Investigation of Bronchiolitis Obliterans Caused by Diacetyl Inhalation

吸入二乙酰所致闭塞性细支气管炎的调查

• 批准号: 7968193
• 负责人: DANIEL MORGAN
• 金额: $ 14.61万
• 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/7968193
• 关键词: Alveolar Duct; Animal Model; Breathing; Bronchi; Bronchiolitis; Bronchiolitis Obliterans; Bronchitis; Butter; Bypass; Cause of Death; Chemicals; Chronic; Chronic Bronchitis; Data; Development; Diacetyl; Disease; Dose; Early Diagnosis; Employee; Exposure to; Fibrosis; Flavoring; Food Additives; Goals; Graft Rejection; Inflammation; Injury; Investigation; Laryngitis; Lesion; Lung; Lymphocyte; Methods; Nasal cavity; Necrosis; Nose; Occupational; Organ; Oropharyngeal; Pathogenesis; Pattern; Plants; Prevention; Rattus; Rhinitis; Survival Rate; Terminal Bronchiole; Toxic effect; Transplantation; effective therapy; microwave electromagnetic radiation; respiratory; response

Artificial butter flavoring is a potential etiological agent of obliterative bronchiolitis (OB) in employees at microwave popcorn packaging plants; however, the specific toxic component(s),and the mechanisms of toxicity are unknown. We evaluated the respiratory toxicity of diacetyl, the major volatile component of artificial butter flavoring. Subacute exposure to 200 or 400 ppm diacetyl for 5 days caused deaths, necrotizing rhinitis and inflammation of the large bronchi. Reducing the exposure to 1 hr/day (100, 200, 400 ppm) for 4 weeks caused less nasal toxicity, chronic bronchitis and laryngitis, without bronchiolar lesions. Lymphocytic bronchitis and mild nasal injury were observed after exposures to 1200 ppm (15 minutes, 2x/day, 4 weeks). Subchronic exposures to 100 ppm (6 hr/day, 12 wks) caused lymphocytic bronchitis and bronchiolitis with minimal necrosis in the nasal cavity. Treatment with 400 mg/kg by oropharyngeal aspiration to bypass the nose caused foci of fibrosis with little or no inflammation at the junction of the terminal bronchiole and alveolar duct. Collectively, these results indicate that occupationally relevant diacetyl exposures result in a pattern of injury that replicates features of OB. Similar studies are being conducted in the rat.

人造黄油调味剂是微波爆米花包装厂员工闭塞性细支气管炎 (OB) 的潜在病原体；然而，具体的有毒成分和毒性机制尚不清楚。 我们评估了人造黄油调味剂的主要挥发性成分丁二酮的呼吸毒性。 亚急性接触 200 或 400 ppm 双乙酰 5 天会导致死亡、坏死性鼻炎和大支气管炎症。 将接触量减少到每天 1 小时（100、200、400 ppm），持续 4 周，可减少鼻毒性、慢性支气管炎和喉炎，且无细支气管损伤。 暴露于 1200 ppm 后（15 分钟，2 次/天，4 周），观察到淋巴细胞性支气管炎和轻度鼻损伤。 亚慢性暴露于 100 ppm（6 小时/天，12 周）会引起淋巴细胞性支气管炎和细支气管炎，鼻腔内有轻微坏死。 通过口咽抽吸绕过鼻子进行 400 mg/kg 治疗，引起纤维化病灶，在终末细支气管和肺泡管交界处很少或没有炎症。 总的来说，这些结果表明，职业相关的二乙酰暴露会导致复制 OB 特征的损伤模式。 类似的研究也在老鼠身上进行。