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.

项目概要 微塑料现在被认为是重要的新兴环境污染物。微塑料的一个子集， 微塑料纤维 (MPF) 的来源多种多样，包括在纺织品中的广泛应用。由于 由于 MPF 的大量使用，对全球环境造成微塑料污染 规模。大多数关于 MPF 的毒性和健康影响数据都是针对口服暴露，而 尽管有流行病学证据和最近的工作，但与吸入 MPF 相关的研究仍然很少 测量了空气中的 MPF。这些研究表明，吸入暴露与 探索。此外，这些纤维还含有化学添加剂，例如偶氮苯分散染料 （ADD），这可能会显着导致毒性。研究考察ADDs对人类的损害 肺系统是有限的，并且没有研究描述含有 ADD 的 MPF 的毒性。 人类吸入暴露的背景。因此，作为最早研究 MPF 毒性的研究之一 含有 ADD 的药物，我们建议量化这些药物单独和组合的毒性，以达到先进的水平 通过定制和独特的气溶胶输送和体外暴露系统培养肺细胞，并确定 体内肺效应。我们将重点关注与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），因为 ADD 被认为是化学致敏剂 （基于皮肤研究）并且没有研究在这方面检查这些染料。因此，我们建议 第一项调查含 MPF 的 ADD 的毒性以确定毒性是否占主导地位的研究 通过经典的促纤维化机制（MPF）、呼吸致敏（ADD）或两者（混合表型）。我们将 检验总体假设，即染色 MPF 最显着的急性肺毒性归因于 ADD 从纤维中滤出并充当呼吸敏化剂。此外，呼吸 致敏部分是通过肺细胞中 ADD 蛋白加合物的形成来驱动的，其表现为 过敏性气道疾病。我们的方法包含 2 个具体目标；第一个评估毒性和 相关机制（蛋白质加合物形成）在体外通过雾化纤维（未染色和染色） 复杂的上皮细胞和免疫细胞培养；第二个目标将侧重于记录肺毒性 哮喘小鼠模型。这些研究将填补我们对危险造成的理解的一个关键空白 包含 ADD 的 MPF 和此类研究将有助于更好地了解长期健康 后果和改进的风险评估。