Table 2.

Summary of the acute, sub-acute and sub-chronic oral toxicity studies with bacterial cellulose.

Type of study	Animal model	Dosages	Main results	Ref.
Acute oral toxicity	Sprague-Dawley rats	Single oral dosage of 2000 mg/Kg of body weight (bw), corresponding to 1000 mg/kg bw	After 15 days: –No deaths occurred during the study; –No gross pathologic lesions were observed in any of the animals at necropsy	Schmitt et al. [28]
	Kunming mice	Two oral dosages were fed at 4 and 6hr, totaling 15.0 g/kg bw	No deaths occurred during the study; Anatomical observation of the organs were normal	Li-ming et al. [29]
Sub-acute oral toxicity	F344 rats	Meals incorporating: 0, 1.25, 2.5, and 5.0% “fermented cellulose” (60% BC, 20% carboxymethyl cellulose (CMC) and 20% sucrose)	After 28 days: There were no –treatment-related deaths and clinical signs; –variation in any of the treated groups. –inter-group differences in food or water consumption. –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. The animals in the dose group were given 1.3, 2.5 and 5.0% cocoa.	After 30 days: –No inter-group differences were noted in –the growth, development and body weights –food or water consumption –deaths and clinical signs –haemoglobin, red blood cell count and leukocytes. –blood serum albumin, alanine aminotransferase, alanine aminotransferase, aspartate aminotransferase, creatinine, cholesterol, triglyceride, blood glucose and albumin –histopathological examination related to BC consumption	Li-ming et al. [29]
Sub-chronic toxicity	Sprague-Dawley rats	13 weeks assay Assay: meals containing either BC or microcrystalline cellulose (MCC), at levels of 0.5 (low dose group) or 10% (high dose group) in the diet.	No deaths attributable to treatment with BC, MCC or control; Malocclusion, lacrimation, alopecia were not indicative of toxic effects;	Schmitt et al. [28]
		Control assay: same diet without BC or MCC.	No differences were observed in the mean body weight or mean body weight gain of male or female rats, made between test and control groups;
			No dose-response relationships were attributed to differences in cell haemoglobin and haematocrit, platelets and monocytes, between the assay and control groups;
			No gross pathologic findings at necropsy, in all groups;
			BC and MCC treatment had no effect on organ weights;
			No lesions or patterns of distribution that might suggest an effect of exposure to BC or MCC or Cellulon;
			No histomorphologic alterations of the gastrointestinal tract were evident between all groups
	Sprague-Dawley rats	30 days assay	No deaths were observed in any group;	Li-ming et al. [29]
		Assay: meals containing 1.3, 2.5, 5.0 g BC/kg bw	No clinical symptoms were deemed related to the feeding of BC; No difference among groups on organ weight and organ/body weight ratio were observed;
		Control: no BC in feed	No significant differences in the total weight gain, total food intake, total food consumption between male and female rats, as compared to the control group;
			Feeding BC had no obvious effect on rats’ haemoglobin, red blood cell count or white blood cell count;
			Rats fed with BC had similar values of serum albumin, alanine aminotransferase, alanine aminotransferase, aspartate aminotransferase, creatinine, cholesterol, triglyceride, blood glucose, albumin as that of the control group;
			No abnormal changes were found between the various groups. In the high dose group and the control group, vacuolization and hepatic blood stasis was observed.
			Liver serosa was intact, and the central vein, hepatic lobule and portal area were clear;
			Hepatocellular cord arranged radially around the central vein;
			The structure of the renal capsule was complete, the glomeruli of the cortex, the structure of the renal capsule was clear;
			The structure of the gastrointestinal serosa, muscularis, mucosa, and submucosal layer was also clear;
			The spleen capsule was complete. Testicular and ovarian albuginea integrity was maintained;
			Visible levels of spermatogenic cells were also recorded