TOXICOLOGY OF NASAL GAS DEPOSITION IN FIVE SPECIES

区域沉积模式决定了向呼吸道输送的剂量 在吸入暴露期间跟踪靶细胞，因此是至关重要的 来确定最终的毒性反应。提出的研究重点是 关于上呼吸道(URT)反应性气体的沉积。 具体地说，这项研究的目的是提供关于 乙醛、丙烯醛和乙醛在城市污水中沉积的物种差异 二氧化氮(NO2)；提供关于沉积的定量数据 这些气体在两种高浓度的吸入气体中，例如在 吸入毒性测试，而且更低，更环保 浓度；以及检查暴露在混合物中的动物的沉积 以确定同时暴露的条件，如 那些发生在环境中的物质会改变这些物质的沉积模式 三种反应性气体。此外，这些实验将检验 在单向和循环流动条件下的沉积 确定常用单向流获取的数据是否 方法合理地预测在更多的情况下发生的事件 生理性的循环流动条件。为了实现这些目标，沉积 乙醛、丙烯醛和/或亚硝酸根将在恒速下测量。 手术隔离的城市轨道交通中的单向和循环流动条件 麻醉SD大鼠、B6C3F1小鼠、叙利亚仓鼠和 哈特利豚鼠，四种常见的吸入性毒性 测试。将在暴露于每种气体的动物身上进行测量。 在单独和暴露于这些气体组合的动物中也是如此。 吸入剂量学关系是准确危害的必要条件 评估，特别是比较动物之间的毒性数据 物种，将高剂量(浓度)研究外推到低剂量 情景，以及从个人接触中获得的毒性数据的使用 用于预测更复杂的多种毒物暴露的毒性的试剂 设置。通过提供关于每一项的详细剂量信息 在危险评估领域，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 如本研究中使用的反应性气体的数据。此外, 这项拟议的研究旨在检验一种广泛使用的 未经验证的城市轨道交通反应气体沉积传质数学模型。 这些建模工作不仅将提供对关键因素的洞察 控制沉积机制，但也可能导致 城市轨道交通沉降量预测模型。因此，拟议的研究由 提高我们理解、推断和预测城市轨道交通剂量的能力 反应性气体的关系，将极大地促进我们的知识 在这一重要的吸入毒理学领域。

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.