聚苯乙烯塑膠微粒對水域生物及小鼠之毒理動力/毒理動態模擬及暴露風險評估

Abstract

塑膠微粒可定義為粒徑小於5毫米之微小塑膠。近十年，塑膠微粒污染所衍生之生態隱憂與健康風險已引起全世界的關注。已有大量文獻指出塑膠微粒極可能累積於水域與陸域生物群中，然而以機制性觀點究其與生物體交互作用引發毒性之資訊則更為有限。本論文以毒理動力/動態模式擬合已發表之數據評估斑馬魚、紅尼羅吳郭魚及小鼠系統中，聚苯乙烯塑膠微粒於器官內累積與生物標誌反應。此外，本研究利用已發表之海洋與淡水生態系統中聚苯乙烯塑膠微粒之環境相關濃度數據，以推估包含貽貝之水域模式生物之暴露風險。 本研究指出於特定粒徑之聚苯乙烯塑膠微粒暴露下，可得其於斑馬魚、紅尼羅吳郭魚及小鼠特定器官之毒理動力參數與體內平均停留時間。本研究發現吸收速率常數最高分別於斑馬魚肝臟、紅尼羅吳郭魚與小鼠腸道中。結果顯示所有器官對聚苯乙烯塑膠微粒之生物濃縮因子皆遠大於1，顯示聚苯乙烯塑膠微粒於動物體內具潛在之累積能力。此外，與小鼠相比，斑馬魚器官對聚苯乙烯塑膠微粒普遍具較高之生物濃縮因子。 聚苯乙烯塑膠微粒於生物體肝臟內誘發之免疫反應、氧化壓力、解毒能力、能量與脂肪代謝，可藉由毒理動態評估以決定生物標誌之敏感性。基於劑量反應分析之擬合結果，這些濃度與效應間之關係隨各系統使用物種、暴露時間及聚苯乙烯塑膠微粒粒徑不同而變化，導致聚苯乙烯塑膠微粒之毒性閾值具有很大之變異。由嚴謹的閾值濃度結果顯示，各系統受聚苯乙烯塑膠微粒暴露下，反應最敏感之生物標誌分別為貽貝：巨噬細胞；斑馬魚：超氧化物歧化酶；紅尼羅吳郭魚：7-乙氧基異酚惡唑正脫乙基酶；及小鼠：超氧化物歧化酶。 本研究進一步使用以風險為基礎之機率模式，整合聚苯乙烯塑膠微粒之預測環境濃度值，以超越風險與危害商數量化海洋貽貝與淡水魚所受之潛在危害。全球五大塑料環流中，北太平洋對貽貝造成之風險為最高，而南太平洋海域則最低。而就淡水魚而言，美國之溫約灣於所有選定的淡水域中具最高風險。針對全球塑膠微粒污染造成水域生物之危害，本研究結果值得予以關注，特別是敏感性物種如斑馬魚將首當其衝受到長期毒性之風險。 此外，以小鼠為模式生物所得之毒理動力參數與閾值標準有助於研究之健全規劃，以評估塑膠微粒於人體攝食之危害。本研究提出一濃度外推架構，以健康風險評估觀點，機制性地從小鼠推估至人類體內塑膠微粒毒性閾值。總體而言，由毒理動力/動態評估、韋伯閾值模式及生態風險評估所得之結果，可應用於快速檢測及評估各種塑膠微粒濃度暴露下所誘發之毒性影響。嚴謹之塑膠微粒閾值可作為環境管理之建議值，且可提供人體攝食風險評估計畫建立之工具。

Microplastics (MPs), are defined as tiny plastics with particle size less than 5 mm. Ecological concerns and health risks of MPs contamination have been attracting a worldwide attention within a decade. While a large body of literature has shown that MPs are highly likely to be accumulated in aquatic and terrestrial biota, information about the toxic interactions of MPs on organisms from a mechanistic point of view is more limited. This thesis filled this knowledge gap by assessing polystyrene (PS)-MPs in zebrafish, red tilapia, and mice systems based on a toxicokinetic/toxicodynamic (TK/TD) modeling to quantify organ-bioaccumulation and biomarker responses appraised with published datasets. Exposure risks for aquatic model organisms including bivalves were also presented by utilizing the published environmentally relevant concentration data of PS-MPs in marine and freshwater ecosystems. The organ-specific TK-parameters and mean residence times for zebrafish, red tilapia, and mice posed by size-specific PS-MPs could be obtained. The highest uptake rates were in the liver of zebrafish, in the gut of red tilapia and mice, respectively. Results showed that steady-state bioconcentration factors (BCFsss) of PS-MPs among all organs were much greater than 1, indicating the bioaccumulating potential of PS-MPs in animals. In comparison to mice, zebrafish have commonly much greater BCFsss in organs. The sensitivities of biomarkers regarding immunological response, oxidative stress, detoxification, and energy and lipid metabolisms to PS-MPs in liver of organisms were determined by the TD assessment. These concentration-effect relationships based on the Hill model varied with species used, exposure time, and particle size of PS-MPs in each system. As the result, toxicity thresholds of PS-MPs were in a large variability. Results demonstrated that the most sensitive biomarkers in bivalves, zebrafish, red tilapia, and mice systems, based on strict threshold concentrations, were phagocytic cells, superoxide dismutase (SOD), 7-ethoxyresorufin O-deethylase, and SOD, respectively. A risk-based probabilistic model was further used to characterize the potential hazards of marine bivalves and freshwater fish in response to predicted environmental concentrations of PS-MPs quantified by exceedance risks and risk quotients. Among five global plastic-filled gyres, the highest and lowest risks were occurred in the North Pacific and South Pacific Oceans for bivalves, respectively. For freshwater fish, the Winyah Bay in USA appeared to be the greatest risks among the selected local areas. The present results warranted further attention on worldwide MPs pollution posing hazards to aquatic organisms, particularly sensitive species like zebrafish taking the brunt of the long-term toxicity risk. Moreover, the mice-based TK parameters and threshold criteria greatly assist in designing robust researches to evaluate MPs consumption by humans. An extrapolation framework was proposed for mechanistically estimating toxicity thresholds of MPs from mice to humans in a health risk assessment perspective. Overall, results derived from the TK/TD assessment, the Weibull threshold model, and the ecotoxicological risk assessment could be adopted to rapidly evaluate MPs-induced toxicities at various concentrations. The strict thresholds could be recommended as criteria for environmental management of MPs and offer a tool-kit in establishing the scheme for risk assessment of human consumption.