Department of Orthopedic Surgery, Køge Sygehus, Køge, Denmark.
Basic Clin Pharmacol Toxicol. 2014 Jul;115(1):101-9. doi: 10.1111/bcpt.12188. Epub 2014 Jan 31.
Studies on percutaneous penetration are needed to assess the hazards after unintended occupational skin exposures to industrial products as well as the efficacy after intended consumer exposure to topically applied medicinal or cosmetic products. During recent decades, a number of methods have been developed to replace methods involving experimental animals. The results obtained from these methods are decided not only by the chemical or product tested, but to a significant degree also by the experimental set-up and decisions made by the investigator during the planning phase. The present MiniReview discusses some of the existing and well-known experimental in vitro and in vivo methods for studies of percutaneous penetration together with some more recent and promising methods. After this, some considerations and recommendations about advantages and limitations of the different methods and their relevance for the prediction of percutaneous penetration are given. Which method to prefer will depend on the product to be tested and the question asked. Regulatory guidelines exist for studies on percutaneous penetration, but researchers as well as regulatory bodies need to pay specific attention to the vehicles and solvents used in donor and sampling fluids so that it reflects in-use conditions as closely as possible. Based on available experimental data, mathematical models have been developed to aid predictions of skin penetration. The authors question the general use of the present mathematical models in hazard assessment, as they seem to ignore outliers among chemicals as well as the heterogeneity of skin barrier properties and skin conditions within the exposed populations.
需要进行经皮渗透研究，以评估工业产品意外职业性皮肤暴露后的危害，以及有意向消费者使用局部应用的药用或化妆品产品后的效果。在最近几十年中，已经开发出许多方法来替代涉及实验动物的方法。这些方法获得的结果不仅取决于所测试的化学物质或产品，而且在很大程度上还取决于实验装置和研究人员在规划阶段做出的决策。本迷你综述讨论了一些现有的、众所周知的经皮渗透的体外和体内实验方法，以及一些更新颖、更有前途的方法。之后，对不同方法的优缺点及其对经皮渗透预测的相关性进行了一些考虑和建议。选择哪种方法将取决于要测试的产品和要解决的问题。关于经皮渗透的研究已经有了监管指南，但研究人员和监管机构需要特别注意供体和采样液中使用的载体和溶剂，以使它们尽可能接近实际使用条件。基于现有的实验数据，已经开发了数学模型来辅助皮肤渗透的预测。作者对目前在危险评估中普遍使用的数学模型提出了质疑，因为它们似乎忽略了化学物质中的异常值，以及暴露人群中皮肤屏障特性和皮肤状况的异质性。
