Toxicological effects of ingested nanocellulose in in vitro intestinal epithelium and in vivo rat models

Autor: Xiaoqiong Cao, Say Chye Joachim Loo, Ramon M. Molina, Daniel Imbassahy Silva, Joseph D. Brain, Kee Woei Ng, Glen M. DeLoid, Philip Demokritou, Kunal Bhattacharya
Přispěvatelé: School of Materials Science and Engineering, Environmental Chemistry and Materials Centre, Nanyang Environment and Water Research Institute
Rok vydání: 2019
Předmět:
Zdroj: Environ Sci Nano
ISSN: 2051-8161
2051-8153
Popis: Cellulose is widely used as a thickener and filler in foods and drugs. It has been designated “generally regarded as safe” (GRAS). Nanocellulose (NC) has many additional potential applications designed to improve food quality and safety, but has not yet been designated as GRAS. Here we present results of toxicological studies of ingested NC in physiologically relevant in vitro and in vivo systems. In vitro studies employed a gastrointestinal tract simulator to digest two widely-used forms of NC, nanocellulose fibrils (CNF) and cellulose nanocrystals (CNC), at 0.75 and 1.5% w/w, in a fasting diet as well as in a standardized food model based on the average American diet. A triculture model of small intestinal epithelium was used to assess effects of a 24 hour incubation with the digested products (digesta) on cell layer integrity, cytotoxicity and oxidative stress. Other than a 10% increase over controls in reactive oxygen species (ROS) production with 1.5% w/w CNC, no significant changes in cytotoxicity, ROS or monolayer integrity were observed. In vivo toxicity was evaluated in rats gavaged twice weekly for five weeks with 1% w/w suspensions of CNF in either water or cream. Blood, serum, lung, liver, kidney, and small intestine were collected for analysis. No significant differences in hematology, serum markers or histology were observed between controls and rats given CNF suspensions. These findings suggest that ingested NC has little acute toxicity, and is likely non-hazardous when ingested in small quantities. Additional chronic feeding studies are required to assess long term effects, and potential detrimental effects on the gut microbiome and absorbance of essential micronutrients. These studies are underway, and their outcome will be reported in the near future. Nanyang Technological University Accepted version Support for the research reported, including assets and resources required for designing and performing experiments, data analysis, and interpretation, was provided by the Nanyang Technological University-Harvard T. H. Chan School of Public Health Initiative for Sustainable Nanotechnology (NTU-Harvard SusNano; NTU-HSPH 17001). Additional funding for animal studies was provided by the National Institutes of Health (ES-0000002). The engineered nanomaterials used in the research presented in this publication were developed, characterized, and provided by the Engineered Nanomaterials Resource and Coordination Core established at Harvard T. H. Chan School of Public Health (NIH grant # U24ES026946) as part of the Nanotechnology Health Implications Research Consortium.
Databáze: OpenAIRE