Toxicologic Evaluation of Cellulon™ Fiber; Genotoxicity, Pyrogenicity, Acute and Subchronic Toxicity

Abstract

CellulonTM fiber, a cellulose produced by a bacterial fermentation process employing a strain of Acetobacter aceti subsp. xylinum, was tested for genotoxicity in four assays: (1) microbial reverse mutation assay in Salmonella typhimurium (Ames assay), (2) an assay for chromosomal aberrations in Chinese hamster ovary (CHO) cells, (3) an assay for induction of unscheduled DNA synthesis (UDS) in rat primary hepatocytes, and (4) the CHO/HGPRT forward mutation assay. Each assay was conducted at a wide range of dose levels, both with and without metabolic activation (assay 1, 2, and 4). Test results gave no indication that Cellulon fiber possessed any genotoxic potential. The pyrogenicity of five batches of Cellulon fiber was tested in the Limulus Amebocyte Lysate assay, gel-clot method. Test results were negative for the presence of gram-negative bacterial endotoxin. The primary eye and dermal irritation potential of Cellulon fiber were examined in New Zealand White rabbits. The Draize method was employed to evaluate and grade ocular and dermal irritation as a result of test material administration. Test results indicated that Cellulon fiber is a minor ocular irritant up to 1 hour postadministration. However, the resultant irritation was considered to be mechanical and related to the dry, granular form of the test material. In addition, test results indicated that Cellulon fiber is not a dermal irritant in the rabbit. The acute oral toxicity of Cellulon fiber was determined in Sprague-Dawley rats, and the LD50 was found to be greater than 2000 mg/kg of body weight. The subchronic toxicity of Cellulon fiber was examined in Sprague-Dawley rats fed diets containing 0, 5, and 10% Cellulon fiber or microcrystalline cellulose for 13 weeks. No dose-related effects on survival, growth, hematology, blood chemistry, organ weights, or pathologic lesions were observed. The results of these studies indicate that Cellulon fiber and microcrystalline cellulose are toxicologically equivalent and that Cellulon fiber does not possess genotoxic potential, is nonpyrogenic, and that animals are not adversely affected by acute or subchronic exposure to Cellulon fiber.

A 28-day oral toxicity study of fermentation-derived cellulose, produced by Acetobacter aceti subspecies xylinum, in F344 rats

“…Increased cecum weights in this study was considered a physiological adaptation related to the ingestion of large amounts of modified starch, fibrous ingredients, or other carbohydrates which are poorly absorbed and have a high osmotic nature (Leegwater et al, 1974;Newberne et al, 1988;Trout et al, 1983;Yoshioka et al, 1994). The reason for the difference from previous reports that increased cecal weights were not evident in rats fed fermentation-derived cellulose or microcrystalline cellulose at dietary levels up to 10% (JECFA, 1998;Schmitt et al, 1991) remains unclear.…”

“…Fermentation-derived cellulose has been eaten for many years as a dessert food called "nata" or "nata de coco" in the Philippines (Omoto et al, 2000). It is reported to lack genotoxicity, pyrogenicity and acute or subchronic toxicity (Schmitt et al, 1991). Fermentation-derived cellulose is generally accepted to be safe for eating or drinking and is used as a food additive in Japan.…”

BC nanofibres: In vitro study of genotoxicity and cell proliferation

“…BC has unique characteristics including high purity, high crystallinity and remarkable mechanical properties, due to the uniform ultrafine-fibre network structure, the high planar orientation of the ribbon-like fibres when compressed into sheets, the good chemical stability, and the high water holding capacity (Svensson et al, 2005). Several materials based on bacterial cellulose, recognized as non-genotoxic and noncytotoxic, have been commercialized (Schmitt et al, 1991;Jonas and Farah, 1998).…”

“…Indeed, although in vivo studies demonstrate the BC biocompatibility , and lack of mutagenicity (Schmitt et al, 1991), no reports are available on the BC nanofibres toxicity. Although BC is not expected to be degraded in vivo, safety concerns makes this study mandatory.…”

Improvement of biofouling resistance on bacterial cellulose membranes

“…In particular, the non-toxicity and non-mutagenicity enable microbial cellulose to be a popular candidate for wound healing dressings and tissue engineering scaffolds [7][8][9][10][11]. For example, Klemm et al reported using bacterial cellulose for temporary substitutes for skin and artificial blood vessels [12].…”