Nonclinical Safety Evaluation of Nonmutagenic Immunogrit Following Subacute 28-Day Repeated Dose Oral Toxicity in Sprague-Dawley Rats With GLP Compliance.

Abstract

Immunogrit is a traditional Ayurvedic medicine prescribed to patients for their general well-being. In this study, Immunogrit was evaluated for its subacute (28 days) repeated oral dose toxicity in male and female Sprague-Dawley (SD) rats of similar age and body weight following OECD 407 guidelines under Good Laboratory Practices compliance. Mutagenic potential of Immunogrit was also evaluated through Ames assay following OECD 471 guidelines. Phytochemical profiling of the Immunogrit was performed using ultraperformance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight(UPLC/MS-QToF) tandem mass spectrometer. UPLC/MS-QToF analysis of Immunogrit identified 74 phytochemicals, well known for their health benefits. Male and female specific pathogen-free SD rats were orally gavaged to 100, 300, and 1000 mg/kg body weight/day of Immunogrit, over a period of 28 days, with two additional groups for a recovery phase of 14 days. No incidence of mortality, morbidity, or abnormal clinical signs was observed in the Immunogrit-exposed animals. Body weight, behavioral, and food consumption habit were found to be normal throughout the study period. Immunogrit exposure did not induce ophthalmic, neurological, functional, hematological, biochemical, and histopathological irregularities in animals over a period of 28 days. Latent incidence of toxicity was also not observed in the recovery group male and female rats kept under observation for an additional 14 days' post-Immunogrit exposure. Ames test of Immunogrit and its S9-treated fraction in Salmonella typhimurium strains TA1535, TA1537, TA98, and TA100, and Escherichia coli WP2uvrA did not show any induced mutagenic potential, up to the highest dose tested. In conclusion, Immunogrit was found to be nonmutagenic and showed a "no-observed-adverse-effect-level" (NOAEL) of 1000 mg/kg body weight/day in male and female SD rats.