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    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.


    AMMONIUM SALTS OF PHOSPHATIDIC ACIDS

    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. 20) in 1969.

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

    BIOLOGICAL DATA

    BIOCHEMICAL ASPECTS

         These compounds were readily absorbed from the rat
    gastrointestinal tract in the presence of fats without changes in fat
    absorption or gastrointestinal function (Frazer, 1954). No in vitro
    haemolytic effect was seen with this product nor was it any stronger
    than natural lecithin (Frazer, 1954). Incubation of the ammonium salt
    of 32P-phosphatidic acid with simulated gastric juice, homogenate of
    intestinal mucosa, trypsin or chymotrypsin in vitro resulted
    in the liberation of inorganic phosphate. The ammonium salt of
    32P-phosphatidic acid was given to eight male and seven female rats at
    a level of 60 to 30 mg/kg bw. Urine and faeces were collected at
    intervals of one, two, four, six, seven and 24 hours and at 10 and 16
    days after administration rats were killed for examination. Similarly,
    inorganic phosphate labelled with 32P was given to three male and
    three female rats by intubation and rats were killed one, two
    and four hours after administration. Many organs were examined for
    radioactivity. In addition, incorporation of 32P into phospholipids of
    tissues at various intervals after dosing was determined. Percentage
    recoveries after 24 hours were 91.4% males, 91.9% females, after 16
    days 93.4% males, 98.1% females. Thus 79% of the labelled material was
    excreted in the faeces within 24 hours while some 4% was eliminated in
    the urine. The remaining 17% were stored in bone and muscle as
    inorganic phosphate and phosphate ester while the rest of the tissue
    contained oily traces mostly in the phospholipid fraction. Comparison
    with uptake of labelled inorganic phosphate showed similar
    distribution of the phosphate to bone, muscle, liver, gut content
    and urine. The radioactive phospholipid fraction present in the rat
    four hours after administration was found to be nearly identical
    whether 32P was administered as phosphatidic salt or as inorganic
    orthophosphate. The radioactive phospholipid fraction in the liver
    of test rats was chromatographically identical with the liver
    phospholipid of rats fed 32P orthophosphate. The observed tissue
    radioactivity is due to breakdown to inorganic phosphate which enters
    the phosphate and phospholipid pools. There was no evidence of storage

    in tissues of any P containing moiety of the phosphatidic salt. The
    triglyceride moiety was probably hydrolyzed and absorbed by normal
    physiological routes (Feuer, 1967).

    TOXICOLOGICAL STUDIES

    Acute toxicity
                                                             

                                     LD50        Reference
    Animal         Route          (mg/kg bw)
                                                             

    Rat            Oral              5 000       Frazer, 1954

    Rat            I.m.              2 000       Frazer, 1954

    Guinea-pig     I.m.              2 000       Frazer, 1954

    Rabbit         Oral              5 000       Frazer, 1954

    Dog            Oral              2 000       Frazer, 1954
                                                             

         No abnormal pathological findings or behaviour patterns were seen
    (Frazer, 1954).

    Short-term studies

    Rat

         After twice-weekly intraperitoneal injections in rats of 2 g /kg
    for five weeks, there was no deleterious effect on growth, relative
    spleen weight, haematology or corpuscular fragility (Gaunt et al.,
    1967).

         Groups of 15 male and 15 female rats each received diets
    containing 0%, 0.75%, 1.5%, 3.0% and 6.0% of the compound for 90 days.
    No adverse effects were seen on appearance, growth, food consumption,
    haematological indices, liver and kidney function, relative organ
    weights and gross and histological appearance of the organs. Similar
    results were obtained in rats given a dietary level of 6% soya
    lecithins for 90 days except that a slight transient anaemia was seen
    in females (Gaunt et al., 1967).

         Groups of 50 rats each received 0%, 1% or 2.5% compound in their
    diet for 45 weeks. No adverse effects were seen with regard to
    mortality, weight gain, liver function, kidney function and
    histopathology in test groups compared with controls (Frazer, 1954).

    Long-term studies

         None available.

    Comments:

         The biochemical studies show that the ammonium salts of
    phosphatidic acids break down into normal food constituents. The
    available rat studies show this material to be non-toxic at the level
    of 6% in the diet, the highest concentration tested. Because of the
    possible substantial intake of this material by children it is
    necessary to have a long-term study on one species and desirable to
    determine the metabolic fate in man. A long-term study in the rat is
    now in progress.

    EVALUATION

    Level causing no significant toxicological effect

         Rat: 60 000 ppm (6%) in the diet equivalent to 3000 mg/kg bw.

    Estimate of acceptable daily intake for man

         0 to 15 mg/kg bw.*

    FURTHER WORK OR INFORMATION

         Required (by June 1974): Submission of the results of the long-
    term study in the rat and metabolic studies in several species.

         Desirable: Studies on the metabolic fate of these compounds in
    man.

    REFERENCES

    Feuer, G. (1967) Fd Cosmet. Toxicol., 5, 631

    Frazer, A. C. (1954) Unpublished report dated July 1954

    Gaunt, I. F., Grasso, P. & Gangolli, S. D. (1967) Fd Cosmet. Toxicol.,
         5, 623

              

    *    Temporary.


    See Also:
       Toxicological Abbreviations
       Ammonium salts of phosphatidic acids  (FAO Nutrition Meetings Report Series 46a)