Unprecedented multi-endpoint safety assessment of Bacillus coagulans BCM-9 dermal and oral toxicity in rabbits and rats across diverse exposure periods

Abstract Bacillus coagulans BCM-9 is a probiotic strain with potential therapeutic utility, necessitating thorough safety evaluation. This study aimed to assess its dermal and oral toxicity profile following internationally recognized guidelines. Dermal irritation/corrosion potential was evaluated in New Zealand White rabbits (OECD 404). Acute oral toxicity (OECD 425) using a limit dose of 2000 mg/kg, and repeated-dose 28-day (OECD 407) and 90-day (OECD 408) oral toxicity studies using doses of 0, 0.65, 35.72, and 74.76 mg/kg/day were conducted in Sprague-Dawley rats. Assessments included mortality, clinical signs, body weight, food consumption, hematology, clinical biochemistry, urinalysis, and histopathology. Results indicated that BCM-9 was non-irritant and non-corrosive upon dermal application. The acute oral LD50 was determined to be greater than 2000 mg/kg. In both the 28-day and 90-day repeated-dose studies, no mortality or significant treatment-related adverse effects were observed in any parameter evaluated, including clinical signs, body weight, food intake, hematological and biochemical markers, or organ pathology, even at the highest dose. The No-Observed-Adverse-Effect Level (NOAEL) for BCM-9 was established as 74.76 mg/kg/day for both 28 and 90 days of oral administration. These comprehensive findings demonstrate a robust safety profile for Bacillus coagulans BCM-9, supporting its potential for further development and safe use in human therapeutic or supplementary applications.