Assessing the Safety of Mechanically Fibrillated Cellulose Nanofibers (fib-CNF) via Toxicity Tests on Mice: Single Intratracheal Administration and 28 Days' Oral Intake

Yoshihiro Yamashita; Akinori Tokunaga; Koji Aoki; Tamotsu Ishizuka; Hideyuki Uematsu; Hiroaki Sakamoto; Satoshi Fujita; Shuichi Tanoue

doi:10.3390/toxics12020121

Assessing the Safety of Mechanically Fibrillated Cellulose Nanofibers (fib-CNF) via Toxicity Tests on Mice: Single Intratracheal Administration and 28 Days' Oral Intake

Toxics. 2024 Feb 1;12(2):121. doi: 10.3390/toxics12020121.

Authors

Yoshihiro Yamashita¹, Akinori Tokunaga^{2

3}, Koji Aoki^{3

4}, Tamotsu Ishizuka^{3

5}, Hideyuki Uematsu^{3

6}, Hiroaki Sakamoto^{3

6}, Satoshi Fujita^{3

6}, Shuichi Tanoue^{1

3}

Affiliations

¹ Research Center for Fibers and Materials, University of Fukui, 3-9-1 Bunkyo, Fukui 910-8507, Japan.
² Life Science Research Laboratory, University of Fukui, 23-3, Matsuoka Shimoaizuki, Eiheiji-cho, Fukui 910-1193, Japan.
³ Organization for Life Science Advancement Programs, University of Fukui, 3-9-1 Bunkyo, Fukui 910-8507, Japan.
⁴ Department of Pharmacology, Faculty of Medicine, University of Fukui, 23-3, Matsuoka Shimoaizuki, Eiheiji-cho, Fukui 910-1193, Japan.
⁵ Third Department of Internal Medicine, Faculty of Medicine, University of Fukui, 23-3, Matsuoka Shimoaizuki, Eiheiji-cho, Fukui 910-1193, Japan.
⁶ Department of Frontier Fiber Technology and Science, Graduate School of Engineering, University of Fukui, 3-9-1 Bunkyo, Fukui 910-8507, Japan.

Abstract

Mechanically fibrillated cellulose nanofibers, known as fib-CNF (fiber length: 500 nm; diameter: 45 nm), are used in composites and as a natural thickener in foods. To evaluate their safety, we conducted a 28-day study in mice with inhalation exposure at 0.2 mg/body and oral administration of 400 mg/kg/day. Inhalation exposure to fib-CNF caused transient weight loss, changes in blood cell counts, and increased lung weights. These changes were attributed to adaptive responses. The oral administration of fib-CNF for 28 days resulted in no apparent toxic effects except for a slight decrease in platelet counts. The fib-CNF administration using the protocols studied appears to be safe in mice.

Keywords: TG407; TG412; cellulose; in vivo; nanofiber; safety.

Grants and funding

This research was conducted as part of Japan’s NEDO P20009 project entitled “Development of Cellulose Nanofiber Related Technologies Contributing to a Carbon-Circulating Society—Development of Hazard Assessment Methods and Safety Evaluation for Various Product Applications from 2020 to 2024”.