FAO Nutrition Meetings Report Series 
    No. 46A WHO/FOOD ADD/70.36

    The content of this document is the result of the deliberations of the
    Joint FAO/WHO Expert Committee on Food Additives which met in Rome,
    27 May - 4 June 19691

    Food and Agriculture Organization of the United Nations

    World Health Organization

    1 Thirteenth report of the Joint FAO/WHO Expert Committee on Food
    Additives, FAO Nutrition Meetings Report Series, in press;
    Wld Hlth Org. techn.  Rep. Ser., in press.


    Biological Data

    Biochemical aspects

    This compound was readily absorbed from the rat gastro-intestinal
    tract in the presence of fats without changes in fat absorption or
    gastro-intestinal 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
    32Pphosphatidic acid was given to eight male and seven female rats at
    a level of 60-30 mg/kg body weight. Urine and faeces were collected at
    intervals of 1, 2, 4, 6, 7 and 24 h 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 1, 2 and 4 h 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 h were 91.4 per cent. males, 91.9 per cent. females, after 16
    days 93.4 per cent. males, 98.1 per cent. females. Thus 79 per cent.
    of the labelled material was excreted in the faeces within 24 h while
    some four per cent, was eliminated in the urine. The remaining 17 per
    cent. 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 4 h 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).

    Acute toxicity


    Animal         Route         LD50            Reference
                             mg/kg body weight

    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.,

    Groups of 15 male and 15 female rats each received diets containing 0
    per cent., 0.75 per cent., 1.5 per cent., 3.0 per cent. and 6.0 per
    cent. 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 six per cent. soya lecithins for 90 days except
    that a slight transient anaemia was seen in females (Gaunt et al.,

    Groups of 50 rats each received 0 per cent., 1 per cent. or 2.5 per
    cent. 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.


    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 six per
    cent. 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.


    Level causing no significant toxicological effect in the rat

    Six per cent. (= 60 000 ppm) in the diet equivalent to 3000 mg/kg body

    Estimate of acceptable daily intake for man

                                            mg/kg body weight

    Temporary acceptance                           0-15

    Further work required by June 1974

    Submission of the results of the long-term study in the rat and
    metabolic studies in several species.

    For further work on specifications, see ref. 19 Annex 1.


    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

    See Also:
       Toxicological Abbreviations
       Ammonium salts of phosphatidic acids (WHO Food Additives Series 5)