Kimber Ian, Pemberton Mark A
Faculty of Life Sciences, University of Manchester, Manchester, UK.
Systox Ltd, Wilmslow, Cheshire, UK.
Regul Toxicol Pharmacol. 2014 Oct;70(1):24-36. doi: 10.1016/j.yrtph.2014.06.013. Epub 2014 Jun 20.
There is continued interest in, and imperatives for, the classification of contact allergens according to their relative skin sensitising potency. However, achieving that end can prove problematic, not least when there is an apparent lack of concordance between experimental assessments of potency and the prevalence allergic contact dermatitis as judged by clinical experience. For the purpose of exploring this issue, and illustrating the important considerations that are required to reach sound judgements about potency categorisation, the lower alkyl methacrylate esters (LAM) have been employed here as a case study. Although the sensitising potential of methyl methacrylate (MMA) has been reviewed previously, there is available new information that is relevant for assessment of skin sensitising potency. Moreover, for the purposes of this article, analyses have been extended to include also other LAM for which relevant data are available: ethyl methacrylate (EMA), n-butyl methacrylate (nBMA), isobutyl methacrylate (iBMA), and 2-ethylhexyl methacrylate (EHMA). In addressing the skin sensitising activity of these chemicals and in drawing conclusions regarding relative potency, a number of sources of information has been considered, including estimates of potency derived from local lymph node assay (LLNA) data, the results of guinea pig assays, and data derived from in silico methods and from recently developed in vitro approaches. Moreover, clinical experience of skin sensitisation of humans by LAM has also been evaluated. The conclusion drawn is that MMA and other LAM are contact allergens, but that none of these chemicals has any more than weak skin sensitising potency. We have also explored here the possible bases for this modest sensitising activity. Finally, the nature of exposure to LAM has been reviewed briefly and on the basis of that information, together with an understanding of skin sensitising potency, a risk assessment has been prepared.
根据接触性变应原的相对皮肤致敏能力进行分类，一直受到关注且很有必要。然而，要实现这一目标可能会遇到问题，尤其是当效力的实验评估与临床经验判断的过敏性接触性皮炎患病率之间明显缺乏一致性时。为了探讨这个问题，并说明对效力分类做出合理判断所需考虑的重要因素，本文以甲基丙烯酸低级烷基酯（LAM）为例进行研究。尽管之前已对甲基丙烯酸甲酯（MMA）的致敏潜力进行了综述，但有一些新信息与皮肤致敏效力的评估相关。此外，为了本文的目的，分析范围已扩大到还包括其他有相关数据的LAM：甲基丙烯酸乙酯（EMA）、甲基丙烯酸正丁酯（nBMA）、甲基丙烯酸异丁酯（iBMA）和甲基丙烯酸2-乙基己酯（EHMA）。在探讨这些化学品的皮肤致敏活性并就相对效力得出结论时，考虑了多种信息来源，包括从局部淋巴结试验（LLNA）数据得出的效力估计值、豚鼠试验结果，以及来自计算机模拟方法和最近开发的体外方法的数据。此外，还评估了LAM对人类皮肤致敏的临床经验。得出的结论是，MMA和其他LAM是接触性变应原，但这些化学品中没有一种具有超过弱皮肤致敏效力的情况。我们还在此探讨了这种适度致敏活性的可能依据。最后，简要回顾了接触LAM的性质，并基于这些信息以及对皮肤致敏效力的理解，进行了风险评估。
