• International Journal of Stem Cells
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• v.17 no.2
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• pp.120-129
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• 2024

Recent amendments to regulatory frameworks have placed a greater emphasis on the utilization of in vitro testing platforms for preclinical drug evaluations and toxicity assessments. This requires advanced tissue models capable of accurately replicating liver functions for drug efficacy and toxicity predictions. Liver organoids, derived from human cell sources, offer promise as a reliable platform for drug evaluation. However, there is a lack of standardized quality evaluation methods, which hinders their regulatory acceptance. This paper proposes comprehensive quality standards tailored for liver organoids, addressing cell source validation, organoid generation, and functional assessment. These guidelines aim to enhance reproducibility and accuracy in toxicity testing, thereby accelerating the adoption of organoids as a reliable alternative or complementary tool to animal testing in drug development. The quality standards include criteria for size, cellular composition, gene expression, and functional assays, thus ensuring a robust hepatotoxicity testing platform.

• Interdisciplinary Bio Central
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• v.1 no.3
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• pp.10.1-10.5
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• 2009

Toxicity is usually investigated using a set of standardized animal-based studies which, unfortunately, fail to detect all compounds that induce human adverse events and do not provide detailed mechanistic information of observed toxicity. As an alternative to conventional toxicology, toxicogenomics takes advantage of currently advanced technologies in genomics, proteomics, metabolomics, and bioinformatics to gain a molecular level understanding of toxicity and to enhance the predictive power of toxicity testing in drug development and risk/safety assessment. In addition, there has been a renewed interest, particularly in various government agencies, to prioritize and/or supplement animal testing with a battery of mechanistically informative in vitro assays. This article provides a brief summary of the issues, challenges and lessons learned in these fields and discuss the ways forward to further advance toxicology using these technologies.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.26 no.1
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• pp.17-40
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• 2000

Cytotoxicity assays using artificial skins have been proposed as in vitro alternatives to minimize animal ocular and dermal irritation testing. Accordingly, the responses of artificial skins to the well-characterized chemical irritants toluene, glutaraldehyde, and sodium lauryl sulfate (SLS), and the nonirritant polyethylene glycol were studied. The evaluation of the irritating and non-irritating test chemicals was also compared with the responses observed in human dermal fibroblasts and human epidermal keratinocytes grown in a monolayer culture. The responses monitored included an MTT mitochondrial functionality assay. In order to better understand the local mechanisms involved in skin damage and repair, the production of several mitogenic proinflammatory mediators, interleukin-l$\alpha$, 12-HETE, and 15-HETE, was also investigated. Dose-dependent increases in the levels of かIn and the HETEs were observed in the underlying medium of the skin systems exposed to the two skin irritants, glutaraldehyde and SLS. The results of the present study show that both human artificial skins can be used as efficient in vitro testing models for the evaluation of skin toxicity and for screening contact skin irritancy.

• Toxicological Research
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• v.35 no.2
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• pp.201-207
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• 2019

Nanoxel-$PM^{TM}$ (Nanoxel) is a docetaxel-loaded methoxy-poly(ethylene glycol)-block-poly(D,L-lactide) (mPEG-PDLLA). This newly developed and marketed nanoformulation exhibits an improved pharmacokinetic profile, efficacy, and safety. Although the safety of Nanoxel to docetaxel as well as its bioequivalence must be clinically confirmed, all biological activities have not been examined in in vitro or in vivo studies. Here, the toxicity in a cultured cell system and the effects on blood cells were tested with Nanoxel and docetaxel. The in vitro cytotoxicity of Nanoxel was found to be comparable to or slightly lower than that of docetaxel depending on the concentrations tested or the cell types. Neither docetaxel nor Nanoxel induced erythrocytes hemolysis and produced reactive oxygen species up to $100{\mu}M$. However, Nanoxel was able to enhance the aggregatory response of platelets to collagen, whereas docetaxel attenuated such aggregation in a range of $50-100{\mu}M$, while thrombin-induced aggregation was not affected by either of them. Docetaxel or Nanoxel did not alter basal level of $Ca^{2+}$ and 5-hydroxytryptamine-evoked $Ca^{2+}$ transient in vascular smooth muscle cells. These results suggest that the mPEG-PDLLA micellar formulation alters the toxicological properties of docetaxel, and that extra cautions are needed when evaluating the safety of nanomedicine.

• Microbiology and Biotechnology Letters
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• v.32 no.3
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• pp.271-276
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• 2004

$\beta$-Immunan was proteoglycan obtained from mycelium of Ganoderma lucidum IY009. In this study, the protective effects of $\beta$-Immunan, against the CDDP induced in vitro cytotoxicity and in vivo renal toxicity, was measured. Concentration dependent cytotoxicities of CDDP in normal kidney cells (Vero, TCMK-l) were reduced by $\beta$-Immunan treatment. Increased renal toxicity factors, such as elevation of blood urea nitrogen (BUN) and serum creatinine, reduction of kidney weight and malonidialdehyde (MDA), by intraperitoneal administration of CDDP in rats was improved. These results indicated that $\beta$-Immunan have a protective effects against the CDDP induced renal toxicity, however, it needed to confirm the detailed mechanism for therapeutic effects.

