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'-CAROTENOIC ACID, ETHYL AND METHYL ESTERS

    Explanation

         These compounds have 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

         The acid as well as the esters are normal metabolites of apo-
    carotenal. Only a minor fraction of the methyl ester, if given in 
    large doses to rats, is absorbed, most being excreted in the faeces 
    (Wiss & Thommen, 1963). The elimination of ester from the blood of 
    human infants is proportional to the blood concentration and is very 
    rapid (Kübler, 1963).

    TOXICOLOGICAL STUDIES

    Acute toxicity
                                                        

                        LD50
    Animal    Route     mg/kg bw       Reference
                                                        

    Mouse     Oral      > 10 000       (Anonymous, 1966)
                                                        

    Short-term studies

    Rat

         Groups of 16 rats received 0, 100 or 500 mg/kg of methyl ester 
    daily, five days per week, for 34 weeks. No adverse effects on 
    mortality or weight gain were noted, but the male rats receiving
    500 mg/kg bw showed reduced testicular weights compared with   
    controls, and granular pigment deposits in the liver and kidney. No
    deleterious effect on spermatogenesis was noted and their general
    health was satisfactory (Anonymous, 1962; Anonymous, 1966).

    Long-term studies

    Rat

         In a four-generation study, test groups of male and female rats
    of 20 to 40 animals each and control groups of 28 to 39 each were fed
    diets containing 0, 0.1, 0.2 and 0.5 and 1.0% of methyl ester for
    periods of 52 to 104 weeks. No difference was observed between test
    and control groups regarding food consumption and general health;
    mortality was unrelated to the test substance (Anonymous, 1966).

         In another experiment, 15 male rats were fed the ethyl ester at
    1% of their diet for two years, with a control group on 7500 IU of
    Vitamin A per day per animal and another control group on the basic
    diet. Mortality and weight gain were identical in test and control
    groups except for the group fed the Vitamin A supplement. Fertility
    was similarly unaffected except in the group given Vitamin A. No
    adverse effects were noted on general health (Anonymous, 1966).

    Comments:

         Although the toxicological information on each individual ester
    is incomplete, long-term studies have been reported in rats. The use
    of these substances is unlikely to result in an increased level of
    Vitamin A, although the conversion rate for man is not known.
    Similarly to beta-carotene, these substances are poorly absorbed from
    the gastrointestinal tract especially when present in large amounts.
    They 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 submitted to WHO

    Anonymous (1966) Hoffmann-La Roche unpublished report submitted to WHO

    Kübler, W. (1963) Wiss. Veröff. Dtsch. Gesellsch. Ernährung., 9, 222

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

              

    *    As sum of the carotenoids: beta-carotene, beta-apo-8'carotenoic
    acid methylester, beta-apo-8'carotenoic acid ethyl ester, beta-apo-
    8'carotenal.

    See Also:
       Toxicological Abbreviations