A5020112949- Contact Dermatitis and Allergies
- Effects and risks of endocrine disrupting chemicals
- Animal testing and alternatives
- Plant Toxicity and Pharmacological Properties
- Advancements in Transdermal Drug Delivery
- Skin Protection and Aging
- Antimicrobial agents and applications
- Pesticide Exposure and Toxicity
- Immunotoxicology and immune responses
- Occupational exposure and asthma
- Dermatology and Skin Diseases
- Carcinogens and Genotoxicity Assessment
- Neonatal Respiratory Health Research
- Infant Nutrition and Health
- Allergic Rhinitis and Sensitization
- Pharmacogenetics and Drug Metabolism
- Poisoning and overdose treatments
- Infant Development and Preterm Care
- Environmental Toxicology and Ecotoxicology
- Statistical Methods in Clinical Trials
- Botanical Research and Chemistry
- Plant Surface Properties and Treatments
- Computational Drug Discovery Methods
- Gene expression and cancer classification
- Health Systems, Economic Evaluations, Quality of Life
Procter & Gamble (United States)
2013-2024
Procter & Gamble (United Kingdom)
2021
Liverpool John Moores University
2018
Environmental Protection Agency
2017
Skin protein reactivity is a well established key step in the development of skin sensitization. Understanding relationship between chemical's ability to react with or modify and sensitization has led Direct Peptide Reactivity Assay (DPRA) our laboratory. A current limitation DPRA that it cannot readily measure pro-hapten chemical sensitizers. Pro-haptens are sensitizers not directly reactive must be bioactivated vivo form an electrophilic intermediate(s). Results from this work demonstrate...
To establish further a practical quantitative in chemico reactivity assay for screening contact allergens, lysine peptide was incorporated into liquid chromatography and tandem mass spectrometry–based assessments of hapten pre-/pro-hapten chemical sensitizers. Loss determined following 24 h coincubation with test using concentration-response study design. A total 70 chemicals were tested discrete reactions cysteine or peptide, the presence absence horseradish peroxidase-hydrogen peroxide...
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...
Approaches to assess the role of absorption, metabolism and excretion cosmetic ingredients that are based on integration different in vitro data important for their safety assessment, specifically as it offers an opportunity refine assessment. In order estimate systemic exposure (AUC) aromatic amine hair dyes following typical product application conditions, skin penetration epidermal metabolic conversion parent compound was assessed human explants keratinocyte (HaCaT) hepatocyte cultures....
This paper reports on the major contributions and results of 2nd International Workshop Pyrrolizidine Alkaloids held in September 2020 Kaiserslautern, Germany. alkaloids are among most relevant plant toxins contaminating food, feed, medicinal products origin. Hundreds PA congeners with widespread occurrence known, thousands plants assumed to contain PAs. Due certain PAs' pronounced liver toxicity carcinogenicity, their phytomedicines has raised serious human health concerns. is particularly...
A novel approach was developed to help characterize the biokinetics of cosmetic ingredient, phenoxyethanol, assess safety parent and its major stable metabolite. In first step this non-animal tiered approach, primary human hepatocytes were used confirm or refute in silico predicted metabolites, elucidate intrinsic clearance phenoxyethanol. key result identification metabolite, phenoxyacetic acid (PAA), exposure which kidney subsequently far exceed that phenoxyethanol blood other tissues....
Physiologically based pharmacokinetic (PBPK) models are developed from compound‐independent information to describe important anatomical and physiological characteristics of an individual or population interest. Modeling pediatric populations is challenging because the rapid changes that occur during growth, particularly in first few weeks months after birth. Neonates who born premature pose several unique challenges PBPK model development. To provide appropriate descriptions for body weight...
Systemic disposition of dermally applied chemicals is often formulation-dependent. Rapid evaporation the vehicle can result in crystallization active compounds, limiting their degree skin penetration. In addition, choice affect permeant’s penetration into stratum corneum. The aim this study to build a predictive, mechanistic, dermal absorption model that accounts for vehicle-specific effects on kinetics permeant transport skin. An existing extended explicitly include effect volatility over...
Sunscreen products constitute two distinct categories. Recreational sunscreens protect against high-intensity, episodic sun exposure, often applied over the entire body. In contrast, facial sunscreen are designed for sub-erythemal, low-intensity daily exposure. Such different exposures necessitate distinctive product safety assessments. Building on earlier methods predicting dermal disposition, a mechanistic model was developed to simulate plasma concentrations of seven organic active...
The European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) Strategy Document on Toxicokinetics (TK) outlines strategies enable prediction of systemic toxicity by applying new approach methodologies (NAM). central feature the strategy focuses using physiologically-based kinetic (PBK) modelling integrate data generated in vitro and silico methods absorption, distribution, metabolism, excretion (ADME) humans predicting whole-body TK behaviour, environmental...
A peptide reactivity assay with an activation component was developed for use in screening chemicals skin sensitization potential. horseradish peroxidase-hydrogen peroxide (HRP/P) oxidation system incorporated into the characterizing of hapten and pre-/prohapten sensitizers. The assay, named Peroxidase Peptide Reactivity Assay (PPRA) had a predictive accuracy 83% (relative to local lymph node assay) original protocol prediction model. However, apparent false positives attributed cysteine...
Physiologically based pharmacokinetic (PBPK) models of skin absorption are a powerful resource for estimating drug delivery and chemical risk dermatological products. This paper presents PBPK workflow the quantification mechanistic determinants permeability use these quantities in prediction novel contexts. A state-of-the-art model dermal was programmed into an open-source modeling framework. sensitivity analysis performed to identify uncertain compound-specific, individual-specific,...