A5039656905- Computational Drug Discovery Methods
- Animal testing and alternatives
- Effects and risks of endocrine disrupting chemicals
- Contact Dermatitis and Allergies
- HER2/EGFR in Cancer Research
- Phytoestrogen effects and research
- Advancements in Transdermal Drug Delivery
- Microbial Natural Products and Biosynthesis
- Dermatology and Skin Diseases
- Garlic and Onion Studies
- Pharmaceutical studies and practices
- 14-3-3 protein interactions
- Quinazolinone synthesis and applications
- Health Systems, Economic Evaluations, Quality of Life
- Carcinogens and Genotoxicity Assessment
- Antibiotics Pharmacokinetics and Efficacy
- Chemistry and Chemical Engineering
- Biosimilars and Bioanalytical Methods
- Olfactory and Sensory Function Studies
- Pesticide Exposure and Toxicity
- Pharmacogenetics and Drug Metabolism
- Statistical Methods in Clinical Trials
- Optimal Experimental Design Methods
- Protein Degradation and Inhibitors
- Immunotoxicology and immune responses
Beiersdorf (Germany)
2020-2025
Martin Luther University Halle-Wittenberg
2016-2021
Luther University
2016
Francke Foundations
2016
With an increasing need to incorporate new approach methodologies (NAMs) in chemical risk assessment and the concomitant phase out animal testing, interpretation of vitro assay readouts for quantitative hazard characterisation becomes more important. Physiologically based kinetic (PBK) models, which simulate fate chemicals tissues body, play essential role extrapolating effect concentrations vivo bioequivalent exposures. As PBK-based testing approaches evolve, it will become standardise PBK...
We performed an ab initio next-generation risk assessment (NGRA) for a fragrance ingredient, benzyl salicylate (BSal), to demonstrate how cosmetic ingredients can be evaluated systemic toxicity endpoints based on non-animal approaches. New approach methodologies (NAMs) used predict the internal exposure included skin absorption assays, hepatocyte metabolism, and physiologically pharmacokinetic (PBPK) modeling, potential toxicodynamic effects were assessed using pharmacology profiling,...
Introduction: We performed an exposure-based Next Generation Risk Assessment case read-across study using New Approach Methodologies (NAMs) to determine the highest safe concentration of daidzein in a body lotion, based on its similarities with structural analogue, genistein. Two assumptions were: (1) is new chemical and dietary intake omitted; (2) only vitro data were used for daidzein, while legacy vivo genistein considered. Methods: The 10-step tiered approach evaluating systemic toxicity...
All cosmetic ingredients registered in Europe must be evaluated for their safety using non-animal methods. Microphysiological systems (MPS) offer a more complex higher tier model to evaluate chemicals. Having established skin and liver HUMIMIC Chip2 demonstrating how dosing scenarios impact the kinetics of chemicals, we investigated whether thyroid follicles could incorporated potential topically applied chemicals cause endocrine disruption. This combination models Chip3 is new; therefore,...
The first Stakeholder Network Meeting of the EU Horizon 2020-funded ONTOX project was held on 13–14 March 2023, in Brussels, Belgium. discussion centred around identifying specific challenges, barriers and drivers relation to implementation non-animal new approach methodologies (NAMs) probabilistic risk assessment (PRA), order help address issues rank them according their associated level difficulty. aims advance chemical humans, without use animal testing, by developing NAMs PRA line with...
The ADME TF aims to develop in silico skin penetration models using vitro human data for 25 chemicals solubilized wataer. Since there are widely differing opinions on different models, we evaluated 3 open source (DermWin™, CDC and the University of Surrey models) commercial (DSkin, SimCyp TCAT). Simulation cutaneous distribution used a finite dose exposure scenario. None adequately predicted amount chemical that evaporated. This was important since prediction dermal delivery (DD) improved...
Abstract Grouping of chemicals has been proposed as a strategy to speed up the screening and identification potential substances concern among broad chemical universe under REACH. Such grouping is usually based on shared structural features should only be used for prioritization objectives. However, additional considerations (as well similarity) are needed, e.g., mode action, metabolic pathways, reaction products physicochemical properties, when regulatory management measures considered...
