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.



         These compounds have been evaluated for acceptable daily intake
    by the Joint FAO/WHO Expert Committee on Food Additives (see Annex 1,
    Refs Nos 20 and 34) in 1969 and 1973.

         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.



         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 32 P-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 32
    P-phosphatidic acid was given to eight male and seven female rats at a
    level of 60-30 mg/kg bw. 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 32 P 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 32 P into phospholipids of tissues at various
    intervals after dosing was determined. Percentage recoveries after 24
    h 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 h 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 4 h after
    administration was found to be nearly identical whether 32 P was
    administered as phosphatidic salt or as inorganic or thiotostate. The
    radioactive phospholipid fraction in the liver of test rats was
    chromatographically identical with the liver phospholipid of rats fed
    32 P orthosphosphate. The observed tissued radioactivity is due to
    breakdown into 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 adsorbed by normal physiological routes
    (Feuer, 1967).


    Special studies on reproduction


         Groups of 10 male and 30 female weanling rats (Fo) were fed 0 or
    6% compound for 13 weeks. After this time one male and three females
    were mated for 21 days and date of mating established by vaginal
    smears. All pregnant females were caged individually. An F1a
    generation from 30 females was examined for litter parameters and
    weaning performance and all young from 10 parental females were
    autopsied, all weaned pups being autopsied on day 21. No effect was
    seen on fertility, litter number, weaning performance or weight gain
    of pups. Sex ratio was unaffected.

         Rats were remated to produce F1b generation which was observed
    until day 21. Thirty females and 10 males of F1b were fed 0% or 6%
    compound for 13 weeks, the remaining pups were autopsied. After 13
    weeks selected F1b animals were mated to produce an F2a generation.
    After a second remating for F2b seven control and eight treated F1b
    females were examined on day 18 of pregnancy for implantations,
    resorptions, corpora lutea and live fetuses. Fetuses were examined for
    skeletal and organ abnormalities. The F2b generation was observed
    until day 21 and examined. Again no abnormalities were seen in the
    F2a or F2b generation nor were there any deleterious effects on
    implantation. Only one abnormal fetus occurred in a control litter
    (Brantom et al., 1972).

    Acute toxicity

    Animal         Route          mg/kg bw       Reference

    Rat            Oral           5 000          Frazer, 1954

    Rat            l.m.           2 000          Frazer, 1954

    Guinea-pig     l.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


         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%, 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


         Groups of 48 male and 48 female rats were fed in their diet 0, 2%
    or 6% compound for two years. A similar group of rats was fed on a
    diet containing 4% soya lecithin. These treatments had no adverse
    effect on mortality, rate of body weight gain, haematology,
    urinalysis, renal concentrating ability, serum biochemistry or tumour
    incidence. Thyroid weight was increased in all treated groups but this
    was found to be due to an increased parathyroid hyperplasia secondary
    to spontaneous renal changes combined with an elevated intake of
    phosphate. A slightly increased incidence of myocardial fibrosis was
    also associated with the parathyroid hyperplasia. The incidence and
    severity of other histopathological changes were not influenced by
    feeding either compound (Brantom et al., 1972).


         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. A long-term study
    and reproduction studies on one species were also carried out which
    showed no adverse effects.


    Level causing no toxicological effect

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

    Estimate of acceptable daily intake for man

         0-30 mg/kg bw*


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

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

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

    Brantom, P. G. et al. (1972) BIBRA Report 4/1972


    *    The contribution from this compound to phosphate intake must be
    included in the ADI for phosphate.

    See Also:
       Toxicological Abbreviations