Sailstad Denise M, Ward Marsha D W, Boykin Elizabeth H, Selgrade MaryJane K
United States Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Mail Code: B143-04, Research Triangle Park, NC 27711, USA.
Toxicology. 2003 Dec 15;194(1-2):147-61. doi: 10.1016/s0300-483x(03)00338-x.
Exposure to low molecular weight (LMW) chemicals contributes to both dermal and respiratory sensitization and is an important occupational health problem. Our goal was to establish an in vivo murine model for hazard identification of LMW chemicals that have the potential to induce respiratory hypersensitivity (RH). We used a dermal sensitization protocol followed by a respiratory challenge with the evaluation of endpoints typically associated with RH in human disease. Trimellitic anhydride (TMA) was used as a prototype respiratory sensitizer and was compared to the dermal sensitizer; 2,4-dinitrofluorobenzene (DNFB), along with vehicle controls. BALB/c mice were dermally sensitized using two exposure protocols. Mice in both protocols were dermally exposed on experimental days; D-18 and D-17 (abdomen), and D-13 (ear). On D 0 mice received an intratracheal (IT) challenge. The mice in Protocol 2 were abdominally exposed twice with the addition of exposures on D-25 and D-24. Results indicate that mice required the additional dermal sensitization and the IT challenge (Protocol 2) to significantly elevate total IgE in serum and bronchoalveolar lavage fluid (BALF). Additional responses suggestive of RH were seen following Protocol 2, including increases in BALF cell numbers and neutrophils post IT with TMA (but not DNFB). These data suggest that the dermal sensitization and IT challenge followed by evaluation of serum antibodies and lung parameters are a reasonable and logistically feasible approach towards the development of a model for RH responses to LMW chemicals.
接触低分子量（LMW）化学物质会导致皮肤和呼吸道致敏，是一个重要的职业健康问题。我们的目标是建立一种体内小鼠模型，用于识别有潜力诱发呼吸道超敏反应（RH）的LMW化学物质的危害。我们采用了一种皮肤致敏方案，随后进行呼吸道激发，并评估通常与人类疾病中的RH相关的终点指标。偏苯三酸酐（TMA）用作原型呼吸道致敏剂，并与皮肤致敏剂2,4-二硝基氟苯（DNFB）以及赋形剂对照进行比较。使用两种暴露方案对BALB/c小鼠进行皮肤致敏。两种方案中的小鼠均在实验日进行皮肤暴露；D-18和D-17（腹部），以及D-13（耳部）。在D 0天，小鼠接受气管内（IT）激发。方案2中的小鼠在D-25和D-24增加暴露，腹部暴露两次。结果表明，小鼠需要额外的皮肤致敏和IT激发（方案2）才能显著提高血清和支气管肺泡灌洗液（BALF）中的总IgE。在方案2之后观察到了其他提示RH的反应，包括TMA（而非DNFB）进行IT激发后BALF细胞数量和中性粒细胞增加。这些数据表明，皮肤致敏和IT激发，随后评估血清抗体和肺部参数，是开发针对LMW化学物质的RH反应模型的一种合理且在逻辑上可行的方法。
