Comparative toxic potential of polypropylene and polyethylene nanoplastics using a mouse intratracheal instillation model

Nanoplastics are pervasive environmental contaminants, with growing global concern regarding their potential impact on human health, particularly through inhalation exposure. This study investigates the comparative inflammatory and toxicological effects of polyethylene (PE) and polypropylene (PP) nanoplastics using a mouse intratracheal instillation model with diesel exhaust particles (SRM 2975) as a benchmark. PE (357 nm) and PP (473 nm) nanoplastics were synthesized and dispersed using an optimized protein-corona method and administered to mice at doses of 50, 150, and 300 μg/mouse. Bronchoalveolar lavage fluid analysis at 24 h post-instillation revealed acute lung inflammation, as evidenced by increased cellularity, neutrophils, lactate dehydrogenase, total protein, and pro-inflammatory cytokines. The potency ranking differed based on the dose metric: PE ≥ SRM 2975 > PP on a mass-concentration basis and PE > PP > SRM 2975 on a surface area concentration basis. Persistent mild inflammation was observed at 7 and 28 days post-exposure, with a potency ranking consistent with that observed at 24 h. Reactive oxygen species production in alveolar macrophages correlated strongly with inflammation endpoints, highlighting oxidative stress as a primary toxicity mechanism. Transcriptomic analysis revealed significant alterations in inflammatory and immune-regulatory pathways, including genes encoding chemokines (CXCL10, CXCL9), matrix metalloproteinases, and acute-phase proteins (LCN2, SAA1), reflecting a robust inflammatory response. This study demonstrates distinct yet overlapping inflammatory responses and underlying mechanisms induced by PE and PP nanoplastics. These findings highlight oxidative stress-mediated inflammation as a common pathway, thereby providing critical insights into nanoplastic toxicity, which are necessary for accurate risk assessment.