Comprehensive Safety Evaluation of Ekangveer Rasa: A Herbo-Metallic Ayurvedic Formulation in Wistar Rats Following Acute and Sub-Chronic Oral Administration

Ekangveer Rasa (ER) is a traditional herbo-metallic Ayurvedic formulation containing lead, commonly prescribed for neuromuscular disorders. Due to its heavy metal content, there is a growing concern regarding its safety upon oral intake, particularly at doses exceeding the therapeutic range. Thus, the present study aimed to evaluate the acute and sub-chronic toxicity of ER in Wistar rats following OECD guidelines. Acute toxicity was assessed as per OECD guideline 420, while sub-chronic toxicity was conducted for 90 days following OECD guideline 408. Male and female Wistar rats received oral doses of ER at 30, 300, and 600 mg/kg body weight (BW). Animals were monitored weekly for body weight, feed, and water intake. After the exposure period, toxicity assessment included biochemical, hematological, histopathological, genotoxicity, gene expression, and biodistribution studies. No mortality or significant clinical toxicity was observed at 30 and 300 mg/kg BW in both acute and sub-chronic studies. However, the highest dose of 600 mg/kg BW in the sub-chronic study resulted in signs of hepatotoxicity and nephrotoxicity, along with DNA damage and increased apoptotic cell death. Biodistribution studies confirmed lead accumulation, while mercury was undetected in blood. The study concludes that ER is non-toxic at therapeutic dose (30 and 300 mg/kg BW), but higher doses (600 mg/kg BW) can induce systemic toxicity, likely mediated by lead-induced oxidative stress. Therefore, careful adherence to therapeutic dosing is essential to ensure patient safety.