Physical, chemical, and toxicological characterization of sulfated cellulose nanocrystals for food-related applications using in vivo and in vitro strategies

James D Ede; Kimberly J Ong; Marina R Mulenos; Sahar Pradhan; Matthew Gibb; Christie M Sayes; Jo Anne Shatkin

doi:10.1093/toxres/tfaa082

Physical, chemical, and toxicological characterization of sulfated cellulose nanocrystals for food-related applications using in vivo and in vitro strategies

Toxicol Res (Camb). 2020 Dec 3;9(6):808-822. doi: 10.1093/toxres/tfaa082. eCollection 2020 Dec.

Authors

James D Ede¹, Kimberly J Ong¹, Marina R Mulenos², Sahar Pradhan², Matthew Gibb³, Christie M Sayes², Jo Anne Shatkin¹

Affiliations

¹ Vireo Advisors LLC, Boston, MA 02130-4323, USA.
² Institute of Biomedical Studies, Baylor University, One Bear Place #97266, Waco, TX 76798-7266, USA.
³ Department of Environmental Science, Baylor University, One Bear Place #97266, Waco, TX 76798-7266, USA.

Abstract

Cellulose nanocrystals (CNCs) are a next-generation cellulose product with many unique properties including applications in the food industry as a food additive, food coating, and in food-contact packaging material. While CNC is anticipated to be safe due to its similarity to the many forms of cellulose currently used as food additives, special consideration is given to it as it is the first manufactured form of cellulose that is nanoscale in both length and width. A proactive approach to safety has been adopted by manufacturers to demonstrate CNC safety toward responsible commercialization. As part of the safety demonstration, in vivo and in vitro testing strategies were commissioned side-by-side with conventional cellulose, which has been safely used in food for decades. Testing included a 90-day rodent feeding study as well as additional physical, chemical, and biological studies in vitro that follow European Food Safety Authority (EFSA) guidance to demonstrate the safe use of novel food ingredients. The strategy includes assessment of neat materials side-by-side with simulated digestion, mimicking conditions that occur along the gastrointestinal tract as well as intracellularly. An intestinal co-culture model examined any potential toxicological effects from exposure to either pristine or digested forms of CNC including cytotoxicity, metabolic activity, membrane permeability, oxidative stress, and proinflammatory responses. None of the studies demonstrated any toxicity via oral or simulated oral exposure. These studies demonstrate that CNC produced by InnoTech Alberta is similarly safe by ingestion as conventional cellulose with a no-observed-adverse-effect level of 2085.3 (males) and 2682.8 (females) mg/kg/day.

Keywords: 90-day subchronic study; NOAEL; alternative testing strategy; cellulose nanocrystals; in vitro toxicology; intestinal model; simulated digestion.