scholarly journals A Next-Generation Risk Assessment Case Study for Coumarin in Cosmetic Products

2020 ◽  
Vol 176 (1) ◽  
pp. 236-252 ◽  
Author(s):  
Maria T Baltazar ◽  
Sophie Cable ◽  
Paul L Carmichael ◽  
Richard Cubberley ◽  
Tom Cull ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Biological Effects ◽  
In Vitro Assays ◽  
Next Generation ◽  
Animal Testing ◽  
Immunomodulatory Effects ◽  
Margin Of Safety

Abstract Next-Generation Risk Assessment is defined as an exposure-led, hypothesis-driven risk assessment approach that integrates new approach methodologies (NAMs) to assure safety without the use of animal testing. These principles were applied to a hypothetical safety assessment of 0.1% coumarin in face cream and body lotion. For the purpose of evaluating the use of NAMs, existing animal and human data on coumarin were excluded. Internal concentrations (plasma Cmax) were estimated using a physiologically based kinetic model for dermally applied coumarin. Systemic toxicity was assessed using a battery of in vitro NAMs to identify points of departure (PoDs) for a variety of biological effects such as receptor-mediated and immunomodulatory effects (Eurofins SafetyScreen44 and BioMap Diversity 8 Panel, respectively), and general bioactivity (ToxCast data, an in vitro cell stress panel and high-throughput transcriptomics). In addition, in silico alerts for genotoxicity were followed up with the ToxTracker tool. The PoDs from the in vitro assays were plotted against the calculated in vivo exposure to calculate a margin of safety with associated uncertainty. The predicted Cmax values for face cream and body lotion were lower than all PoDs with margin of safety higher than 100. Furthermore, coumarin was not genotoxic, did not bind to any of the 44 receptors tested and did not show any immunomodulatory effects at consumer-relevant exposures. In conclusion, this case study demonstrated the value of integrating exposure science, computational modeling and in vitro bioactivity data, to reach a safety decision without animal data.

scholarly journals Safety Assessment and Biological Effects of a New Cold Processed SilEmulsion for Dermatological Purpose

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Sara Raposo ◽  
Ana Salgado ◽  
Lídia Gonçalves ◽  
Pedro C. Pinto ◽  
Manuela Urbano ◽  
...  
Keyword(s):  
Safety Assessment ◽  
Biological Effects ◽  
Response Assessment ◽  
Skin Surface ◽  
Patch Tests ◽  
Hazard Exposure ◽  
Margin Of Safety ◽  
Skin Surface Lipids

It is of crucial importance to evaluate the safety profile of the ingredients used in dermatological emulsions. A suitable equilibrium between safety and efficacy is a pivotal concern before the marketing of a dermatological product. The aim was to assess the safety and biological effects of a new cold processed silicone-based emulsion (SilEmulsion). The hazard, exposure, and dose-response assessment were used to characterize the risk for each ingredient. EpiSkin assay and human repeat insult patch tests were performed to compare the theoretical safety assessment toin vitroandin vivodata. The efficacy of the SilEmulsion was studied using biophysical measurements in human volunteers during 21 days. According to the safety assessment of the ingredients, 1,5-pentanediol was an ingredient of special concern since its margin of safety was below the threshold of 100 (36.53). EpiSkin assay showed that the tissue viability after the application of the SilEmulsion was 92 ± 6% and, thus considered nonirritant to the skin. The human studies confirmed that the SilEmulsion was not a skin irritant and did not induce any sensitization on the volunteers, being safe for human use. Moreover, biological effects demonstrated that the SilEmulsion increased both the skin hydration and skin surface lipids.

scholarly journals Evaluation of the Biocompatibility and Endothelial Differentiation Capacity of Mesenchymal Stem Cells by Polyethylene Glycol Nanogold Composites

Polymers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 4265
Author(s):  
Huey-Shan Hung ◽  
Yi-Chin Yang ◽  
Wei-Chien Kao ◽  
Chun-An Yeh ◽  
Kai-Bo Chang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Polyethylene Glycol ◽  
Au Nanoparticles ◽  
Biological Effects ◽  
In Vitro Assays ◽  
Endothelial Differentiation ◽  
Vascular Regeneration

