111

3,790 千元

科技發展-化學物質科學研究

2022/02/11

2022/11/30

陳柏霖

化學局

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）、替代測試方法、整合型測試評估方法

Replacement, Reduction and Refinement (3Rs), Alternative test methods, Integrated Approaches to Testing and Assessment (IATA)

王應然；侯文哲

蔡昀達

02-77306566#174

yunda.tsai@apollotech.com.tw

本年度蒐研國際組織認可之替代測試方法、奈米物質化學品登錄資訊及替代測試方法之最新進展，更新替代測試方法清單並完成2式指引文件（皮膚刺激性/腐蝕性替代測試方法指引及眼睛刺激性替代測試方法指引）。為達以替代測試方法完備我國化學物質登錄所需毒理及生態毒理資訊之目標，以15種化學物質（累計共22種物質）及數種定量結構活性關係(Quantitative Structure-Activity Relationship, QSAR)等替代測試方法，試行毒理及生態毒理項目資料推估。在毒理方面，基因毒性具有良好的表現；在生態毒理方面，丹麥定量結構活性關係資料庫(Danish QSAR Database)及毒性預測軟體工具(Toxicity Estimation Software Tool, T.E.S.T.)之群體貢獻方法(Group contribution method)對水生急毒性預測能力表現良好。體外測試(in vitro assay)部分，本年度完成5種化學物質（累計共25種物質）的體外魚類胚胎試驗，試行結合定量結構活性關係及體外試驗之整合型測試策略(Integrated approaches to testing and assessment, IATA)，結果顯示分級準確率可達88%。本年度亦以2種定量結構活性關係模式進行10種有機錫化合物之物化特性與環境宿命之預測，模擬結果對於第一類毒性化學物質之分類準確率為88%。另以11種定量結構活性關係模式預測106種化學物質之生物濃縮因子(BCF)，總體預測準確率為95.8%。

取代、減量及精緻化（優化）、替代測試方法、整合型測試評估方法

成果報告.pdf

10MB

2023/2/1 上午 12:00:00

For applying the animal alternative test data on chemical assessment, the new information for alternative test strategies, nano-substance registration, and the recent development of alternative test methods were continuously collected and analyzed. Furthermore, the list of alternative test methods was updated, and 2 guidance documents for how to use alternative tests were established (“Guidance on Alternatives of Acute Dermal Irritation and Corrosion” and “Guidance on Alternatives of Eye Irritation”). To strengthen the application of alternative methods on toxicological and eco-toxicological information required by chemical substances registration, quantitative structure-activity relationship (QSAR) models were used to predict the health and environmental hazards of 15 substances (22 substances in total). The choose QSAR models showed good performances on genotoxicity. Danish QSAR Database and the group contribution method in Toxicity estimation software tool (T.E.S.T.) also provided well predictions on the classification of acute fish toxicity. This year, we also evaluated the acute fish toxicity of 5 substances (25 substances in total) using fish embryo acute toxicity Test (FET). By combining the data of QSAR (T.E.S.T. Group contribution method and ECOSAR) and FET, we successfully optimized the integrated approaches to testing and assessment (IATA). Our results showed that the accuracy of IATA could reach 88%. In the other hand, we also predicted the physical and chemical properties and environmental fate of 10 organotin compounds by 2 different QSAR model. The classification accuracy for class 1 toxic chemical substances could reach 88%. For avoiding unnecessary animal tests, the bioconcentration factor (BCF) of 106 substances which should be completed standard registration before 2024 were predicted by 11 kinds of QSAR and the accuracy of prediction reached 95.8%.

Replacement, Reduction and Refinement (3Rs), Alternative test methods, Integrated Approaches to Testing and Assessment (IATA)