飼料中的PFOS與PFOA之健康風險評估

Abstract

全氟與多氟烷基物質（Per- and polyfluoroalkyl substances , PFASs），具有抗水、抗油和耐高溫的特性，被廣泛應用於消防泡沫、食品包裝和個人護理用品等，並在環境中無處不在。多種PFASs被認為是致癌物，並具有生殖毒性與發育毒性，由於其在各種環境介質中的持久性和生物累積性，其潛在的健康影響備受關注。 在各種PFAS暴露途徑（exposure scenarios）中，經由日常食用肉類和動物源性產品而間接暴露於動物飼料中的PFASs尚未得到研究，但這對於傳統上經常食用養殖動物內臟的臺灣人群和亞洲國家居民尤為關鍵。 目前，轉移因子（Transfer factor, TF）和基於生理學的毒物動力學（physiologically based toxicokinetics, PBTK）模型已被用來估算從飼料轉移到動物組織中的危害，但由於其複雜性和高不確定性，缺乏對動物群體個體差異的考慮，並未被廣泛使用。為了解決這些問題，本研究旨在以全氟辛酸（Perfluorooctanoic acid, PFOA）和全氟辛烷磺酸（Perfluorooctane sulfonic acid, PFOS）為例，通過貝氏統計（Bayesian statistics）方法建立其在動物組織中的濃度與飼料中濃度的關係，以此進行健康風險評估，並提出飼料中PFOA和PFOS的最大限量（maximum limits, MLs），評估結果將可提供我國政府與國際間作為制定飼料中PFOS 與 PFOA 殘留標準之參考。 我們建立了用於評估危害物質從飼料到動物轉移的框架，該框架能夠根據半衰期和飼養期去選擇合適的計算方法，不僅考量了物種間和物種內的差異，同時也較容易上手，可用於數據有限的情況。在這個框架下，我們首先比較動物飼養期和化合物於動物體內的半衰期的長短，接著建立單室藥代動力學模型，求解後以泰勒級數（Tayor’s series）展開，由此獲得短半衰期化合物的轉移因子，長半衰期化合物的線性和時間依賴（time dependent）的轉移因子，介於兩者之間的其餘化合物，則將使用毒物動力學推導而來的公式，以估算這些動物在食入受PFOS 和 PFOA 汙染後，PFASs 在動物組織與器官的分布。 針對短半衰期化合物和長半衰期化合物，我們收集了牛、羊、豬、雞的 PFOS 和 PFOA之轉移數據，作為貝氏統計建模的先驗信息，以估算這些五種家禽和家畜中轉移因子和殘留濃度的後驗分佈；並蒐集介於兩者之間的化合物，蒐集其生理參數、半衰期與動物實驗數據等，使用蒙地卡羅模擬進行殘留濃度的估計。 最後，使用國家攝食資料庫（National Food Consumption Database）中的肉類和內臟攝食量（consumption rates），結合各動物群體組織中的PFOS和PFOA殘留濃度分佈情形，進行機率健康風險評估（probabilistic risk assessment）。 我們假設動物在整個飼養期內，每天皆暴露於含有1 μg/kg PFOA/PFOS的動物飼料，估算了殘留濃度，PFOS 部分，殘留濃度估計值由高至低依序為豬肝、豬腎、牛肝、羊肝、雞蛋、鴨肝、其他豬內臟、羊腎等；PFOA 則依序為：豬腎、豬肝、雞蛋、其他雞內臟。 這些數據進一步用於機率風險評估。我們以蒙地卡羅模擬進行10,000次試驗（10,000 trials），評估在 General public和 Consumer only下，臺灣各年齡組的平均每日攝取劑量（Average daily intyake , ADD）和終生平均每天暴露劑量（Lifetime average daily dose, LADD），並計算危害商數（Hazard quotient, HQ），以提出 MLs 建議值。 我們提出的飼料 MLs如下：PFOS 為 2.1×10^(-4) 至 2.6×10^(-3) μg∕kg，PFOA 為 2×10^(-4) 至 2.2 ×10^(-3) μg∕kg，這遠低於當前已有文獻記載的飼料濃度，其顯示當前的飼料濃度對人類的間接暴露存在健康風險。然而，這也遠低於當前的偵測與定量限，因此未來應增進飼料中微量物質分析之能力，並制定飼料之PFOS 與 PFOA之限量基準，以維護國人健康。

