The evaluations contained in this publication were prepared by the
    Joint FAO/WHO Expert Committee on Food Additives which met in Rome,
    4-13 June 19741

    World Health Organization     Geneva     1975


    1  Eighteenth Report of the Joint FAO/WHO Expert Committee on
    Food Additives, Wld Hlth Org. techn. Rep. Ser., 1974, No. 557.
    FAO Nutrition Meetings Report Series, 1974, No. 54.




         GMP is widely distributed as a component of RNA in living
    organisms. GMP is dephosphorylated to guanosine, hydrolyzed further to
    guanine, deaminated to xanthine and oxidized finally to uric acid or
    allantoin in mammals. Two-thirds of this is excreted in the urine, the
    rest is excreted and further broken down in the gut. Digestion appears
    to take place mainly in the duodenum, the nucleosides being probably
    absorbed actively, the purines probably by diffusion across the
    intestinal wall. The greater portion of GMP in the body is derived
    from de novo purine bio-synthesis, the rest derived from preformed
    dietary purines. Biosynthesized IMP is the precursor of GMP to which
    it is converted by oxidation to xanthosine-5 mono-phosphate and
    amination. Dietary or endogenous purine bases and ribo-nucleosides are
    also converted to the 5'-ribonucleotides by phosphorylation (Kojima,

         500 mg/kg i.v. GMP produced in mice abdominal postures, slight
    respiratory depression and slight depression of avoidance response
    after 15 minutes. There was no muscular relaxation but depression of
    rotating activity for one hour, no modification of electroshock
    convulsion but a decrease, dose-dependent, of the convulsive dose of
    metrazole as well as increased loss of righting reflex (Kojima, 1973).
    100 mg/kg GMP intragastric in mice did not affect intestinal transport
    as measured by charcoal transportation. Concentrations below 10-4g/ml
    had no effect on the contractile response of isolated guinea-pig ileum
    to acetylcholine, histamine or barium chloride. 100 mg/kg GMP s.c. in
    rats did not affect gastric juice secretion but slightly increased pH
    and depressed total acidity. 100 mg/kg s.c. GMP in mice depressed
    salivary secretion (Kojima, 1973).

         Rapid intracarotid injection increased the cerebral blood flow
    but did not affect the oxygen consumption and glucose uptake of the
    perfused cat brain (Otsuki et al., 1968). Intravenous GMP had no
    significant effect on the B.P. heart-rate and ECG of the anaesthetized
    rabbit (Yabo, 1964). Parenteral GMP produced transient changes in the
    EEG of rabbits (Hirayama, 1968) and i.p. GMP had no marked effect on
    the conditioned avoidance response of the rat (Hirayama, 1968).
    Topical GMP enhanced the electrical response of the chordatympani to
    topical MSG in the rat (Sato et al., 1965).

         25 mg/kg GMP intragastrically had no diuretic effect in rats.
    Oral 500 mg/kg GMP in mice did not affect the analgesic response of
    mice or carrageenin oedema in rats (Kojima, 1973). Male and pregnant
    (day 10 or 18 of gestation) rats were given by gavage 25 mg/kg bw of
    8-14C GMP. Plasma radioactivity reached a maximum within 30 minutes
    after ingestion and decreased abruptly to practically zero within 24
    hours, the half life being about one hour. About 84% of total activity
    appeared in urine, 0.2% in faeces, none in expired air, between 0-0.6%
    remained in organs, about 12% in organ-free carcass of males and 18
    day pregnant females 24 hours after treatment. The foetus contained
    about 0.01% activity 24 hours after treatment (Ohara et al., 1973).
    Groups of five male rats (control group 10) were given 0%, 1% and 4%
    GMP for five or 10 days in a purine free basal diet. Levels of uric
    acid in serum and urine were hardly affected, most of the exogenously
    ingested GMP was rapidly excreted in urine as allantoin. Only liver
    hypoxanthine-guamine phosphoribosyl transferase and adenine
    phosphoribosyl transferase activities were increased and also the
    ratio of liver uricase/xanthine oxidase activity suggesting metabolism
    by shunt pathways for exogenously ingested GMP (Hashimoto et al.,


    Special studies on teratogenicity


         One group of nine pregnant rats was given daily 100 mg/kg bw of
    GMP during days 9-15 of pregnancy. No significant effects on fetuses
    were noted (Kaziwara et al., 1971).


