TOXICOLOGY OF NASAL GAS DEPOSITION IN FIVE SPECIES

毒理学的一个原则是剂量反应，即，的 反应的大小取决于毒物的剂量。 区域 沉积在确定局部剂量方面很重要，因此， 呼吸道对吸入有毒气体的反应。 以前的研究 在该实验室中已经显示了乙醇和丙酮鼻沉积 Sprague-Dawley大鼠中的蒸汽可通过肺 通气-灌注模型提示鼻上皮膜 足够薄以允许气体分子在 吸入的空气和鼻腔毛细血管的血液。 建议的实验是 旨在确定肺通气-灌注模型是否可以 成功地应用于描述各种鼻沉积过程 提供物种间的详细信息， 鼻腔气体沉积过程的可变性。 为了实现这些目标， 丙酮和乙醇的沉积效率将在 手术分离麻醉小鼠，仓鼠， Fischer 344大鼠、豚鼠和家兔在各种生理条件下 吸气速率，并将通过类比分析获得的数据， 肺通气-灌注模型。 吸入毒理学研究的目标包括预测毒性风险 在动物研究的基础上， 中毒性损伤 由于区域沉积是首要的， 确定全国各地区吸入有毒物质的剂量 呼吸道，了解区域气体的种间变异性 沉积将是非常有用的选择适当的物种， 吸入研究以及解释和比较毒性反应 吸入有毒气体的危害 拟议的研究，由 提供了关于鼻粘膜中物种特异性变异的详细信息， 气体沉积过程，将，在长期，推进科学的， 吸入毒理学 此外，这些实验可以阐明 一般哺乳动物的现象，即，惰性气体交换与平衡 气体分子穿过鼻腔以及肺泡上皮细胞膜。

One tenet of the science of toxicology is that of dose-response, viz., the magnitude of the response is dependent upon the dose of toxicant. Regional deposition is important in determining the local dose and, therefore, the response of the respiratory tract to inhaled toxic gases. Previous studies in this laboratory have shown that nasal deposition of ethanol and acetone vapors in the Sprague-Dawley rat can be described by pulmonary ventilation-perfusion models suggesting that the nasal epithelial membrane is sufficiently thin to allow equilibration of gas molecules between the inspired air and the nasal capillary blood. The proposed experiments are aimed at determining if pulmonary ventilation-perfusion models can be successfully applied to describe the nasal deposition process in a variety of species, and at providing detailed information on interspecies variability in the nasal gas deposition process. Towards these ends, acetone and ethanol deposition efficiencies will be measured in the surgically isolated nasal cavity of the anesthetized mouse, hamster, Fischer 344 rat, guinea pig and rabbit at a variety of physiologic inspiratory rates, and the data obtained will be analyzed by analogy to pulmonary ventilation-perfusion models. Goals of inhalation toxicologic research include prediction of toxic risk to man on the basis of animal studies, and elucidation of mechanisms of toxic injury. Since regional deposition is of primary importance in determining the dose of inhaled toxicant received by various regions of the respiratory tract, knowledge of interspecies variability in regional gas deposition would be extremely useful in selecting appropriate species for inhalation research and in interpreting and comparing the toxic responses of various species to inhaled gaseous toxicants. The proposed research, by providing detailed information on species-specific variability in the nasal gas deposition process, will, in the long-term, advance the science of inhalation toxicology. In addition, these experiments may elucidate a general mammalian phenomenon, viz., the exchange and equilibration of inert gas molecules across the nasal as well as the alveolar epithelial membranes.