Assessing the Pulmonary Toxicity of Microplastic Fibers Complexed with Azo Dyes

项目总结 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)有多种来源，包括在纺织品中的广泛使用。由于 由于MPFS的大量使用，对全球环境的微塑料污染有很大贡献 比例。MPFS的大部分毒性和健康影响数据都是针对口腔接触的，而 尽管有流行病学证据和最近的工作，但与吸入MPFS相关的研究很少 这已经测量了空气中的MPF。这些研究表明，吸入暴露对 探索。此外，已知这些纤维含有化学添加剂，如偶氮苯分散染料 (补充)，这可能会显著增加毒性。研究ADS对人体的危害 肺系统是有限的，而且还没有研究表征MPFS的毒性 人类吸入暴露的背景。因此，作为首批调查强积金毒性的研究之一- 我们建议量化这些药物单独和联合使用对晚期患者的毒性。 通过定制和独特的气雾剂输送和暴露系统在体外培养肺细胞，并确定 活体内的肺部效应。我们将重点介绍与经典纤维毒性相关的机制。 (肺纤维化)和过敏性呼吸道疾病(哮喘)，因为ADDS被推定为化学致敏剂 (基于皮肤研究)，没有研究在这方面检查这些染料。因此，我们建议 首次研究含有MPF的ADDS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)、呼吸道敏化(ADS)或两者兼而有之(混合表型)。我们会 测试总体假设，即染色MPFS最显著的急性肺毒性归因于 添加从纤维中渗出的物质，作为呼吸道敏感剂。此外，呼吸道 敏化部分是通过肺细胞中添加蛋白加合物的形成来驱动的，这表现为 过敏性呼吸道疾病。我们的方法包括两个具体目标；第一个评估毒性和 通过气雾化纤维(未染色和染色)在体外形成蛋白质加合物的相关机制 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一种 哮喘小鼠模型。这些研究将填补我们在理解病毒构成的危险方面的一个重要空白 含有ADD的MPF和这样的研究路线将导致对长期健康的更好理解 结果和改进的风险评估。

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.