• Proceedings of the Korean Society of Toxicology Conference
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• 2006.11a
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• pp.95-101
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• 2006

Compare to the toxicity tests using experimental animals, the GLP application and compliance in toxicity studies using cell culture systems may be less straightforward elucidated in the two documents published by the OECD Working Croup on GLP 'The Application of the GLP Principles to Short Term Studies (1999)' and 'The Application of the Principles of GLP to in vitro Studies (2004)' The object of this presentation is to show how to interpret the GLP principles and to apply with actual performances in a well known toxicity test using cell culture, chromosome aberration study. The presentation will cover test substance, test system (cell line), study environment management, documentation, quality assurance, and study protocol and report.

• International Journal of Stem Cells
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• v.17 no.2
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• pp.141-146
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• 2024

Recent advancements in organoid technology have led to a vigorous movement towards utilizing it as a substitute for animal experiments. Organoid technology offers versatile applications, particularly in toxicity testing of pharmaceuticals or chemical substances. However, for the practical use in toxicity testing, minimal guidance is required to ensure reliability and relevance. This paper aims to provide minimal guidelines for practical uses of kidney organoids derived from human pluripotent stem cells as a toxicity evaluation model in vitro.

• Toxicological Research
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• v.29 no.4
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• pp.263-278
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• 2013

The silkworm extract powder contain 1-deoxynojirimycin (DNJ), a potent ${\alpha}$-glycosidase inhibitor, has therapeutic potency against diabetes mellitus. Therefore, natural products containing DNJ from mulberry leaves and silkworm are consumed as health functional food. The present study was performed to evaluate the safety of the silkworm extract powder, a health food which containing the DNJ. The repeated toxicity studies and gentic toxicity studies of the silkworm extract powder were performed to obtain the data for new functional food approval in MFDS. The safety was evaluated by a single-dose oral toxicity study and a 90 day repeated-dose oral toxicity study in Sprague-Dawley rats. The silkworm extract powder was also evaluated for its mutagenic potential in a battery of genetic toxicity test: in vitro bacterial reverse mutation assay, in vitro chromosomal aberration test, and in vivo mouse bone marrow micronucleus assay. The results of the genetic toxicology assays were negative in all of the assays. The approximate lethal dose in single oral dose toxicity study was considered to be higher than 5000 mg/kg in rats. In the 90 day study, the dose levels were wet at 0, 500, 1000, 2000 mg/kg/day, and 10 animals/sex/dose were treated with oral gavage. The parameters that were monitored were clinical signs, body weights, food and water consumptions, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy findings, organ weights, and histopathological examination. No adverse effects were observed after the 90 day administration of the silkworm extract powder. The No-Observed-Adverse-Effect-Level (NOAEL) of silkworm extract powder in the 90 day study was 2000 mg/kg/day in both sexes, and no target organ was identified.

• Journal of Environmental Health Sciences
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• v.44 no.1
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• pp.31-43
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• 2018

Objectives: Effective genetic toxicology and molecular biology research techniques and strategies that are highly correlated with the carcinogenic inhalation toxicity test and related research are required. The aim of this study was to maximize the utilization of chemical substances to prevent workers' occupational diseases. Methods: We surveyed the literature, domestic and international references, and the status of relevant domestic and foreign professional organizations. Expert advisory opinions were reflected, and experts were consulted by participating in domestic and overseas academic conferences. Results: The current status of domestic and international genotoxic toxicity evaluation was examined through various documents from related organizations. Cell models for in vitro lung toxicology were investigated and summarized, and the human resources and performance results of genetic toxicity studies and pilot projects were compared and analyzed by holding an advisory meeting. We examined domestic and international genotoxicity guidelines and investigated new test methods for the development of genotoxicity and carcinogenicity. Ultimately, we described long-term future predictions, including the implementation of our researchers' recommendations and occupational genetic toxicology forecasts for future worker health protection. Conclusions: This research project aims to establish current genetic toxicology and molecular biology research techniques and strategies that can maximize the linkage with the carcinogenic inhalation toxicity test and research in the future. We expanded the study of genetic toxicity and establish a foundation forgenetic toxicity in accordance with research trends in Korea and abroad.

• Archives of Pharmacal Research
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• v.16 no.1
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• pp.62-67
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• 1993

A series of 12 pyrimidine derivatives were prepared and tested in vitro against growth, sporulation and nucleic acids of Fusarium oxysporum f. sp. lycopersici and Helminthosporium oryzae. Intorduction of thiazole ring together with two aryl groups to 2-aminopyrimidine induced drastic toxicity for both fungi. Pyrimidine derivatives with aryl groups were less toxic. Nitro groups were found to enhance the toxicity of the pyrimidine derivatives especially when substituted in ortho-position of the aryl groups. Inhibition of nudeic acids synthesis of both fungi was attributed mainly to the presence of thiazole ring.