利用動態經皮暴露腔探討個人保健用品中致敏性香精以及抗菌防腐成分的皮膚滲透特性

Determining the Permeation Characteristics of Dermal Exposure to Fragrance allergens and Preservatives from Personal Care Products by Using Vertical Diffusion Cell

邵詩甯(Shih-Ning Shao)

指導教授 ： 蔡詩偉

國立臺灣大學/公共衛生學院/環境與職業健康科學研究所/碩士(2020年)

https://doi.org/10.6342/NTU202002948

摘要

個人保健用品(舉凡洗髮精、沐浴乳、洗面乳等等)，被廣泛運用在我們生活中，是我們日常生活的必需品，而其中因為為了增加香味、刺激消費者的購買慾望甚至是增加產品的保存期限，許多廠商在產品中添加許多化學物質，而致敏性香精、抗菌防腐劑(例如：對羥基苯甲酸酯(parabens)及三氯沙(triclosan)等)則是常見的添加物。另一方面，由於塑膠製品常做為個人保健用品之容器，因此使用相關產品時亦可能因為釋出雙酚A (bisphenol-A)而造成暴露。
隨著這些化學物質的使用日漸上升，致敏性香精、抗菌防腐劑以及雙酚A也在環境中廣為流佈，研究發現：空氣、土壤以及動植物體內，都可檢測出這些物質，甚至於人體內都有相關的研究證明，而健康問題隨之出現。而暴露途徑包括呼吸、飲食以及皮膚暴露。由於個人保健用品是我們直接塗抹在皮膚上的產品，因此皮膚暴露是一個最主要的途徑，這些化學物質可能經過使用個人保健用品後被皮膚吸收，進入系統造成其他組織器官的危害，但是關於皮膚吸收率，目前研究只有用假設的數值以及電腦模擬來計算，並沒有實際關於消費者使用的數據。
為了獲得符合實際狀況的致敏性香精、抗菌防腐劑以及雙酚A經皮膚吸收的資訊，本研究利用經皮吸收擴散槽 (Hanson Vertical Diffusion Cell , VDC)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)為樣本，進行相關實驗。在實驗中，以豬皮代替人體皮膚，暴露腔的接收液體則以磷酸鹽緩衝生理食鹽水(Phosphate buffered saline, PBS)模擬人體血液以及組織液。而每次實驗進行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數據。
本研究發現，致敏性香精、抗菌防腐劑以及雙酚A都可以滲透進入皮膚，而當其濃度越高時，暴露的量也隨之增高。而不同類型的個人保健用品中，同樣物質顯示不同的數據，像是在沖洗式產品(Rinse-off products),本研究使用沐浴露以及嬰兒沐浴露進行研究，物質的滲透數據(包含延遲時間,lag time以及通量,flux),都大於其於免沖洗產品(Leave-on products)中。也因此，消費者日後在購買產品時，也可以依照數據選擇適當的產品，例如減少購買香味濃郁以及抗菌防腐劑濃度較高的日用品，減少對其物質的暴露。
本研究發現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、電腦模擬所假設的吸收率進行計算。而日後若能對皮膚不同部位以及更多產品進行比較，則是未來研究的期望。

關鍵字

致敏性香精 ； 抗菌防腐劑 ； 個人保健用品 ； 皮膚暴露 ； 滲透曲線 ； 固相微萃取

並列摘要

Introduction/ Purpose: Many personal care products (PCPs), which are made from various ingredients, are widely used in our daily life. To enhance the odor or prolong storage life, some fragrance allergens and preservatives are added into PCPs for decades. However, more and more health concerns related to the exposures to fragrances allergens and preservatives have been raised. But, only hypothetical absorption rates were available to conduct the assessment nowadays. Hence, to reduce the uncertainty, the aim of this study is to ensure the permeation parameters and skin absorption rates of fragrance allergens and preservatives by dermal exposure.
Methods: These study focus on 11 chemicals that including 5 fragrance allergens and 4 preservatives; also, the triclosan and Bisphenol A (BPA) are taken into study design. According to European regulation, the PCPs are divided into two categories, leave-on products and rinse-off products, and the most common types of PCPs are chosen in this study. The Hanson Vertical Diffusion Cell (VDC), which was an in vitro method, was applied to stimulate the conditions for skin contact. Porcine skin is used as the substituted skin. PBS is selected as the receptor media. After exposures, all samples are analyzed with solid-phase microextraction (SPME) and GC/MS/MS.
Results: The results showed that these ingredients can permeate through skin via skin exposure. Moreover, the concentrations of fragrance allergens and preservatives in PCPs also affect the permeability. As the concentration increased, the flux was higher than the lower concentration. In addition, different types of PCPs have different permeation data of these chemicals, they have higher flux data in rinse-off products than they are in the leave-on products.
Discussion/ Conclusion: It was observed that these ingredients have different permeability data in different PCPs, it may relate to the matrix of the sample. For example, body lotion and baby body lotion (leave-on products) is thicker than body wash and baby body wash (rinse-off products). Because rinse-off products have higher flux and permeability coefficient (Kp), customers should be careful the cleanliness after washing with the body wash gel.
Also, more and more PCPs are used in our life, the results can provide information to consumers before they buying or using the products.

並列關鍵字

Fragrance allergens ； preservatives ； triclosan ； BPA ； personal care products ； dermal exposure assessment ； permeation curve

參考文獻

1. Comiskey, D., Api, A. M., Barratt, C., Daly, E. J., Ellis, G., McNamara, C., ... Tozer, S. (2015). Novel database for exposure to fragrance ingredients in cosmetics and personal care products. Regulatory Toxicology and Pharmacology, 72(3), 660-672.

2. Cashman, A. L., Warshaw, E. M. (2005). Parabens: a review of epidemiology, structure, allergenicity, and hormonal properties. Dermatitis, 16(2), 57-66.

3. SCCS, opinion on fragrance allergens in cosmetic products, 2013.

4. Johansen, J. D. (2003). Fragrance contact allergy. American journal of clinical dermatology, 4(11), 789-798.

5. Elder, R. L. (1984). Final report on the safety assessment of methylparaben, ethylparaben, propylparaben, and butylparaben. J. Am. Coll. Toxicol., 3, 147-209.