Toxicity and mutagenicity studies of DN-50000((R)) and RP-1((R)) enzymes

Area of Science:

• Food Science
• Biotechnology
• Toxicology

Background:

• Yeast extract is a source of 5'-nucleotides used as food flavor enhancers.
• Microbial nucleotidases, 5'-phosphodiesterase (RP-1) and 5'-adenylic deaminase (DN-50000), can improve 5'-nucleotide yields.
• These enzymes are being developed as a food flavor enhancer called Aromild.

Purpose of the Study:

• To assess the safety of DN-50000 and RP-1 enzymes for food applications.
• To determine the no-observed-effect level (NOEL) for each enzyme in a rodent model.
• To evaluate the potential genotoxicity of DN-50000 and RP-1.

Main Methods:

• Rats were fed diets containing DN-50000 or RP-1 at various doses (500, 2000, 8000 mg/kg) for 35 days.
• Standard toxicological parameters were monitored, including body weight, water consumption, hematology, blood chemistry, and histopathology.
• Genotoxicity was assessed using the Ames assay with bacterial strains.

Main Results:

• DN-50000 showed no significant dose-related adverse effects, with a NOEL of 2000 mg/kg. Increased submaxillary gland weight occurred at 8000 mg/kg.
• RP-1 also showed no significant dose-related adverse effects, with a NOEL of 500 mg/kg. Increased submaxillary gland weight and hypertrophy occurred at 2000 and 8000 mg/kg.
• Neither enzyme demonstrated mutagenicity in the Ames assay.

Conclusions:

• DN-50000 and RP-1 are safe for use as food flavor enhancers at the tested levels.
• The observed submaxillary gland effects are considered adaptive and reversible, similar to other enzymes like pancreatin.
• The enzymes do not pose a genotoxic risk.