Pre-clinical Safety Evaluation of Drde/wh-02: a Challenging Wound Healing Formulation for Sm Induced Skin Lesions

Sulphur mustard (SM), chemically bis (2-chloroethyl) sulphide is a bifunctional alkylating agent that causes cutaneous blisters in human or animals. There is no specific therapy for SM induced skin injury, however, DRDE/WH-02 (containing PVP-I, Aloe vera gel and betaine) has proved to be an effective remedy for SM dermatotoxicity in preclinical studies. This study was planned to evaluate safety of DRDE/WH-02 for risk assessment and dose interpolation in humans during clinical trials. Skin corrosiveness and skin irritation potential was assessed by primary skin irritation test (Draize test) which showed that DRDE/WH-02 is not irritant to the rabbit’s skin. Acute toxicity studies were carried out using two doses viz. 3.2 g/kg or 6.4 g/kg by oral or dermal route. There were no adverse clinical/ toxic signs and pre terminal deaths. The evaluated median lethal dose LD50 of the test item was found to be more than 6.4 g/kg body weight by either dermal or oral route. Cumulative biological effect of DRDE/WH-02 was evaluated in Wistar rats by dermal route at dose of 1g and 2 g/kg daily for 90 days. There were no toxic/clinical signs, pre-terminal deaths and inter group differences in body weights and feed and water intake in different groups. There were no treatment related changes in haematology, clinical chemistry, organ weights and gross or histopathological findings in different groups. No Observed Adverse Effect Level (NOAEL) of DRDE/WH-02 in repeated dermal administration to Wistar rats was found to be more than 2 g/kg body weight under the testing conditions.