Safety evaluation of Streptomyces murinus glucose isomerase

A glucose isomerase enzyme, obtained from Streptomyces murinus, was produced by a fermentation process and subjected to a series of tests to investigate its safety in use and manufacture. It was not mutagenic (Ames test, using liquid culture) nor did it provoke chromosomal damage (rat bone marrow cytogenetics test). It did not contain (nor did the organism produce) antimicrobial activity or macrolidpolyene antibiotics. It had no teratogenic activity when administered to pregnant rats at 100,000 ppm in the diet. It was without effect upon rats when administered at this dietary concentration for 4 weeks. Dietary administration at 5000, 15,000 or 50,000 ppm to rats for 13 weeks resulted in nephrocalcinosis in females at all dosages (probably a physiological response to the altered calcium:phosphate ratio in the admixed diet) and status spongiosus in the brains of males receiving 50,000 ppm. As the finding of nephrocalcinosis in rats is generally agreed to be of no toxicological importance with regard to the use in man, the dietary concentration of 15,000 ppm was considered to be highest no-effect level. This level corresponds to an intake of some 1000 mg/kg/day, which represents approximately 8000 times the human intake based on a conservative estimation.