Toxicity of Subchronic Fungal Exposures

霉菌因毒理学特征而被提名参加NTP，基于他们的吸入、真菌学和免疫学专业知识，NIOSH被聘请为合作伙伴，对模拟真实世界暴露的单个生物或霉菌混合物进行多次亚慢性(13周)暴露研究。NIOSH已经开发出一种系统，可以通过吸入精确控制暴露在颗粒物中。这种方法克服了以前在实验动物模型中进行的霉菌暴露研究的一些限制，这些模型使用不太相关的暴露方法来评估真菌毒性。作为这一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。以烟曲霉菌为模型生物进行了初步研究。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B6C3F1/N小鼠暴露于真菌的全身影响。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，然后是木霉(产生真菌毒素和不产生化学类型)。初步数据表明，与先前评估的烟曲霉菌相比，暴露于这种微生物后所产生的肺部炎症反应不同。在2015财年，NTP研究设计被批准用于13周的毒理学研究，使用这些生物。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任务，以改进特定物种的真菌鉴定，并更好地评估与真菌暴露有关的健康影响。从这些项目中获得的知识将有助于制定改进的环境真菌量化测试方法，并产生数据，以加强真菌暴露风险评估的科学基础。这些项目还将涉及NIOSH和NIEHS的具体研究目标，以减少环境和职业原因或在工人人口和儿童中导致急慢性疾病和疾病的因素。

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.