Subchronic and Chronic Toxicity Assessment of Sublancin in Sprague-Dawley Rats.

Abstract

Sublancin, an S-linked antimicrobial (glycol) peptide produced by Bacillus subtilis, has emerged as a novel and promising veterinary drug due to its unique antibacterial mechanism, low risk of resistance, and properties that modulate the immune system, reduce inflammation, and promote gut health. This study comprehensively assessed the subchronic (90-day) and chronic (180-day) toxicity of Sprague-Dawley (SD) rats, following the guidelines issued by the Ministry of Agriculture of China. Rats were orally administered sublancin at doses of 2000, 10,000, or 50,000 mg/kg feed, representing 1666-5000 times the efficacious dose (1.0-1.2 mg/kg) reported in mice via the same administration route. Throughout this study, a wide range of physiological and behavioral parameters were monitored to access the toxicity of sublancin, including appetite, water intake, body weight gain, and organ weights. Hematological and biochemical analyses, as well as histopathological examinations of the major organs, were conducted at the end of each study period. The results indicated no adverse effects on any measured parameters at any dose level, with no significant differences observed between the sublancin-treated groups and the control group (p > 0.05). Notably, even the highest dose of 50,000 mg/kg did not induce growth inhibition or physiological dysfunction. A histopathological examination also revealed no tissue abnormalities in the major organs. The no-observed-effect level (NOEL) was determined to be 50,000 mg/kg for both study periods. These results demonstrate the long-term safety of sublancin in Sprague-Dawley rats, with no adverse effects during 180 days of oral administration at doses 1666-5000-fold the documented antimicrobially effective and immune-enhancing doses.