Vanoirbeek Jeroen A J, Mandervelt Cindy, Cunningham Albert R, Hoet Peter H M, Xu Haiyan, Vanhooren Hadewijch M, Nemery Benoit
Pneumology (Lung Toxicology), Katholieke Universiteit Leuven, Leuven, Belgium.
Toxicol Sci. 2003 Dec;76(2):338-46. doi: 10.1093/toxsci/kfg235. Epub 2003 Sep 26.
A piperidinyl chlorotriazine (PCT) derivative, used as a plastic UV-stabilizer, caused an outbreak of occupational asthma. We verified, in BALB/c mice, the sensitizing potential of PCT in comparison to a known respiratory sensitizer (toluene diisocyanate [TDI]) and a known dermal sensitizer (oxazolone), using three different methods in order to evaluate the validity of current models of sensitization. These included the local lymph node assay (LLNA) and the mouse IgE test. In addition, respiratory hyper-reactivity was assessed following a novel protocol involving dermal sensitization (20 microl of a 3% solution on each ear for three days) and intranasal challenge (0.1% or 1%, 10 microl per nostril on day 10), followed, after 24 h, by a methacholine challenge (using whole-body plethysmography), bronchoalveolar lavage, and histology. PCT was also used for structure-activity relationship (SAR) models for (respiratory) sensitization. High concentrations of PCT (10 and 20%) resulted in significant responses in the local lymph node assay (LLNA; stimulation indices (SI) of 2.7 +/- 0.9 and 3.2 +/- 0.6, respectively). The mouse IgE test was positive with 20% PCT only. Methacholine responsiveness was increased only in previously sensitized mice receiving a challenge with TDI or PCT. However, there was no evidence for pulmonary inflammation. The SAR studies indicated that PCT could be a respiratory sensitizer. Based on an approved test protocol such as the LLNA and the mouse IgE test, PCT proved to be a weak sensitizer when compared to TDI and oxazolone. However, in a protocol involving an intranasal challenge, PCT appeared to be a respiratory sensitizer of similar potency to TDI.
一种用作塑料紫外线稳定剂的哌啶基氯三嗪（PCT）衍生物引发了职业性哮喘疫情。我们在BALB/c小鼠中，将PCT的致敏潜力与一种已知的呼吸道致敏剂（甲苯二异氰酸酯[TDI]）和一种已知的皮肤致敏剂（恶唑酮）进行了比较，使用三种不同方法来评估当前致敏模型的有效性。这些方法包括局部淋巴结测定法（LLNA）和小鼠IgE试验。此外，按照一种新方案评估呼吸高反应性，该方案包括皮肤致敏（每只耳朵上涂抹20微升3%溶液，共三天）和鼻内激发（第10天每侧鼻孔10微升0.1%或1%溶液），24小时后接着进行乙酰甲胆碱激发（使用全身体积描记法）、支气管肺泡灌洗和组织学检查。PCT还用于（呼吸道）致敏的构效关系（SAR）模型。高浓度的PCT（10%和20%）在局部淋巴结测定法（LLNA）中产生了显著反应（刺激指数[SI]分别为2.7±0.9和3.2±0.6）。仅20%的PCT使小鼠IgE试验呈阳性。乙酰甲胆碱反应性仅在先前接受TDI或PCT激发的致敏小鼠中增加。然而，没有肺部炎症的证据。SAR研究表明PCT可能是一种呼吸道致敏剂。基于诸如LLNA和小鼠IgE试验等已批准的试验方案，与TDI和恶唑酮相比，PCT被证明是一种弱致敏剂。然而，在涉及鼻内激发的方案中，PCT似乎是一种与TDI效力相似的呼吸道致敏剂。
