飲用水中三鹵甲烷與全氟及多氟烷基物質混合毒性作用與健康風險評估

Abstract

為確保飲用水安全，加氯消毒廣泛應用於飲用水處理流程，以有效去除水中病原微生物。然而，消毒過程亦可能產生消毒副產物，其中三鹵甲烷（trihalomethanes, THMs）為飲用水中常見的消毒副產物。此外，全氟及多氟烷基物質（per- and polyfluoroalkyl substances, PFAS）具有高度環境持久性、廣泛分布及潛在健康危害，近年亦受到高度關注。由於 THMs 與 PFAS 皆可能存在於飲用水中，人體可能同時暴露於多種污染物，而非僅暴露於單一化合物。然而，目前對於 THMs 與 PFAS 共同暴露所造成的毒性影響仍缺乏充分了解。 過去體外毒性研究多採用短時間及高濃度暴露條件，以評估污染物所造成的細胞毒性反應；然而，實際飲用水暴露主要來自長期攝入低濃度污染物。因此，低濃度及長時間暴露下的毒性效應，以及多種污染物共同暴露所產生的影響，仍有進一步探討之必要。本研究選取飲用水中常見且具代表性的 THMs（TCM、BDCM、DBCM）與 PFAS（PFOA、PFOS、PFHxS、PFBS），利用已分化之 HepaRG 細胞進行體外細胞毒性試驗，採用較低濃度並連續暴露 7 天，以評估單一及混合暴露之細胞毒性效應。混合毒性分析採用濃度加成模型（concentration addition model, CA），並利用模式偏差比值（model deviation ratio, MDR）評估 THMs 與 PFAS 混合暴露所產生的交互作用。此外，本研究依據飲用水監測資料建立暴露情境，並採用蒙地卡羅模擬法（Monte Carlo simulation）考量污染物濃度之變異性，以評估 THMs（TCM、BDCM、DBCM、TBM）與 PFAS（PFOA、PFOS、PFHxS）之非致癌及致癌風險。 細胞毒性試驗結果顯示，THMs 中以 TCM 的細胞毒性最高，其次依序為 DBCM 與 BDCM；PFAS 中則以 PFOS 的細胞毒性最高，其次依序為 PFOA、PFHxS 及 PFBS。混合毒性分析結果顯示，不同污染物組合所產生的交互作用有所差異，其中 BDCM 及 DBCM 與 PFAS 混合暴露時較常觀察到協同作用，而 TCM 與 PFAS 混合暴露則主要呈現加成作用，顯示含溴 THMs 與 PFAS 共同暴露可能產生較明顯的交互作用。 人體健康風險評估結果顯示，THMs 的非致癌風險皆低於美國環境保護署所建議之危害基準；而台灣各地區之累積終生致癌風險皆高於 1×10^(-6) 之可接受風險值。其中，TCM 為多數地區致癌風險之主要貢獻化合物，而離島地區則以 DBCM 之貢獻最高。PFAS 方面，PFHxS 於不同暴露情境下皆呈現最高之非致癌風險；PFOA 於所有評估暴露情境下之累積終生致癌風險皆高於 1×10^(-6) 之可接受風險值，而 PFOS 則於第 50 及第 95 百分位數下高於該值。 本研究整合體外細胞毒性試驗與人體健康風險評估，探討 THMs 與 PFAS 之細胞毒性效應、混合暴露所產生之交互作用，以及飲用水暴露下之潛在健康風險。結果顯示，不同 THMs 與 PFAS 組合可能產生不同程度之交互作用，且部分污染物於飲用水暴露下具有較高之潛在健康風險。研究結果可作為未來飲用水中多重污染物共同暴露之健康風險評估及相關管理策略制定之參考。

Ensuring drinking water quality is crucial for safeguarding public health. Chlorination is a common method used to eliminate harmful microorganisms, but it can produce disinfection by-products (DBPs) like trihalomethanes (THMs), often found in drinking water. Additionally, per- and polyfluoroalkyl substances (PFAS) have gained increasing concern because of their environmental persistence, widespread occurrence, and potential health effects. Because THMs and PFAS may co-occur in drinking water, human exposure may involve multiple contaminants rather than individual compounds. However, the toxicological effects associated with co-exposure to THMs and PFAS remain insufficiently understood. This study evaluated the cytotoxic effects and mixture interactions of representative THMs (TCM, BDCM, and DBCM) and PFAS (PFOA, PFOS, PFHxS, and PFBS) using differentiated HepaRG cells under relatively low-concentration exposure conditions for 7 days. Mixture toxicity was assessed using the concentration addition (CA) model and the model deviation ratio (MDR). In addition, human health risk assessments were conducted based on drinking water monitoring data, with Monte Carlo simulation used to account for variability in contaminant concentrations. Non-cancer and cancer risks were evaluated for THMs (TCM, BDCM, DBCM, and TBM) and PFAS (PFOA, PFOS, and PFHxS). Among the individual compounds, TCM exhibited the highest cytotoxicity among THMs, followed by DBCM and BDCM, while PFOS showed the highest cytotoxicity among PFAS, followed by PFOA, PFHxS, and PFBS. When THMs were combined with PFAS, mixture toxicity varied across contaminant combinations, with synergistic interactions more frequently observed for brominated THMs (BDCM and DBCM), whereas TCM predominantly exhibited additive interactions. Human health risk assessment showed that non-cancer risks associated with THMs were below the acceptable risk level recommended by the U.S. Environmental Protection Agency, whereas cumulative lifetime cancer risks exceeded 1×10^(-6) across all regions of Taiwan. TCM was the primary contributor to cancer risk in most regions, while DBCM contributed the most in offshore island regions. For PFAS, PFHxS exhibited the highest non-cancer risk across the evaluated exposure scenarios. Cumulative lifetime cancer risks associated with PFOA exceeded 1×10^(-6) across all evaluated exposure scenarios, whereas PFOS exceeded this level at the 50th and 95th percentiles. This study integrates in vitro cytotoxicity testing and human health risk assessment to investigate the cytotoxic effects, mixture interactions, and potential health risks associated with THMs and PFAS in drinking water. The findings provide a basis for understanding the potential health implications of co-occurring contaminants in drinking water and may support future risk assessment and management strategies for multiple contaminants.