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Background: Kisspeptin has been proposed as an effect biomarker to understand the mechanisms by which some environmental chemicals adversely affect the human reproductive system. Objective: To ascertain whether kisspeptin serum protein and DNA methylation levels are associated with exposure to several environmental chemicals (individually and as a mixture) and serum reproductive hormone levels in adolescent males. Methods: Three phenols (bisphenol A [BPA], methyl-paraben [MPB], and benzophenone-3 [BP3]); two toxic metals (arsenic and cadmium); and four metabolites of non-persistent pesticides, including insecticides (2-isopropyl-6- methyl-4-pyrimidinol [IMPy], malathion diacid [MDA], and dimethylcyclopropane carboxylic acid [DCCA]) and fungicides (ethylene thiourea [ETU]) were measured in first-morning urine samples of 133 adolescent males aged 15–17 years from the INMA-Granada cohort. In blood samples collected on the same day, KISS1 gene DNA methylation was measured at four CpGs from the Exon IV, as well as serumlevels of kiss54 protein, total testosterone (T), estradiol (E2), sex hormone binding-globulin, dehydroepiandrosterone sulfate, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Multiple linear regression and mixture (quantile g-computation) models were fit. Results: UrinaryMDA and DCCA concentrations were associatedwith higher kiss54 levels [%change (95%CI) for each log-unit increase in concentration = 2.90 (0.32;5.56), and 1.93 (0.45,3.43), respectively]; IMPy with lower DNA methylation percentage at CpG1 and total CpGs [% change (95%CI) = −1.15 (−1.96;-0.33): −0.89 (−1.73;- 0.01), respectively]; and BP3 and DCCA with lower total CpGs methylation [−0.53 (−1.04;-0.01) and − 0.69 (−1.37;-0.01), respectively]. The pesticide mixture and the whole chemical mixture were associated with higher kiss54 [% change (95%CI) = 9.09 (3.29;15.21) and 11.61 (3.96;19.82), respectively] and lower methylation levels at several CpGs. Additionally, serum kiss54 in the third tertile was associated with higher LH levels [% change (95%CI) = 28.69 (3.75–59.63)], and third-tertile CpG1, CpG2, and total CpG methylation percentages were associated with lower FSH and E2. Conclusion: The findings of the present study and the negative correlation between serumkiss54 levels and KISS1 DNA methylation percentages suggested that kisspeptin may be a promising effect biomarker., European Union's Horizon 2020 research and innovation program 733032 CP16/00085, Instituto de Salud Carlos III PI 17/01526 PT17/0019, Human Genotyping Laboratory at the Spanish National Cancer Research Centre UCE-PP2017-06, Instituto de Salud Carlos III European Commission European Commission, Biomedical Research Networking Center-CIBER de Epidemiologia y Salud Publica (CIBERESP), University of Granada CPII21/00014, Ramon Areces Foundation, Miguel Servet Type II program of the ISCIII, European Commission, Spanish Government

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 vali- dated 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 toxi- cological 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′ -deoxyguanosine and untargeted metabolomic profile in urine, to investigate, for example, biological changes in response to hexavalent chromium Cr(VI) exposure. The use of effect biomarkers in HBM4EU has demonstrated their ability to detect early biological effects of chemical exposure and to identify subgroups that are at higher risk. The roadmap developed in HBM4EU con- firms the utility of effect biomarkers, and support one of the main objectives of HBM research, which is to link exposure biomarkers to mechanistically validated effect and susceptibility biomarkers in order to better un- derstand the public health implications of human exposure to environmental chemicals., European Union’s Horizon 2020 research and innovation program projects HBM4EU 733032

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.

Most car manufacturers predict that in the first half of the next decade there will be fully autonomous vehicles on our roads. Such vehicles would have to communicate in order to mitigate problems caused by single-viewpoint approach. So there are a lot of researches and developments when it comes to communication layer of V2X (Vehicle-to-Everything), but there is still a lot to be done when it comes to data layer of this communication. This is why we propose using Semantic Web Technologies (SWT) to fill in gaps within data layer of V2X communication. By using SWT (Semantic Web Technologies) and Linked data, we plan to interconnect various data sources, in order to provide homogeneous way for connected autonomous vehicles (CAV) to access relevant information. Such information is currently contained in three distinctive type of sources. These are: Geo-stationary Static data sources (Maps, City models), Geostationary Dynamic data sources (IoT devices) and Non-geostationary Dynamic sources (Vehicles). Using SWT, our goal is to develop ontology(s), in such a way that in-vehicle algorithms can extract and process information about environment they are in, while taking into account available network bandwidth.

Toxicological risk assessment of contaminants of emerging concern (CEC) in (sources of) drinking water is required to identify potential health risks and prioritize chemicals for abatement or monitoring. In such assessments, concentrations of chemicals in drinking water or sources are compared to either (i) health-based (statutory) drinking water guideline values, (ii) provisional guideline values based on recent toxicity data in absence of drinking water guidelines, or (iii) generic drinking water target values in absence of toxicity data. Here, we performed a toxicological risk assessment for 163 CEC that were selected as relevant for drinking water. This relevance was based on their presence in drinking water and/or groundwater and surface water sources in downstream parts of the Rhine and Meuse, in combination with concentration levels and physicochemical properties. Statutory and provisional drinking water guideline values could be derived from publically available toxicological information for 142 of the CEC. Based on measured concentrations it was concluded that the majority of substances do not occur in concentrations which individually pose an appreciable human health risk. A health concern could however not be excluded for vinylchloride, trichloroethene, bromodichloromethane, aniline, phenol, 2-chlorobenzenamine, mevinphos, 1,4-dioxane, and nitrolotriacetic acid. For part of the selected substances, toxicological risk assessment for drinking water could not be performed since either toxicity data (hazard) or drinking water concentrations (exposure) were lacking. In absence of toxicity data, the Threshold of Toxicological Concern (TTC) approach can be applied for screening level risk assessment. The toxicological information on the selected substances was used to evaluate whether drinking water target values based on existing TTC levels are sufficiently protective for drinking water relevant CEC. Generic drinking water target levels of 37 μg/L for Cramer class I substances and 4 μg/L for Cramer class III substances in drinking water were derived based on these CEC. These levels are in line with previously reported generic drinking water target levels based on original TTC values and are shown to be protective for health effects of the majority of contaminants of emerging concern evaluated in the present study. Since the human health impact of many chemicals appearing in the water cycle has been studied insufficiently, generic drinking water target levels are useful for early warning and prioritization of CEC with unknown toxicity in drinking water and its sources for future monitoring. Keywords: Contaminants of emerging concern, Chemical water quality screening, Human health risk assessment, (Provisional) drinking water guideline values, Threshold of Toxicological Concern

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