An overview of the safety evaluation of the Rhizomucor miehei lipase enzyme.

The Rhizomucor miehei lipase enzyme expressed in Aspergillus oryzae, is used in the production of specialty fats, the production of existing fats from new raw materials, or new fats with improved nutritional or functional qualities. It is produced by A. oryzae containing the structural gene for the precursor of R. miehei triglyceride lipase. It was subjected to a series of toxicological tests to document the safety in use. The enzyme preparation was not found to be mutagenic either in bacterial cultures (Ames test) or in the mammalian cell cultures (mouse lymphoma assay), nor did it cause chromosomal damage (human lymphocyte assay). Dietary concentrations up to 1600 mg/kg diet for up to 13 weeks caused no adverse effect in rats. At higher concentrations there were effects upon food intake, possibly arising from some irritant property of the enzyme preparation in the diet at such high levels, with consequential effects upon bodyweight and energy metabolism. A minor effect upon renal function was indicated by increased kidney weight and changes in the urine. At 40,000 mg/kg diet the enzyme was considered to have exacerbated the onset of normally-occurring chronic myocarditis in male Sprague-Dawley rats.