Cardiovascular Diseases (CVDs) such as atherosclerosis, where inflammation occurs in the blood vessel wall, are one of the major causes of death worldwide. Mesenchymal Stem Cells (MSCs)-based treatment coupled with nanoparticles is considered to be a potential and promising therapeutic strategy for vascular regeneration. Thus, angiogenesis enhanced by nanoparticles is of critical concern. In this study, Polyethylene Glycol (PEG) incorporated with 43.5 ppm of gold (Au) nanoparticles was prepared for the evaluation of biological effects through in vitro and in vivo assessments. The physicochemical properties of PEG and PEG–Au nanocomposites were first characterized by UV-Vis spectrophotometry (UV-Vis), Fourier-transform infrared spectroscopy (FTIR), and Atomic Force Microscopy (AFMs). Furthermore, the reactive oxygen species scavenger ability as well as the hydrophilic property of the nanocomposites were also investigated. Afterwards, the biocompatibility and biological functions of the PEG–Au nanocomposites were evaluated through in vitro assays. The thin coating of PEG containing 43.5 ppm of Au nanoparticles induced the least platelet and monocyte activation. Additionally, the cell behavior of MSCs on PEG–Au 43.5 ppm coating demonstrated better cell proliferation, low ROS generation, and enhancement of cell migration, as well as protein expression of the endothelialization marker CD31, which is associated with angiogenesis capacity. Furthermore, anti-inflammatory and endothelial differentiation ability were both evaluated through in vivo assessments. The evidence demonstrated that PEG–Au 43.5 ppm implantation inhibited capsule formation and facilitated the expression of CD31 in rat models. TUNEL assay also indicated that PEG–Au nanocomposites would not induce significant cell apoptosis. The above results elucidate that the surface modification of PEG–Au nanomaterials may enable them to serve as efficient tools for vascular regeneration grafts.

Chloro-s-triazenes – toxicokinetic, toxicodynamic, human exposure, and regulatory considerations

2021 ◽  
Vol 22 ◽  
Author(s):  
Khaled Abass ◽  
Olavi Pelkonen ◽  
Arja Rautio
Keyword(s):  
Risk Assessment ◽  
Metabolic Pathways ◽  
Human Exposure ◽  
Biological Effects ◽  
Active Compounds ◽  
Structure Activity ◽  
Toxicological Risk ◽  
Toxicological Risk Assessment

: Chloro-s-triazenes - atrazine, cyanazine, propazine, simazine, and terbuthylazine - are structurally similar herbicides, differing only in specific s-triazine 4- and 6-N alkyl substituents. It is generally regarded that their toxicokinetics, including metabolic pathways, biological effects and toxicities, also share more similar features than differences. Consequently, it is useful to compare their characteristics to potentially find useful structure-activity relationships or other similarities or differences regarding different active compounds, their metabolites, and biological effects, including toxic outcomes. The ultimate goal of these exercises is to apply the knowledge summarized, as far as it is possible regarding a patchy and often inadequate database, to cross the in vitro-in vivo and animal-human borders and integrate the available data to enhance toxicological risk assessment for the benefit of humans and ecosystems.

scholarly journals A retrospective analysis to explore the applicability of fish biomarkers and sediment bioassays along contaminated salinity transects

2009 ◽  
Vol 66 (10) ◽  
pp. 2089-2105 ◽  
Author(s):  
Cor A. Schipper ◽  
Joost Lahr ◽  
Paul J. van den Brink ◽  
Steve G. George ◽  
Peter-Diedrich Hansen ◽  
...  
Keyword(s):  
Retrospective Analysis ◽  
Large Scale ◽  
Biological Effects ◽  
In Vitro Assays ◽  
Multivariate Statistical ◽  
Large Scale Field ◽  
Hepatic Metallothionein ◽  
Fish Biomarkers

Abstract Schipper, C. A., Lahr, J., van den Brink, P. J., George, S. G., Hansen, P-D., da Silva de Assis, H. C., van der Oost, R., Thain, J. E., Livingstone, D., Mitchelmore, C., van Schooten, F-J., Ariese, F., Murk, A. J., Grinwis, G. C. M., Klamer, H., Kater, B. J., Postma, J. F., van der Werf, B., and Vethaak, A. D. 2009. A retrospective analysis to explore the applicability of fish biomarkers and sediment bioassays along contaminated salinity transects. – ICES Journal of Marine Science, 66: 2089–2105. Biological-effects monitoring in estuarine environments is complex as a result of strong gradients and fluctuations in salinity and other environmental conditions, which may influence contaminant bioavailability and the physiology and metabolism of the organisms. To select the most robust and reliable biological-effect methods for monitoring and assessment programmes, a large-scale field study was conducted in two estuarine transects in the Netherlands. The locations ranged from heavily polluted harbour areas (the ports of Rotterdam and Amsterdam) to cleaner coastal and freshwater sites. Assessment methods used included a variety of biomarkers in flounder (Platichthys flesus) and a range of in vitro (sediment extracts) and in vivo bioassays. Multivariate statistical analysis was applied to investigate correlations and relationships between various biological effects and contaminant levels in flounder liver or sediments. Several biological methods seemed to be too much affected by salinity differences for routine use in estuaries. The most discriminative biomarkers in the study were hepatic metallothionein content and biliary 1-OH pyrene in fish. Mechanism-based in vitro assays DR-CALUX and ER-CALUX applied to sediment extracts for screening of potential toxicity were much more responsive than in vivo bioassays with macro-invertebrates using survival as an endpoint.

