112

3,247 千元

科技發展-化學物質科學研究

2023/04/13

2023/11/30

陳柏霖

化學署評估管理組

張容蓉

瑞昶科技股份有限公司

科技計畫

取代、減量及精緻化（優化）、替代方法使用指引、整合型測試評估方法

Replacement, Reduction and Refinement (3Rs), Guidance on Alternative Methods, Integrated Approaches to Testing and Assessment (IATA)

王應然；洪偉毅

籃翊

02-77306566#173

i.lan@veolia.com

本計畫蒐集及分析國際組織認可之物質替代測試方法與我國化學物質登錄資訊，並建立我國適用之替代測試策略。在我國替代方法使用指引部分，研析國際對眼睛刺激性分級之最新替代策略及指引，提出優化之眼睛刺激性指引草案，解決過去無法以替代方法辨別第2級之問題。另為完善過去建立之皮膚刺激性∕腐蝕性替代方法使用指引，以及本年度優化之眼睛刺激性替代方法使用指引，已蒐集並參酌產業、部會和學界之專家意見，微調指引內容與敘述方式，但整體架構無大幅變動。而奈米物質新測試方法學的研析結果顯示，與我國毒理登錄項目相關的方法仍在開發中，待開發完成後可考量用於奈米化學物質的安全性評估。為建立我國可運行之替代測試模式與策略，以15種物質試行魚類細胞株急毒性試驗，結果顯示有8種物質可有效推估EC50，其中7種物質(87.5%)在細胞株試驗的EC50與成魚急毒性試驗的LC50之間相差小於10倍。與前期胚胎急毒性試驗相比，胚胎試驗和成魚試驗結果的相關性較佳，大部分物質(93.3%)的LC50數值差距小於10倍。本年度亦納入魚類細胞株試驗結果，優化整合型測試評估方法(Integrated Approaches to Testing and Assessment, IATA)，結果顯示以胚胎試驗優先的IATA與細胞株試驗優先的IATA具有相同的準確率。最後，探討4年期科技計畫的施行成效及提出後續策略規劃。分析登錄資訊，動物替代的推動在毒理項目具有相當成效，但生態毒理項目則因魚類毒性及生物蓄積項目皆以傳統動物實驗繳交測試資料而尚有進步空間，建議逐步規劃運用魚類急毒性IATA架構與納入更多國際認可之生態毒理測試替代方法，輔助登錄人以替代方法繳交生態毒理資料的相關策略，以有效減少使用實驗動物。

取代、減量及精緻化（優化）、替代方法使用指引、整合型測試評估方法

成果報告.pdf

8MB

成果報告（公開完整版）

2024/2/10 上午 12:00:00

In this project, we collected and analyzed the information required in Taiwan chemical substance registration and the alternative testing methods recommended by international organizations to establish the strategy for promoting animal alternative method in our country. Regarding the guidance for Taiwan chemical registration and the latest international guidelines for eye irritation, an optimized draft guidance on how to conduct a hazard classification of eye irritation using alternative methods for chemical substances was proposed. This optimized draft guidance could improve the insufficiency in the previous version, which is the inability to identify the substances that should be classified as category 2. In addition, to improve 2 guidance documents (“Guidance on Alternatives of Acute Dermal Irritation and Corrosion” and “Optimized Guidance on Alternatives of Eye Irritation”), expert opinions from industry, ministries, and academia were collected to fine-tune the guidance. Still, the overall structure has not changed significantly. In this project, we also attempted to analyze the strategy for the safety evaluation of nanomaterials. According to the latest international information, the new testing methods for evaluating the hazard of nanomaterials on human health are still under development. They could be considered for application in the safety assessment once the development is completed. Moreover, to establish and validate the alternatives to animal approaches for environmental assessments. 15 substances were used to conduct the fish cell line acute toxicity test (FCT). The results indicated 8 substances predicted the EC50 effectively. The EC50 of 7 substances (87.5%) obtained from FCT could be considered correct, because the differences between the values of EC50 obtained from FCT and fish acute toxicity test were within 10 times. When compared with embryonic studies, embryo acute toxicity test (FET) showed a better correlation and accuracy (93.3%) than FCT. Furthermore, FCT results were used to optimize the IATA. In the IATA framework, regardless of whether embryos or cell lines were used first, the accuracy rate remains the same. Finally, the implementation effectiveness of the 4-year technology plan was discussed and follow-up strategic planning was proposed. The analysis results of chemical registration information showed that the promotion of alternative testing has been effective in the toxicological evaluations. However, for ecotoxicology evaluations, more efforts are needed to reduce the uses of experimental animals, because the test data of fish toxicity and bioaccumulation were all from traditional animal experiments. Therefore, it is recommended to gradually plan the use of IATA framework to evaluate fish acute toxicity and incorporate more international alternative ecotoxicological testing methods, which could assist registrants to submit their ecotoxicological information obtained from alternative methods. It could help to achieve the goal of further reducing the use of experimental animals.

Replacement, Reduction and Refinement (3Rs), Guidance on Alternative Methods, Integrated Approaches to Testing and Assessment (IATA)