Safety evaluation of lipase produced from Rhizopus oryzae: summary of toxicological data.

The toxicity of Lipase D, an enzyme preparation, was evaluated in a series of studies. Lipase D selectively hydrolyzes triglycerides of fatty acids. It also catalyzes the interesterification of edible fats and oils. In a 13-week gavage study, Sprague-Dawley rats received Lipase D at levels of 0, 500, 1000, or 2000 mg/kg body wt./day. A dose dependent decrease in urinary pH was observed, but there were no effects on electrolyte balance, kidney weight, or histology of the kidney. The no-observed-adverse-effect level in rats was 1000 mg/kg body wt./day. In common with other enzyme preparations, Lipase D was not genotoxic. Lipase D was tested in the Ames assay, the mouse lymphoma forward mutation assay, and the chromosome aberration assay. Finally, the particular strain of Rhizopus oryzae used to prepare Lipase D was shown to have low to moderate pathogenicity when injected into the tail vein of mice at doses up to 1.3 x 10(6) colony-forming units (CFU) per animal. No effects were observed when mice received up to 2.2 x 10(5) CFU by gavage or in their diets daily for 28 days. The results indicate that this particular strain can be handled using ordinary safety practices current in the fermentation industry. These studies support a conclusion that Lipase D is safe when used as described in the processing of dietary fatty acids and glycerides of fatty acids.