Basketter D A, Scholes E W, Kimber I
Unilever Environmental Safety Laboratory, Sharnbrook, Bedford, UK.
Food Chem Toxicol. 1994 Jun;32(6):543-7. doi: 10.1016/0278-6915(94)90112-0.
For many years, tests in the guinea pig have been the favoured option for the identification of the skin sensitization potential of chemicals. However, the mouse has been used widely in immunology research and can represent a viable alternative. A variety of murine assays have been described, including several methods based on ear swelling as an endpoint. Another option is to assess induced lymph node cell proliferation and it is this which forms the basis of the murine local lymph node assay (LLNA). The LLNA has undergone several successful interlaboratory validations and compares well with standard guinea pig assays. In the present study, the performance of the LLNA was examined with chemicals tested previously in the human maximization test (HMT). 30 chemicals, 23 of which proved positive in the HMT and seven of which were negative, have been tested. All but four of the materials found positive in the HMT also tested positive in the LLNA. Of these four, sulfanilamide and paraben esters would not classify as skin sensitizers in the guinea pig maximization test and nickel has been found to yield variable results in a number of predictive animal tests. Of the seven substances which proved negative in the HMT, six were also negative in the LLNA, the exception being sodium dodecyl sulfate. These data demonstrate that the LLNA is able to identify accurately chemicals which have the potential to cause significant allergic contact dermatitis in humans.
多年来，豚鼠试验一直是鉴定化学品皮肤致敏潜力的首选方法。然而，小鼠已广泛应用于免疫学研究，并且可以作为一种可行的替代方法。已经描述了多种小鼠试验方法，包括几种以耳部肿胀为终点的方法。另一种选择是评估诱导的淋巴结细胞增殖，这就是小鼠局部淋巴结试验（LLNA）的基础。LLNA已经历了几次成功的实验室间验证，并且与标准豚鼠试验相比效果良好。在本研究中，用先前在人体最大化试验（HMT）中测试过的化学品检测了LLNA的性能。已对30种化学品进行了测试，其中23种在HMT中被证明为阳性，7种为阴性。在HMT中发现呈阳性的材料中，除了4种之外，其他所有材料在LLNA中也呈阳性。在这4种材料中，磺胺和对羟基苯甲酸酯在豚鼠最大化试验中不会被归类为皮肤致敏剂，并且已发现镍在许多预测性动物试验中产生的结果不一致。在HMT中被证明为阴性的7种物质中，有6种在LLNA中也为阴性，例外的是十二烷基硫酸钠。这些数据表明，LLNA能够准确识别有可能在人类中引起严重过敏性接触性皮炎的化学品。
