Toxicity of Subchronic Fungal Exposures

根据他们的吸入、真菌学和免疫学专业知识，NIOSH被提名为NTP的毒理学特征，并作为合作伙伴参与对个体生物体或模仿现实世界暴露的霉菌混合物进行多次亚慢性（13周）暴露研究。NIOSH开发了一种系统，可以通过吸入精确控制颗粒暴露。这种方法克服了以前在实验动物模型中使用不太相关的暴露手段来评估真菌毒性的霉菌暴露研究的一些局限性。作为合作伙伴关系的一部分，声学产生系统（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品。选择烟曲霉作为初步研究的模式生物。2015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B6C3F1/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，首先是曲霉，然后是Stachybotrys chartarum（产生霉菌毒素和不产生霉菌毒素的化学型）。对沙氏葡萄曲霉进行了初步研究，初步数据表明，与先前评估的烟曲霉相比，暴露于这种有机体后产生的肺部炎症反应不同。在2015财年，NTP研究设计被批准使用这些生物进行为期13周的毒理学研究。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改进真菌的物种特异性鉴定并更好地评估与真菌接触有关的健康影响，从而支持国家结核控制项目的使命。从这些项目中获得的知识将有助于开发用于环境真菌量化的改进测试方法，并产生将加强真菌暴露风险评估的科学基础的数据。这些项目还将解决NIOSH和NIEHS的具体研究目标，以减少造成工人和儿童急性和慢性疾病的环境和职业原因或促成因素。

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.