Introduction : Epidemiological studies in children suggested that utero exposure to chlorpyrifos (CPF), an organophosphate insecticide, may cause developmental neurotoxicity (DNT). We applied quantitative vitro – vivo extrapolation (QIVIVE) based on concentration and non-choline esterase-dependent effects data combined with Benchmark dose (BMD) modelling predict oral maternal CPF during pregnancy leading fetal brain effect concentration. By comparing the results from epidemiological studies,...
Chemoinformatics has been successfully employed in safety assessment through various regulatory programs for which information from databases, as well predictive methodologies including computational methods, are accepted. One example is the European Union Cosmetics Products Regulations, Europe (CE) research activities non-animal methods have managed by Long Range Science Strategy (LRSS) program. The vision to use mechanistic aspects of existing New Approach Methodologies (NAMs), demonstrate...
Abstract As part of the safety assessment salicylate esters in cosmetics, we developed a metabolism factor based on vitro to vivo extrapolation (IVIVE) provide better estimation aggregate internal exposure common metabolite, salicylic acid. Optimal incubation conditions using human liver S9 were identified before measuring acid formation from 31 substances. Four control substances, not defined as but which could be mistaken such due their nomenclature, did form For remaining higher intrinsic...
Abstract Sensitivity analyses are important components of physiologically based pharmacokinetic (PBPK) model development and required by regulatory agencies for PBPK submissions. They assess the impact parametric uncertainty variability on estimates, aid optimization identifying parameters requiring calibration, enable testing assumptions within models. One‐at‐a‐time (OAT) sensitivity quantify a output in response to changes single parameter while holding others fixed. Global analysis (GSA)...
Ethical and legal considerations have led to increased use of non-animal methods evaluate the safety chemicals for human use. We describe development qualification a physiologically-based kinetics (PBK) model cosmetic UV filter ingredient, homosalate, support its without need generating further animal data. The intravenous (IV) rat PBK model, using PK-Sim
Abstract OECD test guideline compliant skin penetration studies, which also comply with the SCCS basic criteria, are lacking for genistein and daidzein. Therefore, we have measured their metabolism using ex vivo explants of fresh (i.e., metabolically viable) pig skin, frozen human Phenion full‐thickness (FT) models. Preliminary studies helped to define optimal experimental conditions. The dermal absorption 10 nmoles/cm 2 daidzein in ethanol was comparable all four A first‐pass glucuronide...
All cosmetic ingredients must be evaluated for their safety to consumers. In the absence of
With ongoing resistance problems against the marketed EGFR inhibitors having a quinazoline core scaffold there is need for development of novel modified and, thus, expected lower problems. An additional problem concerning inhibitor an observed heterodimerization with PDGFR-β that neutralises sole activity towards EGFR. We developed pyrimido[4,5-b]indoles varied substitution patterns at 4-anilino residue to evaluate their and inhibiting properties. identified dual both in nanomolar range...
Abstract In a read‐across assessment of the safety genistein and daidzein in cosmetic products, additional information was required to account for differences their systemic exposure after topical application typical body lotion formulation. Therefore, we measured penetration metabolism two doses (3 30 nmoles/cm 2 ) applied ethanol formulation fresh pig skin, frozen human PhenionFT models. Both chemicals readily penetrated all skin models when ethanol. The same sulfate glucuronide...
Novel 4-benzylamino benzo-anellated pyrrolo[2,3-b]pyridines have been synthesized with varied substitution patterns both at the molecular scaffold of ring and residue. With a structural similarity to substituted thieno[2,3-d]pyrimidines as epidermal growth factor receptor (EGFR) inhibitors, we characterized inhibition EGFR for our novel compounds. As heterodimerization gained certain interest mechanism cancer cells become resistant against protein kinase additionally measured insulin-like...
Abstract Natural product (NP)-derived drugs can be extracts, biological macromolecules, or purified small molecule substances. Small originally from NPs, represent semisynthetic molecules, natural fragments containing are fully synthetic molecules that mimic compounds. New NP-like entering the pharmaceutical market almost every year and reveal growing interests in application of fragment-based approaches for NPs. Thus, several NP databases were constructed to implemented drug design (FBDD)...