INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY

    WORLD HEALTH ORGANIZATION



    TOXICOLOGICAL EVALUATION OF SOME
    FOOD COLOURS, ENZYMES, FLAVOUR
    ENHANCERS, THICKENING AGENTS, AND
    CERTAIN FOOD ADDITIVES



    WHO FOOD ADDITIVES SERIES 6







    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.

    PATENT BLUE V

    Explanation

         This compound has been evaluated for acceptable daily intake by
    the Joint FAO/WHO Expert Committee on Food Additives (see Annex 1,
    Refs Nos 10 and 20) in 1964 and 1969.

         Since the previous evaluation additional data have become
    available and are summarized and discussed in the following monograph.
    The previously published monographs have been expanded and are
    reproduced in their entirety below.

    BIOLOGICAL DATA

    BIOCHEMICAL ASPECTS

         After intravenous injection into the rat of 0.5 ml of an aqueous
    solution containing 5 g per 100 ml the colour is excreted in the urine
    which is coloured blue during the 12 hours following the injection.
    Findings are similar in the case of man when the colour is injected
    subcutaneously for the detection of peripheral lymphatic trunks and
    nodes for the purpose of lymphography (Truhaut, 1962).

    TOXICOLOGICAL STUDIES

    Special studies on surface activity

         The dye (as the Ca salt) had slight surface activity. The Na salt
    had considerable surface activity. Protein binding and lipophilic
    activity were negligible for both salts. The authors conclude that the
    difference in surface activity explains the difference in the local
    reactions to the two salts (Cangolli et al., 1967).

    Acute toxicity
                                                    

    Animal    Route     LD50           Reference
                        per kg bw
                                                    

    Mouse     Oral      > 3.0 g        Truhaut, 1962

    Mouse     i.v.      1.2 g           "

    Rat       Oral      > 5.0 g         "

    Rat       i.v.      5.0 g           "
                                                    

    Short-term studies

    Rat

         Subcutaneous injections of 1 ml of 0.8% aqueous solution twice
    weekly for five weeks produced only slight tissue reactions (Grasso &
    Goldberg, 1966).

    Cat

         Three cats were given daily per os doses of 0.25, 0.50 and
    0.75 g of a 5% aqueous solution of the colour. No abnormalities were
    found (Truhaut, 1962).

    Long-term studies

    Rat

         Sixty rats, half males and half females, were given in their diet
    10 000 ppm of the colour for their life span. The used colour was pure
    (no impurities were found by paperchromatography studies). The average
    life span of treated animals was 24 months and the last animal died at
    an age of 37 months, two weeks. The average intake of the colour was
    approximately 80 g. Forty animals were used as controls. The average
    life span of these animals was 22 months, two weeks. For the second
    experiment 30 rats, half males and half females, were given the same
    diet with 10 000 ppm and also for 15-19 months once a week a
    subcutaneous injection of 1 ml of a 1% aqueous solution. The average
    life span of the animals was 18 months. The last animal died at an age
    of 30 months. Twenty-six rats were used as controls and were given
    1 ml of distilled water subcutaneously for the same period as the
    treated animals. The average life span of these animals was 19 months.

         In both experiments it was found that growth, blood composition,
    reproduction and the three generations of animals which were bred were
    not influenced. Also, no abnormal histopathological findings or
    sarcomas at the site of injection were observed (Truhaut, 1962).

    Comments:

         Information on the metabolism of the colour is lacking. Long-term
    and reproduction studies in the rat did not reveal any significant
    toxicological effects. A long-term study in a second species is
    required as well as a short-term study in a non-rodent species. These
    have not been supplied.

    EVALUATION

         The previous temporary ADI has been withdrawn.

    REFERENCES

    Gangolli, S. D., Grasso, P. & Goldberg, L. (1967) Fd. Cosmet.
         Toxicol., 5, 601

    Grasso, P. & Goldberg, L. (1966) Fd. Cosmet Toxicol., 4, 269

    Truhaut, R. (1962) Aliment. et Vie, 50, 77

    See Also:
       Toxicological Abbreviations
       Patent blue V  (FAO Nutrition Meetings Report Series 46a)
       PATENT BLUE V (JECFA Evaluation)