環境資源報告成果查詢系統

化學物質替代測試方法多元應用與評估計畫

中文摘要 參考國際經驗,動物試驗替代方案通常需發展多元技術,並建立技術間互相支持的策略,而最需要發展的技術可分為4大面向:加強應用現有資料、以電腦模擬進行預測、建立非動物的測試方法,及利用多元資料發展風險評估技術。本年度根據上述4大面向開啟工作內容,第1部分結合現有資料與電腦預測,規劃後續填補資料的策略;第2部分為建立國際常用之替代測試技術;第3部分為統整過去執行經驗,研擬未來減少化學物質登錄使用實驗動物之政策推動方向;最後則是研擬如何應用上述資訊於風險評估,逐步推動以動物替代相關資訊進行化學物質評估。分項說明如下。應用資訊學方法部分,利用3個國際資料庫及2種定量結構活性關係(QSAR)模型,蒐集或預測43種單一成分有機物之皮膚毒性資訊,現有資訊可分別辨識約53%和63%物質的皮膚刺激性∕腐蝕性和皮膚過敏性資訊,其餘物質建議可以體外測試或個案探討方式評估危害。此外,文獻回顧結果顯示體外至體內之外推估(IVIVE)技術在毒理學研究頗具潛力,並已應用於健康與生態評估,且有公開工具支持其實施。儘管IVIVE仍面臨一些挑戰,例如體外試驗結果與體內生物反應之間的關聯性尚有不確定性,但透過跨學科合作,IVIVE技術持續進步中,未來可望為毒理學研究提供更可靠的支持。而為了評估奈米物質應用於現有皮膚刺激性∕腐蝕性及皮膚過敏性體外測試的可行性,蒐研彙整奈米物質前處理和測試標準相關之國際期刊文章、經濟合作暨發展組織(OECD)測試指引與國際標準化組織(ISO)文件,撰寫《奈米物質前處理與測試標準作業流程草案》1式。考量奈米物質尚毒性評估相關指導文件,參考OECD測試指引應用於奈米物質之試行結果,撰寫2式奈米物質皮膚刺激性與腐蝕性測試標準作業流程草案,及3式奈米物質皮膚過敏性測試標準作業流程草案。體外試驗試行填補毒理資訊部分,提出5類常見奈米物質之物化特性分析數據、10種物質分別以溶液與粉末2種型態進行的皮膚刺激性∕腐蝕性危害分級判斷及皮膚過敏性數據判定結果,未來應用性仍需針對不同奈米物質驗證,並適時調整流程以完善測試結果。為評估化學物質替代測試方法之法規接受性,參考化學品分類及標示全球調和制度(GHS)第10版最新替代策略,顯示我國動物減量策略已與國際接軌,對於尚未採納的部分,則依照我國化學物質登錄架構分析並提出登錄指引調修建議。此外,借鑑我國與歐盟化粧品管理法規禁用動物試驗之經驗,對於我國化學物質標準登錄特定項目以非動物測試方法繳交資料,經評估具有可行性,但需謹慎設計配套措施與保留例外情境因應。為逐步將替代測試方法導入化學物質評估,評析美國、OECD(加拿大參與)及歐盟等國家或國際組織以替代測試方法導入化學物質評估之架構,並蒐研相關化學物質應用案例,皆優先考量暴露機率,以不同試驗方法驗證毒性假說,並以IVIVE等模型推估化學物質暴露濃度,求得體內暴露限值;彙整不同案例研究結果可知,選擇不同替代測試方法與模型參數皆影響最終評估結果。利用本年度各工作項目執行成果,未來可進一步發展技術間之連結,並加強與替代測試推動政策之部會合作。
中文關鍵字 替代測試方法、奈米物質、化學物質登錄、化學物質評估

基本資訊

專案計畫編號 經費年度 113 計畫經費 10200 千元
專案開始日期 2024/04/24 專案結束日期 2024/11/30 專案主持人 陳秀玲
主辦單位 化學署評估管理組 承辦人 崔君至 執行單位 國立成功大學

成果下載

類型 檔名 檔案大小 說明
期末報告 化學物質替代測試方法多元應用與評估計畫.pdf 26MB

Project for Evaluating the Integration of Alternative Testing Methods for Assessments of Chemicals

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.
英文關鍵字 Alternatives to Animal Testing, Nanomaterials, Chemical Substances Registration, Chemical Substance Assessment