以生理為基礎之藥理動力學模式研析超細微粒中多環芳香烴化合物之人體健康風險中文摘要本三年計畫之目的在於發展一機制模式，以人類暴露於超細微粒中含多環芳香烴化合物之人體健康風險有進一步的瞭解。總括而言，計劃嘗試以肺部區塊模式及以生理為基礎之藥理動力學模式建立人體暴露濃度、標的器官之效應濃度及時間-濃度曲線之關係。本計劃試圖顯現超細微粒中多環芳香烴化合物濃度與指標代謝物(1-hydroxypyrene (1-OHP)濃度)之交互作用關係所扮演之關鍵性角色，並建構以人類生理參數為基礎之藥理動力學模式。計劃之研究重點在於超細微粒中多環芳香烴化合物之毒理動態、標的器官之效應濃度及隨時間轉變之劑量-效應變化模擬。預期目標為當人體標的器官之生理代謝機制及劑量-反應的關係已知時，可較精確的評估超細微粒中多環芳香烴化合物對於人體健康風險的危害潛勢。 Construction the Physiologically Based Pharmacokinetic (PBPK) Modeling of Ultrafine Polycyclic Aromatic Hydrocarbons (PAHs) for Human Health Risk Assessment ABSTRACT The goal of this 3-year proposal is to develop mechanistic models to understand better the human health risk assessment for exposed to ultrafine polycyclic aromatic hydrocarbons (PAHs). The overall proposal paradigm is trying to establish a relationship among exposure concentration and internal effect concentrations and target time-concentration profiles based on compartmental lung model and physiologically based pharmacokinetic (PBPK) model. This proposal seeks to show the crucial role of ultrafine PAHs exposure concentration, interactions with metabolism biomarkers (urinary 1- hydroxypyrene (1-OHP) levels) and to construct a PBPK model for human. Emphasis on the proposal is on ultrafine PAHs toxicology dynamics, and time perspective of dose-response studies. If the metabolism mechanism to target organ and the dose-response relationship are known, the inherent adverse effect of exposure to ultrafine PAHs can be better estimated.
