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    INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY

    WORLD HEALTH ORGANIZATION



    SUMMARY OF TOXICOLOGICAL DATA OF CERTAIN FOOD ADDITIVES



    WHO FOOD ADDITIVES SERIES NO. 12






    The data contained in this document were examined by the
    Joint FAO/WHO Expert Committee on Food Additives*
    Geneva, 18-27 April 1977




    Food and Agriculture Organization of the United Nations
    World Health Organization



    * Twenty-first Report of the Joint FAO/WHO Expert Committee on Food
    Additives, Geneva, 1977, WHO Technical Report Series No. 617

    COCHINEAL, CARMINE AND CARMINIC ACID

    Explanation

         Cochineal is a red colouring matter consisting of the dried
    bodies of the female insect Coccus cacti (Dactylopius coccus  Costa,
    Fam. Coccidae), containing eggs and larvae. The insect grows on
    various species of the cactus, Nopalea (Fam. Cactacea), in the
    Canary Islands and Central and South America. The colouring matter is
    carminic acid. Carmine is the aluminium/calcium lake of carminic acid
    (Meloan et al., 1971).

    EVALUATION FOR ACCEPTABLE DAILY INTAKE

    BIOLOGICAL DATA

    BIOCHEMICAL ASPECTS

         No information available.

    TOXICOLOGICAL STUDIES

    Special studies on skin sensitization

         Three subjects with lip lesions gave positive patch tests when
    tested with red lip salve containing carmine (the Al/Ca lake of
    carminic acid), but negative reactions to colourless lip salve. Since
    the coloured product had previously been used by each individual, the
    symptoms of allergic sensitivity were ascribed to carmine (Sarkany et
    al., 1961).

    Special studies on mutagenicity

         Carminic acid was negative in the Bacillus subtilis rec-assay
    for DNA-damaging ability (Kada et al., 1972). Carminic acid was not
    mutagenic for several strains of Salmonella typhimuriam in the
    presence of liver microsomal preparations or enzymatic extracts of rat
    cecal micro-flora (Brown and Brown, 1976; Brown et al., 1977).

    Teratogenicity studies

         The embryotoxicity and teratogenicity of carmine has been studied
    in mice. Mice were killed on day 19 of gestation, after i.p.
    injections of lithium carmine or sodium carmine on day 8. Treated
    animals of both groups showed resorption rates (20%) higher than those
    of control groups (2%). The malformation rate was about 16% in the
    lithium carmine group and 2.5% after injection of sodium carmine. Only
    animals given sodium carmine showed an increase in the number of
    retarded foetuses (Schluter, 1970).

         Groups of mice were injected once with 2.5% lithium carmine at a
    dose of 150 mg earmine/kg on day 6, 8, 10, 12 or 14 of pregnancy. A
    teratogenic effect was observed on the first three treatment days,
    with the maximal response on day 8 (Schluter, 1971a and b).

    Acute toxicity

         No information available.

    Short-term studies

    Mouse

         Mice (number not stated) were given intraperitoneal injections of
    a 1 to 2% aqueous solution of the lithium salt of carminic acid for a
    period of 60 days. The only abnormality observed was proliferation of
    spleen tissue (Harada, 1931).

    Rat

         Groups of 40 rats, equally divided by sex, received ammoniacal
    cochineal carmine in 0.4% aqueous gum tragacanth by intubation at
    dosage levels of 0, 2.5, 5.0 and 10.0 mg/kg five days per week for
    13 weeks. Body weight was recorded bi-weekly. Blood counts were made
    three times. Gross and microscopic findings were not remarkable aside
    from a dose-related accumulation of colour in the tissues of the rats
    receiving the two higher dosage levels. No haematological effects were
    noted. At the two highest levels some decreased growth was apparent.
    Urine and faeces of the treated rats were coloured during the period
    of administration (Battelle, 1962).

         Groups of 50 weanling rats equally divided by sex were fed
    carmine in the diet at levels of 0, 50, 250 and 500 mg/kg bw/day for
    90 days. Blood counts, blood glucose, blood urea nitrogen and
    urinalyses were performed three times. No effects due to the carmine
    were reported in terms of growth, haematology and other clinical
    findings. Gross and microscopic pathology were not remarkable (FDRL,
    1962).

    Rabbit

         Five rabbits were given intravenous injections every five to
    seven days, of 3 to 10 ml of a 2 to 4% aqueous solution of the lithium
    salt of carminic acid. The treatment was continued for periods
    varying from 130 to 529 days. No tumours were observed, but great
    proliferation of the tissue of the spleen was noted (Harada, 1931).

    Long-term studies

         Four groups of 30 mated female rats received daily 0, 200, 500 or
    1000 mg/kg bw of carmine by gastric intubation as aqueous solution
    during pregnancy days 0 to 20. A group of 17 similar animals received
    a solution of chlorides to provide an intake of sodium, potassium and
    ammonium equal to that resulting from the highest dose level of
    carmine. No adverse effects were noted on body weight, pregnancy rate
    pre-implantation losses, the average number of live young litter
    weight or foetal weight. The group given the highest dose of carmine
    and the cations control had an increased number of implantation sites
    and of post-implantation losses. The latter was considered to be due
    to an inability to maintain the increased numbers of implantations
    rather than to an embryotoxic effect. No teratogenic effects were
    noted in the foetuses and the degree of ossification of those from the
    carmin treated rats tended to be more advanced than those from the
    control (Gaunt et al., 1976).

    REFERENCES

    Battelle Memorial Institute (1962) Unpublished report submitted to WHO

    Brown, J.P. and Brown, R. J. (1976) Mutation Res., 40, 203

    Brown, J.P., Roehm, G. W. & Brown, R. J. (1977) Environ. Mutagen
    Sec. 8th Ann. Meet., Abst., p. 33

    Food and Drug Research Laboratories (1962) Unpublished report
    submitted to WHO

    Gaunt, I. F., Clode, S. A. and Lloyd, A. G. (1976) Unpublished report
    from B.I.B.R.A., submitted to WHO - Studies of the teratogenicity and
    embryotoxicity of carmine in the rat. Report 162/1/76, July 1976

    Harada, M. (1931) cited by Hartwell, J. L.: Survey of compounds which
    have been tested for carcinogenic activity, second edition, 1951, p.
    118

    Meloan, S. N., Valentine, L. S. and Puchtler, H. (1971) Histochemie,
    27, 87

    Kada, T., Tutikawa, K. and Sadaie, Y. (1972) Mutation Res., 16,
    165

    Sarkany, R. H., Meara, R. H. and Everall, J. (1961) Trans. St.
    John's Hosp. Derm. Soc., 48, 39

    Schluter, G. (1970) Z. Anat. Entwickl.-Gesch., 131, 228

    Schluter, G. (1971a) Naunyn-Schmiedebergs Arch. Pharmak., 270, 56

    Schluter, G. (1971b) ibid, 270, 316


    See Also:
       Toxicological Abbreviations