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

Abstract

-This study was designed to evaluate any adverse effect of fermentation-derived cellulose, produced by Acetobacter aceti subspecies xylinum, when administered to both sexes of F344 rats at dietary levels of 0, 1.25, 2.5, and 5.0% for 28 days. The treatment had no adverse effects on clinical signs, mortality, body weights and food and water consumption, or on urinalysis, ophthalmology, hematology, blood biochemistry, and histopathology findings. At necropsy, slight increased absolute and relative cecum weights, evident in females ingesting 2.5% and 5.0% dietary levels, were considered to be a physiological adaptation to the poorly absorbed fermentation-derived cellulose. The non-observed-adverseeffect level (NOAEL) from the present study was concluded to be 5.0% in the diet (5,331 mg/kg body weights/day for males, and 5,230 mg/kg body weights/day for females).Key words: Fermentation-derived cellulose, Food additive, Subacute toxicity, F344 rats Correspondence: Akihiro Hagiwara (E-mail: hagiwara@dims.co.jp) Original ArticleThe Journal of Toxicological Sciences (J. Toxicol. Sci.) Vol.35, No.3, 317-325, 2010 Vol. 35 No. 3 317 MATERIALS AND METHODSThe present study was conducted in compliance with the Good Laboratory Practice (GLP) Standards of the Japanese Ministry of Health and Welfare Ordinance No. 21 (March 26th, 1997) and in accordance with the "Guidelines for Designation of Food Additives and for Revision of Standards for Use of Food Additives" of the Japanese Ministry of Health and Welfare (Eika No. 29, March 22nd, 1996). The animals were given fermentation-derived cellulose at dietary levels of 0% (the control), 1.25%, 2.5% and 5.0% for 28 days. The selection of the highest dose was based on the maximum dietary level conforming to the above-mentioned Guideline, and lower levels were set at 2.5% and 1.25% with a proportionality factor of 2. Test materialThe fermentation-derived cellulose used in the present study was supplied by San-Ei Gen F.F.I. Inc., with specifications as follows: label name, fermented cellulose; Lot No., 98-452P; 60% in purity, mixed with 20% sodium carboxymethylcellulose, and 20% sucrose; milky white powder; storage condition, at room temperature. The primary structure of fermentation-derived cellulose is illustrated in Fig. 1 (Omoto et al., 2000). Diet preparation and analysisThe test material, fermentation-derived cellulose, was incorporated at the required levels into Labo MR stock powdered diet (Nihon Nosan Kogyo, K.K., Tokyo, Japan) and mixed with a blender, model KS101 (Shin Kantou Inc., Tokyo, Japan) for about 30 min. Treatment diets were put in sterile cans and stored at room temperature. Diet preparation was carried out only once, prior to the start of the experiment. Stability and concentration analysis of test material in the prepared diets could not be performed, since analytical methods have yet to be established. As cellulose is a major constituent of many foods of plant origin, and quite inert material, fermentation-derived cellulose in the prepared diet migh...

A multipurpose natural and renewable polymer in medical applications: Bacterial cellulose

“…Regardless the systemic toxicity, Hagiwara et al, (2010) evaluated the adverse effects of fermentation-derived BC when administered for both sex of F344 rats at dietary for 28 days. No macroscopic changes were observed neither adverse effects were manifested in hematology results.…”

Ninety-Day Oral Toxicity Assessment of an Alternative Biopolymer for Controlled Release Drug Delivery Systems Obtained from Cassava Starch Acetate

“…Despite the potential use of starch-derived biopolymers and the belief that their natural origin ensures low toxicity, some studies have shown that even natural products commonly used as additives or coatings in food products may have toxic effects. Nevertheless, most of these studies have only investigated the toxicity of compounds obtained from microorganisms, crustaceans, or nonstarch derivatives [ 15 – 17 ].…”

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“… treatment-related ophthalmological abnormalities treatment-related adverse effects were apparent from the haematology results. Hagiwara et al [30] On blood biochemistry, alanine aminotransferase was higher in males of the 2.5 and 5.0% groups; Statistically significant elevation of relative salivary gland weights was noted in both sexes of the 5.0% group and of relative kidney weights and relative adrenal weights in 5.0% females; The No Adverse Observed Effect Level (NOAEL) is set at the highest dose of 5.0% “fermented cellulose” in the feed, equivalent to 5331 mg/kg bw/day for males and 5230 mg/kg/day for females. Kunming mice The assay group was fed with 0 (control) 1.3, 2.5, and 5.0 g “fermented cellulose”/kg bw.…”

“…Hagiwara et al [30] evaluated the effect of BC sub-acute administration to both sexes of F344 rats for 28 days ( Table 2 ). For this, a commercial product labelled “fermented cellulose” (composed of 60% BC, 20% carboxymethyl cellulose (CMC) and 20% sucrose) was incorporated at different proportions (0, 1.25, 2.5, and 5.0%) into the rat’s stock powdered diet.…”

“…Hagiwara et al [30] evaluated the mutagenic potential of nata de coco (BC) in mutant strains of S. typhimurium (TA97, TA98, TA100, TA102), according to the norm GB 15193-2003 ( Table 3 ). For this, SPF-grade Sprague-Dawley (SD) rats’ liver S9 mixture was used as the exogenous metabolic activation system.…”