A5067443701- Contact Dermatitis and Allergies
- Computational Drug Discovery Methods
- Animal testing and alternatives
- Dermatology and Skin Diseases
- Advancements in Transdermal Drug Delivery
- Effects and risks of endocrine disrupting chemicals
- Allergic Rhinitis and Sensitization
- Biosimilars and Bioanalytical Methods
- Phytoestrogen effects and research
- Immunotoxicology and immune responses
- Science, Research, and Medicine
- Carcinogens and Genotoxicity Assessment
- Occupational exposure and asthma
- Stress Responses and Cortisol
- 3D Printing in Biomedical Research
- Skin Protection and Aging
- Pesticide Exposure and Toxicity
- Drug-Induced Adverse Reactions
- Garlic and Onion Studies
- Circadian rhythm and melatonin
- Neuroendocrine regulation and behavior
- Asthma and respiratory diseases
- Vitamin C and Antioxidants Research
- Antibiotic Use and Resistance
- Antimicrobial agents and applications
Beiersdorf (Germany)
2014-2024
Unilever (United Kingdom)
2013
University of Münster
2006
Bernhard Nocht Institute for Tropical Medicine
2005
Abstract The neuropeptide hormone oxytocin ( OXT ) mediates a wide spectrum of tissue‐specific actions, ranging from cell growth, differentiation, sodium excretion to stress responses, reproduction and complex social behaviour. Recently, expression was detected in keratinocytes, but its receptor function are still unexplored human skin. Here, we showed that both expressed primary dermal fibroblasts keratinocytes. ‐induced dose‐dependent calcium fluxes types demonstrating the OXTR is...
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...
The retrochalcone licochalcone A (LicA) has previously been shown to possess antimicrobial and anti-inflammatory properties. In this study, we focused on pathways responsible for the antioxidative properties of LicA. vitro, LicA protected from oxidative stress mediated by reactive oxygen species (ROS) activating expression cytoprotective phase II enzymes. induced nuclear translocation NF-E2-related factor 2 (Nrf2) in primary human fibroblasts elevated enzymes heme oxygenase 1...
Chemical sensitization is an adverse immunologic response to chemical substances, inducing hypersensitivity in exposed individuals. Identifying sensitizers of great importance for chemical, pharmaceutical, and cosmetic industries, order prevent the use consumer products. Historically, have been assessed mainly by vivo methods, however, recently enforced European legislations urge promote development animal-free test methods able predict sensitizers. Recently, we presented a predictive...
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,...
Significant progress has been made in the development and validation of non-animal test methods for skin sensitization assessment. At present, three four key events Adverse Outcome Pathway (AOP) are assessable by OECD-accepted vitro methods. The fourth event describes immunological response draining lymph node where activated dendritic cells present major histocompatibility complex-bound chemically modified peptides to naive T cells, thereby priming proliferation antigen-specific cells....
The assessment of skin sensitisation is a key requirement in all regulated sectors, with the European Union's regulation cosmetic ingredients being most challenging, since it requires quantitative based on new approach methodologies (NAMs). To address this challenge, an in-depth and harmonised understanding NAMs fundamental to inform assessment. Therefore, we compiled database NAMs, vivo (human local lymph node assay) reference data. Here, expanded 41 substances highly relevant for industry....
Abstract We used TissUse's HUMIMIC Chip2 microfluidic model, incorporating reconstructed skin models and liver spheroids, to investigate the impact of consumer‐relevant application scenarios on metabolic fate hair dye, 4‐amino‐2‐hydroxytoluene (AHT). After a single topical or systemic AHT models, medium was analysed for parent metabolites over 5 days. The profile high dose (resulting in circuit concentration 100 μM based 100% bioavailability) same after 96‐well EpiDerm™ models. Additional...
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...
Skin sensitization potential or potency is an important end point in the safety assessment of new chemicals and chemical mixtures. Formerly, animal experiments such as local lymph node assay (LLNA) were main form assessment. Today, however, focus lies on development nonanimal testing approaches (i.e., vitro chemico assays) computational models. In this work, we investigate, based publicly available LLNA data, ability aggregated, Mondrian conformal prediction classifiers to differentiate...
The ability to predict the skin sensitization potential of small organic molecules is high importance development and safe application cosmetics, drugs pesticides. One most widely accepted methods for predicting this hazard local lymph node assay (LLNA). goal work was develop in silico models prediction that go beyond state art, with larger LLNA data sets and, importantly, a robust intuitive definition applicability domain, paired additional indicators reliability predictions. We explored...
Methylmalonyl‐CoA epimerase (MCE) is an enzyme involved in the propionyl‐CoA metabolism that responsible for degradation of branched amino acids and odd‐chain fatty acids. This pathway typically functions reversible conversion to succinyl‐CoA. The Caenorhabditis elegans genome contains a single gene encoding MCE ( mce‐1 ) corresponding 15 kDa protein. was expressed Escherichia coli enzymatic activity determined. Analysis protein expression pattern at both tissue subcellular level by...
In recent years, a number of machine learning models for the prediction skin sensitization potential small organic molecules have been reported and become available. These generally perform well within their applicability domains but, as result use molecular fingerprints other non-intuitive descriptors, interpretability existing is limited. The aim this work to develop strategy replace features by predicted outcomes bioassays. We show that such replacement indeed possible few ten...
Abstract The HUMMIC skin–liver Chip2 microphysiological system using EpiDerm™ and HepaRG stellate liver spheroids was used to evaluate the route‐specific metabolism toxicodynamic effects of genistein. Human‐relevant exposure levels were compared: 60 nM representing plasma concentration expected after topical application a cosmetic product 1 μM measured concentrations ingesting soya products. Genistein applied as single repeated and/or systemic doses. kinetics genistein its metabolites over 5...
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...
Abstract The HUMIMIC skin‐liver Chip2 microphysiological systems model using the epidermal model, EpiDerm™, was reported previously to mimic application route‐dependent metabolism of hair dye, 4‐amino‐2‐hydroxytoluene (AHT). Therefore, we evaluated use alternative skin models—SkinEthic™, EpiDermFT™ and PhenionFT™—for same purpose. In static incubations, AHT permeation similar SkinEthic™ EpiDerm™ models. Older Day 21 (D21) models with a thicker stratum corneum did not exhibit greater barrier...
Skin sensitisation is a critical adverse effect assessed to ensure the safety of compounds and materials exposed skin. Alongside development new approach methodologies (NAMs), defined approaches (DAs) have been established promote skin potency assessment by adopting integrating standardised in vitro, chemico, silico methods with specified data analysis procedures achieve reliable reproducible predictions. The incorporation additional NAMs could help increase accessibility flexibility. Using...