         Three groups of 9-10 pregnant rabbits were fed diets containing
    either normal diet (12 animals), or 0.2 g/kg bw or 2.0 g/kg bw GMP
    from days 6-18 of gestation. All except four dams in each group
    were sacrificed on day 29, the remainder was allowed to litter
    spontaneously, pups being observed until 30 days of age. No adverse
    effects were noted on body weight and food consumption except the
    group on 2.0 g/kg which had reduced food consumption. Implantation
    numbers did not differ from controls but mortality of fetuses in the
    2.0 g/kg group was lower than in controls. All groups showed some
    delay in ossification, but no treatment - specific skeletal
    abnormalities. There were no effects on number of delivered fetuses,
    survival rate of the 0.2 g/kg group was greater at weaning. Mean pup
    body weights were normal and no significant malformations were found
    in the pups of both dosage groups (Jojima et al., 1973).

    Chick embryo

         GMP was neither highly toxic nor teratogenic in this system
    (Karnofsky et al., 1961).

    Acute toxicity

    Animal     Route              (mg/kg bw)     References

    Mouse      Oral                10 000        Usui et al., 1971

               Oral (male)         15 000        Ichimura & Muroi, 1973

               Oral (female)       16 300        "         "        "

               s.c. (male)          5 050        "         "        "

               s.c. (female)        5 050        "         "        "

               i.p. (male)          6 800        "         "        "

               i.p. (female)        5 010        "         "        "

               i.v. (male)          3 580        "         "        "

               i.v. (female)        3 950        "         "        "

    Rat        Oral                10 000        Usui et al., 1971

               Oral (male)         17 300        Ichimura & Muroi, 1973

               Oral (female)       17 300        "          "        "

               s.c. (male)          3 550        "          "        "

               s.c. (female)        3 400        "          "        "

               i.p. (male)          4 750        "          "        "

               i.p. (female)        3 880        "          "        "

               i.v. (male)          2 720        "          "        "

               i.v. (female)        2 850        "          "        "

    Short-term studies


         Three groups of 10 male and 10 female rats were given 0%, 
    0.1% and 1% of GMP in their diet daily for three and six months. 
    No significant abnormalities were noted as regards spontaneous 
    behaviour, body weight gain, food intake, haematology, urinalysis, 
    macroscopic and histological examination (Usui et al., 1971).

    Long-term studies

         None available.


         Inosinates, guanylates and ribonucleotides are substances 
    normally present in all tissues and their role in purine metabolism 
    as well as their breakdown in the majority of mammals, but not man, 
    to uric acid and allantoin is well known. The various products have 
    been studied adequately in long-term, reproduction and teratology 
    tests. Ingestion of large amounts of these compounds by man can 
    increase the serum uric acid level and urinary uric acid excretion 
    and this needs to be considered in relation to people with gouty 
    diathesis and those taking uric-acid retaining diuretics. Hence 
    specific mention of the addition of these substances on the level may 
    be indicated. The changes in dietary purine intake from the use of 
    flavour enhancers are no greater than those likely to be occasioned 
    by changes in consumption of those dietary items which are the main 
    contributors of purine.


         Acceptable daily intake not specified1.


    1  The statement "ADI not specified" means that, on the basis of 
    the available data (toxicological, biochemical, and other), the total 
    daily intake of the substance, arising from its use or uses at the 
    levels necessary to achieve the desired effect and from its acceptable 
    background in food, does not, in the opinion of the Committee, 
    represent a hazard to health. For this reason, and for the reasons 
    stated in individual evaluations, the establishment of an acceptable 
    daily intake (ADI) in mg/kg bw is not deemed necessary.


    Hashimoto, S. et al. (1973) Life Sciences Laboratories, Ajinomoto Co.,

    Hirayama, H. (1968) Folia pharmacol, jap., 64, 279

    Ichimura, M. & Muroi, K. (1973) Report of Life Sciences Laboratories,
         Ajinomoto Co. Japan

    Jojima, M. et al. (1973) Report of Life Sciences Laboratories,
         Ajinomoto Co. Japan

    Karnofsky, D. A. & Lacon, C. R. (1961) Biochem. Pharmacol., 7, 154

    Kaziwara, K., Mizutani, M. & Ihara, T. (1971) J. Takeda Res. Lab.,
         30(2), 314-321

    Kojima, K. (1973) Safety evaluation of IMP, GMP and DSRN, Toxicology,
         2, (in press)

    Ohara, V., Matsuzawa, V. & Takeda, J. (1973) Report of Life Sciences
         Laboratories, Ajinomoto Co. Japan.

    Otsuki, S. et al. (1968) Med and Biol., 76, 107

    Sato, M. et al. (1965) Jap. J. Physiol., 15, 53

    Usui, T. et al. (1971) J. Takeda Res. Lab., 30(3), 614-635

    Yabo, S. (1964) Folia pharmacol, jap., 60, 194

    See Also:
       Toxicological Abbreviations