DuPont Haskell Global Centers for Health and Environmental Sciences, Newark, DE, USA.
Regul Toxicol Pharmacol. 2010 Feb;56(1):54-66. doi: 10.1016/j.yrtph.2009.08.016. Epub 2009 Sep 4.
Hundreds of chemicals are contact allergens but there remains a need to identify and characterise accurately skin sensitising hazards. The purpose of this review was fourfold. First, when using the local lymph node assay (LLNA), consider whether an exposure concentration (EC3 value) lower than 100% can be defined and used as a threshold criterion for classification and labelling. Second, is there any reason to revise the recommendation of a previous ECETOC Task Force regarding specific EC3 values used for sub-categorisation of substances based upon potency? Third, what recommendations can be made regarding classification and labelling of preparations under GHS? Finally, consider how to integrate LLNA data into risk assessment and provide a rationale for using concentration responses and corresponding no-effect concentrations. Although skin sensitising chemicals having high EC3 values may represent only relatively low risks to humans, it is not possible currently to define an EC3 value below 100% that would serve as an appropriate threshold for classification and labelling. The conclusion drawn from reviewing the use of distinct categories for characterising contact allergens was that the most appropriate, science-based classification of contact allergens according to potency is one in which four sub-categories are identified: 'extreme', 'strong', 'moderate' and 'weak'. Since draining lymph node cell proliferation is related causally and quantitatively to potency, LLNA EC3 values are recommended for determination of a no expected sensitisation induction level that represents the first step in quantitative risk assessment.
有数百种化学物质是接触过敏原，但仍需要准确地识别和描述致敏危害。本次审查有四个目的。首先，在使用局部淋巴结检测（LLNA）时，需要考虑是否可以定义并使用低于 100%的暴露浓度（EC3 值）作为分类和标签的阈值标准。其次，是否有任何理由修改之前 ECETOC 专题小组关于基于效力对物质进行亚分类时使用特定 EC3 值的建议。第三，关于 GHS 下制剂的分类和标签，有哪些建议？最后，考虑如何将 LLNA 数据纳入风险评估，并提供使用浓度反应和相应的无效应浓度的基本原理。尽管具有高 EC3 值的致敏化学物质可能对人类的风险相对较低，但目前无法定义低于 100%的 EC3 值作为分类和标签的适当阈值。从审查用于描述接触过敏原的不同类别使用情况得出的结论是，根据效力对接触过敏原进行最适当、基于科学的分类是确定四个亚类：“极端”、“强”、“中”和“弱”。由于引流淋巴结细胞增殖与效力存在因果关系和定量关系，因此建议使用 LLNA EC3 值来确定代表定量风险评估第一步的无预期致敏诱导水平。
