Genotoxicity: Evidence, Mechanisms, and Safety Implications

Genotoxicity assessment is essential for evaluating engineered nanomaterials, particularly fibrous nanoscale materials that may induce foreign-body-type responses in the lungs. Nanocellulose materials (NCMs)—including cellulose nanofibrils (CNFs, also referred to as cellulose nanofibers) and cellulose nanocrystals (CNCs)—are increasingly used across industrial and biomedical sectors, prompting examination of their potential genotoxic hazards. This chapter reviews published evidence together with findings from large-scale studies commissioned by the New Energy and Industrial Technology Development Organization (NEDO), emphasizing investigations conducted in accordance with OECD Test Guidelines to ensure high regulatory relevance. NCMs are also considered within the broader context of fibrous nanomaterial risk assessment, including comparisons with certain carbon nanotube types classified by the International Agency for Research on Cancer (IARC). Reported outcomes vary with surface chemistry, dimensions, additives, biological models, and assay design. Although some CNF formulations have shown localized DNA damage or oxidative-stress-related effects under specific conditions, OECD-compliant studies employing genotoxicity test batteries are predominantly negative. NEDO studies likewise reported consistently negative findings across assays for gene mutation and chromosomal damage. Overall, the available evidence indicates that the evaluated NCMs present a low genotoxic concern, while underscoring the importance of material-specific and exposure-relevant assessments.