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.

A data-derived reference mixture representative of European wastewater treatment plant effluents to complement mixture assessment.

Aquatic environments are polluted with a multitude of organic micropollutants, which challenges risk assessment due the complexity and diversity of pollutant mixtures. The recognition that certain source-specific background pollution occurs ubiquitously in the aquatic environment might be one way forward to approach mixture risk assessment. To investigate this hypothesis, we prepared one typical and representative WWTP effluent mixture of organic micropollutants (EWERBmix) comprised of 81 compounds selected according to their high frequency of occurrence and toxic potential.

Modernizing persistence-bioaccumulation-toxicity (PBT) assessment with high throughput animal-free methods.

The assessment of persistence (P), bioaccumulation (B), and toxicity (T) of a chemical is a crucial first step at ensuring chemical safety and is a cornerstone of the European Union's chemicals regulation REACH (Registration, Evaluation, Authorization, and Restriction of Chemicals). Existing methods for PBT assessment are overly complex and cumbersome, have produced incorrect conclusions, and rely heavily on animal-intensive testing. We explore how new-approach methodologies (NAMs) can overcome the limitations of current PBT assessment.

Molecular Responses of Daphnids to Chronic Exposures to Pharmaceuticals.

Pharmaceutical compounds are among several classes of contaminants of emerging concern, such as pesticides, heavy metals and personal care products, all of which are a major concern for aquatic ecosystems. The hazards posed by the presence of pharmaceutical is one which affects both freshwater organisms and human health-via non-target effects and by the contamination of drinking water sources. The molecular and phenotypic alterations of five pharmaceuticals which are commonly present in the aquatic environment were explored in daphnids under chronic exposures.

The Effects of Single and Combined Stressors on Daphnids-Enzyme Markers of Physiology and Metabolomics Validate the Impact of Pollution.

The continuous global increase in population and consumption of resources due to human activities has had a significant impact on the environment. Therefore, assessment of environmental exposure to toxic chemicals as well as their impact on biological systems is of significant importance. Freshwater systems are currently under threat and monitored; however, current methods for pollution assessment can neither provide mechanistic insight nor predict adverse effects from complex pollution.

The Eco-Exposome Concept: Supporting an Integrated Assessment of Mixtures of Environmental Chemicals.

Organisms are exposed to ever-changing complex mixtures of chemicals over the course of their lifetime. The need to more comprehensively describe this exposure and relate it to adverse health effects has led to formulation of the exposome concept in human toxicology. Whether this concept has utility in the context of environmental hazard and risk assessment has not been discussed in detail.

Photomotor response data analysis approach to assess chemical neurotoxicity with the zebrafish embryo.

The photomotor response (PMR) of zebrafish embryos, a light pulse-triggered undirected movement, is known to be altered by neuroactive chemicals. Here, we developed an approach for data analysis of the distribution of PMR movement activities along the time axis; differences between treatment and respective controls are expressed by an aggregated value integrating the time-resolved density of the movement parameter as a measure for a chemically elicited PMR effect. Logistic concentration-PMR effect relationships were modeled for neuroactive test compounds with different modes of action (acetylcholinesterase inhibition, activation and inhibition of voltage-gated sodium channels); 50% effect concentrations (EC50) were in the low to medium μM range (EC50 < 10 μM for flucythrinate, esfenvalerate, azinphos-methyl, propoxur; EC50 > 10 μM for tricaine).

Pesticides are the dominant stressors for vulnerable insects in lowland streams.

Despite elaborate regulation of agricultural pesticides, their occurrence in non-target areas has been linked to adverse ecological effects on insects in several field investigations. Their quantitative role in contributing to the biodiversity crisis is, however, still not known. In a large-scale study across 101 sites of small lowland streams in Central Europe, Germany we revealed that 83% of agricultural streams did not meet the pesticide-related ecological targets.

Assessing Combined Effects for Mixtures of Similar and Dissimilar Acting Neuroactive Substances on Zebrafish Embryo Movement.

Risk assessment of chemicals is usually conducted for individual chemicals whereas mixtures of chemicals occur in the environment. Considering that neuroactive chemicals are a group of contaminants that dominate the environment, it is then imperative to understand the combined effects of mixtures. The commonly used models to predict mixture effects, namely concentration addition (CA) and independent action (IA), are thought to be suitable for mixtures of similarly or dissimilarly acting components, respectively.

Chemical Pollution Levels in a River Explain Site-Specific Sensitivities to Micropollutants within a Genetically Homogeneous Population of Freshwater Amphipods.

Anthropogenic micropollutants alter chemical and ecological conditions of freshwater ecosystems and impact aquatic species that live along the pollution gradient of a river. Species sensitivity to micropollutants depends on the site-specific exposure; however, it remains unclear to what degree this sensitivity relates to the species' genetic structure. Here, we explored the relationship between the toxic sensitivity and genetic structure of the amphipod species (Linnaeus, 1758) along an organic micropollutant gradient in the Holtemme River in central Germany.

Transcriptome-Wide Prediction and Measurement of Combined Effects Induced by Chemical Mixture Exposure in Zebrafish Embryos.

