農藥之皮膚過敏性評估與動物替代新穎策略

由於農民在從事農業行為中，可能暴露到農藥進而引起皮膚過敏的可能性，各國的農藥監管機構為保護對相關族群的健康，須要評估農藥產品對於皮膚過敏性的危害分類資訊，以作為制定相關登記產品警告標示及建議之個人防護裝備使用。傳統上評估農藥皮膚過敏性會進行天竺鼠加佐劑最大化試驗（guinea pig maximization test, GPMT）、天竺鼠無佐劑過敏檢測法（Buehler test, BT）或小鼠局部淋巴結細胞增殖分析法（local lymph node assay, LLNA）等體內試驗，為考量實驗動物福祉等緣由，包括美國或歐盟等國際相關化學品評估機關皆在精進並期望發展能完全取代動物試驗的新穎技術。在眾多農藥毒理學測試的評估指標中，皮膚過敏性為導入健康危害途徑概念（adverse outcome pathway, AOP）作為評估策略的代表範例，針對相關因果關聯事件（key events, KE），經濟合作暨發展組織（Organization for Economic Cooperation and Development, OECD）已分別公開對應評估技術之測試指引，尤其包括化學測試及體外試驗等動物替代技術（alternative methods），惟目前相關的替代試驗方法，考量預測能力等因素，建議整合多項替代試驗資訊，使用綜合測試與評估方式（integrated approach to testing and assessment, IATA）中的定義方法（defined approach, DA）進行評估，以取代動物試驗。雖然目前相關替代試驗仍有對於混合物預測能力有限等疑慮，但以一般單一物質化學品而言，以定義方法等評估策略不僅可有效預測動物試驗結果，甚至與實際人體暴露結果相比，其準確率更高於動物試驗。目前美國、日本等國家農藥主管機關已陸續修訂相關規範而開始接受動物替代試驗，因此透過此文回顧已被國際組織完成驗證的皮膚過敏性動物替代研究技術及新穎評估策略，並建議未來應將相關策略導入國內現行之農藥登記規範，以減少實驗動物之使用，並同時符合管理上對於風險評估的要求。

關鍵字

農藥；皮膚過敏性；動物替代技術；健康危害途徑；綜合測試與評估方式；定義方法

並列摘要

Farmers and agricultural workers are at risk of pesticide exposure, which can lead to skin sensitization. State pesticide regulatory agencies are responsible for determining hazard classifications and using related information to create warning labels and recommend appropriate personal protective equipment. Traditionally, the skin sensitization potential of pesticides has been evaluated using in vivo tests, including the guinea pig maximization test (GPMT), Buehler test (BT), or murine local lymph node assay (LLNA). However, to improve the welfare of laboratory animals, international chemical assessment agencies such as the United States or the European Union increasingly seek new approach methodologies (NAMs) that can replace animal tests. Among the many toxicological endpoints for the testing of pesticides, skin sensitization is a representative model of introducing the concept of adverse outcome pathway (AOP) as an evaluation strategy. The Organization for Economic Cooperation and Development (OECD) has published test guidelines for different key events by using AOP concept in assessment of skin sensitization. These guidelines include alternative methods to animal testing, such as in chemico and in vitro methods. To improve the predictive ability of animal-free NAMs, the OECD recommends to integrate multiple alternative tests and use the defined approach (DA) in the integrated approach to testing and assessment (IATA) to replace animal studies. Although doubts remain about the ability of animal-free NAMs to predict mixtures, for general monoconstituent substances, evaluation strategies such as DA (1) can effectively predict the results of animal tests and (2) have a higher accuracy rate in assessing actual human exposure results than do animal tests. Pesticide authorities in the United States and Japan have revised relevant regulations pertaining to the pesticide certification and begun to accept alternative tests. Therefore, in this study, we reviewed animal-free skin-sensitization NAMs to identify alternative tests and novel assessment strategies that have been verified by OECD and other international validation institutes. We suggest that future domestic regulations to certify pesticides using results of animal-free NAMs and promote pesticide-testing methods that effectively assess risk while also reducing the need for laboratory animals.

並列關鍵字

pesticide ； skin sensitization ； animal alternative methods ； adverse outcome pathway (AOP) ； integrated approach to testing and assessment (IATA) ； defined approach (DA)

主題瀏覽