Mesothelioma Potential: Comparative Insights and Safety Findings

Fibrous nanomaterials raise concerns regarding the potential risk of mesothelioma following inhalation exposure, analogous to asbestos; however, the mesothelioma-inducing potential of nanocellulose materials remains unclear. This chapter first provides an overview of mesothelioma and mesothelial cell-related biological responses induced by asbestos and multiwalled carbon nanotubes, based on existing studies. Proposed mechanisms include oxidative stress induction, disruption of cell division, and adsorption of harmful substances. Phagocytosis by mesothelial cells, long-term retention, and the influence of fiber morphology, rigidity, and iron contamination are also considered critical factors. This chapter then presents findings from the NEDO project evaluating the mesothelioma-inducing potential of cellulose nanofibrils (CNFs; also called cellulose nanofibers) using long-term intraperitoneal administration in mice and complementary in vitro assays with mesothelial cells and macrophages. Three CNF types—mechanically fibrillated, TEMPO-oxidized, and phosphorylated—were administered and observed for 2 years; no mesothelioma was detected in any CNF-treated group. Although chemokine and inflammatory cytokine induction was observed in macrophages in vitro, no sustained inflammation occurred in vivo after 1 month, inflammatory and mesothelioma-related biomarkers did not increase, and no notable CNF-related pathological changes were observed. These findings suggest that the three types of CNFs are unlikely to induce sustained inflammation or mesothelioma.