Preclinical Safety Evaluation of Acute and Subacute Intranasal Administration of Polyphenols-based Cinnamon Bark Extract in Laboratory Rats

Background: Polyphenols-based standardized cinnamon (Cinnamomum zeylanicum) bark extract (IND02) demonstrated efficacy against allergic rhinitis in animal models and human clinical study. Objectives: To assess the acute and subacute intranasal toxicity of the IND02 nasal solution (IND02-NS). Methods: Acute and 28-days subacute toxicity using the intranasal route of administration of IND02-NS was evaluated using Wistar rats as per Organisation for Economic Co-operation and Development guidelines. For acute intranasal toxicity study, a single dose of 100 μg/rat/day was administered in five male and female rats and observed for the incidence of mortality and signs of toxicity for 14 days. For a 28-days subacute intranasal toxicity study, doses of 20, 50, and 100 μg/rat/day were administered to a group of five male and female rats. Results: The IND02-NS did not show mortality or treatment-related adverse signs during acute (limit dose of 100 μg/rat/day) and subacute intranasal (28-days repeated dose of 20, 50, and 100 μg/rat/day with 14 days of reversal period) administration. The IND02-NS showed a maximum tolerated dose greater than 100 μg/rat during the acute intranasal toxicity study. The no-observed adverse effect level of IND02-NS was 100 μg/rat/day in rats during the subacute intranasal toxicity study. Conclusion: IND02-NS was found safe at 100 μg/rat/day during acute and subacute (28 days repeated dose) for nasal administration in rats.