A5026959014- Effects and risks of endocrine disrupting chemicals
- Animal testing and alternatives
- Carcinogens and Genotoxicity Assessment
- Pharmacogenetics and Drug Metabolism
- Pesticide Exposure and Toxicity
- Contact Dermatitis and Allergies
- Drug Transport and Resistance Mechanisms
- Advancements in Transdermal Drug Delivery
- Liver physiology and pathology
- Agricultural safety and regulations
- Drug-Induced Hepatotoxicity and Protection
- Computational Drug Discovery Methods
- Skin Protection and Aging
- 3D Printing in Biomedical Research
- Pancreatic function and diabetes
- Pesticide Residue Analysis and Safety
- Immunotoxicology and immune responses
- Dermatology and Skin Diseases
- Insect and Pesticide Research
- Phytoestrogen effects and research
- Organ Transplantation Techniques and Outcomes
- Chemical Safety and Risk Management
- Plant Surface Properties and Treatments
- Pluripotent Stem Cells Research
- Garlic and Onion Studies
Scientific Research and Development (Germany)
2009-2025
Cosmetics Europe
2016-2024
Procter & Gamble (United States)
2021
Medicyte (Germany)
2012-2013
Beiersdorf (Germany)
2013
Institute for In Vitro Sciences
2002-2006
Merck (Germany)
2000-2003
Abstract: The 7th Amendment to the EU Cosmetics Directive prohibits use of animals in cosmetic testing for certain endpoints, such as genotoxicity. Therefore, skin vitro models have replace chemical vivo . However, metabolic competence neither human nor alternative has so far been fully characterized, although is first‐pass organ accidentally or purposely (cosmetics and pharmaceuticals) applied chemicals. Thus, there an urgent need understand xenobiotic‐metabolizing capacities compare these...
This paper presents a 10-step read-across (RAX) framework for use in cases where threshold of toxicological concern (TTC) approach to cosmetics safety assessment is not possible. RAX builds on established approaches that have existed more than two decades using chemical properties and silico toxicology predictions, by further substantiating hypotheses similarity substances, integrating new methodologies (NAM) the biological kinetic domains. NAM include types data observations from, example,...
1: The metabolism by HepG2 cell from two sources (M1, M2) of 12 substrates is reported: ethoxyresorufin, ethoxycoumarin, testosterone, tolbutamide, chlorzoxazone, dextromethorphan, phenacetin, midazolam, acetaminophen, hydroxycoumarin, p-nitrophenol and 1-chloro-2,4-dinitrobenzene (CDNB), a pharmaceutical compound, EMD68843. 2: Activities varied markedly. Some were present in M1 (CYP1A, CYP2C9, CYP2E1) but absent M2. had more complete set Phase I enzymes than CYP1A2, CYP2D6, CYP2E1 CYP3A...
Several human skin models employing primary cells and immortalized cell lines used as monocultures or combined to produce reconstituted 3D constructs have been developed. Furthermore, these included in European genotoxicity sensitization/irritation assay validation projects. In order help interpret data, Cosmetics Europe (formerly COLIPA) facilitated research projects that measured a variety of defined phase I II enzyme activities created complete proteomic profile xenobiotic metabolizing...
Skin is important for the absorption and metabolism of exposed chemicals such as cosmetics or pharmaceuticals. The Seventh Amendment to EU Cosmetics Directive prohibits use animals cosmetic testing certain endpoints, genotoxicity; therefore, there an urgent need understand xenobiotic metabolizing capacities human skin compare these activities with reconstructed 3D models developed replace animal testing. We have measured Phase I enzyme cytochrome P450 (CYP) cyclooxygenase (COX) in ex vivo...
