英文摘要 |
Based on international experiences, achieving the goal of replacing experimental animal testing requires the establishment of multiple technologies and strategies to integrate these technologies effectively. Key areas of development include utilizing existing data, hazard prediction through in silico methods, developing alternative testing methods, and conducting risk assessments using New Approach Methodology (NAM). This project was structured around these four focus areas. In the first phase, we utilized 3 international databases and 2 Quantitative Structure–Activity Relationship (QSAR) models to collect or predict skin toxicity information on 43 organic compounds. The current information can identify about 53% and 63% of their skin irritation/corrosion and skin sensitization in 43 substances respectively. For others, it is recommended that in vitro tests or case studies be used to assess the hazards. In addition, the literature review indicates that in vitro-to-in vivo extrapolation (IVIVE) technology shows significant potential in toxicological research and has already been applied in both health and ecological assessments, with publicly available tools supporting its implementation. Although IVIVE faces challenges, such as uncertainties in the correlation between in vitro test results and in vivo biological responses, ongoing interdisciplinary collaboration is driving continuous advancements. IVIVE is expected to provide more reliable support for toxicological research in the future. To evaluate the feasibility of applying nanomaterials in existing in vitro tests for skin irritation/corrosion and skin sensitization, journal articles, Organisation for Economic Cooperation and Development (OECD) test guidelines, and International Organization for Standardization (ISO) documents related to nanomaterial pretreatment and testing were collected and reviewed. A draft of the "Standard Operating Procedures (SOP) for Nanomaterial Sample Preparation and Testing," was prepared. Considering the relevant guidance documents for toxicity assessment of nanomaterials, as well as trial results of applying OECD test guidelines to nanomaterials, two drafts were written for SOPs for nanomaterial skin irritation and corrosion testing, and three drafts for standard operating procedures for nanomaterial skin sensitization testing. Through in vitro experimental to fill gaps in toxicological information, data were provided on the physicochemical properties of five common nanomaterials, as well as the results for skin irritation/corrosion and skin sensitization based on tests of 10 substances in both solution and powder forms. For application in the future, further validation of different nanomaterials will be necessary, and the procedures should be adjusted as needed to optimize test results. To assess the regulatory acceptability of alternative testing methods for chemical substances, we referred to the latest alternative strategy of the 10th edition of Globally Harmonized System of Classification and Labelling of Chemicals (GHS) and found that our strategy of experimental animal reduction has been in line with international. For the parts that have not been adopted yet, we analyzed and proposed registration guideline modification suggestions based on our country's chemical substance registration framework. In addition, drawing on the experience of banning animal testing in cosmetics regulations in both our country and the European Union (EU), we evaluated the use of non-animal testing methods for submitting data on specific items in the registration of chemical substances in our country. We found that this approach is feasible, but supporting measures must be carefully designed, and exceptions should be reserved for certain situations. Finally, to promote the application of alternative testing methods in risk assessment, we reviewed chemical evaluation frameworks from the United States, OECD, and the EU, as well as related case studies. These frameworks prioritize exposure probability, validate toxicity hypotheses through targeted testing, and use IVIVE models to simulate exposure concentrations for establishing exposure limits. The literature reveals that the choice of alternative testing methods and the selection of model simulation parameters significantly impact the final assessment outcomes. In conclusion, this project achieved preliminary results in multiple technological areas. Future efforts should focus on integrating these technologies and strengthening collaboration among relevant government agencies in Taiwan.
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