Safety Assessment of TLPL/AY/03/2008, A Polyherbal Formulation in Sprague Dawley Rats

Objectives: TLPL/AY/03/2008 is a polyherbal formulation intended for treatment of osteoarthritis, rheumatoid arthritis, lumbago, spondylitis etc., Acute and repeated dose 90‑days studies were conducted to evaluate the safety profile of TLPL/AY/03/2008 in rats. Materials and Methods: In acute study, TLPL/AY/03/2008 was orally administered to Sprague Dawley rats at 2000 mg/kg. In repeated dose study, TLPL/AY/03/2008 was administered to rats at 200, 500 and 1000 mg/kg through oral gavage for 90 days and assessed for treatment related changes in body weight, feed consumption, hematological, biochemical and pathological parameters. Histopathological examination was conducted for tissues from control and the high dose groups and was extended to target organs from the lower dose and recovery groups. Results: In acute study, the test item did not produce any mortality or adverse clinical signs. In the 90‑days oral toxicity study, animals did not exhibit any toxicity symptoms and no deaths were observed. No significant changes were found in hematological and biochemical endpoints. Also, toxicologically significant alterations in relative organ weights were not observed. Microscopic findings of mild to marked, diffuse hepatocellular degeneration (vacuolar changes with granular of cytoplasm and pyknotic nuclei of hepatocytes) was noticed in males at 1000 mg/kg body weight. Animals of recovery group (1000 mg/kg) did not show any changes when compared with control group animals indicating the complete reversal. Conclusions: Based on the findings of the study, the median lethal dose of TLPL/AY/03/2008 was found to be more than 2000 mg/kg. The No Observed Adverse Effect Level (NOAEL) of TLPL/AY/03/2008 can be considered as 1000 mg/kg in both male and female rats, under the experimental conditions and doses employed.