標題: 芳香族化合物之毒性與作用機制研究
The Toxicity and Modes of Action of Nitroaromatic Compounds
作者: 楊詔棻
Yang, Chao-Fen
陳重元
Chen, Chung-Yuan
環境工程系所
關鍵字: 硝基芳香族;月牙藻;毒性作用機制;階層分析;nitroaromatics;Pseudokirchneriella subcapitata;modes of action;PCA;HCA
公開日期: 2013
摘要: 本篇研究以月牙藻為試驗物種進行密閉式藻類毒性試驗,以溶氧變化量(ΔDO)、最終細胞產量(Final Yield)及生長率(Growth Rate)為反應終點,評估硝基芳香族化合物(包括硝基苯胺及硝基甲苯)之毒性反應。毒性試驗結果中,敏感性最高者為Final Yield,其次是ΔDO,最不敏感之試驗終點則是Growth Rate。就結構而言,可以發現此類化合物的毒性會隨著苯環上硝基(-NO2)數目增加而增強,且即使是結構相似的化學物質,也會因為取代基種類與位置的不同而造成毒性有很大的差異。而在歐盟水體生物風險分級標準中,本研究所選用的25個化合物有13個在分級中屬於對環境具有危害性(harmful)的化學物質,有9個被分在有毒(toxic),另外2,6-dinitroaniline 、3,5-dinitroaniline以及2,5-dinitrotoluene三個化合物更是被區分在極具毒性(very toxic)的等級,表示此類化合物會對水體環境造成風險,且本篇研究是利用食物鏈最底層的藻類進行試驗,若經由食物鏈之傳遞將會對環境及生物產生更大的影響,由此可見,對於這些毒性物質的研究是有其必要性的。 為了研究此類化合物對藻類之毒性作用機制,本研究利用毒性數據與常用的物化參數(辛醇與水係數(logKow)及最低軌域躍遷能量(Elumo))進行群集分析方法―以Principal Component Analysis(PCA)與Hierarchical Cluster Analysis(HCA)將化學物質分群。利用文獻中水蚤(Daphnia manga)之毒性數據以PCA分析的結果,部分苯胺類化合物原被分類在毒性機制較弱的非極性麻醉作用,但經此法分類後發現與反應性物質分在同一群,此結果與文獻中苯胺類會對Daphnia造成特殊作用之結果相符,另外以本研究中三個不同試驗終點的藻類毒性數據分析結果,有三個非極性麻醉性物質(3-nitroaniline、2-nitro-1,4-benzenediamine、3-nitro-1,2-benzenediamine)有遠離非極性麻醉物質族群的情形產生,此三個化合物的共同結構是苯環上同時具有單一硝基(-NO2)與胺基(-NH2)且兩者為間位結構;再以HCA分析確認分類結果,所得結論與PCA結果相同;並以基線毒性關係證明,此種結構化合物具有明顯之超量毒性(excess toxicity, Te),顯示其致毒機制應為高於基線毒性的極性麻醉性或反應性。因此用PCA及HCA統計方法將生物急毒性數據與常見的物化參數―logKow與Elumo值一同進行分析,可以有系統的將化學物質依其本身特性及對生物體的反應進行毒性作用機制分類,以彌補傳統作用機制分類沒有考慮到對生物反應之闕漏,即使是同分異構物也可以達到很好的區分效果。
The present study evaluates the toxicity of 25 nitroaromatic compounds, including nitroanilines and nitrotoluenes. A closed-system algal toxicity test was applied because these chemicals are semi-volatile/volatile substances. The green alga, Pseudokirchneriella subcapitata, was the test organism and the dissolved oxygen production (DO), final yield and growth rate were used as the test endpoint. Three toxicants (2,6-dinitroaniline, 3,5-dinitroaniline and 2,5-dinitrotoluene) tested in the present study are classified as very toxic to aquatic organisms (R50 class) according to the classification of chemicals defined by European Union. In addition, nine other nitroaromatic compounds are considered as moderately toxic (> 1.0 mg/L - 10 mg/L, R51 class). Furthermore, significant controversies have been found from previous literatures regarding the modes of action of organic chemicals. Principal component analysis(PCA) and hierarchical cluster analysis(HCA), based on chemical’s toxicity and certain physical-chemical descriptors (i.e., hydrophobicity, and the lowest unoccupied molecular orbital energy), were used to comprehend the modes of action of various nitroaromatic compounds. The above analyses indicate that compounds with nitro- substituent on the meta-site to an amine group on the benzene ring are polar narcotic or reactive in nature. The results demonstrated that PCA and HCA analyses were helpful to modify the modes of action of nitroaromatics.
URI: http://140.113.39.130/cdrfb3/record/nctu/#GT079419520
http://hdl.handle.net/11536/73945
Appears in Collections:Thesis