Background: Humans and environmental organisms are constantly exposed to complex mixtures of chemicals. Extending our knowledge about the combined effects of chemicals is thus essential for assessing the potential consequences of these exposures. In this context, comprehensive molecular readouts as retrieved by omics techniques are advancing our understanding of the diversity of effects upon chemical exposure.

Unravelling the chemical exposome in cohort studies: routes explored and steps to become comprehensive.

Environmental factors contribute to the risk for adverse health outcomes against a background of genetic predisposition. Among these factors, chemical exposures may substantially contribute to disease risk and adverse outcomes. In fact, epidemiological cohort studies have established associations between exposure against individual chemicals and adverse health effects.

Disentangling multiple chemical and non-chemical stressors in a lotic ecosystem using a longitudinal approach.

Meeting ecological and water quality standards in lotic ecosystems is often failed due to multiple stressors. However, disentangling stressor effects and identifying relevant stressor-effect-relationships in complex environmental settings remain major challenges. By combining state-of-the-art methods from ecotoxicology and aquatic ecosystem analysis, we aimed here to disentangle the effects of multiple chemical and non-chemical stressors along a longitudinal land use gradient in a third-order river in Germany.

Computational material flow analysis for thousands of chemicals of emerging concern in European waters.

Knowledge of exposure to a wide range of chemicals, and the spatio-temporal variability thereof, is urgently needed in the context of protecting and restoring aquatic ecosystems. This paper discusses a computational material flow analysis to predict the occurrence of thousands of man-made organic chemicals on a European scale, based on a novel temporally and spatially resolved modelling framework. The goal was to increase understanding of pressures by emerging chemicals and to complement surface water monitoring data.

Statement on advancing the assessment of chemical mixtures and their risks for human health and the environment.

The number of anthropogenic chemicals, manufactured, by-products, metabolites and abiotically formed transformation products, counts to hundreds of thousands, at present. Thus, humans and wildlife are exposed to complex mixtures, never one chemical at a time and rarely with only one dominating effect. Hence there is an urgent need to develop strategies on how exposure to multiple hazardous chemicals and the combination of their effects can be assessed.

Combined effects of environmental xeno-estrogens within multi-component mixtures: Comparison of in vitro human- and zebrafish-based estrogenicity bioassays.

Some recent studies showed that in vitro bioassays based on fish or human estrogen receptor (ER) activation may have distinct responses to environmental samples, highlighting the need to better understand bioassay-specific ER response to environmental mixtures. For this purpose, we investigated a 12-compound mixture in two mixture ratios (M1 and M2) on zebrafish (zf) liver cells stably expressing zfERα (ZELHα cells) or zfERβ2 (ZELHβ2 cells) and on human ER-reporter gene (MELN) cells. The mixture included the well-known ER ligands bisphenol A (BPA) and genistein (GEN), and other compounds representatives of a freshwater background contamination.

Can Environmentally Relevant Neuroactive Chemicals Specifically Be Detected with the Locomotor Response Test in Zebrafish Embryos?

Chemicals considered as neuroactive (such as certain pesticides, pharmaceuticals, and industrial chemicals) are among the largest groups of bioactive substances recently detected in European rivers. However, the determination of nervous-system-specific effects has been limited using in vitro tests or conventional end points including lethality. Thus, neurobehavioral tests using in vivo models (e.

Environmental mixtures of nanomaterials and chemicals: The Trojan-horse phenomenon and its relevance for ecotoxicity.

The usage of engineered nanomaterials (NM) offers many novel products and applications with advanced features, but at the same time raises concerns with regard to potential adverse biological effects. Upon release and emission, NM may interact with chemicals in the environment, potentially leading to a co-exposure of organisms and the occurrence of mixture effects. A prominent idea is that NM may act as carriers of chemicals, facilitating and enhancing the entry of substances into cells or organisms, subsequently leading to an increased toxicity.

Mixture effects in samples of multiple contaminants - An inter-laboratory study with manifold bioassays.

Chemicals in the environment occur in mixtures rather than as individual entities. Environmental quality monitoring thus faces the challenge to comprehensively assess a multitude of contaminants and potential adverse effects. Effect-based methods have been suggested as complements to chemical analytical characterisation of complex pollution patterns.

Meta-analysis of fish early life stage tests-Association of toxic ratios and acute-to-chronic ratios with modes of action.

Fish early life stage (ELS) tests (Organisation for Economic Co-operation and Development test guideline 210) are widely conducted to estimate chronic fish toxicity. In these tests, fish are exposed from the embryonic to the juvenile life stages. To analyze whether certain modes of action are related to high toxic ratios (i.

Use of prospective and retrospective risk assessment methods that simplify chemical mixtures associated with treated domestic wastewater discharges.

A framework is presented that is intended to facilitate the evaluation of potential aquatic ecological risks resulting from discharges of down-the-drain chemicals. A scenario is presented using representatives of many of the types of chemicals that are treated domestically. Predicted environmental chemical concentrations are based on reported loading rates and routine removal rates for 3 types of treatment: trickling filter, activated sludge secondary treatment, and activated sludge plus advanced oxidation process as well as instream effluent dilution.