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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

基本信息

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
项目类别：
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

项目摘要

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.

项目总结