Atla-Alternatives To Laboratory Animals最新文献

In Korea, Institutional Animal Care and Use Committees (IACUCs) have been legally required to apply the Three Rs principles (i.e. replacement, reduction and refinement) and undertake the ethical review of animal study protocols, since 2008. According to Korean law, each IACUC is required to appoint at least one lay member recommended by a non-governmental animal protection organisation, who participates in the ethical review process as part of this role. Despite the importance of the Three Rs and the ethical review process, limited information and practical resources are available for IACUC members in the Korean language, particularly for lay members who are inexperienced in animal experimentation. In January 2020, the Animal and Plant Quarantine Agency announced the funding for a six-month research project to develop guidance to assist IACUC members in carrying out effective and efficient protocol reviews in line with Korean legislative requirements. This funding was awarded for the production of two IACUC guidance documents - 'Guide for Animal Study Protocols' and 'Guide for the IACUC Lay Member' - which were published in December 2020. These guidance documents aim to foster the implementation of the Three Rs and provide practical resources for IACUC members, researchers and other relevant personnel. This paper describes the framework for animal use in Korea and the overall production of these two IACUC Guidance Documents.

Liver cancer is the third leading cause of cancer-related mortality, and hepatocellular carcinoma (HCC) is the most common form of liver cancer, and it usually occurs in the setting of chronic liver disease and cirrhosis. For patients with advanced HCC, systemic treatment is the first choice - however, resistance occurs frequently. Sorafenib was the first tyrosine kinase inhibitor approved for advanced HCC, and resistance to the therapy is a serious concern. When sorafenib therapy fails in a patient, it can be challenging to decide whether they can undergo a second-line therapy, and to determine which therapy they will be able to tolerate. Thus, physiologically relevant in vitro preclinical models are crucial for screening potential therapies, and 3-D tumour spheroids permit studies of tumour pathobiology. In this study, a drug-resistant 3-D tumour spheroid model was developed, based on sorafenib-resistant hepatocellular carcinoma cells, LX2 stellate cells and THP-1 monocytes. Model tumour spheroids that were formed with the sorafenib-resistant cells demonstrated lower diffusion of doxorubicin and exhibited increased resistance to regorafenib. Moreover, in the sorafenib-resistant spheroids, there was increased presence of CD68-positive cells and a reduction in inflammatory marker secretion. The sorafenib-resistant cell line-derived spheroids also showed a higher expression of FGF-19, PDGF-AA and GDF-15, which are known to be involved in malignancies. This multi-cell type spheroid model represents a potentially useful system to test drug candidates in a microenvironment that mimics the drug-resistant tumour microenvironment in HCC.

Human hair follicles traverse the epidermis and dermis, and are comprised of specialised cells including dermal papilla cells (DPCs). DPCs play a critical role in the development and growth of both hair and follicle structure. While exposure of DPCs to undiluted exogenous compounds is unlikely, exposure to diluted compounds is possible should dermal penetration occur. The goal of this study was to evaluate the impact on hair and scalp health following application of a hair care product. Due to the lack of standardised and validated test systems for evaluating hair follicle health, the HairSkin^® model, which uses intact human scalp samples, was adapted to evaluate hair follicle and scalp health. Similarly, the Franz diffusion cell assay and matrix-assisted laser desorption ionisation-Fourier transform ion cyclotron resonance (MALDI-FTICR) were adapted to evaluate dermal penetration. The results of this study demonstrate that application of the hair care product does not result in appreciable dermal penetration, suggesting that DPCs are unlikely to be exposed to undiluted product. Additionally, hair follicle health was not impacted following product application. While this study is exploratory, these results suggest that the combination of test systems utilised herein provides valuable insight and warrants further development and validation.

Animal testing has been prohibited for the safety assessment of cosmetic ingredients or finished products. Thus, alternative non-animal methods, followed by confirmatory clinical studies on human volunteers, should be used as the sole legally acceptable approach within the EU. The safety assessment of cosmetic products requires the involvement of multiple scientific disciplines, including analytical chemistry and biomedicine, as well as in chemico, in vitro and in silico toxicology. Recent data suggest that fragrance components may exert multiple adverse biological effects, e.g. cytotoxicity, skin sensitisation, (photo)genotoxicity, mutagenicity, reprotoxicity and endocrine disruption. Therefore, a pilot study was conducted with selected samples of fragrance-based products, such as deodorant, eau de toilette and eau de parfum, with the aim of integrating results from a number of alternative non-animal methods suitable for the detection of the following toxicological endpoints: cytotoxicity (with 3T3 Balb/c fibroblasts); skin sensitisation potential (in chemico method, DPRA); skin sensitisation potential (LuSens in vitro method, based on human keratinocytes); genotoxicity potential (in vitro Comet assay with 3T3 Balb/c cells); and endocrine disruption (in vitro YES/YAS assay). The presence of twenty-four specific known allergens in the products was determined by using GC-MS/MS. The strategies for estimation of the NOAEL of a mixture of allergens, which were proposed by the Scientific Committee on Consumer Products in their 'Opinion on Tea tree oil' document and by the Norwegian Food Safety Authority in their 'Risk Profile of Tea tree oil' report, were used as models for the NOAEL estimation of the mixtures of allergens that were identified in the individual samples tested in this study.

Since a return to in-office working after the extensive disruption caused by the COVID-19 pandemic and associated challenges, many conversations are still being had with regard to what the 'new normal' might look like in professional spaces and networks, and what lessons can be learnt from long periods of remote working. The regulation of animal research practice in the UK is no exception here and, like many other systems, it has been transformed by the increasingly recognised value of streamlining procedures through the use of virtual online spaces. In early October 2022, the author attended an AWERB-UK meeting in Birmingham (convened by the RSPCA, LAVA, LASA and IAT), which focused on the induction, training and Continuing Professional Development (CPD) opportunities for Animal Welfare and Ethical Review Body (AWERB) members. This comment article reflects on this meeting and raises some interesting questions surrounding animal research governance in an evolving online era, specifically the associated ethical and welfare dimensions.