Inhalation Effects: Pulmonary Responses and Long-Term Considerations

Inhalation exposure is a primary route of concern for nanocellulose materials (NCMs), including cellulose nanofibrils (CNFs, also referred to as cellulose nanofibers) and cellulose nanocrystals (CNCs), owing to their respirable size and expanding industrial and consumer use. This chapter provides an integrated assessment of pulmonary responses and long-term considerations associated with NCM inhalation, synthesizing evidence from the published literature with findings from studies commissioned by the New Energy and Industrial Technology Development Organization (NEDO). Studies on cellulose and microcrystalline cellulose provide a toxicological context suggesting that fibrous cellulose may induce transient pulmonary inflammation following intratracheal instillation. Across animal and in vitro studies, CNFs generally elicit milder pulmonary inflammation than CNCs and substantially weaker responses than rigid fibrous nanomaterials such as multi-walled carbon nanotubes (MWCNTs), as well as other hazardous fibrous materials including asbestos. Reported effects include acute neutrophilic inflammation, cytokine modulation, and oxidative stress–related responses. Overall, current evidence indicates a comparatively low inhalation hazard for NCMs, while highlighting remaining uncertainties related to biopersistence, chronic low-dose exposure, and material-specific properties influencing long-term toxicity.