農藥之皮膚刺激性評估與動物替代性研究發展新趨勢

皮膚是農民在使用農藥時最常暴露的途徑之一，可能造成接觸性皮膚炎（contact dermatitis）如刺激性（irritant）反應，出現包括潮紅（redness）或水腫（edema）等症狀，因此農藥申請登記時將視情形提供皮膚刺激性試驗報告供管理單位審查，俾利產品危害分類及標示使用（classification and labeling）。試驗主要依循經濟合作暨發展組織（Organization for Economic Cooperation and Development, OECD）公開之白兔皮膚刺激毒性試驗指引執行，針對皮膚刺激性評估，目前國際動物替代驗證中心主要接受的體外試驗為重建人類表皮測試方式（reconstructed human epidermis test method, RhE），該方式為使用人類的皮膚角質形成細胞，在特定環境條件培養增殖下可分化成具有相似人類表皮的3 維組織，試驗單位可利用相關皮膚組織衍生之商品化套組並以細胞存活試驗（MTT assay）方式評估皮膚刺激性。另外，在評估策略上國際趨勢強調使用試驗及評估綜合測試系統（integrated approach to testing and assessment, IATA），依據現有資料及證據權重（weight of evidance）原則給予加權及整合，並提供必要時應再執行新試驗以獲得關鍵數據的判定基準，最終結果可供監管單位進行評估及決策使用。雖然目前體外試驗相較傳統動物試驗，除符合動物福利不須使用動物外，還具備高效率及較低資源成本等優勢，但針對使用非動物試驗替代動物試驗的主要爭議點，在於是否具足夠的人體危害預測能力。目前研究顯示以RhE方式評估農藥皮膚刺激性，仍存在對於混合物之預測準確率可能下降及化學品分類適用性等問題點，後續仍需要科學研究釐清或修訂現行法規以對應，而無法完全替代傳統動物試驗方式，但建議仍可先導入IATA之評估系統作為管理決策所參考，除了可增加預測面向之完整性，尚可減少實驗動物之使用或減輕其痛苦，符合目前國際持續追求實驗動物福祉的趨勢。

關鍵字

農藥；皮膚刺激性； 3R ；重建人類表皮測試方式；試驗及評估綜合測試系統

並列摘要

The skin is one of the most common routes of exposure for farmers when using pesticides. Pesticide exposure may cause contact dermatitis and lead to irritation signs including redness and/or swelling. Therefore, to accurately classify hazards, register new products and assign pesticide labels, the regulatory unit will require test reports of skin irritation for pesticide. The skin irritation test is mainly performed using white rabbits and is in accordance with guidelines by the Organization for Economic Cooperation and Development (OECD). Currently, around the world, the scientificce communities that worldwide of conducting animal experiments all giveare striving to work in better accordance with high attention to the 3R spirit (replacement, reduction and refinement). Researchers, and continue to develop and promote alternative tests that can replacefeature alternatives to the use of live animals. For the assessment of skin irritation, the in vitro test currently recommended by the International Center for Coordinating Committee on the Validation of Alternative Methods is ＂Reconstructed Human Epidermis Test Method (RhE)＂. This method uses human skin keratinocytes which can differentiate into three-dimensional tissues with similar human epidermis under specific environmental conditions. In assessing skin irritation, the experimental unit performs an MTT assay (cell viability assay on commercial sets derived from relevant skin tissues. In addition, the international has emphasized the importance of adopting Integrated Approach to Testing and Assessment (IATA) approaches in evaluating strategy. IATA approaches involve the use of existing data and employ the weight of evidence (WoE) method to weight and integrate different test results. IATA approaches can also determine whether additional tests are needed to obtain critical data. Regulatory agencies can use the final result to help evaluate and make regulatory decisions about new products. In addition to not requiring the use of live animals and improving animal welfare, in vitro tests offer other advantages over in vivo tests as well, such as higher efficiency and lower costs. However, the use of in vitro testing remains limited due to questions about how accurately non-animal tests predict human hazards. Recent research revealed that barriers to using the RhE method in assessing skin irritation, including reduced accuracy in predicting mixtures and the applicability of chemical classification that cannot completely replace traditional animal testing methods, especially for formulation of pesticide. Therefore, additional research is needed to clarify or amend current regulations. However, it is nonetheless recommended that the IATA evaluation system be introduced as a reference for decision-making to reduce the use of experimental animals and meet the current international trend of continuously improving the welfare of experimental animals.

並列關鍵字

pesticide ； skin irritation ； 3R ； Reconstructed Human Epidermis (RhE) ； Integrated Approach to Testing and Assessment (IATA)

國際替代計量

農藥之皮膚刺激性評估與動物替代性研究發展新趨勢

全文下載

主題瀏覽