Toxicological evaluation of some food
    additives including anticaking agents,
    antimicrobials, antioxidants, emulsifiers
    and thickening agents



    WHO FOOD ADDITIVES SERIES NO. 5







    The evaluations contained in this publication
    were prepared by the Joint FAO/WHO Expert
    Committee on Food Additives which met in Geneva,
    25 June - 4 July 19731

    World Health Organization
    Geneva
    1974

              

    1    Seventeenth Report of the Joint FAO/WHO Expert Committee on
    Food Additives, Wld Hlth Org. techn. Rep. Ser., 1974, No. 539;
    FAO Nutrition Meetings Report Series, 1974, No. 53.


    alpha-TOCOPHEROL AND MIXED TOCOPHEROLS CONCENTRATE

    Explanation

         These substances have been evaluated for acceptable daily intake
    by the Joint FAO/WHO Expert Committee on Food Additives (see Annex 1,
    Ref. No. 6) in 1961.

         The previously published monograph has been revised and is
    reproduced in its entirety below.

    BIOLOGICAL DATA

    BIOCHEMICAL ASPECTS

         The metabolic fate of alpha-tocopherol is not fully known. When
    rats are given 3.5 mg daily by mouth 3 to 15% appears in the faeces.
    With doses larger than this, up to 25% may appear in the faeces. There
    is practically no urinary excretion of tocopherols, but from studies
    with labelled material it appears that one or more metabolites of
    tocopherols are excreted in the urine (Sternberg & Pascoe-Dawson,
    1959).

         When more than the daily requirement is administered, there is
    some storage of tocopherol in the liver (Sebrell & Harris, 1954).

    TOXICOLOGICAL STUDIES

    Acute toxicity

         LD50 values are not known.

    Short-term studies

    Rat and Mouse

         Rats receiving alpha-tocopherol in a dosage of 100 mg/rat per day
    for 19 weeks showed an increase in phosphorus metabolism, but no
    effect was found when the dose was 10 mg/rat per day (Weissburger &
    Harris, 1943).

         It has been found that mice will tolerate oral doses of 50 g/kg
    and rats 4 g/kg daily for two months (Demole, 1939).

    OBSERVATIONS IN MAN

         Adult humans have tolerated 1 g per day for months or larger
    doses for shorter periods with no undesirable effects.
    Therapeutically, daily doses of 20 to 600 mg of alpha-tocopherol or

    its acetate are often taken with no toxic effects (Finkler, 1949;
    McLaren, 1949; Sebrell & Harris, 1954). The clinical literature
    contains references to complaints of gastric distress and other
    symptoms in patients receiving much smaller dosages; these symptoms
    are probably attributable to fatty substances present in alpha-
    tocopherol concentrates or, in some instances, to psychic factors
    (Sebrell & Harris, 1954).

    Comments:

         Though the toxicological studies are less than would normally be
    required for foreign substances used as food additives, it is
    considered that alpha-tocopherol is a nutrient. The clinical
    experience with this vitamin is used as the basis for the evaluation.

    EVALUATION

    Estimate of acceptable daily intake for man

         0-2* mg/kg bw.**

    REFERENCES

    Demole, V. (1939) Int. Z. Vitaminforsch., 8, 338

    Finkler, R. S. (1949) J. clin. Endocr., 9, 89

    McLaren, H. C. (1949) Brit. med. J., 2, 1378

    Sebrell, W. H. jr & Harris, R. S. (1954) The vitamins, New York,
         Academic Press, vol. 3, p. 481

    Sternberg, J. & Pascoe-Dawson, E. (1959) Canad. med. Ass. J., 80, 266

    Weissburger, L. H. & Harris, P. L. (1943) J. biol. Chem., 151, 543

              

    *    Calculated as alpha-tocopherol.

    **   Total.

    See Also:
       Toxicological Abbreviations