Neurotoxic mixture effects of chemicals extracted from blood of pregnant women.

Human biomonitoring studies typically capture only a small and unknown fraction of the entire chemical universe. We combined chemical analysis with a high-throughput in vitro assay for neurotoxicity to capture complex mixtures of organic chemicals in blood. Plasma samples of 624 pregnant women from the German LiNA cohort were extracted with a nonselective extraction method for organic chemicals. 294 of >1000 target analytes were detected and quantified. Many of the detected chemicals as well as the whole extracts interfered with neurite development. Experimental testing of simulated complex mixtures of detected chemicals in the neurotoxicity assay confirmed additive mixture effects at concentrations less than individual chemicals' effect thresholds. The use of high-throughput target screening combined with bioassays has the potential to improve human biomonitoring and provide a new approach to including mixture effects in epidemiological studies.

The impact of repeated pyrethroid pulses on aquatic communities.

Pesticides are considered to be one of the main causes of the decline in macroinvertebrate biodiversity in small streams. In particular, pyrethroids are detected in agricultural surface waters worldwide and pose a high risk to aquatic invertebrates. Due to their knock-down effect, even short pyrethroid exposure pulses can have significant short- and long-term effects on macroinvertebrate communities. Therefore, it is necessary to consider more realistic exposure scenarios for the environmental risk assessment of pyrethroids and, consequently, to obtain more realistic effect data by using multi-stressor test systems. In an experimental setup with artificial indoor streams (AIS), four pyrethroid pulses simulated the exposure scenario of heavy rainfall events. Effects of these 12 h-exposures at different concentrations of deltamethrin (0.64 ng/L, 4 ng/L, 16 ng/L, 64 ng/L) with intervening recovery periods of six days were assessed on an aquatic community consisting of Gammarus pulex, Ephemera danica, Lumbriculus variegatus and Potamopyrgus antipodarum with various lethal and sub-lethal endpoints. The mortality rate of G. pulex significantly increased with increasing deltamethrin concentrations, whereas the mean number of offspring significantly decreased (NOECoffspring: 16 ng/L, LOECoffspring: 64 ng/L). The biomass of L. variegatus decreased with increasing deltamethrin concentrations (NOECdry weight: 16 ng/L, LOECdry weight: 64 ng/L). The findings of this study clearly demonstrate that 12 h-deltamethrin pulses at environmentally relevant concentrations adversely affect an aquatic community. Based on the results of this study a RAC value of 5.33 ng/L is assumed, which is below the concentrations measured in rivers of up to 58.8 ng/L. Unacceptable effects on the entire freshwater environment can therefore not be ruled out. The experimental AIS approach is a useful tool for assessing the effects of repeated pulse exposures that occur during surface runoff events.

Hydrogen isotope labeling unravels origin of soil-bound organic contaminant residues in biodegradability testing.

Biodegradability testing in soil helps to identify safe synthetic organic chemicals but is still obscured by the formation of soil-bound 'non-extractable' residues (NERs). Present-day methodologies using radiocarbon or stable (13C, 15N) isotope labeling cannot easily differentiate soil-bound parent chemicals or transformation products (xenoNERs) from harmless soil-bound biomolecules of microbial degraders (bioNERs). Hypothesizing a minimal retention of hydrogen in biomolecules, we here apply stable hydrogen isotope - deuterium (D) - labeling to unravel the origin of NERs. Soil biodegradation tests with D- and 13C-labeled 2,4-D, glyphosate and sulfamethoxazole reveal consistently lower proportions of applied D than 13C in total NERs and in amino acids, a quantitative biomarker for bioNERs. Soil-bound D thus mostly represents xenoNERs and not bioNERs, enabling an efficient quantification of xenoNERs by just measuring the total bound D. D or tritium (T) labeling could thus improve the value of biodegradability testing results for diverse organic chemicals forming soil-bound residues.

Co-occurrence and spatial distribution of organic micropollutants in surface waters of the River Aconcagua and Maipo basins in Central Chile.

