Laboratory for Health Protection Research, National Institute for Public Health and the Environment-RIVM, PO Box 1, NL-3720BA Bilthoven, The Netherlands.
Toxicology. 2012 Sep 4;299(1):20-4. doi: 10.1016/j.tox.2012.05.002. Epub 2012 May 4.
The concept that thresholds exist for the induction of allergic contact dermatitis by chemicals with skin sensitizing properties has been used for a quantitative risk assessment approach. In this approach the potency of skin sensitizers as determined in the Local Lymph Node Assay is used to calculate the threshold for induction of sensitization. These are then used to estimate safe exposure levels for consumers. Whether these exposure levels will protect subjects that are already sensitized is unknown. The elicitation of allergic contact dermatitis supposedly occurs above a certain threshold as well and this threshold is most likely lower than that for the induction. It is unclear if induction thresholds can be extrapolated to elicitation thresholds. The aim of this study was to assess the potency of sensitizers with different sensitizing potencies in the elicitation phase in a mouse model for elicitation. Mice were sensitized by topical application on days 0 and 7 using equipotent concentrations of oxazolone, 2,4-dinitrochlorobenzene (DNCB) and eugenol to ensure that the sensitization strength would not influence the elicitation potency. Mice were challenged on day 21 by topical application on the ears in a dose-dependent manner and dose-response data were used to calculate the elicitation potency. Unexpectedly, sensitizers with different sensitizing potencies induced not the same dose-response curves in sensitized mice. The most potent sensitizer in the elicitation phase was oxazolone, followed by DNCB and eugenol. Similar to the induction phase, under equipotent sensitization conditions strong sensitizers such as oxazolone and DNCB elicit allergic reactions at lower concentrations than weak sensitizers such as eugenol. Our results indicate that elicitation thresholds cannot be readily deduced from sensitization thresholds.
化学物质具有皮肤致敏性，其诱导过敏接触性皮炎的概念已被用于定量风险评估方法。在这种方法中，皮肤致敏剂的效力通过局部淋巴结测定来确定，用于计算致敏诱导的阈值。然后，这些被用于估计消费者的安全暴露水平。然而，这些暴露水平是否会保护已经致敏的受试者是未知的。过敏接触性皮炎的激发也被认为发生在一定的阈值之上，而且这个阈值很可能低于诱导的阈值。尚不清楚诱导阈值是否可以外推到激发阈值。本研究旨在评估不同致敏强度的致敏剂在激发阶段的效力，使用不同致敏强度的致炎剂进行致敏。在致敏阶段，0 天和 7 天通过在耳朵上进行不同浓度的二硝基氯苯（DNCB）和丁香酚涂抹处理，在小鼠模型中进行致敏。致敏强度不会影响激发效力，所以选择了不同致敏强度的致炎剂，以确保致炎剂的浓度相同。在第 21 天，通过在耳朵上进行剂量依赖性涂抹处理进行激发挑战，使用剂量-反应数据计算激发效力。出乎意料的是，不同致敏强度的致敏剂在致敏小鼠中并未诱导出相同的剂量-反应曲线。在激发阶段最有效的致敏剂是 2,4-二硝基氯苯，其次是丁香酚和氧芴酮。与诱导阶段相似，在相同的致敏条件下，强致敏剂如氧芴酮和 DNCB 比弱致敏剂如丁香酚在较低浓度下引发过敏反应。我们的结果表明，激发阈值不能轻易从致敏阈值推断出来。
