Subchronic toxicity studies in dogs and in utero-exposed rats fed diets containing Bacillus megaterium amylase derived from a recombinant DNA organism

Abstract

Subchronic toxicity studies were performed using a food-grade enzyme product from a recombinant Bacillus subtilis containing the B. megaterium amylase gene. Beagle dogs (four/sex/group) and Fischer 344 rats (25/sex/group) were fed diets containing 0, 20, 60 or 100 units amylase/g food. The dogs received treated diets for 13 wk. The parental (F 0) rats received treated diets for 4 wk before breeding and through weaning of the F 1 pups; 25 F 1 rats/sex/group received treated diets for at least 13 wk (from weaning until necropsy). All animals appeared healthy throughout the studies. Treated animals had sporadic significant differences in body weight and food consumption values when compared with those of controls, but they were not considered toxicologically meaningful. There were no treatment-related effects on reproduction indices, growth variables or litter data in rats. There were no changes in clinical pathology values, organ weights or macroscopic and microscopic observations that were related to treatment. Based on the results of this study, the no-observable-effect level for this amylase fed to dogs or rats is no less than 100 units/g food. This is 6000–12,700 times the predicted human use level.