Assessment of skin sensitization potency of hair dye molecules in vitro
Assessment of skin sensitization potency of hair dye molecules in vitro
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染发剂分子体外皮肤致敏性评估
DOI：
10.1111/cod.12780
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发表时间：
2017
影响因子：
5.5
通讯作者：
B. Blömeke
中科院分区：
文献类型：
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作者：
J. Hennen;B. Blömeke
今天，化妆品成分和产品诱导皮肤致敏的潜力必须在不使用动物方法的情况下确定。因此，能够预测化学物质对皮肤致敏的相对效力的替代体外方法对于定量风险评估至关重要。这对于某些应用（如染发）所需的活性分子来说是特别重要的。对苯二胺（PPD）和甲苯-2,5-二胺（PTD）在染发剂相关的接触性皮炎中起主要作用(1)，目前，80-99%的市售氧化染发剂中存在PPD或PTD(2)。根据小鼠局部淋巴结测定（LLNA），基于危险的表征将PPD和PTD归类为强致敏剂，而其已知的三聚体PPD氧化产物Bandrowski 's碱（BB）被归类为极端致敏剂，这表明效力的增加与PPD自氧化的程度有关（3,4）。相比之下，最近引入的PPD衍生物2-甲氧基甲基-对苯二胺（ME-PPD）被归类为中等增敏剂，因为在LLNA中诱导增敏所需的浓度比PPD或PTD高约30至40倍(5)。在这里，我们研究了LLNA中确定的对PPD、PTD、ME-PPD和BB的不同增敏效力是否也可以通过我们基于人类细胞系的共培养模型来区分。该模型由人角化细胞（HaCaT细胞）和THP-1细胞作为替代树突状细胞（dc）组成，并使用可诱导THP-1细胞上共刺激分子CD86和/或粘附分子CD54显著上调的化学浓度作为致敏效能的标记物（6,7）。
Today, the potential of cosmetic ingredients and products to induce skin sensitization must be determined without the use of animal methods. Therefore, alternative in vitro methods that are able to predict the chemicals’ relative potencies for skin sensitization are essential for quantitative risk assessment. This is of special importance for reactive molecules needed for certain applications such as hair dyeing. p-Phenylenediamine (PPD) and toluene-2,5-diamine (PTD) play a major role in hair dye-associated contact dermatitis (1), and, currently, either PPD or PTD is present in 80–99% of commercially available oxidative hair dyes (2). Hazard-based characterization classifies PPD and PTD as strong sensitizers on the basis of the murine local lymph node assay (LLNA), whereas its known trimeric PPD oxidation product, Bandrowski’s base (BB), is classified as an extreme sensitizer, showing that the increase in potency is related to the degree of PPD autoxidation (3, 4). In contrast, the recently introduced PPD derivative 2-methoxymethyl-p-phenylenediamine (ME-PPD) is classified as a moderate sensitizer, as approximately 30to 40-fold higher concentrations than with PPD or PTD were needed for the induction of sensitization in the LLNA (5). Here, we investigated whether the different sensitizing potencies determined in the LLNA for PPD, PTD, ME-PPD and BB can also be distinguished by the use of our human cell line-based coculture model. This model consists of human keratinocytes (HaCaT cells) and THP-1 cells as surrogate dendritic cells (DCs), and uses the chemical concentration that induces significant upregulation of the costimulatory molecule CD86 and/or adhesion molecule CD54 on THP-1 cells as a marker for sensitizing potency (6, 7).