Organic Micropollutants (OMPs) might pose significant risks to aquatic life and have potential toxic effects on humans. These chemicals typically occur as complex mixtures rather than individually. Information on their co-occurrence and their association with land use is largely lacking, even in industrialized countries. Furthermore, data on the presence of OMPs in freshwater ecosystems in South America is insufficient. Consequently, we assessed the co-occurrence and distribution of OMPs, including pharmaceuticals, pesticides, personal care products, surfactants, and other industrial OMPs, in surface waters of two river basins in central Chile. We focused on identifying and ranking quantified chemicals, classifying their mode of actions, as well as correlating their occurrence with distinct land uses. We identified and quantified 311 compounds that occurred at least once in the River Aconcagua and River Maipo basins, encompassing compounds from urban, agricultural, industrial, and pharmaceutical sectors. Pharmaceuticals were the most frequently occurring chemicals, followed by pesticides, personal care and household products. OMPs with neuroactive properties dominated surface waters in Central Chile, along with OMPs known to alter the cardiovascular and endocrine systems of humans and aquatic animals. Finally, we observed positive correlations between agricultural and urban land uses and OMPs. Our findings represent a step forward in extending current knowledge on the co-occurrence patterns of OMPs in aquatic environments, particularly in developing countries of the southern hemisphere.

Pesticide residues and polyphenols in urine - A combined LC-HRMS screening to reveal intake patterns.

Human exposure to pesticides in the general population occurs mainly through food consumption. However, specific dietary habits or food products that contribute to pesticide exposure are often unknown. In this study, we propose a combined screening for polyphenols and pesticide residues by liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) to assess the diet and the associated pesticide exposure. We measured 587 urine samples from women around the 34th week of pregnancy of a prospective mother-child cohort. A non-targeted screening for flavonoid-like compounds related to fruit and vegetable consumption was performed, prioritizing 164 features and identifying a total of 46 features by spectral library search. Based on a subset of markers, k-means clustering was performed, leading to four clusters with presumably similar dietary habits. The clusters were compared against food questionnaire data collected within the period of sample collection. Suspect screening of more than 500 pesticide residues including metabolites was performed, with a total of 40 residues being reported for 27 different pesticides. The detection of pesticide residues was compared across the different clusters of dietary habits. Indications were found that pyrimethanil metabolites might be associated with the consumption of citrus fruits or derivate products. We demonstrate that the method used has the potential to reveal patterns of pesticide intake from specific food commodities.

Mind your tyres: The ecotoxicological impact of urban sediments on an aquatic organism.

The presence of tyre and road wear particles (TRWP) in the environment is an underestimated threat due to their potential impact on ecosystems and human health. However, their mode of action and potential impacts on aquatic ecosystems remain largely unknown. In the present study, we adopted a sediment exposure scenario to investigate the influence of sediment coming from an urban runoff sedimentation basin on the life cycle of Chironomus riparius. Targeted broad-spectrum chemical analysis helped to characterise the urban sediments and confirmed the significant contribution of contaminants from traffic (e.g. tyre wear contribution, Polycyclic Aromatic Hydrocarbons [PAHs], metals, tyre rubber additives). First-stage chironomid larvae were subjected to increasing concentrations of urban whole sediment. The results showed that exposure to this urban sediment influenced all measured endpoints. In vivo quantification of ROS showed that larvae exposed to the lowest concentration of contaminated sediment exhibited increased fluorescence. The contaminated sediment conditions increased mortality by almost 30 %, but this effect was surprisingly not concentration-dependent. Fertility decreased significantly and concentration-dependently. The results of the Mean Emergence Time (EmT50) and larval size showed an optimality curve. Furthermore, as a consequence of the effects on fitness, the Population Growth Rate (PGR) exhibited a significant decrease, which was concentration-dependent. Therefore, after a single generation, PGR calculation can be adopted as a sensitive tool to monitor pollution caused by complex matrices, i.e. composed of several contaminants. Our research highlights the importance of effective management of road runoff and underlines the need for further investigation to better understand the toxicity of TRWPs.

Progress, applications, and challenges in high-throughput effect-directed analysis for toxicity driver identification - is it time for HT-EDA?

