Basketter D A, Whittle E, Griffiths H A, York M
Unilever Environmental Safety Laboratory, Sharnbrook, Bedford, UK.
Food Chem Toxicol. 1994 Aug;32(8):769-75. doi: 10.1016/s0278-6915(09)80010-0.
There exist various regulatory instruments the purpose of which is to ensure that the intrinsic toxic hazards associated with substances and preparations are identified. In the context of identification of skin irritation potential, the method is normally the Draize test. Guidance notes provided by the OECD and the EEC expect that corrosive substances will have been screened out by a variety of methods. Substances or preparations which cause a sufficient degree of skin irritation will be classified as skin irritants. The primary motivation behind the present work was to introduce the concept that it is possible to assess the hazard potential of a substance or preparation to produce skin irritation in a human study. In the example presented here, 20% sodium lauryl sulfate (SLS) has been chosen as the positive control. With the protocol currently devised, occluded patch treatment with 20% SLS for up to 4 hr produces an irritant response in just over half of the panel. An irritant response is taken as a clinically evident and significant increase in erythema, oedema or dryness--a minimum of a+ reaction on the ICDRG scale. At such a level of response with the positive control (both in terms of intensity and in proportion of the panel), it is then possible to judge and/or to determine statistically, whether the test material has produced a level of skin irritation which is similar to, greater, or lower than the positive control. In this way a human patch test protocol can form a fundamental component of a strategy for the replacement of animals in determination of skin irritation and corrosion potential. By use of a careful and progressive protocol and by comparison of test data against a positive control it is both possible and practical to classify substances and preparations in terms of their skin irritation potential using that endpoint in the species of concern, man.
存在各种监管手段，其目的是确保识别出与物质和制剂相关的内在毒性危害。在确定皮肤刺激可能性的背景下，通常采用的方法是Draize试验。经合组织（OECD）和欧洲经济共同体（EEC）提供的指导说明预计，腐蚀性物质已通过多种方法筛选出来。引起足够程度皮肤刺激的物质或制剂将被归类为皮肤刺激物。本研究的主要动机是引入这样一种概念，即在人体研究中可以评估物质或制剂产生皮肤刺激的潜在危害。在这里给出的例子中，选择20%的月桂醇硫酸酯钠（SLS）作为阳性对照。按照目前设计的方案，用20%的SLS进行长达4小时的封闭贴片处理，在略多于一半的受试者中会产生刺激反应。刺激反应被视为临床上明显且显著的红斑、水肿或干燥增加——在国际接触性皮炎研究组（ICDRG）量表上至少为+反应。在阳性对照达到这样的反应水平时（无论是在强度方面还是在受试者比例方面），就有可能通过判断和/或统计确定测试物质产生的皮肤刺激程度是否与阳性对照相似、更高或更低。通过这种方式，人体贴片试验方案可以成为在确定皮肤刺激和腐蚀可能性时替代动物的策略的一个基本组成部分。通过使用谨慎且逐步推进的方案，并将测试数据与阳性对照进行比较，就可以根据所关注的物种（人类）的该终点，对物质和制剂的皮肤刺激可能性进行分类，这既是可行的也是实际的。
