Petry Thomas, Bosch Axel, Coste Xavier, Eigler Dorothea, Germain Pierre, Seidel Shawn, Jean Paul A
ToxMinds BVBA, Product Safety & Regulatory Affairs, B-1200 Brussels, Belgium.
Wacker Chemie AG, Corporate Product Safety, D-84489 Burghausen, Germany.
Regul Toxicol Pharmacol. 2017 Mar;84:64-76. doi: 10.1016/j.yrtph.2016.12.009. Epub 2016 Dec 23.
The skin sensitization potential of chemicals has traditionally been evaluated in vivo according to OECD testing guidelines in guinea pigs or the mouse local lymph node assay. There has lately been a great emphasis on establishing in vitro test methods reflecting the key biological events in the adverse outcome pathway (AOP) for skin sensitization as published by the OECD. Against this background, a group of 8 polysiloxanes and silanes, seven of them aminofunctionalised, for which in vivo data were already available, has been tested in vitro in the direct peptide reactivity assay (DPRA), the KeratinoSens™ and the human cell line activation test (h-CLAT) and in the modified myeloid U937 skin sensitization test (mMUSST) as far as technically feasible. The main objective of the programme was to determine the utility of these systems for this heterogeneous group of silicone-based substances, recognizing that some substances are outside the assays applicability domains. The presented data provided some interesting mechanistical insights into the performance of these assays for functionalised siloxanes and silanes. The data also allow for a preliminary evaluation of proposed integrated testing strategies (ITS) to determine the skin sensitization potential of chemicals which were not considered in the training sets of the respective ITS.
传统上，化学物质的皮肤致敏潜力是根据经合组织（OECD）的测试指南，在豚鼠体内或采用小鼠局部淋巴结试验进行评估的。最近，人们非常重视建立体外测试方法，以反映经合组织公布的皮肤致敏不良结局途径（AOP）中的关键生物学事件。在此背景下，一组8种聚硅氧烷和硅烷（其中7种为氨基官能化），其体内数据已经可得，已在体外进行了直接肽反应性试验（DPRA）、KeratinoSens™试验、人细胞系激活试验（h-CLAT），并在技术可行的情况下进行了改良髓系U937皮肤致敏试验（mMUSST）。该项目的主要目标是确定这些系统对这一异类有机硅基物质组的适用性，同时认识到有些物质超出了这些试验的适用范围。所提供的数据为这些试验针对官能化硅氧烷和硅烷的性能提供了一些有趣的机理见解。这些数据还允许对提议的综合测试策略（ITS）进行初步评估，以确定在各自ITS的训练集中未考虑的化学物质的皮肤致敏潜力。
