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    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.

    QUINOLINE YELLOW

    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

    Special studies on mutagenicity

         This colour was tested for mutagenic effect in a concentration of
    0.5 and 1.0 g/100 ml in cultures of Escherichia coli. No mutagenic
    effect was found (Lück & Rickerl, 1960).

    Special studies on sensitizing effects

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

    Special studies on teratogenicity

    Rat

         Groups of 20-24 pregnant Long-Evans rats received by gavage from
    days 6 to 15 of gestation 0, 15, 50 or 150 mg/kg/day. Three control
    groups were used and a positive control group of 22 rats was given
    30 mg Trypan Blue/kg/day s.c. from days 7 to 9. Rats were sacrificed
    at day 20. No signs of maternal or fetal toxicity or anomalies were
    seen attributable to the colour. Trypan Blue produced the expected
    abnormalities (Anonymous, 1972a).

    Rabbit

         Groups of 15 pregnant rabbits received by gavage from day
    6 to 18 of gestation 0, 15, 50 and 150 mg/kg/day. Three control
    groups were used and a positive control group of 15 rabbits was given
    150 mg/kg/day thalidomide. Animals were sacrificed on day 29. No
    significant maternal or fetal abnormalities due to the colour were
    noted. Thalidomide produced the expected abnormalities (Anonymous,
    1972b).

    Acute toxicity
                                                           

                        LD50
    Animal    Route     mg/kg bw       Reference
                                                           

    Rat       Oral      2 000          Lu & Lavallee, 1964
                                                           

    Short-term studies

    Rat

         Groups of five male and five female rats were fed diets
    containing 0, 0.25%, 0.5%, 1.0%, 2.0% and 5.0% for 90 days. No effect
    on body weight, food intake, blood cell counts and organ weights was
    observed (Hansen et al., 1960).

         Ten male and 10 female rats were given a total of 55 subcutaneous
    injections of 1 ml of 2% aqueous solution over a period of seven
    months, then observed until death. No local tumours developed and
    total tumour incidence was less than in control groups given similar
    injections of glucose or salt solution (Oettel et al., 1965).

    Dog

         Groups of three male and three female dogs were fed diets
    containing 0.03 and 0.2% of the colour for two years. The control
    group consisted of 10 animals of each sex. No colour induced effects
    were noted in terms of body weight, food consumption, gross and
    microscopic pathology (Anonymous, 1967b).

    Long-term studies

    Rat

         Groups of 20 male and 20 female rats or more were fed diets
    containing 0 and 1% of the colour for two years. A similar test group
    was formed from the first filial generation and was fed at 1% level

    for a similar period of time. No effect of the diet was noted in the
    test groups and gross and microscopic examination of the animals
    disclosed no charges attributable to the test diet. There was no
    significant difference in tumour incidence between the groups (Oettel
    et al., 1965).

         Groups of 25 male and 25 female rats were fed diets containing
    0.0, 0.2 and 0.1% of the colour for up to two years. No colour induced
    effects were seen in terms of body weight, food intake, survival,
    haematology, urinalyses, organ weights, gross and microscopic
    pathology (Anonymous, 1967b).

         Twenty rats, half males and half females, received twice weekly
    s.c. 1 ml of a 2% aqueous solution into the same site. A total of 55
    injections was given for seven months and animals observed for 32
    months. Three groups of 20 rats acted as controls. No significant
    effects on behaviour, growth, mortality, microscopic appearance of
    principal organs was noted. No tumours appeared at the site of
    injection of test animals but one sarcoma at the injection site and
    two tumours of ovary and uterus appeared in controls (Oettel et al.,
    1965).

    Comments:

         There is no biochemical information but an adequate long-term
    study in rats is available. At the previous evaluation a large safety
    factor was used but since there are now available additional studies
    in non-rodent species, this colour may be evaluated on a basis similar
    to other food colours. Multigeneration studies are in progress but
    embryotoxicity including teratology has been studied in two species.

    EVALUATION

    Level causing no toxicological effect

         Rat: 0.1% (= 1000 ppm) in the diet equivalent to 50 mg/kg bw.

    Estimate of acceptable daily intake for man

         0-0.5 mg/kg bw*

              

    *    Temporary.

    FURTHER WORK OR INFORMATION

         Required by June 1978

         Metabolic studies in several species preferably including man.
    Adequate long-term study in another species. Results of multi-
    generation studies.

    REFERENCES

    Anonymous (1967a) Unpublished report submitted to WHO by Hazelton
         Laboratories Inc.

    Anonymous (1967b) Unpublished report submitted to WHO by Hazelton
         Laboratories Inc.

    Anonymous (1972a) Unpublished report submitted to WHO by Biodynamics
         Inc.

    Anonymous (1972b) Unpublished report submitted to WHO by Biodynamics
         Inc.

    Bär, F. & Griepentrog, F. (1960) Med. u. Ernähr., 1, 99

    BIBRA (1973) Personal communication

    Hansen, W. H., Wilson, D.C. & Fitzhugh, O. C. (1960) Fed. Proc., 19,
         390

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

    Lück, H. & Rickerl, E. (1960) Z. Lebensm.-Untersuch., 112, 157

    Oettel, H. et al. (1965) Arch. für Toxikol., 21, 9


    See Also:
       Toxicological Abbreviations
       Quinoline yellow  (FAO Nutrition Meetings Report Series 46a)
       Quinoline Yellow (WHO Food Additives Series 8)
       Quinoline yellow (WHO Food Additives Series 13)
       Quinoline yellow (WHO Food Additives Series 19)
       QUINOLINE YELLOW (JECFA Evaluation)