In Vivo Evaluation of the Pulmonary Toxicity of Cellulose Nanocrystals: A Renewable and Sustainable Nanomaterial of the Future

Abstract

The use of cellulose as building blocks for the development of novel functional materials is rapidly growing. Cellulose nanocrystals (CNC), with advantageous chemical and mechanical properties, have gained prominence in a number of applications, such as in nanofillers in polymer composites, building materials, cosmetics, food, and the drug industry. Therefore, it becomes critical to evaluate the potential health effects associated with CNC exposures. The objective of this study was to compare pulmonary outcomes caused by exposure of C57BL/6 mice to two different processed forms of CNC derived from wood, i.e., CNCS (10 wt %; gel/suspension) and CNCP (powder), and compare to asbestos induced responses. Pharyngeal aspiration with CNCS and CNCP was found to facilitate innate inflammatory response assessed by an increase in leukocytes and eosinophils recovered by bronchoalveolar lavage (BAL). Biomarkers of tissue damage were elevated to a higher extent in mice exposed to CNCP. Compared to CNCP, CNCS caused a significant increase in the accumulation of oxidatively modified proteins. The up-regulation of inflammatory cytokines was higher in the lungs after CNCS treatments. Most importantly, CNCP materials were significantly longer than CNCS. Taken together, our data suggests that particle morphology and nanosize dimensions of CNCs, regardless of the same source, may be critical factors affecting the type of innate immune inflammatory responses. Because various processes have been developed for producing highly sophisticated nanocellulose materials, detailed assessment of specific health outcomes with respect to their physical–structural–chemical properties is highly warranted.

Toxicity of Cellulose Nanocrystals: A Review

“…Yanamala et al assessed the adverse effects of CNCs produced by the US Forest Service's Cellulose NanoMaterials Pilot Plant at the Forest Products Laboratory (Madison, WI) in adult female C57BL/6 mice upon pharyngeal aspiration. 21 The plant produces CNCs from machine-dried prehydrolysis kraft rayon-grade dissolving wood pulp by hydrolysis with 64% sulfuric acid at 45°C for 90 min, followed by dilution, neutralization of the acid with NaOH, and membrane filtration. 22 It should be noted that the plant's purification process involves the addition of hypochlorite for color removal, which is generally not used in lab-scale methods and might affect the product's toxicity.…”

Non-isothermal crystallization behaviors of poly(lactic acid)/cellulose nanofiber composites in the presence of CO2

“…CNF also has a very low coefficient of thermal expansion at 1 Â 10 À7 K À1 along the longitudinal direction [57]. Additionally, CNFs have huge potential in biomedical applications due to their low cytotoxicity and genotoxicity [37,58,59]. These intriguing properties make CNFs an attractive component for high performance polymer nanocomposites.…”

Cytocompatibility and immunomodulatory properties of wood based nanofibrillated cellulose

“…These results were in accordance with in vitro studies showing that CNFs did not induce toxicity of mouse and human fibroblasts (Mathew et al 2012;Alexandrescu et al 2013;Hua et al 2014), mouse and human macrophages (Vartiainen et al 2011), human monocytic leukaemia cells (Kollar et al 2011) and human cervix carcinoma cells (Pitkänen et al 2014). Recently, in contrast, it seems that cellulose nanocrystals (CNCs) thinner and much shorter than CNFs, might be even toxic and proinflammatory, after pulmonary exposition in vivo, as judged by the accumulation of inflammatory cells within the bronchoalveolar fluid and increased production of pro-inflammatory cytokines and chemokines (Yanamala et al 2014). Such a phenomenon for CNCs was confirmed in a model of 3D human lung cell culture in vitro.…”