Oral Toxicity: Experimental Findings and Safety Implications for Nanocellulose

Cellulose nanofibrils (CNFs; also called cellulose nanofibers) and cellulose nanocrystals (CNCs) have potential applications in food products; however, unlike conventional microcrystalline cellulose, their oral safety remains unestablished. This chapter summarizes findings from published studies and the NEDO project regarding their oral effects. Overall, the available evidence demonstrates low acute and subchronic toxicity for both CNFs and CNCs, with 50% lethal dose values exceeding 2000–5000 mg/kg and no-observed-adverse-effect levels generally corresponding to the highest tested doses. Most studies report no treatment-related abnormalities in clinical signs, hematology, serum chemistry, organ weights, or histopathology. However, some investigations indicate physiological effects under specific conditions, such as altered nutrient absorption, changes in gut microbiota, or reduced body weight. Results from 28-day repeated-dose studies conducted under the NEDO project further support the low toxicity of mechanically fibrillated CNFs in rats and mice, with no pathological findings and only mild changes, such as slight body-weight reductions or decreased platelet counts. Beyond conventional toxicity endpoints, recent research highlights the importance of assessing gastrointestinal behavior and mucoadhesive properties. While current data suggest a level of safety comparable to that of conventional cellulose, additional long-term and nutritional studies are needed to support regulatory evaluation of nanocellulose for food applications.