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It is important to detect injection site reactions during the nonclinical phases of drug development. However, differentiating between normal changes following needle trauma and changes due to the toxicity of injected drugs can be challenging. Therefore, we used the Sprague-Dawley rat model to evaluate the pathological findings expected following a single subcutaneous injection of normal saline. Rats were subcutaneously administered with normal saline, and the injection sites were examined microscopically. Inflammation was evident in most of the injection sites, mostly in minimal severity. Parakeratosis/epithelial crust was also seen in several sites, and necrosis was observed in a minority of the cases. These findings indicate that needle puncture trauma can present with some degree of inflammation and necrosis. Although limited to a specific time point and strain, this study shows that inflammation following subcutaneous injection can be attributed in part to the needle trauma and not necessarily to the drug itself.

Fructooligosaccharide (FOS) has been used in infant formula and conventional foods as prebiotics. Short chain FOS (FOSSENCETM) is produced by a patented process of biotransformation of sucrose by the action of enzyme from live microbial cells, hence toxicology studies were initiated to assess its safety. The objective of the present study was to determine safety of FOSSENCETM in acute, 14-day, and subchronic (90-day) toxicity studies. In acute and 14-day studies, administration of the FOSSENCETM to Wistar rats did not cause any mortality or clinical signs and changes in body weights, feed consumption, and gross pathology at the doses of 2000, 5000, and 9000 mg/kg body weight. In the subchronic (90-day) toxicity study, FOSSENCETM was administered by oral gavage to Wistar rats at the doses of 0, 2000, 5000, and 9000 mg/kg/day for 90 days. No treatment-related clinical signs or mortalities were observed. Similarly, no treatment-related toxicologically or biologically significant changes in body weight, feed consumption, ophthalmological findings, neurological effects, hematology, clinical chemistry, urinalysis, and gross pathological findings were noticed. However, statistically significant increase in weight of cecum (without correlative microscopic change) was noted at all the test item-treated groups in males and females and was considered to be a trophic effect and not a toxic effect in rats.

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