Nasal dosimetry of diacetyl and butyric acid vapors

二乙酰和丁酸蒸气的鼻剂量测定

• 批准号: 6963496
• 负责人: JOHN B MORRIS
• 金额: $ 7.4万
• 依托单位: UNIVERSITY OF CONNECTICUT STORRS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6963496
• 关键词: antipyrine; bronchus disorder; butyrates; dosage; food additives; laboratory rat; larynx; occupational disease /disorder; physical chemical interaction; pulmonary respiration; respiratory system; toxicology; toxin metabolism; trachea; vapor

DESCRIPTION (provided by applicant): The inhalation toxicity of inspired materials is critically dependent on their inhalation dosimetric patterns; this may be particularly true for the vapors derived from artificial butter flavorings. Although generally recognized as safe as food additives, exposure of workers to these vapors is associated with bronchiolitis obliterans. It has recently been shown that inhalation exposure of the rat to butter flavoring vapors results in necrosis of the nasal, bronchial and bronchiolar airways. Exposure to diacetyl (2,3 butadiene), a major component of butter flavoring vapors, results in necrosis of the nasal and trachea, but not the intrapulmonary airways. Diacetyl is metabolized by dicarbonyl reductase, an enzyme that is expressed in human and rodent respiratory tissues. Butyric acid, another major component of butter flavoring vapors, is a potent inhibitor of dicarbonyl reductase. As for other weak organic acids, it is likely that butyric acid deposits efficiently in the upper respiratory tract. Nasal metabolism is known to enhance uptake of inspired metabolized vapors, inhibition of nasal metabolism diminishes uptake in that site. This small grant proposal is aimed at characterizing upper respiratory tract uptake of diacetyl and testing the hypothesis that co-exposure to butyric acid vapor results in diminished upper respiratory tract uptake and enhanced penetration of inspired diacetyl to the target site- the lower airways. To achieve these aims uptake of diacetyl will be measured in the surgically isolated upper respiratory tract of the anesthetized rat at a variety of inspiratory flow rates and inspired concentrations, the effects of co-exposure to butyric acid on nasal diacetyl uptake will be examined, and the ability of butyric acid to inhibit nasal diacetyl metabolism in vitro will be assessed. The proposed research will provide much information that will significantly enhance our ability to quantitatively assess the risks associated with diacetyl/butter flavoring vapors, but the primary health significance lies in the use of this example to examine a novel metabolically-based mechanism for inspired vapor-vapor interactions. The URT is a metabolically competent organ expressing many xenobiotic metabolizing systems; such vapor-vapor interaction mechanisms could have relevance to a wide variety of air pollutants. Thus, in the long term, the proposed studies have the potential to enhance our ability to understand and perhaps more importantly, predict, toxicologically relevant vapor-vapor interactions that may occur during complex real world exposure scenarios.

描述（由申请方提供）：吸入材料的吸入毒性主要取决于其吸入剂量测定模式;这对于源自人造黄油调味剂的蒸汽尤其如此。 虽然一般认为作为食品添加剂是安全的，但工人暴露于这些蒸气与闭塞性细支气管炎有关。 最近已经表明，大鼠吸入暴露于黄油调味品蒸气导致鼻、支气管和细支气管气道坏死。 暴露于丁二酮（2，3丁二烯），黄油调味品蒸汽的主要成分，导致鼻和气管坏死，但不会导致肺内气道坏死。 双乙酰通过二羰基还原酶代谢，这是一种在人类和啮齿动物呼吸组织中表达的酶。 丁酸是黄油调味蒸汽的另一种主要成分，是二羰基还原酶的有效抑制剂。 至于其他弱有机酸，丁酸可能有效地沉积在上呼吸道中。 已知鼻代谢增强吸入的代谢蒸气的摄取，抑制鼻代谢减少该部位的摄取。 这项小额资助提案旨在表征双乙酰的上呼吸道摄取，并测试共同暴露于丁酸蒸汽导致上呼吸道摄取减少和吸入双乙酰向靶部位-下呼吸道渗透增强的假设。 为了实现这些目标，将在麻醉大鼠的手术分离的上呼吸道中以各种吸气流速和吸气浓度测量双乙酰的摄取，将检查共暴露于丁酸对鼻双乙酰摄取的影响，并将评估丁酸体外抑制鼻双乙酰代谢的能力。 拟议的研究将提供大量信息，这些信息将显着提高我们定量评估与双乙酰/黄油调味品蒸汽相关的风险的能力，但主要的健康意义在于使用该示例来检查一种新的基于代谢的机制，用于激发蒸汽-蒸汽相互作用。 URT是一个有代谢能力的器官，表达许多异生物质代谢系统;这种蒸气-蒸气相互作用机制可能与各种空气污染物有关。 因此，从长远来看，拟议的研究有可能提高我们的理解能力，也许更重要的是，预测，在复杂的真实的世界暴露场景中可能发生的毒理学相关的蒸气-蒸气相互作用。