The rapid increase in the production and global use of chemicals and their mixtures has raised concerns about their potential impact on human and environmental health. With advances in analytical techniques, in particular, high-resolution mass spectrometry (HRMS), thousands of compounds and transformation products with potential adverse effects can now be detected in environmental samples. However, identifying and prioritizing the toxicity drivers among these compounds remain a significant challenge. Effect-directed analysis (EDA) emerged as an important tool to address this challenge, combining biotesting, sample fractionation, and chemical analysis to unravel toxicity drivers in complex mixtures. Traditional EDA workflows are labor-intensive and time-consuming, hindering large-scale applications. The concept of high-throughput (HT) EDA has recently gained traction as a means of accelerating these workflows. Key features of HT-EDA include the combination of microfractionation and downscaled bioassays, automation of sample preparation and biotesting, and efficient data processing workflows supported by novel computational tools. In addition to microplate-based fractionation, high-performance thin-layer chromatography (HPTLC) offers an interesting alternative to HPLC in HT-EDA. This review provides an updated perspective on the state-of-the-art in HT-EDA, and novel methods/tools that can be incorporated into HT-EDA workflows. It also discusses recent studies on HT-EDA, HT bioassays, and computational prioritization tools, along with considerations regarding HPTLC. By identifying current gaps in HT-EDA and proposing new approaches to overcome them, this review aims to bring HT-EDA a step closer to monitoring applications.

Seasonal hot spots of pollution and risks in Western Kenya: A spatial-temporal analysis of almost 800 organic micropollutants.

The release of chemicals into the environment presents a significant threat to aquatic ecosystems dependent on the proximity to emission sources and seasonal dynamics of emission and mobilization. While spatial-temporal information on water pollution in Europe is increasing, there are substantial knowledge gaps on seasonal pollution dynamics in tropical countries. Thus, we took Lake Victoria South Basin in western Kenya as a case study to identify spatial and seasonal hot spots of contamination, quantified toxic risks to different groups of organisms, and identified seasonal risk drivers. For this purpose, we analyzed grab water samples from five rivers with agricultural and wastewater treatment plants in their catchment in four different seasons. We used liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS) with a target list of 785 organic micropollutants. A total of 307 compounds were detected with concentrations ranging from 0.3 ng/L to 6.6 µg/L. Using a Toxic Unit (TU) approach based on mixture toxicity to standard test organisms, crustaceans were identified as the most affected group followed by algae and fish. For crustaceans, chronic risk thresholds were exceeded in 96 % of all the samples, while 56 % of all samples are expected to be acutely toxic, with the highest risk in February during the dry season. High toxic unit values for algae and fish were recorded in July dry season and May wet season. Diazinon, imidacloprid, clothianidin and pirimiphos-methyl were the major drivers for crustacean toxicity while triclosan and different herbicide mixtures drive risks to algae in dry and wet seasons, respectively. A total of 18 chemicals were found to exceed acute and chronic environmental risk thresholds. With this study, strong spatial-temporal patterns of pollution, risks and risk drivers could be confirmed informing prioritization of monitoring and abatement to enhance water quality and reduce toxic risks.

Occurrence, removal and risk assessment of chemicals of emerging concern in selected rivers and wastewater treatment plants in western Kenya.

Water resources play a crucial role in sustaining life on earth yet chemicals of emerging concern (CECs) arising from extensive human applications are an increasing threat towards their existence. In this study, we examined the occurrence, removal and potential risk of CECs found in rivers and wastewater treatment plants (WWTPs) in western Kenya. Samples were prepared by solid-phase extraction and analysed using high performance liquid chromatography-mass spectrometry with a target list of 785 compounds. Out of these, 333 and 352 (influent 322, effluent 265) compounds were quantified in rivers and wastewater respectively, with pharmaceuticals, industrial compounds, and pesticides being frequently detected in both rivers and WWTPs. Compounds with highest concentrations included saccharin (9.9 µg/L), metformin (7.5 µg/L), and oxypurinol (6.5 µg/L) in rivers whereas caffeine (280 µg/L), deoxycholic acid (179 µg/L), 2-oxindole (10.9 µg/L) and ibuprofen (8.1 µg/L) were found at high concentrations in WWTPs. Based on the types of crops grown, samples from maize growing regions recorded the highest number of pesticides (75) which coincided with the spraying season. The WWTP showed the capacity to eliminate some compounds although the removal efficiencies varied greatly with 204 compounds exhibiting an average removal efficiency exceeding 50 %. Based on the risk assessment, crustaceans had the highest potential risk for toxicity with toxic unit (TU) values up to 5.4 driven primarily by diazinon and dichlorvos followed by algae (TU up to 0.07) and fish (TU up to 0.01) in rivers. A similar trend was observed in WWTP with diazinon (TU up to 5.5), diuron (TU up to 0.07) and carbendazim (TU up to 0.006) driving the risk for crustaceans, algae and fish respectively. These findings highlight the significance of surface water and WWTPs as sources and sinks of CECs in the environment translating to potential risks on aquatic organisms and humans.

