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.

    INDANTHRENE BLUE RS

    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 1966 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

         No information available.

    TOXICOLOGICAL STUDIES

    Acute toxicity
                                                          

                        LD50
    Animal    Route     mg/kg bw       Reference
                                                          

    Rat       Oral      2 000          Lu & Lavalleé, 1964
                                                          

         In experiments with guinea-pigs it was found that this colour has
    no sensitizing activity (Bär & Griepentrog, 1960). Cats received daily
    doses of 0.1 g/kg colour for seven days. No increase in Heinz bodies
    was noted in the blood of test animals (Oettel et al., 1965).

    Short-term studies

    Rat

         This colour was fed to 21 rats at 0.1% in the diet for 184 days.
    No increased tumour incidence was observed. Eight rats which survived
    for more than 400 days (432-683) showed no abnormality. Twelve rats
    also received monthly subcutaneous injections of 2 ml of a 2.5%
    aqueous suspension of the colour. Six rats survived for 417-570 days.
    No tumours were seen at the site of injection (Umeda, 1956).

    Long-term studies

    Rat

         Eighty-five rats received this colour at 0.1% in their diet. No
    increased tumour incidence was observed over their life-span. Twenty
    rats, given 1% of the colour in their diet for two years, showed no
    increased tumour incidence. Eleven animals died before the end of the
    experiment (DFG, 1957).

         Groups of 20 male and 20 female rats or more were fed diets
    containing 0 ppm (0%) and 1% of the colour for two years. A similar
    test group was formed from the first filial generation and was fed the
    1% level for a similar period. No deleterious effects appeared in the
    test groups, and gross and microscopic examination of the animals
    disclosed no changes attributable to the test diet. There was no
    significant difference in tumour incidence between the groups (Oettel
    et al., 1965).

    Comments:

         The available long-term study in rats is not adequate as only
    some selected parameters have been examined. There is no information
    on metabolism or on its effect on reproduction, embryotoxicity and
    teratogenicity. Previously this colour had been allocated a temporary
    ADI subject to the provision of further essential information by 1974.
    This has not been forthcoming.

    EVALUATION

         The previous temporary ADI has been withdrawn.

    REFERENCES

    Bär, F. & Griepentrog, F. (1960) Med. u. Ernär., 1, 9

    Deutsche Forschungsgemeinschaft, Farbstoff Kommission (1957)
         Mitteilung 6

    Lu, F. C. & Lavalleé, A. (1964) Canad. pharm. J., 97, 30

    Oettel, H., Frohberg, H., Nothdurft, H. & Wilhelm, G. (1965) Arch. für
         Toxikol., 21, 9

    Umeda, M. (1956) Gann, 47, 57

    See Also:
       Toxicological Abbreviations
       INDANTHRENE BLUE RS (JECFA Evaluation)