Evaluation of inflammatory and mesothelioma-related responses in mice following the intraperitoneal administration of cellulose nanofibers

Abstract

Mesothelioma can develop from long-term exposure to fine fibrous materials including asbestos and carbon nanotubes, and chronic inflammation is critical for its development. Inflammatory responses and key related markers associated with the development of mesothelioma were evaluated over time in relation to cellulose nanofibers (CNFs), which are being developed as new plant-derived materials, for the purpose of risk management Three types of CNFs, mechanically fibrillated CNFs, TEMPO-oxidized CNFs, and phosphorylated CNFs, were administered intraperitoneally to mice at doses of 0.1 and 1.0 mg per animal, and progress was observed for up to 2 years. In the group receiving mechanically fibrillated CNFs, white substances were observed adhering to the liver surface throughout the observation period. This white substance was presumed to be cellulose. Some CNFs have been shown to persist in the body. During this period, inflammation markers and mesothelioma-related markers were evaluated at 1, 2, and 6 months, and 1, and 2 years after administration. No significant symptoms were observed in animals administered one of the three types of CNFs intraperitoneally during the observation period. Inflammatory markers in the peritoneal lavage fluid remained below the detection limit throughout the entire observation period. Additionally, no significant increase in blood levels of mesothelioma or the major related markers mesothelin, osteopontin, or HMGB1 was observed. In this study, although some CNFs remained in the body, no inflammatory response was observed in vivo under the concentration conditions and observation periods used. Furthermore, no evidence of long-term effects, such as cancer, was found.