Dearman R J, Hilton J, Evans P, Harvey P, Basketter D A, Kimber I
Zeneca Central Toxicology Laboratory, Macclesfield, Cheshire, UK.
J Appl Toxicol. 1998 Jul-Aug;18(4):281-4. doi: 10.1002/(sici)1099-1263(199807/08)18:4<281::aid-jat506>3.0.co;2-4.
The local lymph node assay is an alternative method for the prospective identification of chemicals that have the potential to cause skin sensitization. Activity in the assay is measured as a function of proliferative responses by draining lymph node cells induced by topical exposure of mice to the test chemical. Positive responses are defined as those where a test chemical, at one or more application concentrations, is able to induce a stimulation index of 3 or greater compared with concurrent vehicle-treated control values. Although the method has been evaluated extensively, the stability over time of responses induced in the local lymph node assay has not previously been addressed formally. It was the purpose of the investigations described here to consider this issue and, to this end, responses provoked in the local lymph node assay by hexyl cinnamic aldehyde (HCA)--a skin sensitizing chemical of moderate potency--were assessed in five separate experiments conducted in a single laboratory over a 10-month period. In each case, HCA elicited a positive response. Although some significant inter-experimental variation was recorded, this was attributable entirely to the stimulation by HCA of slightly more vigorous responses in one of the five experiments. When the results of this experiment were excluded from the data set, significant variations were lost. Finally, for each experiment an EC3 value was derived, this being the estimated concentration of test chemical required to induce a stimulation index of 3. Similar EC3 values were derived in each experiment. These data demonstrate the relative stability over time of activity in the local lymph node assay.
局部淋巴结试验是一种前瞻性鉴定具有皮肤致敏潜力化学物质的替代方法。该试验中的活性通过小鼠局部暴露于受试化学物质后引流淋巴结细胞的增殖反应来衡量。阳性反应定义为在一个或多个应用浓度下，受试化学物质与同时期赋形剂处理的对照值相比能够诱导刺激指数为3或更高的反应。尽管该方法已得到广泛评估，但局部淋巴结试验中诱导反应随时间的稳定性此前尚未得到正式研究。本文所述研究的目的是考虑这个问题，为此，在一个单一实验室于10个月内进行的五项独立实验中，评估了己基肉桂醛（HCA，一种中等效力的皮肤致敏化学物质）在局部淋巴结试验中引发的反应。在每种情况下，HCA均引发了阳性反应。尽管记录到了一些显著的实验间差异，但这完全归因于在五项实验之一中HCA刺激的反应稍强。当将该实验的结果从数据集中排除时，显著差异消失了。最后，为每个实验得出一个EC3值，即诱导刺激指数为3所需的受试化学物质的估计浓度。每个实验得出的EC3值相似。这些数据证明了局部淋巴结试验中活性随时间的相对稳定性。