Preliminary dataset of emerging contaminants in surface water, bottom water, porewater, and sediment: Urban and aquaculture impacts in Coliumo bay and Caucahue Channel in the central and southern coast of Chile.

Synthetic organic chemicals, including pesticides, pharmaceuticals, and industrial compounds, pose a growing threat to marine ecosystems. Despite their potential impact, data on the co-occurrence of these contaminants in multiple compartments, including surface water, bottom water, porewater, and sediment in the marine environment remains limited. Such information is critical for assessing coastal chemical status, establishing environmental quality benchmarks, and conducting comprehensive environmental risk assessments. In this study, we describe a multifaceted monitoring campaign targeting pesticides, pharmaceuticals, surfactants, additives, and plasticizers among other synthetic chemicals in four sampling sites. One site was located in the small Coliumo bay affected by urban settlements and tourism in central-south and additionally, we sampled three sites, Caucahue Channel, affected by urban settlements and salmon farming in northern Patagonia in Chile. Surface water, bottom water, porewater, and adjacent sediment samples were collected for target screening analysis in LC- and GC-HRMS platforms. Our results show the detection of up to 83 chemicals in surface water, 71 in bottom water, 101 in porewater, and 244 in sediments. To enhance data utility and reuse potential, we provide valuable information on the mode of action and molecular targets of the identified chemicals. This comprehensive dataset contributes to defining pollution fingerprints in coastal areas of the Global South, including remote regions in Patagonia. It serves as a critical resource for future research including marine chemical risk assessment, policymaking, and the advancement of environmental protection in these regions.

Dataset on target chemical and bioassay analysis-Exploring contaminants of emerging concern in a low mountain river of central Germany.

Chemical pollution of the aquatic environment is nowadays characterised by increasing levels of anthropogenic organic compounds at low concentrations and is recognised as one of the main drivers of the deteriorated ecological state of European waterbodies. To improve the understanding of the impact of chemical pollution in surface waters, a combined approach of chemical and bioanalytical testing is considered necessary for effective ecologically oriented water management. For this dataset, six 25-L water samples were collected at six sampling sites along the Holtemme River in Central Germany using large-volume solid phase extraction. All samples were analysed by targeted high-resolution liquid chromatography-mass spectrometry (LC-MS) and a selected bioanalytical test battery using effect-based methods. These methods included cytotoxicity assessment, several mechanism-specific CALUXⓇ tests to identify endocrine and oxidative stress-related effects and the fish embryo acute toxicity test to investigate (sub)lethal effects in the model species Danio rerio. This approach provided a dataset that offers a longitudinal characterisation of the chemical pollution and ecotoxicological impacts. The combination of chemical analysis and effect-based analysis is valuable for future studies as it will help researchers, risk assessors and authorities to identify hot spots of chemical pollution, monitor environmental quality standards and recommend mitigation strategies.

One like all? Behavioral response range of native and invasive amphipods to neonicotinoid exposure.

