利用動態經皮暴露腔探討人造麝香的皮膚滲透特性

Determining the Permeation Characteristics of Dermal Exposure to Synthetic Musks from Personal Care Products by Using Vertical Diffusion Cell

徐雅羚(Ya-Ling Hsu)

指導教授 ： 蔡詩偉

國立臺灣大學/公共衛生學院/環境衛生研究所/碩士(2016年)

https://doi.org/10.6342/NTU201602070

摘要

近年來健康意識日漸抬頭，然而過去數十年來隨著化學合成工業的發展，有許多非天然物質被使用在日常生活中，例如：人造麝香就是其中一項。根據文獻指出，自1992年到2004年人造麝香的市場需求量快速上升，而其中以多環麝香以及硝基麝香的使用最為普遍。不過，隨著健康意識的抬頭，陸續有許多研究證實部分人造麝香對人體潛在不良的健康效應，例如：硝基麝香經由動物實驗發現可能產生急毒性以及慢性毒性，另外也可能導致突變以及相關的基因毒效應。多環麝香的暴露則可能造成陸生動物體內的氧化壓力上升；除此之外，人造麝香也被證實為內分泌干擾物。
隨著大量使用，人造麝香在環境中廣為流佈，包括：空氣、水、土壤以及動物體內等都可被檢測出，而近年來甚至在人體樣本中也可發現其存在。過去文獻指出，呼吸、攝食以及皮膚暴露等都可能是人造麝香進入人體的途徑，其中又以皮膚接觸為最主要，然而目前並沒有足夠且確切的暴露資料；例如：相關研究多是以假設的10% 滲透數據做為依據進行相關計算。
為了獲得符合實際狀況的人工麝香經皮膚吸收資訊，本研究利用經皮吸收擴散槽搭配固相微萃取(Solid-phase microextraction, SPME)技術以及三重四極桿氣相層析串聯式質譜儀進行相關的皮膚滲透模擬與分析。本研究選擇市售個人保健用品(Personal care products; PCPs)(包括：乳液及沐浴乳作等)為樣本，進行相關實驗以探討基質以及待測物濃度對皮膚滲透的影響。實驗中，以豬皮為替代皮膚，暴露腔的接收液則為添加10%乙醇的生理緩衝液；每次實驗進行8小時，前四個小時中每半個小時進行一次收樣，後四個小時則是每小時收樣一次，最後再將8小時的收樣樣本進行分析，進而得到滲透曲線及滲透速率等皮膚暴露相關資料。
本研究發現，佳樂麝香(HHCB)、粉檀麝香(AHMI)以及吐納麝香(AHTN)確實可以經由皮膚暴露而滲透。當人造麝香濃度越高時，滲透通量也會越高，而沐浴乳的滲透參數數值(通量及滲透係數)則都高於乳液；其中，乳液的滲透係數範圍為10-10 -10-8 cm/hr，而沐浴乳的滲透係數範圍為10-7 -10-6 cm/hr。人造麝香在兩種產品的滲透分佈現象也不相同；乳液中0.001-0.4%會滲透、沐浴乳3-12%會滲透。不過，不論人造麝香存在於那種基質，其延遲時間都小於30分鐘(代表其滲透速度非常快)。
本研究發現不同人造麝香的皮膚滲透現象會受產品基質以及待測物濃度所影響，因此進行皮膚吸收的暴露評估時不應只簡單利用文獻所假設的 10%吸收率進行計算。另一方面，透過本研究所使用的體外動態皮膚暴露系統(Vertical Diffusion Cell)，則可以獲得實際的暴露參數。

關鍵字

人造麝香 ； 皮膚暴露 ； 個人保健用品 ； 固相微萃取 ； 滲透曲線

並列摘要

Objective: Many personal care products (PCPs), which are made from various ingredients, are widely used in our daily life. To enhance the odor or to change the smell of the products, synthetic musks have been added into PCPs for decades. For example, previous studies pointed out that the demand of synthetic musks increased rapidly from 1992-2004. However, some of the synthetic musks have been confirmed that they can cause health problems, such as allergy, cancer, acute toxicity, etc. In addition, synthetic musks also belong to the endocrine disrupting compounds (EDCs). The most common way to expose synthetic musks is dermal contact. However, only hypothetical absorption rate was available to conduct the assessment. Hence, to reduce the uncertainty, the aim of this study was to validate the permeation parameters (eg., permeation coefficient(Kp), lag time and flux) of synthetic musks by dermal exposure.

Methods: Two kinds of PCPs, including lotion and shower bath gel, were tested in this study. In addition to sample matrix, the effect of concentration on permeation was also examined in this study. The Hanson Vertical Diffusion Cell (VDC), which was an in vitro method, was applied to simulate the conditions for skin contact. For sample analysis, solid-phase microextraction (SPME) coupled with GC/MS/MS was performed. Porcine skin was used as the substituted skin. PBS was selected as the receptor media. For a set of the experiment, the test was conducted for 8 hours. During the first 4 hours, the samples were collected every half hour. For the followings, the samples were taken periodically with the interval of an hour.

Results: The SPME procedure coupled with GC/MS/MS analysis for the determination of synthetic musks in PBS solution was established in this study. It was observed that synthetic musks can permeate through skin via dermal exposure. The permeabilities, including flux and Kp, for synthetic musks (e.g., AHTN and HHCB) through skin were different for PCPs with various sample matrixes. Compared with lotion, the flux and Kp for shower bath gel was higher, which means the synthetic musks in shower bath permeated through skin easier. In addition, the permeation coefficients through skin were 10-10 -10-8 cm/hr and 10-7 -10-6 cm/hr for synthetic musks contained in lotion and shower bath gel, respectively. It was also observed that around 0.001~0.4% and 3~12% of the synthetic musks in lotion and shower bath gel, respectively will permeate through skin. Moreover, the concentrations of synthetic musks in PCPs affected the permeability as well. As the concentration increased, the flux was higher no matter which kind of sample matrix was tested. Besides, the Kp (permeation coefficient) also depended on the sample matrix and the concentrations of synthetic musks. It was observed that the lag time for AHTN, HHCB, and AHMI were all below 0.5 hour, which meaned the synthetic musks permeated shortly once the PCPs were applied on the skin.

Conclusion: This research demonstrated that the hypothetical parameters for skin absorption were not consistent with what were found the in vitro testing system. To reduce uncertainty when assessing dermal exposure in the future, the using of Vertical Diffusion Cell will have great benefits apparently.

並列關鍵字

Synthetic musks ； personal care products ； dermal exposure assessment ； permeation curve ； SPME

參考文獻

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