Safety of Mechanically Fibrillated Cellulose Nanofibers (CNFs) by Inhalation Exposure Based on TG412

An investigation into the acute toxicity of mechanically fibrillated cellulose nanofibers (fib-CNFs), with a fiber length ranging from 500 to 600 nm, was conducted in accordance with the OECD TG412 guidelines. In this study, rats were exposed to fib-CNFs via nasal inhalation for 6 h daily over a 28-day period. The highest exposure concentration was set at 35 mg/m³, with intermediate and low concentrations at 7.0 mg/m³ and 1.5 mg/m³, respectively. No significant differences were observed in body weight, hematological parameters, or biochemical profiles between the fib-CNF-exposed groups and the control group. However, the histopathological examination of lung tissue revealed elevated macrophage counts in both the alveolar spaces and lymph nodes, accompanied by a significant increase in lung weight. The most severe effects were observed in the high-concentration group, while the low-concentration group exhibited only mild inflammatory changes. Based on these findings, the no observable adverse effect level (NOAEL) for the acute toxicity of fib-CNFs is estimated to be below 1.5 mg/m³.