Limitations of recent cellulose studies: How overzealous dispersion technique, fluorescence labeling and interpretation limit the findings of recent safety assessments for cellulose materials

Microfibrillated, nanofibrillated, and nanocrystalline cellulose materials are next-generation biobased cellulose materials with applications in the food industry as food contact materials and functional ingredients. Manufacturers have adopted a proactive approach to demonstrate the safety of these cellulose materials as they contribute toward a more sustainable economy. Animal studies and alternative testing approaches are needed to fill data gaps in the literature for the physicochemical and toxicological characterization of cellulose materials. Recently, the European Food Safety Authority (EFSA) funded a project that used New Approach Methodologies (NAMs) to assess the hazards of nanofibers, including methods to evaluate simulated gastrointestinal digestion, cellular uptake, local effects via simulated oral exposure, and gut-on-a-chip toxicity models. Upon review, we identified methodological and analytical limitations in these studies, which may affect the study conclusions that oral exposure to cellulose materials is associated with adverse effects. The aim of this Short Communication is to discuss the limitations of the reported findings in the NAM study and provide a balanced perspective of the study and of the safety of cellulose materials. This Short Communication highlights a major concern that the NAM study was published in the public domain without any peer review from cellulose experts. We identify and discuss several major limitations, including an unrealistic dispersion method, lack of controls in fluorescent labeling, lack of proper control groups in the experimental design, incomplete reporting of statistical analyses, bias toward reporting adverse effects, and inconsistent explanations of discordant results within the greater scientific literature.