Native and invasive species often occupy similar ecological niches and environments where they face comparable risks from chemical exposure. Sometimes, invasive species are phylogenetically related to native species, e.g. they may come from the same family and have potentially similar sensitivities to environmental stressors due to phylogenetic conservatism and ecological similarity. However, empirical studies that aim to understand the nuanced impacts of chemicals on the full range of closely related species are rare, yet they would help to comprehend patterns of current biodiversity loss and species turnover. Behavioral sublethal endpoints are of increasing ecotoxicological interest. Therefore, we investigated behavioral responses (i.e., change in movement behavior) of the four dominant amphipod species in the Rhine-Main area (central Germany) when exposed to the neonicotinoid thiacloprid. Moreover, beyond species-specific behavioral responses, ecological interactions (e.g. parasitation with Acanthocephala) play a crucial role in shaping behavior, and we have considered these infections in our analysis. Our findings revealed distinct baseline behaviors and species-specific responses to thiacloprid exposure. Notably, Gammarus fossarum exhibited biphasic behavioral changes with hyperactivity at low concentrations that decreased at higher concentrations. Whereas Gammarus pulex, Gammarus roeselii and the invasive species Dikerogammarus villosus, showed no or weaker behavioral responses. This may partly explain why G. fossarum disappears in chemically polluted regions while the other species persist there to a certain degree. But it also shows that potential pre-exposure in the habitat may influence behavioral responses of the other amphipod species, because habituation occurs, and potential hyperactivity would be harmful to individuals in the habitat. The observed responses were further influenced by acanthocephalan parasites, which altered baseline behavior in G. roeselii and enhanced the behavioral response to thiacloprid exposure. Our results underscore the intricate and diverse nature of responses among closely related amphipod species, highlighting their unique vulnerabilities in anthropogenically impacted freshwater ecosystems.

Handling of problematic ion chromatograms with the Automated Target Screening (ATS) workflow for unsupervised analysis of high-resolution mass spectrometry data.

Liquid chromatography (LC) or gas chromatography (GC) coupled to high-resolution mass spectrometry (HRMS) is a versatile analytical method for the analysis of thousands of chemical pollutants that can be found in environmental and biological samples. While the tools for handling such complex datasets have improved, there are still no fully automated workflows for targeted screening analysis. Here we present an R-based workflow that is able to cope with challenging data like noisy ion chromatograms, retention time shifts, and multiple peak patterns. The workflow can be applied to batches of HRMS data recorded after GC with electron ionization (GC-EI) and LC coupled to electrospray ionization in both negative and positive mode (LC-ESIneg/LC-ESIpos) to perform peak annotation and quantitation fully unsupervised. We used Orbitrap HRMS data of surface water extracts to compare the Automated Target Screening (ATS) workflow with data evaluations performed with the vendor software TraceFinder and the established semi-automated analysis workflow in the MZmine software. The ATS approach increased the overall evaluation performance of the peak annotation compared to the established MZmine module without the need for any post-hoc corrections. The overall accuracy increased from 0.80 to 0.86 (LC-ESIpos), from 0.77 to 0.83 (LC-ESIneg), and from 0.67 to 0.76 (GC-EI). The mean average percentage errors for quantification of ATS were around 30% compared to the manual quantification with TraceFinder. The ATS workflow enables time-efficient analysis of GC- and LC-HRMS data and accelerates and improves the applicability of target screening in studies with a large number of analytes and sample sizes without the need for manual intervention.

Innovative analytical methodologies for characterizing chemical exposure with a view to next-generation risk assessment.

The chemical burden on the environment and human population is increasing. Consequently, regulatory risk assessment must keep pace to manage, reduce, and prevent adverse impacts on human and environmental health associated with hazardous chemicals. Surveillance of chemicals of known, emerging, or potential future concern, entering the environment-food-human continuum is needed to document the reality of risks posed by chemicals on ecosystem and human health from a one health perspective, feed into early warning systems and support public policies for exposure mitigation provisions and safe and sustainable by design strategies. The use of less-conventional sampling strategies and integration of full-scan, high-resolution mass spectrometry and effect-directed analysis in environmental and human monitoring programmes have the potential to enhance the screening and identification of a wider range of chemicals of known, emerging or potential future concern. Here, we outline the key needs and recommendations identified within the European Partnership for Assessment of Risks from Chemicals (PARC) project for leveraging these innovative methodologies to support the development of next-generation chemical risk assessment.

A multi-scenario risk assessment strategy applied to mixtures of chemicals of emerging concern in the River Aconcagua basin in Central Chile.

