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    BEET RED AND BETANINE

    EXPLANATION

         Beet red is the colour obtained from the red beetroot, the
    principal component of which is betanine. This food colour was last
    reviewed at the twenty-sixth meeting of the Committee (Annex 1,
    reference 59), when the previously allocated temporary ADI "not
    specified" was withdrawn because the additional information required
    by the Committee at its eighteenth and twenty-second meetings was not
    available, that is, data on metabolism and long-term toxicity (Annex
    1, references 35 and 47).

         Since the previous evaluation, additional data have become
    available and are summarized and discussed in the following monograph.

    BIOLOGICAL DATA

    Biochemical aspects

    Absorption, distribution, metabolism, and excretion

         When betanine (4.5 µmole) was injected i.v. to rats, urinary
    excretion was rapid, 88% of the dose appearing in urine within 4
    hours, and the plasma half-life was 32 minutes. Orally-administered
    betanine was poorly absorbed in rats and most of the dose was
    metabolized in the gastrointestinal tract; approximately 3% of the
    oral dose appeared in urine and a similar amount in faeces
    (Krantz et al., 1980).

    Toxicological studies

    Special studies on carcinogenicity

    Rats

         In a two-generation study, rats were given 50-78 mg betanine/kg
    b.w./day in drinking water throughout their lives. No evidence of
    carcinogenicity was reported (Druckrey, 1959).

         No increase in tumours was observed in rats given repeated doses
    of betanine by subcutaneous injection (Druckrey, 1959).

         A short-term study was performed to assess the ability of beet
    red to initiate or promote hepatocarcinogenesis in rats. Groups of
    female Sprague-Dawley rats (6-11 animals/group) were partially
    hepatectomized and treated with four different beet pigment
    preparations to assess their ability to initiate carcinogenesis;
    fermented betacyanin solution (50 mg/kg), pure betanine (50 mg/kg),
    degraded betanine (50 mg/kg), or a diet containing 2000 mg
    betacyanin/kg. N-Nitrosodiethylamine (10 mg/kg) was used in a positive
    control group. Another group previously initiated with
    N-nitrosodiethylamine was given a betacyanin solution (100 ppm,
    equivalent to 3.5 mg/rat/day) to determine the ability of betacyanin
    to promote carcinogenesis after initiation relative to control and
    phenobarbitone-pretreated rats. After 6 months (promotion studies) or
    8 months (initiation studies) the livers were examined histologically
    and histochemically for gamma-glutamyl peptidase foci. There was no
    evidence that betalain preparations initiated or promoted
    hepatocarcinogenesis (Schwartz et al., 1983).

    Special studies on mutagenicity

         Beet red was found to be non-mutagenic against 5 strains of
    Salmonella typhimurium in the Ames test, with or without metabolic
    activation by S-9 preparations, at concentrations of 500-2500 µg/plate
    (von Elbe & Schwartz, 1981). At higher concentrations (50 mg/plate),
    beet red was reported to be weakly mutagenic against S. typhimurium,
    with or without metabolic activation (Ishidate et al., 1984).

         No mutagenic activity was detected in studies using
    Escherichia coli or S. typhimurium assays, with or without
    metabolic activation by rat S-9 preparations, or intestinal microbial
    preparations. No DNA damage was detected in the E. coli rec assay
    (Haveland-Smith, 1981).

         Beet red did not induce chromosomal aberrations in Chinese
    hamster fibroblast cells in culture (Ishidate et al., 1984).

    Acute toxicity

    Rats

         No deaths were reported in rats given high oral doses of beetroot
    red (Druckrey, 1959).

         Single doses of betanine injected i.v. into anaesthetised rats
    caused a transient increase in blood pressure and heart rate, the
    effect of 0.9 µmole betanine being about equivalent to that of 2 µmole
    adrenalin (Kranz et al., 1980).

    Short-term studies

    Rats

         Groups of six rats were fed beet red preparations containing
    2000 ppm betalains in the diet for 7 days. No significant differences
    were noted in body-weight gain, food intake, or gross pathological
    features relative to controls (von Elbe & Schwartz, 1981).

    Long-term studies

         (see "Special studies on carcinogenicity").

    Observations in man

         No information available.

    COMMENTS AND EVALUATION

         Previous Committees had considered beet red together with its
    major colour component, betanine. This Committee decided that it would
    be appropriate to evaluate these food colours separately and pointed
    out that, for the compound betanine, insufficient data were available
    to establish an ADI, since the information available to the Committee
    did not meet currently accepted standards.

         In evaluating beet red, the Committee took into account the
    principles laid down by the Committee at its twenty-first meeting
    (Annex I, reference 44) and endorsed in Annex III of "Principles for
    the Safety Assessment of Food Additives and Contaminants in Food"
    (Annex 1, reference 76). Thus, when the concentrate is used to enhance
    the colour of beet products, it could be considered as food. If, on
    the other hand, the concentrate is used more generally as a colourant,
    careful specifications need to be established. Because nitrate is a
    component of beet red, it is necessary to ensure that levels of
    nitrate do not exceed the specifications. Under these conditions beet
    red could be used according to good manufacturing practice with an ADI
    "not specified", keeping in mind the need to limit the nitrate content
    of foods produced for infants and young children.

    REFERENCES

    Druckrey (1959). Unpublished data submitted to WHO.

    von Elbe, J.H. & Schwartz, S.J. (1981). Absence of mutagenic activity
    and a short-term toxicity study of beet pigments as food colourants.
    Arch. Toxicol., 49, 93-98.

    Haveland-Smith, R.B. (1981). Evaluation of the genotoxicity of some
    natural food colours using bacterial assays. Mutation Res., 91, 285.

    Ishidate, M., Sofuni, T., Yoshikawa, K., Hayashi, M., Nohmi, T.,
    Sawada, M., & Matsuoka (1984). Primary mutagenicity screening of food
    additives currently used in Japan. Fd. Chem. Toxicol., 22, 623.

    Krantz, C., Monier, M., & Wahlstrom, B. (1980). Absorption, excretion,
    metabolism and cardiovascular effects of beetroot extract in the rat.
    Fd. Cosmet. Toxicol., 18, 363-366.

    Schwartz, S.J., von Elbe, J.H., Pariza, M.W., Goldsworthy, T., &
    Pitot, H.C. (1983). Inability of red beet betalain pigments to
    initiate or promote hepatocarcinogenesis. Fd. Chem. Toxicol.,
    21, 531-535.
    


    See Also:
       Toxicological Abbreviations
       Beet red (WHO Food Additives Series 6)
       BEET RED (JECFA Evaluation)