title: Toxicity and mutagenicity studies of DN-50000((R)) and RP-1((R)) enzymes.
abstract: Improved yields of 5'-nucleotides from yeast extract for food flavouring purposes is possible through use of microbial nucleotidases, which will be available to food processors as the flavour enhancer Aromild. The safety of these enzymes, 5'-phosphodiesterase (RP-1) and the 5'-adenylic deaminase (DN-50000) was investigated in male and female rats. Feeding rats a diet admixed with 500, 2000 and 8000 mg/kg body weight of DN-50000 for 35 days resulted in no significant dose-related changes in body weight, water consumption, urinalysis, haematological profiles, blood chemistry or histopathological profiles of either male or female rats from consumption of the enzyme preparation. There was an increase in the absolute and/or relative organ weights of the submaxillary (salivary) glands in both sexes at 8000 mg/kg. The no-observed-effect level (NOEL) for DN-50000 was clearly evident at 2000 mg/kg. Consumption of RP-1 enzyme for 35 days at dietary levels of 500, 2000 and 8000 mg/kg body weight resulted in no significant changes in the above mentioned parameters, which could be directly attributed to a dose-related effect, with the exception of an increase in the absolute and relative weights of submaxillary glands of both male and female rats in the 2000 and 8000 mg/kg groups. The increase in weight of the submaxillary glands was associated with histological evidence of acinar cell hypertrophy. The NOEL for dietary consumption of RP-1 was clearly evident at 500 mg/kg. In a follow-up study in which rats were gavaged with 2000 mg/kg RP-1, submaxillary gland hypertrophy did not occur. These studies suggest that DN-50000 and RP-1 exert an action on submaxillary glands similar to that which has been previously reported for the enzyme pancreatin. Neither DN-50000 nor RP-1 were mutagenic in the Ames assay using Salmonella typhimurium strains TA100, TA1535, TA98, TA1537 or Escherichia coli strain WP2uvrA, in the presence or absence of S9 mix.
authors.affiliation: Burdock & Associates, Inc., 622 Beachland Blvd, Suite B, Vero Beach, FL 32963, USA. george@burdockandassociates.com
authors.forename: G A
authors.initials: GA
authors.lastname: Burdock
authors.forename: W G
authors.initials: WG
authors.lastname: Flamm
authors.forename: I G
authors.initials: IG
authors.lastname: Carabin
mesh_terms: D000659:AMP Deaminase / Q000633:toxicity*; D000818:Animals; D001230:Aspergillus / Q000737:chemistry / Q000201:enzymology; D001772:Blood Cell Count / Q000187:drug effects; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000502:physiology; D004032:Diet; D005260:Female; D005421:Flavoring Agents / Q000633:toxicity*; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009183:Mycotoxins / Q000032:analysis; D009929:Organ Size / Q000187:drug effects; D010407:Penicillium / Q000737:chemistry / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012259:Ribonuclease, Pancreatic / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013363:Submandibular Gland / Q000473:pathology
chemical_list: D005421:Flavoring Agents; D007202:Indicators and Reagents; D009153:Mutagens; D009183:Mycotoxins; D012259:Ribonuclease, Pancreatic; D000659:AMP Deaminase