Assessing the Pulmonary Toxicity of Microplastic Fibers Complexed with Azo Dyes

评估与偶氮染料复合的微塑料纤维的肺部毒性

• 批准号: 10593414
• 负责人: Tara L Sabo-Attwood
• 金额: $ 23.29万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-12-15 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10593414
• 关键词: Acute; Address; Aerosols; Air; Allergic; Allergic Reaction; Asbestos; Asthma; Binding; Cell Culture Techniques; Cell Differentiation process; Cells; Chemicals; Chronic; Coculture Techniques; Color; Complex; Custom; Data; Dendritic Cells; Dermal; Development; Disease; Dissociation; Distant; Dyes; Ecosystem; Environment; Environmental Pollutants; Epidemiology; Epithelial Cells; Epithelium; Event; Exposure to; Fiber; Gene Expression Profiling; Genes; Health; House Dust; Household; Human; Immune; Immune response; Impairment; In Vitro; Industrialization; Inflammation; Inhalation; Inhalation Exposure; Interstitial Lung Diseases; Investigation; Knowledge; Lead; Liquid substance; Lung; Macrophage; Mass Spectrum Analysis; Measures; Mineral Fibers; Molecular; Mus; Oral; Outcome; Pathway interactions; Phenotype; Plastics; Pollution; Polyesters; Polyethylene Terephthalates; Process; Production; Property; Proteins; Proteomics; Pulmonary Fibrosis; Research; Risk Assessment; Skin; Source; Structure of parenchyma of lung; System; TGFB1 gene; Testing; Textiles; Time; Toxic effect; Toxicology; Water; Work; adduct; aerobic respiration control protein; aerosolized; air sampling; airway epithelium; allergic airway disease; allergic response; asthma model; azobenzene; bronchial epithelium; carcinogenicity; cytokine; cytotoxicity; epidemiology study; experimental study; exposure route; hazard; immunogenic; improved; in vivo; injured airway; lung injury; manufacturing process; mouse model; novel; respiratory; response

PROJECT SUMMARY Microplastics are now recognized as significant emerging environmental pollutants. A subset of microplastics, microplastic fibres (MPFs), originate from a variety of sources, including their extensive use in textiles. Due to their high volume use, MPFs contribute significantly to microplastic pollution of the environment on a global scale. Much of the toxicity and health effects data on MPFs had been directed towards oral exposures whereas studies associated with inhalation of MPFs are scarce despite epidemiological evidence and more recent work that has measured MPFs in air. These studies suggest that inhalation exposures are of equal importance to explore. In addition, these fibers are known to harbor chemical additives, such as azobenzene disperse dyes (ADDs), that may contribute significantly to toxicity. Studies examining the damage of ADDs to the human pulmonary system are limited, and no studies have characterized the toxicity of MPFs that harbor ADDs in the context of human inhalation exposures. Therefore, as one of the first studies to investigate the toxicity of MPF- containing ADDs we propose to quantify the toxicity of these agents, singly and in combination, to advanced lung cell cultures via a custom and unique aerosol delivery and exposure system in vitro and determine the pulmonary effects in vivo. We will focus on mechanisms associated with classical fiber-based toxicity (pulmonary fibrosis) and on allergic airway disease (asthma) as ADDs are presumed to be chemical sensitizers (based on dermal studies) and no studies have examined these dyes in this context. Therefore, we propose the first studies to investigate the toxicity of MPF-containing ADDs to determine whether toxicity is dominated by classic pro-fibrotic mechanisms (MPFs), respiratory sensitization (ADDs) or both (mixed phenotype). We will test the overall hypothesis that that the most significant acute lung toxicity of dyed MPFs is attributed to ADDs that leach from the fibers and act as respiratory sensitizers. Furthermore, respiratory sensitization is driven, in part, through ADD-protein adduct formation in lung cells, which manifest as allergic airway disease. Our approach encompasses 2 specific aims; the first to assess toxicity and associated mechanisms (protein adduct formation) in vitro through aerosolized fibers (undyed and dyed) to complex epithelial and immune cell cultures; the second aim will focus on documenting pulmonary toxicity in a mouse model of asthma. These studies would fill a critical void in our understanding of the hazards posed by ADD-containing MPFs and such lines of research will lead to a better understanding of long term health consequences and improved risk assessment.

项目摘要 现在，微塑料被认为是重要的新兴环境污染物。微塑料的子集， 微型纤维（MPF）源自多种来源，包括它们在纺织品中的广泛使用。由于 它们的大量使用，MPF在全球上对环境的微塑性污染做出了重大贡献 规模。对MPF的大部分毒性和健康影响数据都针对口腔暴露，而 尽管流行病学证据和较新的工作，但与吸入MPF相关的研究仍然很少 这已经测量了空气中的MPF。这些研究表明，吸入暴露与 探索。此外，已知这些纤维具有化学添加剂，例如偶氮苯分散染料 （添加），这可能对毒性产生重大贡献。研究检查人类的损害的研究 肺系统有限，没有研究表征港口增加的MPF的毒性 人类吸入暴露的背景。因此，作为研究MPF-毒性的最早研究之一 包含添加的添加，我们建议单独和联合量化这些药物的毒性 通过定制和独特的气溶胶输送和暴露系统在体外通过肺部细胞培养物，并确定 体内肺作用。我们将重点介绍与基于经典纤维毒性相关的机制 （肺纤维化）和过敏性气道疾病（哮喘）被认为是化学敏化剂 （基于真皮研究）和在这种情况下没有研究这些染料。因此，我们提出 研究含MPF的毒性的第一批研究增加了毒性是否主导 通过经典的促纤维化机制（MPF），呼吸敏化（ADD）或两者（混合表型）。我们将 检验总体假设，即染色MPF的最重要的急性肺毒性归因于 补充说，从纤维中浸出并充当呼吸敏化剂。此外，呼吸道 敏化是通过肺细胞中的添加蛋白加合物形成驱动的，肺细胞表现为 过敏性气道疾病。我们的方法包括2个特定目标；第一个评估毒性和 通过雾化纤维（未染色和染色）在体外的相关机制（蛋白质加合物形成）至 复杂的上皮和免疫细胞培养物；第二个目标将重点是记录A中的肺毒性 哮喘的小鼠模型。这些研究将填补我们对由 含有附加的MPF和此类研究路线将使人们对长期健康有更好的了解 后果和改善风险评估。