Resumen: Cellulose nanofibrils (CNFs) have emerged as sustainable options for a wide range of applications. However, the high aspect ratio and biopersistence of CNFs raise concerns about potential health effects. Here, we evaluated the in vivo pulmonary and systemic toxicity of unmodified (U-CNF), carboxymethylated (C-CNF), and TEMPO (2, 2, 6, 6-tetramethyl-piperidin-1-oxyl)-oxidized (T-CNF) CNFs, fibrillated in the same way and administered to mice by repeated (3x) pharyngeal aspiration (14, 28, and 56 mu g/ mouse/aspiration). Toxic effects were assessed up to 90 days after the last administration. Some mice were treated with T-CNF samples spiked with lipopolysaccharide (LPS; 0.02- 50 ng/mouse/aspiration) to assess the role of endotoxin contamination. The CNFs induced an acute infammatory reaction that subsided within 90 days, except for T-CNF. At 90 days post-administration, an increased DNA damage was observed in bronchoalveolar lavage and hepatic cells after exposure to T-CNF and C-CNF, respectively. Besides, LPS contamination dose-dependently increased the hepatic genotoxic effects of T-CNF. Idioma: Inglés DOI: 10.1021/acs.biomac.2c00072 Año: 2022 Publicado en: BIOMACROMOLECULES 23, 7 (2022), 2752–2766 ISSN: 1525-7797 Factor impacto JCR: 6.2 (2022) Categ. JCR: BIOCHEMISTRY & MOLECULAR BIOLOGY rank: 56 / 285 = 0.196 (2022) - Q1 - T1 Categ. JCR: POLYMER SCIENCE rank: 6 / 85 = 0.071 (2022) - Q1 - T1 Categ. JCR: CHEMISTRY, ORGANIC rank: 3 / 52 = 0.058 (2022) - Q1 - T1 Factor impacto CITESCORE: 11.1 - Chemical Engineering (Q1) - Materials Science (Q1)