Toxicity of Subchronic Fungal Exposures

霉菌被提名给NTP进行毒理学表征，基于其吸入、真菌学和免疫学专业知识，NIOSH作为合作伙伴对单个微生物或霉菌混合物进行多次亚慢性（13周）暴露研究，模拟真实世界的暴露。NIOSH开发了一种系统，可以通过吸入精确控制颗粒物的暴露。这种方法克服了与先前在实验动物模型中进行的霉菌暴露研究相关的许多局限性，这些研究使用了不太相关的暴露手段来评估真菌毒性。作为该合作伙伴关系的一部分，开发的声学生成系统（AGS）以模拟自然室内真菌污染物暴露的方式向小鼠提供真菌测试物品。选择烟曲霉作为初始研究的模式生物。在2015财年，NIOSH进行了一项为期13周的亚慢性毒理学研究，以检查真菌暴露对B6 C3 F1/N小鼠的全身影响。 NIOSH已经开始优化另外两种感兴趣的真菌的暴露条件，首先是杂色曲霉，然后是Stachyboboesthartarum（产生和不产生霉菌毒素的化学型）。初步研究进行了水苏糖，初步数据表明，所产生的肺部炎症反应不同暴露于这种生物体相比，以前评估的烟曲霉。 在2015财年，NTP研究设计获批用于使用这些微生物进行13周毒理学研究。 作为这一机构间协议的一部分开展的项目通过开发分析试剂来支持NTP的使命，以改进真菌的物种特异性鉴定，并更好地评估与真菌暴露相关的健康影响。从这些项目中获得的知识将有助于开发更好的测试方法，以量化环境真菌，并产生数据，加强真菌接触风险评估的科学基础。这些项目还将解决具体的NIOSH和NIEHS研究目标，以减少环境和职业原因或促成因素的急性和慢性疾病和疾病的工人人口以及儿童。

Mold was nominated to the NTP for toxicological characterization and based on their inhalation, mycological, and immunological expertise, NIOSH was engaged as a partner to conduct multiple sub-chronic (13-week) exposure studies to individual organisms or mixtures of molds mimicking a real-world exposure. NIOSH has developed a system that allows for precisely controlled exposures to particulates via inhalation. This approach overcomes a number of limitations associated with previous mold exposure studies in experimental animal models that have used less relevant means of exposure to assess fungal toxicity. The acoustical generation system (AGS) developed as part of this partnership delivers fungal test articles to mice in a manner that simulates natural indoor fungal contaminant exposure. Aspergillus fumigatus was selected as a model organism for the initial studies. In FY15 NIOSH conducted a 13-week sub chronic toxicology study to examine systemic effects of fungal exposures in B6C3F1/N mice. NIOSH has begun to optimize exposure conditions for two additional fungi of interest, beginning with Aspergillus versicolor, and then Stachybotrys chartarum (mycotoxin producing and non-producing chemotypes). Pilot studies were conducted with Stachybotrys chartarum and preliminary data suggests that the resulting pulmonary inflammatory responses differ following exposure to this organism as compared to the previously evaluated Aspergillus fumigatus. In FY15, the NTP study design was approved for 13 week toxicology studies using these organisms. The projects conducted as part of this interagency agreement support the NTP mission through the development of analytical reagents for improved species-specific identification of fungi and to better evaluate the health effects associated with fungal exposures. The knowledge gained from these projects will assist in the development of improved testing methods for the quantification of environmental fungi, as well as generate data that will strengthen the scientific base for fungal exposure risk assessment. These projects will additionally address specific NIOSH and NIEHS research goals for reducing environmental and occupational causes or contributing factors to acute and chronic illness and disease in worker populations as well as children.