Per- and polyfluoroalkyl substances (PFASs), resistant to water, oil, and temperature, are widely applied in industries like the production of firefighting foams, food packaging, and personal care items and ubiquitous in environment. Several PFASs are carcinogens and reproductive and developmental toxicants and their potential health effects have been of great concerns due to their persistence and bioaccumulation in various environmental media. Among the various scenarios of PFAS exposures, the indirect exposures to PFASs in animal feed via daily consumption of meats and animal products have not been assessed, but particularly critical for the Taiwanese populations and people in Asia countries, traditionally consuming offal of farmed animals. Currently, the transfer factor (TF) and physiologically-based Toxicokinetics (PBTK) have been used to estimate hazard residues in tissues of animals transferred from feed. But, the former lacks theoretic basis and conditions of utilization, and the later lacks consideration of inter-individual differences in an animal population and are not popular with its complexity and high uncertainty. To improve the current methods, the objective of this study is to use PFOA and PFOS as examples to establish the relationships of their concentrations in the tissues of animals with those in feed using Bayesian statistics for health risk assessment and to propose maximum limits (MLs) of PFOA and PFOS in feed. These results will provide a valuable reference for the Taiwanese government and international regulatory agencies in establishing standards for PFOS and PFOA residues in animal feed.

We developed a framework for estimating the residual concentration of a hazard in tissues of farmed animals transferred from feed, which features: easy to use, an appropriate method selected by using half life and feeding period, suitable for cases with limited data, with considering inter- and intra-species variability. Under this framework, an one-compartment pharmacokinetics will be formulated, solved, and expanded with the Tayor’s series to obtain a TF for a short-half-life compound and linear and time-dependent TF for a long-half-life compound compared with animal feeding periods. For compounds with intermediate half-lives, we used pharmacokinetic-derived formulas to estimate the distribution of PFASs in animal tissues and organs after ingestion of PFOS and PFOA-contaminated feed. For short- and long-half-life compounds, TF data of PFOS and PFOA in cattle, sheep, pigs, hens, ducks (Only PFOS) will be cited to serve as prior information for Bayesian statistical modeling to estimate the posterior distributions of their TFs and residues in tissues of these poultry and livestock; For intermediate-half-live compounds, we collected physiological parameters, half-life data, and animal experiment data to estimate residue concentrations using Monte Carlo simulations. The distributions of meat and offal consumption rates are cited from the National Food Consumption Database and used to probabilistically assess health risk with the distributions of PFOS and PFOA residues in tissues of each animal population. We assumed that animals were exposed daily to feed containing 1 μg/kg of PFOA/PFOS throughout the feeding period and estimated the residue concentrations. For PFOS, the estimated residue concentrations from highest to lowest were pig liver, pig kidney, cattle liver, sheep liver, chicken eggs, duck liver, other pig organs, and sheep kidney. For PFOA, they were pig kidney, pig liver, chicken eggs, and other chicken organs in that order. According to our assessment, the HQs for different age groups under general public and consumer only in Taiwan are based to propose MLs in feed: PFOS ranges from 2.1×〖10〗^(-4) to 2.6×10^(-3) μg/kg, and PFOA ranges from 2×10^(-4) to 2.2 ×10^(-3) μg/kg. These levels are much lower than the current PFOS and PFOA levels in feed, indicating potential health concerns due to indirect human exposures to both compounds in feed. Moreover, these levels are also much lower than current detection and quantification limits, and advanced analytical methods with sufficient sensitivity are needed for trace analysis of them in animal feed to ensure that the newly-revised standards of PFOS and PFOA in feed can be enforced to protect public health.