Nonclinical Safety Evaluation of Renogrit: In Vitro Nonmutagenicity (OECD 471) and 28‐Day Repeated Oral Dose Toxicity (OECD 407) in Sprague Dawley Rats

Renogrit is a prescription medicine developed by employing the traditional knowledge of Ayurveda for the management of kidney disorders. To support its extensive clinical investigations, Renogrit requires robust nonclinical safety assessments. Accordingly, in this study, in vitro mutagenicity assay and in vivo subacute toxicity were conducted as per the Organization for Economic Co‐operation and Development (OECD) guidelines. Mutagenic potential of Renogrit was tested using Salmonella typhimurium and Escherichia coli uvrA tester strains in the presence and absence of metabolic activation. DMSO stock solution of Renogrit was assessed at 0.05, 0.15, 0.5, 1.5, and 5.0 mg/plate concentrations, in triplicates, along with the vehicle (DMSO) control and respective positive controls. The revertant colonies were counted after 64‐ to 72‐h incubation period at 37°C. Renogrit was administered to Sprague Dawley (SD) rats by oral route for 28 consecutive days, at the dose levels of 100, 300, and 1000 mg/kg/day. Animals were monitored for all major toxicological parameters, such as morbidity and mortality, clinical signs, body weight, feed consumption, ophthalmological examinations, and functional observational battery (FOB) assessments during the live phase of the study. At study termination, all animals were subjected to hematological analysis, clinical chemistry analysis, examination of organs for gross pathology, and histopathological investigations. The revertant colonies counted in the Renogrit‐incubated plates were not significantly increased when compared to vehicle‐treated plates, thereby signifying its nonmutagenic potential. Additionally, the subacute toxicity study revealed no toxicologically significant changes attributable to Renogrit administration up to a dose of 1000 mg/kg/day. In conclusion, Renogrit was found to be a nonmutagenic at the evaluated concentrations, and its No Observed Adverse Effect Level (NOAEL) was determined to be 1000 mg/kg/day. The study outcomes provide future nonclinical safety assessments of Renogrit and its detailed clinical evaluation.