Background: Pomegranate (Punica granatum) is a significant source of bioactive compounds. However, its toxicity is not intensively studied. Objectives: The current study investigated the safety and tolerability of pomegranate peel extract (PPE) in BALB/c mice. Materials and Methods: A total of 25 female BALB/c mice were randomly grouped. Each experimental group consisted of five animals. Repeated doses including 0.5, 1.9 and 7.5 mg/kg body weight of PPE were gavaged to BALB/c mice, for 22 days and the single intra-dermal injection (224 mg/kg) was done in one dose. The control group administrated with distilled water was also included. In addition, intra dermal injection for skin allergy testing was also performed. Blood was collected to evaluate glucose, cholesterol, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as indicators of liver toxicity. Macroscopic and histopathological evaluation of tongue, trachea, and larynx tissues were also performed on 22 days post administration. Results: Toxicological potential of PPE studies revealed no toxic effects, clinical signs, histopathological effect in epithelial cells layer of tongue, larynx and trachea, behavioral alterations and adverse effects or mortality in BALB/c mice. Repeated administrations did not alter or cause local irritation of the oral mucosa. Skin allergy test was negative in the last group. Conclusions: The current study showed that PPE had no toxicity and its use is suggested with potential applications against diseases.
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