Assuring Consumer Safety without Animal Testing: A Feasibility Case Study for Skin Sensitisation

2008 ◽  
Vol 36 (5) ◽  
pp. 557-568 ◽  
Author(s):  
Gavin Maxwell ◽  
Maja Aleksic ◽  
Aynur Aptula ◽  
Paul Carmichael ◽  
Julia Fentem ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Conceptual Framework ◽  
New Technologies ◽  
The European Union ◽  
Animal Testing ◽  
Safety Risk ◽  
Skin Sensitisation ◽  
Consumer Safety

Allergic Contact Dermatitis (ACD; chemical-induced skin sensitisation) represents a key consumer safety endpoint for the cosmetics industry. At present, animal tests (predominantly the mouse Local Lymph Node Assay) are used to generate skin sensitisation hazard data for use in consumer safety risk assessments. An animal testing ban on chemicals to be used in cosmetics will come into effect in the European Union (EU) from March 2009. This animal testing ban is also linked to an EU marketing ban on products containing any ingredients that have been subsequently tested in animals, from March 2009 or March 2013, depending on the toxicological endpoint of concern. Consequently, the testing of cosmetic ingredients in animals for their potential to induce skin sensitisation will be subject to an EU marketing ban, from March 2013 onwards. Our conceptual framework and strategy to deliver a non-animal approach to consumer safety risk assessment can be summarised as an evaluation of new technologies (e.g. ‘omics’, informatics), leading to the development of new non-animal ( in silico and in vitro) predictive models for the generation and interpretation of new forms of hazard characterisation data, followed by the development of new risk assessment approaches to integrate these new forms of data and information in the context of human exposure. Following the principles of the conceptual framework, we have been investigating existing and developing new technologies, models and approaches, in order to explore the feasibility of delivering consumer safety risk assessment decisions in the absence of new animal data. We present here our progress in implementing this conceptual framework, with the skin sensitisation endpoint used as a case study.

Peptide Binding Identifies an ERα Conformation That Generates Selective Activity in Multiple In Vitro Assays

2005 ◽  
Vol 10 (6) ◽  
pp. 590-598 ◽  
Author(s):  
Christopher J. Larson ◽  
Deborah L. Osburn ◽  
Katherine Schmitz ◽  
Leslie Giampa ◽  
Shau-Ming Mong ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Biological Effects ◽  
Peptide Binding ◽  
In Vitro Assays ◽  
Response Elements ◽  
Estrogen Response ◽  
Estrogen Response Elements ◽  
In Vivo Effects

Drugs such as tamoxifen, which act at the estrogen receptor (ER), have very different in vitro and in vivo effects from those of the native hormone. Previous research has established that different ligands induce distinct conformational changes in the ER, thus affecting the interactions of the receptor with cell-specific coactivating or corepressing proteins (cofactors) and estrogen response elements (EREs), thus potentially driving differing biological effects. Affinity-selected peptides have been used to probe the conformational changes that occur within the ER upon binding various ligands. In this study, the authors characterize the ability of several peptides to be recruited to liganded ER under cellular conditions. Approximating ER conformation via recruitment of this peptide to the ER is concluded to be a better predictor of the agonist nature of an ER ligand under these different cellular contexts than is a canonical cotransfection transactivation assay.

scholarly journals Current Strategies in Assessment of Nanotoxicity: Alternatives to In Vivo Animal Testing

2021 ◽  
Vol 22 (8) ◽  
pp. 4216
Author(s):  
Hung-Jin Huang ◽  
Yu-Hsuan Lee ◽  
Yung-Ho Hsu ◽  
Chia-Te Liao ◽  
Yuh-Feng Lin ◽  
...  
Keyword(s):  
In Silico ◽  
Biological Effects ◽  
Animal Experiments ◽  
Quantitative Structure Activity Relationship ◽  
Alternative Methods ◽  
Animal Testing ◽  
Qsar Modeling ◽  
Experimental Animals

Millions of experimental animals are widely used in the assessment of toxicological or biological effects of manufactured nanomaterials in medical technology. However, the animal consciousness has increased and become an issue for debate in recent years. Currently, the principle of the 3Rs (i.e., reduction, refinement, and replacement) is applied to ensure the more ethical application of humane animal research. In order to avoid unethical procedures, the strategy of alternatives to animal testing has been employed to overcome the drawbacks of animal experiments. This article provides current alternative strategies to replace or reduce the use of experimental animals in the assessment of nanotoxicity. The currently available alternative methods include in vitro and in silico approaches, which can be used as cost-effective approaches to meet the principle of the 3Rs. These methods are regarded as non-animal approaches and have been implemented in many countries for scientific purposes. The in vitro experiments related to nanotoxicity assays involve cell culture testing and tissue engineering, while the in silico methods refer to prediction using molecular docking, molecular dynamics simulations, and quantitative structure–activity relationship (QSAR) modeling. The commonly used novel cell-based methods and computational approaches have the potential to help minimize the use of experimental animals for nanomaterial toxicity assessments.

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