建立我國利用風險分析作為化學物質管理決策工具之前期規劃專案工作計畫
The Development of Decision-making Tool for Chemical Management Based on Risk Analysis: A Pilot Study

臺灣近年發生的數起化學物質不當使用之事件，造成環境與民眾的危害，為了更有效的進行源頭控管，我國於105 年12 月成立行政院環境保護署毒物及化學物質局，強化有害化學物質之控制、理和監督，進而維護民眾的健康。本計畫彙整歐盟、美國與加拿大之化學物質分類評估架構，探討其中以風險評估作為基準的化學物質分類方式作法，針對其法規架構、評估篩選流程以及使用工具與準則依序詳細說明。此外，也探討國際在化學物質篩選過程中之趨勢。國際化學物質之管理與評估逐漸開始將化學物質單一評估轉變成先將化學物質依據相似之特性分類以後，再同時評估同一類的物質。其中，依據作用模式分類也逐漸被重視，不僅用於原先的致癌性評估，在非致癌效應與內分泌效應甚至是生態評估都逐漸的使用依據作用方法分類的評估方式。風險評估過程需要依賴相關的毒理資料，特別是在有害物質鑑定與劑量反應評估的步驟中。 有害物質鑑定與劑量反應評估的毒理資料主要來自於動物實驗數據。因此，本研究開始建立資料品質評估與使用非實驗的毒理數據的方法，包括：高通量(highthroughput)、計算毒理學 (computational toxicology) 電腦運算方法 (in-silico methods)以及整試驗策略 (Integrated Testing Strategies, ITSs)。希望藉由上述之方法運用在風險評估中來取代活體內實驗 (in-vivo) 與體外實驗 (in-vitro)。為提升化學物質管制效率，本研究也同時探討現有高通量 (high-throughput)、計算毒理學以及電腦運算方法 (in-silico methods) 、整試驗策略 (Integrated Testing Strategies,ITSs) 的使用，也探討現有風險評估報告項目準則，以及風險評估結果與政策決策之連結。依據目前趨勢以及國際化學物質管理架構，本計畫分析在國內管理架構下第四類毒性化學物質與關注化學物質的定義差別，討論作用模式 (Mode of action) 與人類適用性 (Mode of action/human relevance, MoA/HR) 來區分兩種化學物質可行性，規劃現有工具與QSAR 模型來建立基於風險評估之自動化篩選過程的可行性，提出目前挑戰與規劃未來改善之建議，進而提升我國化學物質之管理量能。本計畫統整歐盟、美國與加拿大之風險評估標準並一一陳述上述各國之風險評估範疇、問題界定、毒性、劑量反應關係、不確定性分析以及資料呈現的方法。相對而言，臺灣所公告之風險評估指引則缺乏暴露情境的重視、作用模式以及基準劑量方法。在化學物質管理的過程中，時常必須在資料不全的情況下訂定決策。然而，決策最大的挑戰並非一定來自資料的缺乏，而是來自並未能清楚定義決策的目標與基準。決策基準的不確定性來自於定義的不明確。在風險評估過程中需考量所有的利害團體的利益，因此需要花費長時間來達成群體的共識。為了要適當的考慮社會、經濟、政治、科技項目以及健康與環境風險，本計畫在經濟、政策與社會面針對化學物質管理之工具與案例分析進行探討。因此本研究研析了包括社會經濟分析 (socio-economic analysis, SEA) 、多準則決策分析 (Multiple Criteria Decision Analysis, MCDA) 、證據地圖 (Evidence Map) 等基於化學物質的暴露情況來協助化學物質篩選與決策過程之工具並提出建議。

In recent years, several incidents of improper use of chemical substances have occurred in Taiwan, causing harm to the environment and the public. In order to more effectively control the source, in 2016, the Toxic and Chemical Substances Bureau of the Environmental Protection Administration of the Executive Yuan was established to strengthen the control, management and supervision of hazardous chemicals for the safeguard of people's health. This project consolidates the classification and assessment frameworks of chemical substances in the European Union, the United States and Canada to discuss the risk-assessment-based classification methods of chemical substances, specifically focusing on their regulatory framework, evaluation and screening process, and use of tools and selection criteria. In addition, the current international trend of advancements in the process of chemical screening are also discussed. The management and evaluation of chemical substances has gradually begun to transform from evaluating single substances to a grouping approach where chemical substances are first classified into groups with similar characteristics, and then evaluating the same class of substances at the same time. Among the many classification schemes, classification based on the chemical’s mode of action is gradually being emphasized, not only for carcinogens, but also non-carcinogenic effects, endocrine effects and ecological assessments. The risk assessment process relies heavily on relevant toxicological information, especially in the steps of hazard identification and dose-response assessment, which make use of data collected from animal experiments. Research has begun to establish methods for data quality assessments and the use of non-experimental toxicological data, including high-throughput screening, computational toxicology, in-silico methods, and integrated testing strategy in risk assessment in hope to replace traditional in-vitro and in-vivo approach. Based on current international trends of chemical substance management framework, this project analyzes the definition of the class 4 toxic chemical substances and concerned chemical substances under the current regulatory framework. The feasibility of distinguishing the two classes of chemicals by their mode of action and human relevance is discussed. Recommendations are made for planning future development and applications of automated chemical screening tools based on existing data analysis tools and Quantitative Structure Activity Relationship (QSAR) models. For risk assessment report criteria, recommendations are made to strengthen requirement for characterizing problem formulation, dose response and uncertainty analysis. Finally, for risk management decision-making, we recommend consideration for adopting multi-criteria decision analysis and evidence map development. This project summarized the risk assessment criteria of various countries, including the European Union, the United States, and Canada. The description of each criteria, such as the scope, problem formulation, toxicity, dose-response assessment, uncertainty analysis, and the presentation of information were investigated. In comparison, Taiwan's risk assessment guidance lacks the emphasis on the characterization of the exposure scenario, mode of action and the use of benchmark dose methods. In the process of managing chemical substances, it is often necessary to make decisions without complete information. However, the difficulty of decision-making is not necessarily due to the lack of information, but from the lack of clear definition of decision goals and benchmarks. The uncertainty of the decision-making benchmark comes from the difficulty of its definition. In the process, all aspects of the stakeholders must be considered. It often takes a long time to communicate to reach a consensus. To adequately consider social, economic, political and technical objectives in addition to health and environmental risks, tools and case studies for chemical management considering economic, policy, technical and social aspects were examined. Reviewed tools include socio-economic analysis (SEA), multiple criteria decision analysis (MCDA), Evidence Map and other tools to assist in screening and decision-making recommendations based on the exposure status of chemical substances.