Physiology-informed toxicokinetic model for the zebrafish embryo test developed for bisphenols.

Zebrafish embryos (ZFE) is a widely used model organism, employed in various research fields including toxicology to assess e.g., developmental toxicity and endocrine disruption.

A comprehensive untargeted metabolomics study in zebrafish embryos exposed to perfluorohexane sulfonate (PFHxS).

Perfluorohexane sulfonate (PFHxS) is one of the short-chain perfluoroalkyl substances (PFASs), and frequently detected in the environment, humans, and wildlife, but a detailed mechanism of toxicity has been not studied yet. In this study, a comprehensive set of polar metabolites was determined in i) the developing zebrafish embryo (4, 24, 48, 72, and 120 h post fertilization (hpf)), and ii) in the developing zebrafish after exposure to four concentrations of PFHxS (0.3, 1, 3, and 10 μM) from 24to 120 hpf.

Metabolite alterations in zebrafish embryos exposed to hydroxylated polybrominated diphenyl ethers.

Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) are formed by metabolism from the flame retardants polybrominated diphenyl ethers (PBDEs). In the aquatic environment, they are also produced naturally. OH-PBDEs are known for their potential to disrupt energy metabolism, the endocrine system, and the nervous system.

Physiologically Based Toxicokinetic Modeling of Bisphenols in Zebrafish () Accounting for Variations in Metabolic Rates, Brain Distribution, and Liver Accumulation.

Bisphenol A (BPA) is an industrial chemical, which has raised human health and environmental concerns due to its endocrine-disrupting properties. BPA analogues are less well-studied despite their wide use in consumer products. These analogues have been detected in water and aquatic organisms around the world, with some analogues showing toxic effects in various species including fish.

Getting more out of the zebrafish light dark transition test.

In (eco-)toxicological studies the light/dark transition (LDT) test is one of the most frequently used behaviour assays with zebrafish eleutheroembryos. However, study results vary regarding data presentation and analysis and mostly focus on a limited amount of the recorded data. In this study, we investigated whether monitoring two behavioural outcomes (time and distance moved) together with analysing multiple parameters can improve test sensitivity and data interpretation.

Using comprehensive lipid profiling to study effects of PFHxS during different stages of early zebrafish development.

PFHxS (Perfluorohexane sulfonic acid) is one of the short-chain perfluoroalkyl substances (PFASs) which are widely used in many industrial and consumer applications. However, limited information is available on the molecular mechanism of PFHxS toxicity (e.g.

Assessment of oil refinery wastewater and effluent integrating bioassays, mechanistic modelling and bioavailability evaluation.

Water is used in petroleum oil refineries in significant volumes for cooling, steam generation and processing of raw materials. Effective water management is required at refineries to ensure their efficient and responsible operation with respect to the water environment. However, ascertaining the potential environmental risks associated with discharge of refinery effluents to receiving waters is challenging because of their compositional complexity.

Cross platform solutions to improve the zebrafish polar metabolome coverage using LC-QTOF MS: Optimization of separation mechanisms, solvent additives, and resuspension solvents.

Untargeted metabolomics has been widely used for studies with zebrafish embryos. Until now, the number of analytical approaches to determine metabolites in zebrafish is limited, and there is a lack of consensus on the best platforms for comprehensive metabolomics analysis of zebrafish embryos. In addition, the capacity of these methods to detect metabolites is unsatisfactory and the confidence level for identifying compounds is relatively low.

Developmental Neurotoxicity of Environmentally Relevant Pharmaceuticals and Mixtures Thereof in a Zebrafish Embryo Behavioural Test.

Humans are exposed daily to complex mixtures of chemical substances via food intake, inhalation, and dermal contact. Developmental neurotoxicity is an understudied area and entails one of the most complex areas in toxicology. Animal studies for developmental neurotoxicity (DNT) are hardly performed in the context of regular hazard studies, as they are costly and time consuming and provide only limited information as to human relevance.

Neurobehavioral effects of cyanobacterial biomass field extracts on zebrafish embryos and potential role of retinoids.

Cyanobacteria are known for their ability to produce and release mixtures of up to thousands of compounds into the environment. Recently, the production of novel metabolites, retinoids, was reported for some cyanobacterial species along with teratogenic effects of samples containing these compounds. Retinoids are natural endogenous substances derived from vitamin A that play a crucial role in early vertebrate development.

Evaluation of LC-MS and LC×LC-MS in analysis of zebrafish embryo samples for comprehensive lipid profiling.

In this study, both conventional one-dimensional liquid chromatography (1DLC) and comprehensive two-dimensional liquid chromatography (2DLC) coupled to a high-resolution time-of-flight mass spectrometer (HR-TOF MS) were used for full-scale lipid characterization of lipid extracts from zebrafish embryos. We investigated the influence on annotated lipids and different separation mechanisms (HILIC, C18, and PFP), and their different orders arranged in the first and the second dimensions. As a result, the number of lipid species annotated by conventional one-dimensional LC-MS was between 212 and 448.

Effects of 25 thyroid hormone disruptors on zebrafish embryos: A literature review of potential biomarkers.

It is estimated that many organic compounds found in our environment can interfere with the thyroid system and act as thyroid hormone (TH) disruptor. Despite that, there is a clear lack of assays to identify TH disruptors. Recently zebrafish embryos were suggested as screening tool to identify compounds which impact thyroid synthesis.

An ecotoxicological view on neurotoxicity assessment.

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.

Time-Integrative Passive sampling combined with TOxicity Profiling (TIPTOP): an effect-based strategy for cost-effective chemical water quality assessment.

