陳文貴胡超群醫學研究所2026-10-289999-12-311994https://handle.ncl.edu.tw/11296/bubm3shttps://scholars.csmu.edu.tw/handle/123456789/34818本研究測定以甲苯為主要溶劑之塗料工廠二十三位員工尿液中甲苯與另一使用溶劑二甲苯之代謝物，探討甲苯之生物檢測所得之數據與環境測定值之關係，發現甲苯代謝物中之馬尿酸，二甲苯代謝物中之甲基馬尿酸與員工個人採樣器所呈現之個人環境曝露量，呈正相關性。而臨床生化值中可作為初期腎傷害指標之乙醞葡萄甘胺酸酵素之活性，在甲苯高曝露組(>1/10 PEL)　員工尿液中亦明顯的高於低曝露組（P<0.05），顯示甲苯之生物檢測雖然主要以尿液中代謝物之含量為依據，但由甲苯曝露所引起之臨床生化值改變亦可做為輔助性之數據，以評估環境中甲苯對個人健康之影響。　　因為一般工廠所使用之甲苯中往往混有其他有機溶劑，如本研究採樣之工廠，其溶劑除甲苯外亦含有二甲苯及少量之乙基苯。為了進一步了解其他有機溶劑對甲苯代謝機制之影響，本研究以鼠肝微粒體酵素系統為模本，比較二甲苯、正丁醇對甲苯在此酵素系統中形成苯甲醇之效應，發現兩者均會抑制甲苯之代謝，而且二甲苯以較高之比率降低苯甲醇之形成。如比較二甲苯及正丁醇對對硝基酚之代謝抑制作用發現兩者以相同的比率幹擾對硝基酚之代謝物對硝基二酚之形成，顯示二甲苯較專一性的抑制甲苯之代謝。　　本研究另外再探討甲苯曝露與微粒體中脂質過氧化形成之關聯。結果顯示甲苯代謝會引發微粒體脂質過氧化程度之上昇，而此機制可能與細胞色素P450氧化酵素及其輔助因子NADPH有關。Toluene, as one of the most abudent organic solvents in industrial usage, is thought to be an important environmental and occupational pollutant This xenobiotics is mainly absorbed by resperatory inhalation and skin infiltration, then oxidized in liver cytochrome P450　monooxygenase. The final products of toluene is urinary excretion were the glycine conjugated benzoic acid termed hippuric acid and ring hydroxylated toluene like o-, m-, p- cresols. By comparing the environmental concentration of toluene in work place and urinary metabolite from exposed wokers or biological parameter, this study estimates the value of biological monitoring for the assessment of human exposure to toluene.　　The urinary metabolites of toluene and xylene from the exposed worker showed a propotional correlation with time average concentration of solvent in the breath zone between the concentration of exposed solvent, and urinary metabolites.　　It's interested to find that NAG value, which were used as an index of early kidney damage, has shown an significanly increasing on the high exposed worker, this data suggested that the biological monitoring of toluene no only reflect the environmental exposure but also provide some informations to evaluate the target organ damage and solvent detoxification.　　The other aspect of this study is to investigate the in vitro metabolism of toluene in microsomal enzyme system. Xylene, as one of the structural analogue of toluene, showed a higher inhibition than n-butanol (xylene 40.2%, n-butanol 23.2%) ratio to benzy1 alcohol formation, but comparing with the metabolism of p-nitrophenol in microsomal enzyme system, xylene showed the some inhibition ratio with n-butanol to p-nitrocatechol formation.　　The MDA concentration also elevated in microsomal portion with increasing the toluene exposure. This enhancement will be decreased by depleting the NADPH generating system from microsomal enzyme, This result suggested that the metabolism of toluene would be inhibited by the coexposure of other solvents in different ratio and the induce effect of toluene to microsomal lipid peroxidation mediated by cytochrome P450 metabolism can be used as a basis to evaluate the biological monitoring toxicity of toluene when coexposed to other solvents.甲苯肝微粒體酵素系統thesis