Abstract OECD test guideline 428 compliant protocol using human skin was used to the penetration of 56 cosmetic‐relevant chemicals. The finite doses (10 μL/cm 2 ) chemicals measured over 24 hours. dermal delivery (DD) (amount in epidermis, dermis and receptor fluid [RF]) ranged between 0.03 ± 0.02 72.61 8.89 μg/cm . DD seven comparable with vivo values. mainly accounted for by amount RF, although there were some exceptions, particularly low While variability due cell outliers donor...
A standard protocol was used to determine partition (K) and diffusion (D) coefficients in dermatomed human skin isolated layers for 50 compounds relevant cosmetics ingredients. K values were measured skin, dermis, whole epidermis, intact stratum corneum (SC), delipidized SC lipids by direct measurements of the radioactivity tissue layers/lipid component vs. buffer samples. D determinations made epidermis using a non-linear regression cumulative receptor fluid content radiolabeled compound,...
Parabens are esters of para-hydroxybenzoic acid that have been used as preservatives in many types products for decades including agrochemicals, pharmaceuticals, food and cosmetics. This illustrative case study with propylparaben (PP) demonstrates a 10-step read-across (RAX) framework practice. It aims at establishing proof-of-concept the value added by new approach methodologies (NAMs) use next-generation risk assessment (NGRA) order to assess consumer safety after exposure PP-containing In...
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,...
The need for alternative approaches to replace the in vivo rabbit Draize eye test evaluation of irritation cosmetic ingredients has been recognised by cosmetics industry many years. Extensive research lead development several assays, some which have undergone formal validation. Even though, date, no single vitro assay validated as a full replacement test, organotypic assays are accepted specific and limited regulatory purposes. Although not formally validated, other models used over decade...
For the assessment of genotoxic effects cosmetic ingredients, a number well-established and regulatory accepted in vitro assays are place. A caveat to use these is their relatively low specificity high rate false or misleading positive results. Due 7th amendment EU Cosmetics Directive ban on vivo genotoxicity testing for cosmetics that was enacted March 2009, it no longer possible conduct follow-up tests ingredients further assess relevance findings. COLIPA, European Association, has...
We have developed a novel technique which causes primary human hepatocytes to proliferate by transducing them with genes that upregulate their proliferation.Upcyte® did not form colonies in soft agar and are immortalised anchorage-independent cells. Confluent cultures expressed liver-specific proteins, produced urea stored glycogen.CYP activities were low but similar 5-day of hepatocytes. CYP1A2 CYP3A4 inducible; moreover, upcyte® predicted the vivo induction potencies known inducers using...
The xenobiotic metabolism of 4 in vitro human skin test systems (2D and 3D) was compared with that the native samples from which had been produced. In total 3 were investigated, each a different donor to exclude variability due gender, or tissue supplier. addition, cultures surrogate liver. Basal induced phase I II enzymes analyzed regarding gene/protein expression as well enzyme activity. distinctions between two dermal compartments (epidermis dermis) more noticeable than any variability....
The Cosmetics Europe (formerly COLIPA) Genotoxicity Task Force has driven and funded three projects to help address the high rate of misleading positives in vitro genotoxicity tests: completed "False Positives" project optimized current mammalian cell assays showed that predictive capacity micronucleus assay was improved dramatically by selecting more relevant cells sensitive toxicity measures. on-going "3D skin model" been developed is now validating use human reconstructed (RS) models...
As part of the safety assessment process, all industrial sectors employ genotoxicity test batteries, starting with well-established in vitro assays. However, these batteries have limited predictive capacity for vivo situation, which may result unnecessary follow-up testing or loss promising substances where animal tests are prohibited not desired. To address this, a project involving regulators, academia and industry was established to develop validate human skin-based assays topically...
This case study on the model substance caffeine demonstrates viability of a 10-step read-across (RAX) framework in practice. New approach methodologies (NAM), including RAX and physiologically-based kinetic (PBK) modelling were used to assess consumer safety caffeine. Appropriate animal systemic toxicity data from most relevant analogue while assuming that no suitable available for Based structural similarities, three primary metabolites target chemical (theophylline, theobromine...
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...