast database were determined and visualized for these suspects, also in regard to water relevant mechanisms of toxicity. More than 500 suspects could be ranked using occurrence/hazard ratios based on more than 1000 different assay endpoints. The comparison showed that different prioritization strategies resulted in significantly different ranking, with only 2 suspects prioritized based on occurrence among the top 20 in the hazard ranking. We therefore propose a novel scheme that integrates both exposure and hazard data, and efficiently prioritizes which features need to be confidently identified first.

A plethora of in vitro bioassays is developed in the context of chemical risk assessment and clinical diagnostics to test effects on different biological processes. Such assays can also be implemented in effect-based monitoring (EBM) of (drinking) water quality in parallel to chemical analyses. EBM can provide insight in the risks for environmental and human health associated with exposure to (unknown) complex low-level mixtures of micropollutants, which fits in the risk-based approach that was recently introduced in the European Drinking Water Directive. Some challenges remain, in particular related to selection and interpretation of bioassays. For water quality assessment, carcinogenesis, adverse effects on reproduction and development, effects on xenobiotic metabolism, modulation of hormone systems, DNA reactivity and adaptive stress responses are considered as the most relevant toxicological endpoints. An evaluation procedure of the applicability and performance of in vitro bioassays for water quality monitoring based on existing information has been developed, which can be expanded with guidelines for experimental evaluations. Besides, a methodology for the interpretation of in vitro monitoring data is required, since the sensitivity of specific in vitro bioassays in combination with sample concentration may lead to responses of chemicals (far) below exposure concentrations that are relevant for human health effects. Different approaches are proposed to derive effect-based trigger values (EBTs), including EBTs based on 1) relative ecotoxicity potency, 2) health-based threshold values for chronic exposure in humans and kinetics of reference chemicals, and 3) read-across from (drinking) water guideline values. EBTs need to be chosen carefully in order to be sufficiently but not over-conservative to indicate potential health effects. Consensus on the crucial steps in the selection and interpretation of in vitro bioassay data will facilitate implementation, as w

The present study explores the ToxCast/Tox21 database to select candidate bioassays as bioanalytical tools for measuring groups of chemicals in water. To this aim, the ToxCast/Tox21 database was explored for bioassays that detect polycyclic aromatic hydrocarbons (PAHs), aromatic amines (AAs), (chloro)phenols ((C)Ps) and halogenated aliphatic hydrocarbons (HAliHs), which are included in the European and/or Dutch Drinking Water Directives. Based on the analysis of the availability and performance of bioassays included in the database, we concluded that several bioassays are suitable as bioanalytical tools for assessing the presence of PAHs and (C)Ps in drinking water sources. No bioassays were identified for AAs and HAliHs, due to the limited activity of these chemicals and/or the limited amount of data on these chemicals in the database. A series of bioassays was selected that measure molecular or cellular effects that are covered by bioassays currently in use for chemical water quality monitoring. Interestingly, also bioassays were selected that represent molecular or cellular effects that are not covered by bioassays currently applied. The usefulness of these newly identified bioassays as bioanalytical tools should be further evaluated in follow-up studies. Altogether, this study shows how exploration of the ToxCast/Tox21 database provides a series of candidate bioassays as bioanalytical tools for measuring groups of chemicals in water. This assessment can be performed for any group of chemicals of interest (if represented in the database), and may provide candidate bioassays that can be used to complement the currently applied bioassays for chemical water quality assessment.

Het doel van dit onderzoek was het beantwoorden van de vraag in hoeverre de kwaliteit van geloosd spuiwater met gewasbeschermingsmiddelen verbetert door het toepassen van (geavanceerde) oxidatietechnieken, en om zicht te krijgen op mogelijke negatieve bijwerkingen van deze technieken op het ecosysteem. Hiervoor zijn verschillende technieken vergeleken: Waterstofperoxide, Waterstofperoxide + Lage druk UV, Waterstofperoxide + middendruk UV, Waterstofperoxide + ozon, Ozon + lage druk UV, Waterstofperoxide + ozon + lage druk UV.