Environmental risk assessments strategies that account for the complexity of exposures are needed in order to evaluate the toxic pressure of emerging chemicals, which also provide suggestions for risk mitigation and management, if necessary. Currently, most studies on the co-occurrence and environmental impacts of chemicals of emerging concern (CECs) are conducted in countries of the Global North, leaving massive knowledge gaps in countries of the Global South. In this study, we implement a multi-scenario risk assessment strategy to improve the assessment of both the exposure and hazard components in the chemical risk assessment process. Our strategy incorporates a systematic consideration and weighting of CECs that were not detected, as well as an evaluation of the uncertainties associated with Quantitative Structure-Activity Relationships (QSARs) predictions for chronic ecotoxicity. Furthermore, we present a novel approach to identifying mixture risk drivers. To expand our knowledge beyond well-studied aquatic ecosystems, we applied this multi-scenario strategy to the River Aconcagua basin of Central Chile. The analysis revealed that the concentrations of CECs exceeded acceptable risk thresholds for selected organism groups and the most vulnerable taxonomic groups. Streams flowing through agricultural areas and sites near the river mouth exhibited the highest risks. Notably, the eight risk drivers among the 153 co-occurring chemicals accounted for 66-92 % of the observed risks in the river basin. Six of them are pesticides and pharmaceuticals, chemical classes known for their high biological activity in specific target organisms.

Curated mode-of-action data and effect concentrations for chemicals relevant for the aquatic environment.

Chemicals in the aquatic environment can be harmful to organisms and ecosystems. Knowledge on effect concentrations as well as on mechanisms and modes of interaction with biological molecules and signaling pathways is necessary to perform chemical risk assessment and identify toxic compounds. To this end, we developed criteria and a pipeline for harvesting and summarizing effect concentrations from the US ECOTOX database for the three aquatic species groups algae, crustaceans, and fish and researched the modes of action of more than 3,300 environmentally relevant chemicals in literature and databases. We provide a curated dataset ready to be used for risk assessment based on monitoring data and the first comprehensive collection and categorization of modes of action of environmental chemicals. Authorities, regulators, and scientists can use this data for the grouping of chemicals, the establishment of meaningful assessment groups, and the development of in vitro and in silico approaches for chemical testing and assessment.

Assessing background contamination of sample tubes used in human biomonitoring by non-targeted liquid chromatography-high resolution mass spectrometry.

Controlling and minimising background contamination is crucial for maintaining a high quality of samples in human biomonitoring targeting organic chemicals. We assessed the contamination of three previous types and one newly introduced medical-grade type of sample tubes used for storing human body fluids at the German Environmental Specimen Bank. Aqueous extracts from these tubes were analysed by non-targeted liquid chromatography-high resolution mass spectrometry (LC-HRMS) before and after a dedicated cleaning procedure. After peak detection using MZmine, Bayesian hypothesis testing was used to group peaks into those originating either from instrumental and laboratory background contamination, or actual tube contaminants, based on if their peak height was reduced, increased or not affected by the cleaning procedure. For all four tube types 80-90% of the 2475 peaks (1549 in positive and 926 in negative mode) were assigned to laboratory/instrumental background, which we have to consider as potential sample tube contaminants. Among the tube contaminants, results suggest a considerable difference in the contaminant peak inventory and the absolute level of contamination among the different sample tube types. The cleaning procedure did not affect the largest fraction of peaks (50-70%). For the medical grade tubes, the removal of contaminants by the cleaning procedure was strongest compared to the previous tubes, but in all cases a small fraction increased in intensity after cleaning, probably due to a release of oligomers or additives. The identified laboratory background contaminants were mainly semi-volatile polymer additives such as phthalates and phosphate esters. A few compounds could be assigned solely as tube-specific contaminants, such as N,N-dibutylformamide and several constituents of the oligomeric light stabiliser Tinuvin-622. A cleaning procedure before use is an effective way to standardise the used sample tubes and minimises the background contamination, and therefore increases sample quality and therewith analytical results.

A First-in-Human Trial of a New Aqueous Ionic Liquid Embolic Material in Distal Embolization Applications.

