Vanoirbeek Jeroen A J, De Vooght Vanessa, Synhaeve Nicholas, Nemery Benoit, Hoet Peter H M
Research Unit Lung Toxicology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.
Toxicol Sci. 2009 Jun;109(2):256-64. doi: 10.1093/toxsci/kfp065. Epub 2009 Mar 30.
Toluene diamine (TDA) is formed when toluene diisocyanate (TDI), a potent sensitizer, comes in contact with an aqueous environment. The sensitizing capacity of TDA and the cross-reactivity between TDI and TDA are unknown. TDA (5-25%) and TDI (0.3%), dissolved in acetone/olive oil (AOO) (4:1) were tested in the mouse local lymph node assay (LLNA). To determine the capacity of TDA to elicit an asthmatic response and to determine the cross-reaction with TDI, a locally developed experimental mouse model of chemical-induced asthma was used. On days 1 and 8, BALB/c mice received 20 microl of TDI (0.3%), TDA (20%), or AOO (4:1) on each ear. On day 15, they received an intranasal instillation of TDI (0.1%), TDA (0.5%) or AOO (3:2). The EC(3) of TDA in the LLNA is 19%. In the model of chemical-induced asthma, TDI induced a ventilatory response [increased Penh after challenge; increased airway hyperreactivity (AHR)], inflammatory changes (bronchoalveolar lavage neutrophils), and immunological changes (increased CD19(+) lymphocytes, IL-4 and total serum IgE), whereas TDA did not show any of these responses. Mice sensitized with TDI and challenged with TDA also did not show any airway or inflammatory response, although they had increased levels of total serum IgE. Mice sensitized with TDA and challenged with TDI did not show any response. According to the classification of sensitizers in the LLNA, TDA is a weak dermal sensitizer. In the experimental mouse model of chemical-induced asthma, TDA does not act as a respiratory sensitizer, at the concentration used. No cross-reactivity between TDI and TDA was found.
当强力致敏剂甲苯二异氰酸酯（TDI）与水环境接触时会形成甲苯二胺（TDA）。TDA的致敏能力以及TDI与TDA之间的交叉反应性尚不清楚。将溶解于丙酮/橄榄油（AOO）（4:1）中的TDA（5 - 25%）和TDI（0.3%）用于小鼠局部淋巴结试验（LLNA）。为了确定TDA引发哮喘反应的能力以及与TDI的交叉反应，使用了局部建立的化学诱导哮喘实验小鼠模型。在第1天和第8天，BALB/c小鼠每只耳朵接受20微升TDI（0.3%）、TDA（20%）或AOO（4:1）。在第15天，它们接受TDI（0.1%）、TDA（0.5%）或AOO（3:2）的鼻内滴注。TDA在LLNA中的半数有效浓度（EC(3)）为19%。在化学诱导哮喘模型中，TDI诱导了通气反应[激发后Penh增加；气道高反应性（AHR）增加]、炎症变化（支气管肺泡灌洗中性粒细胞）和免疫变化（CD19(+)淋巴细胞、IL - 4和总血清IgE增加），而TDA未表现出任何这些反应。用TDI致敏并用TDA激发的小鼠也未表现出任何气道或炎症反应，尽管它们的总血清IgE水平有所升高。用TDA致敏并用TDI激发的小鼠未表现出任何反应。根据LLNA中致敏剂的分类，TDA是一种弱皮肤致敏剂。在化学诱导哮喘的实验小鼠模型中，在所使用的浓度下，TDA不作为呼吸道致敏剂。未发现TDI与TDA之间有交叉反应。
