Basketter D A, Scholes E W, Wahlkvist H, Montelius J
Unilever Environmental Safety Laboratory, Sharnbrook, Bedford, UK.
Contact Dermatitis. 1995 Jul;33(1):28-32. doi: 10.1111/j.1600-0536.1995.tb00443.x.
Although they are subject to some limitations, sensitization tests such as the guinea pig maximization test (GPMT) have for many years provided a valuable basis for the identification of skin sensitization potential. Thus they have been used widely by regulatory authorities, such as those in Europe, as a means to identify significant sensitization hazards associated with new chemicals. However, the standard of performance of guinea pig sensitization assays has been demonstrated to be widely variable. Consequently, the OECD sensitization test guideline (the de facto world standard) has been updated to incorporate recommendations for action whose aim is to achieve a minimum standard of test conduct. The principle is that a test laboratory should be able to demonstrate an acceptable level of response using a moderately sensitizing chemical. A list of 3 such chemicals is provided, hexyl cinnamic aldehyde, mercaptobenzothiazole and benzocaine. It is our experience that whilst good results can readily be obtained with the first 2 of these, benzocaine is much more difficult. Using both the GPMT and the local lymph node assay (LLNA), an OECD-recommended screening test, benzocaine has given highly variable results. A range of from 0% to 60% positive in the GPMT was found and, in most tests, benzocaine would not classify as a skin sensitizer according to EU criteria. In the LLNA, from a series of 12 tests conducted in 2 laboratories, only occasional positive results were obtained. Furthermore, these positive results were not reproducible. Reasons for this variability are discussed. However, the main conclusion must be that benzocaine does not represent a useful moderately sensitizing positive control.
尽管致敏试验存在一些局限性，但诸如豚鼠最大化试验（GPMT）等致敏试验多年来一直为鉴定皮肤致敏潜力提供了有价值的依据。因此，它们被欧洲等监管机构广泛用作识别与新化学品相关的重大致敏危害的手段。然而，已证明豚鼠致敏试验的性能标准差异很大。因此，经济合作与发展组织（OECD）的致敏试验指南（事实上的世界标准）已更新，纳入了旨在实现最低试验操作标准的行动建议。其原则是，测试实验室应能够使用一种中度致敏化学品证明可接受的反应水平。提供了3种此类化学品的清单，己基肉桂醛、巯基苯并噻唑和苯佐卡因。根据我们的经验，虽然使用前两种化学品很容易获得良好的结果，但苯佐卡因要困难得多。使用GPMT和局部淋巴结试验（LLNA，一种经OECD推荐的筛选试验），苯佐卡因产生的结果差异很大。在GPMT中发现阳性率范围为0%至60%，并且在大多数试验中，根据欧盟标准，苯佐卡因不会被归类为皮肤致敏剂。在LLNA中，在两个实验室进行的一系列12次试验中，仅偶尔获得阳性结果。此外，这些阳性结果不可重复。文中讨论了这种变异性的原因。然而，主要结论必须是苯佐卡因并非一种有用的中度致敏阳性对照物。
