A5017357453- Neuroscience and Neural Engineering
- Pluripotent Stem Cells Research
- Anesthesia and Neurotoxicity Research
- Animal testing and alternatives
- Carcinogens and Genotoxicity Assessment
- Antifungal resistance and susceptibility
- 3D Printing in Biomedical Research
- Fungal Biology and Applications
- Medicinal Plants and Neuroprotection
- Plant Pathogens and Fungal Diseases
- Mycotoxins in Agriculture and Food
- Effects and risks of endocrine disrupting chemicals
- Synthesis and Characterization of Heterocyclic Compounds
- Advanced Breast Cancer Therapies
- Mycobacterium research and diagnosis
- Tissue Engineering and Regenerative Medicine
- Neurogenesis and neuroplasticity mechanisms
- Statistical Methods in Clinical Trials
- Tuberculosis Research and Epidemiology
- History and advancements in chemistry
- Synthesis and biological activity
- Peptidase Inhibition and Analysis
- Memory and Neural Mechanisms
- Pesticide Exposure and Toxicity
- Optimal Experimental Design Methods
Leibniz Institute of Environmental Medicine
2020-2025
Deutsche Lepra- und Tuberkulosehilfe
2008
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...
In the European regulatory context, rodent in vivo studies are predominant source of neurotoxicity information. Although they form a cornerstone neurotoxicological assessments, costly and topic ethical debate. While public expects chemicals products to be safe for developing mature nervous systems, considerable numbers commerce have not, or only limited extent, been assessed their potential cause neurotoxicity. As such, there is societal push toward replacement animal models with vitro...
On occasion of the DNT5 meeting in Konstanz, Germany (April-2024), participants brainstormed on future challenges concerning a regulatory implementation developmental neurotoxicity (DNT) vitro test battery (DNT-IVB). The five discussion topics below outline some key issues, opportunities and research directions for next several years: (1) How to contextualize DNT hazard with information potential maternal toxicity or other domains (non-DNT)? Several approaches how use cytotoxicity data from...
Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study
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)...
Proper brain development is based on the orchestration of key neurodevelopmental processes (KNDP), including formation and function neural networks. If at least one KNDP affected by a chemical, an adverse outcome expected. To enable higher testing throughput than guideline animal experiments, developmental neurotoxicity (DNT) in vitro battery (DNT IVB) comprising variety assays that model several KNDPs was set up. Gap analysis revealed need for human-based assay to assess network formation...
The currently accepted methods for neurotoxicity (NT) testing rely on animal studies. However, high costs and low throughput hinder their application large numbers of chemicals. To overcome these limitations, in vitro are being developed based human-induced pluripotent stem cells (hiPSC) that allow higher at lower costs. We applied six different protocols to generate 3D BrainSphere models acute NT evaluation. These include three media 2D neural induction two subsequent differentiation...
Abstract Proper brain development is based on the orchestration of key neurodevelopmental processes, including formation and function neural networks. If at least one process affected by a chemical, an adverse outcome expected. To allow higher testing throughput than guideline animal experiments, developmental neurotoxicity (DNT) in vitro battery (DNT IVB) has been set up that includes variety assays, which model several processes. Gap analyses DNT IVB revealed need human-based assay to...
The vertebrate nervous system is vulnerable to chemical toxicity and the widespread release of chemicals into environment outstrips capacity assess their safety. We devised a battery automated behavior assays in larval zebrafish (Danio rerio), 3R-compliant model amenable higher-throughput screens. captures stereotypical visual acoustic behaviors including habituation, form non-associative learning. Known pharmacological modulators habituation evoked distinct behavioral patterns. By screening...
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 currently accepted methods for neurotoxicity (NT) testing rely on animal studies. However, high costs and low throughput hinder their application large numbers of chemicals. To overcome these limitations, in vitro are developed which based human induced pluripotent stem cells (hiPSC) that allow higher at lower costs. We applied six different protocols to generate 3D BrainSphere models acute NT evaluation. These include three media 2D neural induction two subsequent...
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...