Jowsey Ian R, Basketter David A, Westmoreland Carl, Kimber Ian
Unilever Safety and Environmental Assurance Centre, Sharnbrook, Bedfordshire, UK.
J Appl Toxicol. 2006 Jul-Aug;26(4):341-50. doi: 10.1002/jat.1146.
Current approaches to skin sensitisation risk assessment are dependent upon the availability of information regarding two fundamental parameters. Firstly, data relating to the relative skin sensitising potency of the chemical, and secondly, information regarding likely conditions of human exposure. During the past two decades, much has been achieved in terms of refining methods capable of informing these parameters. For example, the development of the local lymph node assay (LLNA) has made it possible to predict skin sensitising hazard, and to determine relative skin sensitising potency, in a way that was not possible previously. Taken together with accurate information about predicted exposure, such potency data can be used to facilitate the derivation of effective risk assessments. However, although the LLNA provides an integrated assessment of skin sensitising activity, it does require the use of experimental animals and there is growing enthusiasm for designing robust alternative approaches that will reduce or obviate that need. Progress is being made in defining alternative experimental strategies that avoid animal use, but it is clear that accurate characterisation of skin sensitisation hazards will require the effective integration of various sources of information. For this reason, we exemplify here one possible approach that, in theory, provides a framework for not only the identification of skin sensitising chemicals, but also the estimation of relative sensitising potency. This paradigm depends upon development of an understanding of the various biological, biochemical and chemical factors that impact on the allergenic properties of chemicals and the acquisition of skin sensitisation, and an ability to measure these in vitro.
目前的皮肤致敏风险评估方法依赖于两个基本参数的信息获取。首先，是与化学物质相对皮肤致敏效力相关的数据；其次，是关于人类可能接触情况的信息。在过去二十年中，在完善能够提供这些参数信息的方法方面已经取得了很大进展。例如，局部淋巴结试验（LLNA）的发展使得预测皮肤致敏危害以及确定相对皮肤致敏效力成为可能，而这在以前是无法做到的。结合有关预测接触的准确信息，此类效力数据可用于促进有效风险评估的推导。然而，尽管LLNA提供了对皮肤致敏活性的综合评估，但它确实需要使用实验动物，并且人们越来越热衷于设计强大的替代方法，以减少或消除这种需求。在定义避免使用动物的替代实验策略方面正在取得进展，但很明显，对皮肤致敏危害的准确表征将需要有效整合各种信息来源。因此，我们在此举例说明一种可能的方法，从理论上讲，它不仅为识别皮肤致敏化学物质提供了框架，还为估计相对致敏效力提供了框架。这种模式依赖于对影响化学物质致敏特性和皮肤致敏过程的各种生物、生化和化学因素的理解的发展，以及在体外测量这些因素的能力。
