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

Improved yields of 5'-nucleotides from yeast extract for food flavouring pu rposes is possible through use of microbial nucleotidases, which will be av ailable to food processors as the flavour enhancer Aromild(R). The safety o f these enzymes, 5'-phosphodiesterase (RP-1(R)) and the 5'-adenylic deamina se (DN-50000(R) was investigated in male and female rats. Feeding rats a di et admired with 500, 2000 and 8000 mg/kg body weight of DN-50000 for 35 day s resulted in no significant dose-related changes in body weight, water con sumption, urinalysis, haematological profiles, blood chemistry or histopath ological profiles of either male or female rats from consumption of the enz yme preparation. There was an increase in the absolute and/or relative orga n 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 2 000 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-re lated effect, with the exception of an increase in the absolute and relativ e weights of submaxillary glands of both male and female rats in the 2000 a nd 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 fol low-up study in which rats were gavaged with 2000 mg/ kg RP-I, submaxillary gland hypertrophy did not occur. These studies suggest that DN-50000 and R P-1 exert an action on submaxillary glands similar to that which has been p reviously reported for the enzyme pancreatin. Neither DN-50000 nor RP-1 wer e mutagenic in the Ames assay using Salmonella typhimurium strains TA100, T A1535, TA98, TA1537 or Escherichia coli strain WP2uvrA, in the presence or absence of S9 mix. (C) 2000 Elsevier Science Ltd. All rights reserved.