Bacillus subtilis ZB423: 90-Day repeat dose oral (gavage) toxicity study in Wistar rats

J Appl Toxicol. 2024 Dec;44(12):1874-1885. doi: 10.1002/jat.4677. Epub 2024 Aug 21.

Abstract

The novel genetically modified probiotic Bacillus subtilis ZB423 was assessed in a 90-day repeated-dose oral toxicity study adhering to Good Laboratory Practice (GLP) and Organization for Economic Cooperation and Development (OECD) guidelines. Spray-dried spores at a concentration of 1.1E12 CFU/g were administered at doses of 130, 260, and 519 mg/kg body weight/day correlating to 1.43 × 1011, 2.86 × 1011, and 5.71 × 1011 CFU/kg/day, respectively, by oral gavage to Wistar rats for a period of 90 consecutive days. Results showed no toxicologically relevant findings for B. subtilis ZB423 from measured parameters. The no observed adverse effect level (NOAEL) of B. subtilis ZB423 is 519 mg/kg body weight/day corresponding to 5.71 × 1011 CFU/kg/day for lyophilized B. subtilis ZB423 spores under the test conditions employed.

Keywords: B. subtilis ZB423 spores; Wistar rats; food ingredient; safety; sub‐chronic toxicity.

MeSH terms

  • Administration, Oral
  • Animals
  • Bacillus subtilis* / drug effects
  • Bacillus subtilis* / genetics
  • Body Weight / drug effects
  • Dose-Response Relationship, Drug
  • Female
  • Male
  • No-Observed-Adverse-Effect Level*
  • Organ Size / drug effects
  • Probiotics* / administration & dosage
  • Probiotics* / toxicity
  • Rats
  • Rats, Wistar*
  • Spores, Bacterial / drug effects