TOXICOLOGY OF NASAL GAS DEPOSITION IN FIVE SPECIES

区域沉积模式决定了输送到呼吸道的剂量。 在吸入暴露过程中引导靶细胞，因此， 最终的毒性反应。 建议的研究重点 上呼吸道（URT）反应性气体的沉积。 具体而言，这项研究旨在提供以下方面的详细信息： 乙醛、丙烯醛和 二氧化氮（NO2）;提供关于 这些气体在两个高吸入浓度，如那些用于 吸入毒性测试，也更低，更环保 浓度;以及检查接触混合物的动物体内的沉积 以确定是否同时暴露条件， 环境中发生的变化改变了这些物质的沉积模式 三种反应气体 此外，这些实验将检查 在单向和循环流动条件下的沉积， 确定通常使用的单向流动获得的数据是否 方法可以合理地预测在更高的温度下发生的事件。 生理循环流动条件。 为了实现这些目标， 乙醛、丙烯醛和/或NO2将在恒定速度下测量 单向和循环流动的条件下，手术隔离URT的 麻醉的Sprague-Dawley大鼠、B6 C3 F1小鼠、叙利亚仓鼠和 Hartley豚鼠，吸入毒性中常用的四种动物 试验. 将在暴露于每种气体的动物中进行测量 单独地以及在暴露于这些气体的组合的动物中。 吸入剂量测定关系对于准确的危害是必要的 评估，特别是用于比较动物之间的毒性数据 物种，将高剂量（浓度）研究外推至低剂量 使用从个人接触中获得的毒性数据 在更复杂的多毒物暴露中预测毒性的试剂 设置. 通过提供详细的剂量测定信息， 危险评估领域，拟议的研究将，从长远来看， 极大地增强了我们理解和推断毒性的能力 反应性气体的数据，如本研究中使用的数据。 此外，本发明还提供了一种方法， 拟议的研究旨在检查一种广泛使用但 未经验证的数学传质模型URT反应气体沉积。 这些建模工作不仅将提供对关键因素的深入了解， 控制沉积机制，但也可能导致发展 城市轨道交通沉积预测模型。 因此，拟议的研究，由 增强我们理解、推断和预测URT剂量测定的能力 反应性气体的关系，将大大提高我们的知识 吸入毒理学的重要领域

Regional deposition patterns determine the dose delivered to respiratory tract target cells during inhalation exposure and, therefore, are critical in determining the ultimate toxic response. The proposed research focusses on upper respiratory tract (URT) deposition of reactive gases. Specifically, the research is aimed at providing detailed information on species differences in URT deposition of acetaldehyde, acrolein and nitrogen dioxide (NO2); at providing quantitative data on deposition of these gases at both high inspired concentrations, such as those used in inhalation toxicity testing, and also lower, more environmentally relevant concentrations; and at examining deposition in animals exposed to mixtures of these gases to determine if simultaneous exposure conditions such as those occurring in the environment, alter deposition patterns of these three reactive gases. In addition, these experiments will examine deposition under both unidirectional and cyclic flow conditions to determine if data obtained by commonly used unidirectional flow methodologies are reasonably predictive of events occurring under more physiologic, cyclic flow conditions. To meet these aims, deposition of acetaldehyde, acrolein and/or NO2 will be measured under constant velocity unidirectional and cyclic flow conditions in the surgically isolated URT of the anesthetized Sprague-Dawley rat, B6C3F1 mouse, Syrian hamster and Hartley guinea pig, four species commonly employed in inhalation toxicity testing. Measurements will be made in animals exposed to each gas individually and also in animals exposed to combinations of these gases. Inhalation dosimetric relationships are necessary for accurate hazard assessment, particularly for comparison of toxicity data among animal species, extrapolation of high dose (concentration) studies to low dose scenarios, and use of toxicity data derived from exposures to individual agents to predict toxicity in more complicated multi-toxicant exposure settings. By providing detailed dosimetric information on each of these areas of hazard assessment, the proposed research will, in the long-term, dramatically enhance our ability to understand and extrapolate toxicity data for reactive gases such as those used in this research. In addition, the proposed research is aimed at examination of a widely used but unvalidated mathematic mass-transfer model for URT reactive gas deposition. These modeling efforts will not only provide insights into critical factors controlling deposition mechanisms, but also may lead to the development of predictive models of URT deposition. Thus, the proposed research, by enhancing our ability to understand, extrapolate and predict URT dosimetric relationships for reactive gases, will significantly advance our knowledge in this important area of inhalation toxicology.