PURPOSE: A prospective, single-arm, open-label, multicenter, first-in-human, early feasibility study was completed to evaluate the safety and performance of the GPX Embolic Device (Fluidx, Salt Lake City, Utah), a novel liquid embolic agent, for use in the peripheral vasculature when deep distal embolization is desired. MATERIALS AND METHODS: The early feasibility study evaluated the use of the device in the peripheral vasculature. Enrollment consisted of 17 patients with diverse embolization needs requiring deep distal vessel/vessel bed occlusion. Technical success, freedom from adverse events (AEs), and handling/performance characteristics were assessed with follow-up at 30 days. RESULTS: The trial enrolled 17 patients requiring distal vascular penetration of the embolic agent, including 7 with renal angiomyolipomas, 4 with renal cell carcinomas (primary and secondary), 4 with portal veins needing embolization, 1 with pelvic sarcoma, and 1 with polycystic kidney. In all cases (100%), technical success was achieved with target regions fully occluded on the first angiogram (taken immediately after delivery). Furthermore, the material received high usability ratings, as measured by a postprocedural investigator questionnaire. Most patients (15/17, 88.2%) were free from device-related severe AEs, and there were no unanticipated AEs during the study. Each patient completed a 30-day follow-up evaluation, and sites remained fully occluded in each case where imaging was available (6 [35.3%] of 17 patients had follow-up imaging where all sites were deemed occluded [100%] with a mean of 30.2 days after the procedure). CONCLUSIONS: The results of this first-in-human, early feasibility study demonstrate that the GPX Embolic Device may provide safe and effective embolization for arterial or venous applications where deep distal penetration is desired.

Mapping chemical footprints of organic micropollutants in European streams.

There is increasing awareness that chemical pollution of freshwater systems with complex mixtures of chemicals from domestic sources, agriculture and industry may cause a substantial chemical footprint on water organisms, pushing aquatic ecosystems outside the safe operating space. The present study defines chemical footprints as the risk that chemicals or chemical mixtures will have adverse effects on a specific group of organisms. The aim is to characterise these chemical footprints in European streams based on a unique and uniform screening of more than 600 chemicals in 445 surface water samples, and to derive site- and compound-specific information for management prioritisation purposes. In total, 504 pesticides, biocides, pharmaceuticals and other compounds have been detected, including frequently occurring and site-specific compounds with concentrations up to 74 µg/L. Key finding is that three-quarter of the investigated sites in 22 European river basins exceed established thresholds for chemical footprints in freshwater, leading to expected acute or chronic impacts on aquatic organisms. The largest footprints were recorded on invertebrates, followed by algae and fish. More than 70 chemicals exceed thresholds of chronic impacts on invertebrates. For all organism groups, pesticides and biocides were the main drivers of chemical footprints, while mixture impacts were particularly relevant for invertebrates. No clear significant correlation was found between chemical footprints and the urban discharge fractions, suggesting that effluent-specific quality rather than the total load of treated wastewater in the aquatic environment and the contribution of diffuse sources, e.g. from agriculture, determine chemical footprints.

Recovery of 400 Chemicals with Three Extraction Methods for Low Volumes of Human Plasma Quantified by Instrumental Analysis and In Vitro Bioassays.

Human biomonitoring studies are important for understanding adverse health outcomes caused by exposure to chemicals. Complex mixtures of chemicals detected in blood - the blood exposome - may serve as proxies for systemic exposure. Ideally, several analytical methods are combined with in vitro bioassays to capture chemical mixtures as diverse as possible. How many and which (bio)analyses can be performed is limited by the sample volume and compatibility of extraction and (bio)analytical methods. We compared the extraction efficacy of three extraction methods using pooled human plasma spiked with >400 organic chemicals. Passive equilibrium sampling (PES) with polydimethylsiloxane (PDMS) followed by solid phase extraction (PES + SPE), SPE alone (SPE), and solvent precipitation (SolvPrec) were compared for chemical recovery in LC-HRMS and GC-HRMS as well as effect recovery in four mammalian cell lines (AhR-CALUX, SH-SY5Y, AREc32, PPARγ-BLA). The mean chemical recoveries were 38% for PES + SPE, 27% for SPE, and 61% for SolvPrec. PES + SPE enhanced the mean chemical recovery compared to SPE, especially for neutral hydrophobic chemicals. PES + SPE and SolvPrec had effect recoveries of 100-200% in all four cell lines, outperforming SPE, which had 30-100% effect recovery. Although SolvPrec has the best chemical recoveries, it does not remove matrix like inorganics or lipids, which might pose problems for some (bio)analytical methods. PES + SPE is the most promising method for sample preparation in human biomonitoring as it combines good recoveries with cleanup, enrichment, and potential for high throughput.