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Cellulose nanocrystals: more clarity needed on their toxicity
Cellulose nanocrystals are an emerging class of nanomaterials which are attracting attention for a number of possible applications owing to desirable properties. These include their renewable starting materials, such as tunicin, bacterial or algal cellulose or wood pulp, their relatively low production costs and their biodegradability and biocompatibility. They also have desirable physical properties, including high water absorption capacity, mechanical strength, and stiffness. As a result, cellulose nanocrystals are being investigated for potential use in medical materials such as hydrogels, drug-delivery vehicles and wound dressings and in optical films. However, in a new review of the cellulose nanocrystals toxicity literature, published in the journal Industrial Biotechnology, Prof Maren Roman of Virginia Tech suggests that potential adverse health effects of cellulose nanocrystals may be influenced by, for example, exposure routes and that further study is needed before conclusions on non-toxicity of cellulose nanocrystals can be drawn.

Prof Roman reviewed the published literature on effects of cellulose nanocrystals on the respiratory system, gastrointestinal system, skin, and cells. Studies on oral and dermal toxicity had mainly concluded that cellulose nanocrystals lack adverse effects. However, Prof Roman cautions that additional studies required to validate the general conclusion that cellulose nanocrystals are nontoxic on ingestion or skin contact, as the number of studies so far published is very small.

Oral toxicity is assessed in terms of adverse health effects due to entrance into the orogastrointestinal tract, consisting of the oral cavity, the oesophagus, the stomach, and the small and large intestine, through the mouth. While most studies suggest that the nanoparticles pass through the tract and are eliminated via the faeces, some have demonstrated gastrointestinal barrier permeation by micro- and nanoparticles. Prof Roman explained that the size, electrostatic properties, molecular structure, and pH of cellulose nanocrystals properties make it unlikely that they would penetrate the gastrointestinal barrier, but she also noted that only two studies have been published on oral toxicity specifically of cellulose nanocrystals. In terms of dermal toxicity, the three published studies on cellulose nanocrystals toxicity did not indicate any skin sensitization or tissue damage.

For respiratory toxicity, it seems that the body can clear particles from the nasal–pharyngeal–laryngeal (NPL) region to the mouth via the mucociliary escalator. Particles deposited in the alveolar region, by contrast, are cleared primarily by immune cells called alveolar macrophages through phagocytosis, a process by which particles are engulfed and degraded. Very few studies have been published on respiratory toxicity of cellulose nanocrystals, however. Early studies suggested that tissue damage and inflammation were dependent on the form in which the nanocrystals were prepared and delivered, i.e. via dry powder versus suspension in a carrier liquid. While a later study on rats showed no ill effects from inhaled aerosolized cellulose nanocrystals, Prof Roman pointed out that the study did not involve characterization of the aerosolized particles in terms of size, shape and surface charge.

Studies on cytotoxicity of cellulose nanocrystals have been discordant. Most suggest that cellulose nanocrystals are not toxic to cells, however dose is important. Human cells, such as from the brain, throat, and eye, and cells from other animals have been studied. Prof Roman commented: "The discrepancies in the results are not surprising considering that the studies all used different cell lines, cellulose sources, preparation procedures, and post-processing or sample preparation methods." She also pointed out that many studies did not take account of other chemicals that could be present from the processing. She concluded: "Only by careful particle characterization and exclusion of interfering factors will we be able to develop a detailed understanding of the potential adverse health effects of cellulose nanocrystals."

Roman M. Toxicity of Cellulose Nanocrystals: A Review. Industrial Biotechnology (2015) 11(1): 25-33. doi:10.1089/ind.2014.0024.

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