Assessing the Pulmonary Toxicity of Microplastic Fibers Complexed with Azo Dyes

项目摘要 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，包括其在纺织品中的广泛使用。由于 由于MPF的大量使用，它们对全球环境的微塑料污染做出了重大贡献。 规模关于MPF的毒性和健康影响的大部分数据都是针对口服暴露的， 尽管有流行病学证据和最近的工作，但与吸入MPF相关的研究很少 测量空气中MPF的实验室。这些研究表明，吸入暴露与 探索.此外，已知这些纤维含有化学添加剂，例如偶氮苯分散染料 （ADDs），这可能会导致严重的毒性。研究检查ADD对人类的损害 肺系统是有限的，没有研究表明MPF的毒性，在肺系统中含有ADD。 人体吸入接触的情况。因此，作为研究MPF毒性的首批研究之一- 我们建议量化这些药物的毒性，单独和组合，以先进的 肺细胞培养物，并确定 体内肺效应。我们将集中在与经典的纤维为基础的毒性机制 （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），并且没有研究在这种情况下检查这些染料。所以我们提出 第一项研究是调查含MPF的ADD的毒性，以确定毒性是否占主导地位， 通过经典的促纤维化机制（MPFs）、呼吸致敏（ADD）或两者（混合表型）。我们将 检验染色MPF的最显著急性肺毒性归因于以下因素的总体假设 从纤维中滤出并作为呼吸道致敏物的ADD。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括两个具体目标：第一个是评估毒性， 通过雾化纤维（未染色和染色）体外相关机制（蛋白质加合物形成）， 复杂的上皮细胞和免疫细胞培养;第二个目标将集中在记录肺毒性， 小鼠哮喘模型。这些研究将填补一个关键的空白，在我们的理解所造成的危害， 含有ADD的MPF和此类研究将有助于更好地了解长期健康 改善风险评估。

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.