Soluble soybean fiber: a 3-month dietary toxicity study in rats.

Soluble soybean fiber (SSF) is a food ingredient intended for human consumption. SSF was administered in the diet to Sprague-Dawley CD(R) rats at concentrations up to 40,000 ppm for three months. Unformed stool was detected during the early and middle part of the treatment period and was considered an exaggeration of a normal physiological response to the fibre content in the diets, to which the animals appeared to adapt. This finding has been reported with other water-soluble fibres and was not considered an adverse effect. Decreased weight gain and food intake during the first half of the treatment period are possible sequelae of increased intestinal throughput. Adaptation was indicated by subsequently improved weight gain and food consumption. Decreased serum cholesterol occurred in males receiving 30,000 or 40,000 ppm and this has been reported before in rats fed soluble fibre. Haemoconcentration (indicated by increased erythrocyte count, haematocrit and haemoglobin concentration) and decreased spleen weight are likely related to minor fluid imbalances during exposure to high concentrations of dietary fibre and occurred at all SSF concentrations. The spleen was microscopically normal. In conclusion, the no-observed-adverse-effect level (NOAEL) for SSF in this study was 40,000 ppm (equivalent to 2.43 g/kg bodyweight/day for males and 2.91 g/kg bodyweight for females).

[General toxicity study of gadobenate dimeglumine formulation (E7155) (4)--4-week repeated dose intravenous toxicity study followed by 4-week recovery period in dogs].

Gadobenate dimeglumine formulation (E7155), at doses of 0 (physiological saline), 0.25, 0.5, 1 and 2 mmol/kg/day of body weight, was administered intravenously to male and female beagle dogs once daily for 4 consecutive weeks in order to evaluate the subacute toxicity of the test article. Reversibility of toxicity was evaluated during a 4-week recovery period at 1 and 2 mmol/kg/day. No toxicologically significant changes were observed at 0.25 and 0.5 mmol/kg/day. In animals receiving 1 or 2 mmol/kg/day, transient swelling and redness of the facial and eye areas, lethargy, decreased activity, emesis, retching, watery or unformed stool, decreased body weight or body weight gain, decreased food consumption, decreased hematocrit and hemoglobin concentration, increased APTT, increases in plasma ALP, GPT or gamma-GT, decreased plasma inorganic phosphorus, total protein or albumin, increased liver or kidney weight, subacute inflammatory infiltrates, loss of centrilobular hepatocytes or hepatocellular cytoplamic vacuolation in the liver, vacuoles in the epithelial cells of the renal tubles and/or hypocellularity in the bone marrow were seen. The results of toxicokinetic analysis showed that systemic exposure was similar in males and females, and there was no accumulation of the test material over the treatment period, although AUC tended to be enhanced by slightly more than the proportionate dose increase. These effects were recovered or tended to be reversed after a post-dosing period for 4 weeks. In conclusion, the No Observed Adverse Effect Level (NOAEL) was 0.5 mmol/kg/day.