Tuesday, April 23, 2024
4/23/2024
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.
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