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125 In vitro toxicity of micro- and nanoplastics in alveolar macrophages and a 3D-alveolar model: influence of size, polymer, and weathering
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Researchers tested nine types of micro- and nanoplastics — including pristine and UV-weathered polyamide-6 particles made by different synthesis routes, PET, and acrylic paint particles — in alveolar macrophage and 3D lung models, finding that synthesis method, weathering state, and polymer type together determine the degree of oxidative stress, cytotoxicity, and macrophage activation.
Abstract Inhalation represents a significant route of human exposure to micro- and nanoplastics (MNP). However, there is limited knowledge regarding their specific effects on the respiratory tract, particularly concerning the roles of polymer type, weathering, and synthesis method in determining toxicity. To address these gaps, we assessed the effects of nine MNP types, pristine and weathered particles of various sizes, in two in vitro models: one alveolar macrophage model and one 3D-alveolar model. Rat alveolar macrophages (NR8383) were exposed under serum-free conditions at four concentrations (22.5, 45, 90, and 180 µg/mL) to six polyamide-6 (PA-6) particles (pristine or UV-weathered, micro- or nano-sized, synthesized by spray drying or solvent precipitation), polyethylene terephthalate (PET), and multicomponent acrylic paint particles. H2O2 generation was assessed using Ampliflu™ Red after 90 min, while cytotoxicity and macrophage activation were evaluated by lactate dehydrogenase and β-glucuronidase release after 16 h. Cytotoxicity of PET and pristine PA-6 (precipitated) was assessed in EpiAlveolar™. In NR8383, PET and micro-sized precipitated PA-6 induced H2O2 generation. Cytotoxicity was observed for PET, PA-6 (precipitated, micro and nano-sized), and UV-weathered PA-6 (spray drying). These particles, except UV-weathered and nano-sized precipitated PA-6, also induced macrophage activation. In EpiAlveolar™, PET and pristine PA-6 (precipitated) induced a slight cytotoxicity at 300 µg/cm², but not at 60 µg/cm². Our findings show that MNP toxicity is strongly influenced by synthesis method, weathering, and polymer type. Future transcriptomic analyses of these samples will provide mechanistic insights, increasing our understanding of how these factors shape the inhalation toxicity of MNP.
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