Inhalation toxicity of cellulose nanofibrils: A review of key findings and future directions

Cellulose nanofibrils (CNFs) have attracted increasing research attention as sustainable and biodegradable nanomaterials with applications across diverse industrial sectors, including packaging, agriculture, and biomedical engineering. However, owing to their ultrafine size and fibrous morphology, concerns have emerged regarding their potential inhalation toxicity and long-term health effects. This review examines recent studies addressing CNF-induced lung inflammation, pulmonary distribution, retention, clearance, phagocytosis by alveolar macrophages, and in vitro cytotoxicity. Key findings indicate that short-term exposure to CNFs generally induces mild pulmonary inflammation, which is less severe compared to that caused by other fibrous nanomaterials such as carbon nanotubes (CNTs). The fiber length and diameter of CNFs significantly influence their pulmonary distribution and the severity of inflammatory responses. CNFs exhibit prolonged retention in the lung tissue and are phagocytosed by alveolar macrophages, although no significant cytotoxicity has been observed in vitro. Biological impurities, including bacterial endotoxins, are often present in CNF suspensions and may influence toxicity outcomes; however, their exact contributions remain unclear. Due to variations in source materials and processing methods, CNFs require case-by-case inhalation toxicity assessment. This review also highlights the need for standardized characterization, advanced exposure models, and appropriate safety and regulatory measures for their responsible use.