Lyophilized<i>B. subtilis</i>ZB183 Spores: 90-Day Repeat Dose Oral (Gavage) Toxicity Study in Wistar Rats

A 90-day repeated-dose oral toxicological evaluation was conducted according to GLP and OECD guidelines on lyophilized spores of the novel genetically modified strain <i>B. subtilis</i> ZB183. Lyophilized spores at doses of 10⁹, 10¹⁰, and 10¹¹ CFU/kg body weight/day were administered by oral gavage to Wistar rats for a period of 90 consecutive days. <i>B. subtilis</i> ZB183 had no effects on clinical signs, mortality, ophthalmological examinations, functional observational battery, body weights, body weight gains and food consumption in both sexes. There were no test item-related changes observed in haematology, coagulation, urinalysis, thyroid hormonal analysis, terminal fasting body weights, organ weights, gross pathology and histopathology. A minimal increase in the plasma albumin level was observed at 10¹⁰ and 10¹¹ CFU/kg/day doses without an increase in total protein in males or females and was considered a nonadverse effect. The "No Observed Adverse Effect Level (NOAEL)" is defined at the highest dose of 10¹¹ CFU/kg body weight/day for lyophilized <i>B. subtilis</i> ZB183 Spores under the test conditions employed.