This study aimed at demonstrating that effect-based monitoring with passive sampling followed by toxicity profiling is more protective and cost-effective than the current chemical water quality assessment strategy consisting of compound-by-compound chemical analysis of selected substances in grab samples. Passive samplers were deployed in the Dutch river delta and in WWTP effluents. Their extracts were tested in a battery of bioassays and chemically analyzed to obtain toxicity and chemical profiles, respectively.

Exposure to endocrine disrupting chemicals perturbs lipid metabolism and circadian rhythms.

A growing body of evidence indicates that exposure to environmental chemicals can contribute to the etiology of obesity by inappropriately stimulating adipogenesis as well as perturbing lipid metabolism and energy balance. One potential mechanism by which chemical exposure can influence lipid metabolism is through disturbance of circadian rhythms, endogenously-driven cycles of roughly 24hr in length that coordinate biochemical, physiological, and behavioral processes in all organisms. Here we show for the first time that exposure to endocrine disrupting compounds (EDCs), including the pesticide tributyltin, two commercial flame retardants, and a UV-filter chemical found in sunscreens, can perturb both circadian clocks and lipid metabolism in vertebrates.

Enhanced uptake of BPA in the presence of nanoplastics can lead to neurotoxic effects in adult zebrafish.

Plastic particles have been proven to be abundant in the aquatic environment, raising concerns about their potential toxic effects. In the present study, we determined the bioaccumulation potential of bisphenol A (BPA) in adult zebrafish (Danio rerio) in the absence and presence of nano-sized plastic particles (nanoplastics, NPPs). Results show that BPA can accumulate in the viscera, gill, head and muscle of zebrafish with 85, 43, 20, and 3μg/g ww after 1d exposure.

Bisphenol A alternatives in thermal paper from the Netherlands, Spain, Sweden and Norway. Screening and potential toxicity.

Thermal paper contains potentially toxic additives, such as bisphenol A (BPA), as a common color developer. Because of its known endocrine disrupting effects, structural analogues to BPA, such as bisphenol S (BPS), D-8 and Pergafast 201, have been used as alternatives, but little is known about the presence and toxicological effects of alternatives other than BPS. In this study, thermal paper is screened by direct probe ambient mass spectrometry (rapid pre-screening method not requiring sample preparation) and by liquid chromatography (LC) with high resolution time-of flight (TOF-MS) mass spectrometry.

Effects of Hydroxylated Polybrominated Diphenyl Ethers in Developing Zebrafish Are Indicative of Disruption of Oxidative Phosphorylation.

Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) have been detected in humans and wildlife. Using in vitro models, we recently showed that OH-PBDEs disrupt oxidative phosphorylation (OXPHOS), an essential process in energy metabolism. The goal of the current study was to determine the in vivo effects of OH-PBDE reported in marine wildlife.

Fishing for contaminants: identification of three mechanism specific transcriptome signatures using Danio rerio embryos.

In ecotoxicology, transcriptomics is an effective way to detect gene expression changes in response to environmental pollutants. Such changes can be used to identify contaminants or contaminant classes and can be applied as early warning signals for pollution. To do so, it is important to distinguish contaminant-specific transcriptomic changes from genetic alterations due to general stress.

Determination of monoamine neurotransmitters in zebrafish (Danio rerio) by gas chromatography coupled to mass spectrometry with a two-step derivatization.

A sensitive analytical method for the determination of monoamine neurotransmitters (MNTs) in zebrafish larvae was developed using gas chromatography coupled to mass spectrometry. Six MNTs were selected as target compounds for neurotoxicity testing. MNTs underwent a two-step derivatization with hexamethyldisilazane (HDMS) for O-silylation followed by N-methyl-bis-heptafluorobutyramide (MBHFBA) for N-perfluoroacylation.

Lmx1b is required for the glutamatergic fates of a subset of spinal cord neurons.

Background: Alterations in neurotransmitter phenotypes of specific neurons can cause imbalances in excitation and inhibition in the central nervous system (CNS), leading to diseases. Therefore, the correct specification and maintenance of neurotransmitter phenotypes is vital. As with other neuronal properties, neurotransmitter phenotypes are often specified and maintained by particular transcription factors.

Alterations in locomotor activity of feeding zebrafish larvae as a consequence of exposure to different environmental factors.

Behavioral studies are important tools for understanding the development and pathology of neurological diseases. Zebrafish are an emerging alternative model in behavioral and neurological studies as the behavioral repertoire of zebrafish (Danio rerio) is similar to humans, and nervous system structures and functions are highly conserved. In this study, we investigated alterations in day/night locomotor activity of free swimming, feeding wild-type zebrafish larvae (8-15dpf) due to changes in the rhythm of light/dark cycles or caloric content of food.

Changes in Neurotransmitter Profiles during Early Zebrafish (Danio rerio) Development and after Pesticide Exposure.

During early development, neurotransmitters are important stimulants for the development of the central nervous system. Although the development of different neuronal cell types during early zebrafish (Danio rerio) development is well-studied, little is known of the levels of neurotransmitters, their precursors and metabolites during development, and how these levels are affected by exposure to environmental contaminants. A method based on hydrophilic interaction liquid chromatography coupled to tandem mass spectrometry has been applied for the first time to zebrafish embryos and larvae to study five neurotransmitter systems in parallel, including the dopaminergic-andrenergic, glutaminergic-GABAnergic, serotoninergic, histaminergic, and cholinergic systems.

Anthropogenic and naturally produced brominated substances in Baltic herring (Clupea harengus membras) from two sites in the Baltic Sea.

In the eutrophicated Baltic Sea, several naturally produced hydroxylated polybrominated diphenyl ethers (OH-PBDEs) have been found in marine biota. OH-PBDEs are toxic to adult and developing zebrafish and shown to be potent disruptors of oxidative phosphorylation (OXPHOS). Disturbed OXPHOS can result in altered energy metabolism and weight loss.