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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.

    BETA-APO-8'-CAROTENAL*

    Explanation

         This compound has been evaluated for acceptable daily intake by
    the Joint FAO/WHO Expert Committee on Food Additives (see Annex 1,
    Ref. No. 10) in 1966.

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

    BIOLOGICAL DATA

    BIOCHEMICAL ASPECTS

         After administration to rats as the only dietary carotenoid, some
    beta-apo-8'carotenal accumulates in the liver together with Vitamin A
    and beta-apo-8'-carotenoic acid (Thommen, 1962; Brubacher et al.,
    1960).

         Almost all of an excessive dose is excreted in the faeces, only a
    small fraction being absorbed ordinarily (Wiss & Thommen, 1963).

         Dogs absorb it poorly from the gastrointestinal tract and excrete
    it in the urine together with beta-apo-8'-carotenoic acid (Bagdon et
    al., 1960).

         Hypervitaminosis A has not been seen in these dogs. The body fat
    and livers of monkeys show an orange discoloration after oral feeding
    of beta-apo-8'-carotenal, and it is stored in the liver together with
    an unidentified carotenoic acid. Laying hens excrete some into yolk
    (90% as ester, 10% as free beta-apo-8'-carotenoic acid), with
    deepening of colour (Tiews, 1963; Thommen, 1962).

         Hypercholerolemic activity has been noted (Wood, 1963).

         Only 4% of dietary catorenal is converted to Vitamin A in the gut
    of Vitamin A-deficient rats, compared with 10% of beta-carotene.
    Carotenals are easily oxidized to carotenoic acids and less readily
    reduced to alcohols in vivo, pointing to metabolic pathways other
    than beta-oxidation (Wiss & Thommen, 1963; Glover, 1960).

              

    *    Beta-apo-8'-carotenal is found in abundance in the vegetable
    kingdom, e.g. in the pulp and skin of citrus fruits and in various
    fodder plants (Wiss & Thommen, 1963; Thommen, 1962).

    TOXICOLOGICAL STUDIES

    Acute toxicity
                                                                   

                                  LD50
    Animal           Route        mg/kg bw           Reference
                                                                   

    Mouse            Oral         > 10 000           Anonymous, 1966
                                                                   

    Short-term studies

    Rat

         Groups of 16 male rats received 0, 100 or 500 mg/kg of carotenal
    intragastrically five days per week for 34 weeks. No adverse effects
    were seen on body weight gain, general health, survival, liver and
    kidney function and organ weights. The testicular weight of the high
    level test group was significantly lower than that of the controls.
    Microscopic findings were normal except for granular pigment
    deposition in the liver and kidneys of test animals. Fertility as
    shown by monthly mating of four females, was not affected (Anonymous,
    1962; Anonymous, 1966).

    Dog

         Groups of two to three female and three to four male dogs
    received 0, 0.1 or 1.0 g of carotenal daily per animal during 14
    weeks. All remained healthy and no significant effect was noted. No
    pathological lesions related to the test substance were seen at post-
    mortem. Peripheral blood picture, liver function tests, serum enzymes
    and blood urea were normal. Vitamin A and carotenal levels of serum,
    liver, kidney, adrenal and mesenteric fat were estimated. The kidney
    level of Vitamin A was three to five times that of controls. The serum
    level of carotenal was elevated in the group receiving 1.0 g and there
    was an occasional trace in the group on 0.1 g. Tissue amounts were
    variable. The only microscopic finding was pigmentation of the adipose
    tissue, kidney and adrenal cortex. Organ weights were normal (Bagdon
    et al., 1962).

    Long-term studies

    Rat

         A three-generation study in rats at 0 ppm, 1000 ppm, 2000 ppm and
    5000 ppm for two years showed no adverse effect in any generation
    (Anonymous, 1966).

    Comments:

         Beta-apo-8'-carotenal has been adequately tested in rats. The
    use of this substance is unlikely to result in an increased level
    of vitamin A although the conversion rate for man is not known.
    Similarly to beta-carotene, this substance is poorly absorbed from
    the gastrointestinal tract when present in large amounts. It can,
    therefore, be evaluated on the same basis as beta-carotene.

    EVALUATION

    Estimate of acceptable daily intake for man

         0-5 mg/kg bw*

    REFERENCES

    Anonymous (1962) Hoffmann-La Roche, Unpublished report

    Anonymous (1966) Hoffmann-La Roche, Unpublished report

    Bagdon, R. E., Impellizzeri, C. & Osadca, M. (1962) Toxic. Appl.
         Pharm., 4, 444

    Bagdon, R. E., Zbinden, G. & Studer, A. (1960) Toxic. Appl.
         Pharm., 2, 223

    Brubacher, G., Gloor, U. & Wiss, O. (1960) Chimia, 14, 19

    Glover, J. (1960) Vit. Horm., 18, 371

    Thommen, H. (1961) Chimin, 15, 433

    Thommen, H (1962) Naturw., 49, 517

    Tiews, J. (1963) Dtsch. Gesellsch. Ernährung., 9, 236

    Wiss, O. & Thommen, H. (1963) Dtsch. Gesellsch. Ernährung., 9, 179

    Wood, J. D. (1963) Canad. J. Biochem., 41, 1663

              

    *    As sum of the carotenoids: Beta-apo-8'-carotenal

                                    Beta-carotene

                                    Beta-carotenoic acid methyl ester

                                    Beta-carotenoic acid ethyl ester


    See Also:
       Toxicological Abbreviations