Literature review on the safety of Toyocerin®, a non-toxigenic and non-pathogenic Bacillus cereus var. toyoi preparation

Bacillus cereus var. toyoi is a naturally occurring, non-toxigenic and non-pathogenic strain of B. cereus. Safety studies were conducted on a B. toyoi preparation (Toyocerin®), including but not limited to enterotoxicity, eye irritation, genotoxicity, acute, subchronic and chronic toxicity studies and human clinical trials. In rabbits, Toyocerin® did not exhibit enterotoxicity and was only slightly irritating to the eyes. It was non-mutagenic in an Ames assay at up to 10,000 μg/plate and did not exhibit clastogenic activity in a chromosomal aberration test at up to 450 mg/ml. It was non-toxic in acute and repeated-dose (30 and 60 days and 1 year) toxicity studies in rats and mice at up to 3 × 1011 spores/kg bw/day. In an eight-day human clinical trial, Toyocerin® did not cause any adverse effects in healthy male and female subjects at 1 × 109 and 1 × 1010 spores/kg bw/day. In feeding trials, Toyocerin® did not cause any adverse effects in rabbits, pigs, chickens, turkeys and cattle at doses ranging from 8.5 × 107 to 4 × 109 spores/kg bw/day for durations of 2 weeks to 18 months. Taken together, these studies demonstrate that Toyocerin® is safe at the doses tested.