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.

    CITRIC ACID AND ITS CALCIUM, POTASSIUM AND SODIUM SALTS

    Explanation

         These compounds have been evaluated for acceptable daily intake
    by the Joint FAO/WHO Expert Committee on Food Additives (see Annex 1,
    Refs Nos 6, 7 and 13) in 1961, 1963 and 1965.

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

    BIOLOGICAL DATA

    BIOCHEMICAL ASPECTS

         Citric acid is an intermediary substance in oxidative metabolism,
    being engaged in the tricarboxylic acid cycle. Citric acid and
    citrates occur in many foods and are normal metabolites in the body
    (Gruber & Halbeisen, 1948).

         Potassium and sodium citrate in doses of up to 4 g have been
    extensively used in medical practice for many years without giving
    rise to ill effects. The calcium salt probably behaves similarly in
    the body. As food additives, therefore, all the citrates can be
    considered together.

         There is no reason to believe that the use of these citrates as
    food additives constitutes a significant toxicological hazard to man.

    TOXICOLOGICAL STUDIES

    Acute toxicity
                                                                        

                                    LD50
    Animal     Route                (mg/kg bw)  Reference
                                                                        

    Mouse      i.v.                 42          Gruber & Halbeisen, 1948
               (rapid injection)

    Mouse      i.p.                 961         Gruber & Halbeisen, 1948

    Rat        i.p.                 884         Gruber & Halbeisen, 1948
                                                                        

    Short-term studies

    Dog

         A daily oral dose of 1380 mg/kg bw given to three dogs for 112 to
    120 days produced no symptoms or evidence of renal damage (Krop &
    Gold, 1945).

    Long-term studies

    Rat

         Diets containing 1.2% of citric acid had no harmful effect on the
    growth of two successive generations of rats over a period of 90
    weeks. No detrimental effect could be observed on reproduction. No
    significant change could be noted in the blood picture nor was there
    any other pathological finding that could be attributed to the diet.
    Loss of calcium or other fixed bases was not observed. The dental
    attrition was found to be slightly more marked than in the control
    groups (Bonting & Jansen, 1956).

    OBSERVATIONS IN MAN

         Ingestion of citric acid frequently or in large doses may cause
    erosion of teeth and local irritation, apparently because of the low
    pH: the effects also occur with lemon juice which contains about 7% of
    citric acid and has a pH of less than three. A 1% solution has been
    used as a cooling drink in fever. Potassium citrate has been used in
    daily doses totalling up to 10 g as a mild diuretic, to render the
    urine less acid and as a potassium supplement. Sodium citrate has also
    been used in daily doses of up to 10 g to render the urine less acid
    and as a mild diuretic (Martindale, 1972).

    Comments:

         In evaluating the acceptance of citric acid, emphasis is placed
    on its well-established metabolic pathways. Toxicological studies on
    animals supplement this information.

         Citric acid and its calcium, potassium and sodium salts do not
    constitute a significant toxicological hazard to man.

    EVALUATION

    Estimate of acceptable daily intake for man

         Not limited.*

              

    *    See relevant paragraph in the seventeenth report (pp. 10-11).

    REFERENCES

    Bonting, S. L. & Jansen, B. C. (1956) Voeding, 17, 137

    Gruber, C. M & Halbeisen, W. A. (1948) J. Pharmacol. exp. Ther., 94,
         65

    Krop, S. & Gold, H. (1945) J. Amer. pharm. Ass., sci. Ed., 34, 86

    Martindale's Extra Pharmacopoeia, 26th Ed. (1972) The Pharmaceutical
         Press, London

    See Also:
       Toxicological Abbreviations