Investigation of Bronchiolitis Obliterans Caused by Artificial Butter flavoring

人造黄油调味品引起闭塞性细支气管炎的调查

• 批准号: 8553775
• 负责人: DANIEL MORGAN
• 金额: $ 51.03万
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8553775
• 关键词: Animal Model; Area; Biological; Breathing; Bronchiolitis; Bronchiolitis Obliterans; Butter; Chemicals; Chronic; Data; Development; Diacetyl; Disease; Dose; Early Diagnosis; Employee; Epithelium; Event; Exposure to; Female; Fibrosis; Flavoring; Food Additives; Goals; Graft Rejection; Human; Inhalation Exposure; Intervention; Investigation; Lesion; Lung; Methods; Occupational; Organ; Pathogenesis; Plants; Prevention; Rattus; Research Design; Respiratory System; Respiratory tract structure; Rodent; Site; Survival Rate; Time; Toxic effect; Transplantation; consumer product; cytokine; diketone; effective therapy; male; microwave electromagnetic radiation

Diacetyl, a reactive diketone used in artificial butter flavoring has been associated with obliterative bronchiolitis (OB) in employees at microwave popcorn packaging plants; however, the mechanisms of toxicity are unknown. We recently demonstrated that diacetyl, the major volatile component of artificial butter flavoring, caused OB-like lesions in rats after inhalation exposure. Because of concerns about diacetyl toxicity, it is being replaced in some consumer products by 2,3-pentanedione (PD), and possibly 2,3-hexanedione (HD), both structurally-related and untested chemicals. Because the toxicity of inhaled PD and HD are unknown, studies were conducted to characterize the toxicity after inhalation exposure to a range of concentrations in rodents. Male and female Wistar-Han rats were exposed to 0, 50, 100, or 200 ppm PD 6h/d, 5d/wk for up to 2 wk. PD was found to cause OB-like lesions simlar to those caused by diacetyl. The epithelium lining the respiratory tract was the site of toxicity in all rats exposed to 200 ppm. Diacetyl and PD both caused fibrotic airway lesions in rats with pathological features of OB. The histopathological and biological changes observed in rats raise concerns that PD inhalation may also cause OB in exposed humans.nalyzed for cytokines at various timepoints during exposure. Additional studies are underway to investigate the time course of events leading to airway fibrosis, in order to find areas for potential intervention and treatment. HD toxicity is being investigated using the same study design.

二乙酰是一种用于人造黄油调味料的反应性二酮，它与微波爆米花包装厂员工的闭塞性细支气管炎 (OB) 有关；然而，毒性机制尚不清楚。我们最近证明，人造黄油调味剂的主要挥发性成分二乙酰在吸入后会引起大鼠 OB 样病变。 由于担心二乙酰毒性，一些消费品中的二乙酰被 2,3-戊二酮 (PD) 和可能的 2,3-己二酮 (HD) 取代，这两种化学物质都是结构相关且未经测试的化学品。由于吸入 PD 和 HD 的毒性尚不清楚，因此进行了研究来表征啮齿动物吸入暴露于一定浓度后的毒性。 雄性和雌性 Wistar-Han 大鼠暴露于 0、50、100 或 200 ppm PD 6 小时/天、5 天/周，持续长达 2 周。发现 PD 会引起类似于丁二酮引起的 OB 样病变。所有暴露于 200 ppm 浓度的大鼠中，呼吸道内壁上皮是中毒部位。双乙酰和PD均引起具有OB病理特征的大鼠气道纤维化病变。 在大鼠中观察到的组织病理学和生物学变化引起了人们的关注，即吸入 PD 也可能导致暴露的人类发生 OB。在暴露期间的不同时间点分析了细胞因子。 其他研究正在进行中，以调查导致气道纤维化的事件的时间进程，以便找到潜在的干预和治疗领域。正在使用相同的研究设计来研究 HD 毒性。