A5056325101- Anesthesia and Neurotoxicity Research
- Pluripotent Stem Cells Research
- Carcinogens and Genotoxicity Assessment
- Neurogenesis and neuroplasticity mechanisms
- Animal testing and alternatives
- Effects and risks of endocrine disrupting chemicals
- Toxic Organic Pollutants Impact
- 3D Printing in Biomedical Research
- Air Quality and Health Impacts
- Paleontology and Stratigraphy of Fossils
- Biological and pharmacological studies of plants
- Cell Image Analysis Techniques
- Zebrafish Biomedical Research Applications
- Biomedical Ethics and Regulation
- Climate Change and Health Impacts
- MicroRNA in disease regulation
- Infant Nutrition and Health
- Optimal Experimental Design Methods
- Birth, Development, and Health
- Aerospace Engineering and Control Systems
- Pesticide Exposure and Toxicity
- Neonatal Respiratory Health Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Statistical Methods in Clinical Trials
- Neonatal and fetal brain pathology
Leibniz Institute of Environmental Medicine
2018-2025
In this project we set up a human cell-based DNTin vitro testing strategy that is based on test methods with high readiness and data generated therefrom. The underwent afit-for-purpose evaluation considered four key elements: 1. system, 2. the exposure scheme, 3. assay analytical endpoint(s) 4. classification model. This battery was challenged 119 chemicals for which rich toxicological information available (for some of them also their DNT hazard). Testing performed in 5 systems measuring 10...
Developmental neurotoxicity (DNT) is a major safety concern for all chemicals of the human exposome. However, DNT data from animal studies are available only small percentage manufactured compounds. Test methods with higher throughput than current regulatory guideline methods, and improved relevance urgently needed. We therefore explored feasibility hazard assessment based on new approach (NAMs). An in vitro battery (IVB) was assembled ten individual NAMs that had been developed during past...
Abstract Due to their neurodevelopmental toxicity, flame retardants (FRs) like polybrominated diphenyl ethers are banned from the market and replaced by alternative FRs, organophosphorus that have mostly unknown toxicological profiles. To study we evaluated hazard of several FRs including phased-out FRs: 2,2′,4,4′-tetrabromodiphenylether (BDE-47), 2,2′,4,4′,5-pentabromodiphenylether (BDE-99), tetrabromobisphenol A, triphenyl phosphate, tris(2-butoxyethyl) phosphate its metabolite...
There is a call for paradigm shift in developmental neurotoxicity (DNT) evaluation, which demands the implementation of faster, more cost-efficient, and human-relevant test systems than current vivo guideline studies. Under umbrella Organisation Economic Co-operation Development (OECD), guidance document currently being prepared that instructs on regulatory use DNT vitro battery (DNT IVB) fit-for-purpose applications. One crucial issue OECD application methods validation, new approach (NAMs)...
Despite growing awareness of endocrine disrupting chemicals (EDCs), knowledge gaps remain regarding their effects on human brain development. EDC risk assessment focuses primarily EATS modalities (estrogens, androgens, thyroid hormones, and steroidogenesis), overlooking the broader range hormone receptors expressed in developing brain. This limits evaluation for potential to cause disruption-mediated developmental neurotoxicity (ED-DNT). The Neurosphere Assay, an vitro test method (DNT)...
Myelinating oligodendrocytes (OLs) establish saltatory nerve conduction during white matter development. Thus, interference with oligodendrogenesis leads to an adverse outcome on brain performance in the child due aberrant myelination. An intertwined network of hormonal, transcriptional and biosynthetic processes regulates OL development, thereby simultaneously creating various routes for environmental toxicants. The flame retardant tetrabromobisphenol A (TBBPA) is debated as endocrine...
Abstract Adverse outcome pathways (AOPs) are organized sequences of key events (KEs) that triggered by a xenobiotic-induced molecular initiating event (MIE) and summit in an adverse (AO) relevant to human or ecological health. The AOP framework causally connects toxicological mechanistic information with apical endpoints for application regulatory sciences. AOPs very useful link endophenotypic, cellular vitro health effects vivo. In the field developmental neurotoxicity (DNT), such can be...
Neurosphere cultures consisting of primary human neural stem/progenitor cells (hNPC) are used for studying the effects substances on early neurodevelopmental processes in vitro. Differentiating hNPCs migrate and differentiate into radial glia, neurons, astrocytes, oligodendrocytes upon plating a suitable extracellular matrix thus model development. In order to characterize alterations hNPC development, it is an essential task reliably identify cell type each migrated migration area...
Chinese herbal medicine (CHM) is used among pregnant women. However, the question of its safety during pregnancy remains unclear. The use these products relies on history data but there are specific toxicities like developmental neurotoxicity that clearly understudied. Here we zebfrafish embryo toxicity assay (ZEDTA) in combination with two behavioral assays: touch-evoked response and Light/Dark (L/D) transition to evaluate neuro/developmental three commonly CHM [Chinese name (abbreviation;...
Developmental neurotoxicity (DNT) is a major safety concern for all chemicals of the human exposome. However, DNT data from animal studies are available only small percentage manufactured compounds. Test methods with higher throughput than current regulatory guideline methods, and improved relevance urgently needed. We therefore explored feasibility hazard assessment based on new approach (NAMs). An in vitro battery (IVB) was assembled ten individual NAMs that had been developed during past...
Abstract The aim of this study was to develop a rabbit neurosphere culture characterize differences in basic processes neurogenesis induced by intrauterine growth restriction (IUGR). A novel vitro has been established using fresh or frozen neural progenitor cells from newborn (PND0) brains. After surgical IUGR induction pregnant rabbits and cesarean section 5 days later, both control groups were isolated directly cultured at −80°C. These spontaneously formed neurospheres after 7 culture....
Current acceptable chemical exposure levels (e.g., tolerable daily intake) are mainly based on animal experiments, which costly, time-consuming, considered non-ethical by many, and may poorly predict adverse outcomes in humans. To evaluate a method using human vitro data biological modeling to calculate an level through case study 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) developmental neurotoxicity (DNT). We reviewed the literature assays studying BDE-47-induced DNT. Using most sensitive...
Abstract In the field of hazard assessment, Benchmark concentrations (BMC) and their associated uncertainty are particular interest for regulatory decision making. The BMC estimation consists various statistical decisions to be made, which depend largely on factors such as experimental design assay endpoint features. current data practice, experimenter is often responsible analysis therefore relies software without being aware about default settings how they can impact outputs analysis. To...