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    INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY

    WORLD HEALTH ORGANIZATION



    TOXICOLOGICAL EVALUATION OF SOME
    FOOD COLOURS, EMULSIFIERS, STABILIZERS,
    ANTI-CAKING AGENTS AND CERTAIN
    OTHER SUBSTANCES



    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.


    STEARYL CITRATE

    Biological Data

    Stearyl citrate upon enzymic hydrolysis could give rise to stearyl
    alcohol, and citric acid. There is evidence that this hydrolysis
    readily occurs in the dog, and to a lesser extent in the rat (Calbert,
    C. E. et al., 1951).

    The effect of stearyl citrate on fat absorption and digestibility, and
    the digestibility of the compound itself were studied in rats and
    dogs. Four groups of eight - ten female rats were given 15 per cent.
    margarine in the diet with or without addition of stearyl citrate at a
    rate of five per cent. of margarine. Pat absorption after four and six
    hours was unaffected by the presence of the additive. Three groups of
    nine - ten female rats were fed 0.13 per cent., 2.5 per cent. and 10
    per cent. stearyl citrate, margarine being added to bring the total
    level of fat plus test substance to 25 per cent. of the diet.
    Digestibility of fat was determined by eight-day balance studies; the
    normal value of 95 per cent. was reduced respectively to 77 per cent.
    and 71 per cent, at 2.5 per cent. and 10 per cent. level. The
    digestibility of stearyl citrate was 55 per cent., 6 per cent. and 20
    per cent., at 0.13 per cent., 2.5 per cent. and 20 per cent. level
    respectively. Digestibility of fat in dogs was studied over 12 days in
    two groups of three, one as control, the other with 3 per cent.
    stearyl citrate in the diet. Normal fat digestibility was 95 per cent.
    in the controls and 80 per cent. in the test diet, the digestibility
    of stearyl citrate was 52 per cent. at 3 per cent. level (Calbert et
    al., 1951).

    Acute toxicity

                                                                     

    Animal    Route          LD50           Reference
                        mg/kg body-weight 
                                                                     

    Rat       oral          > 5400          Deuel et al., 1951

    Dog       oral          > 5000          Deuel et al., 1951
                                                                     

    Short-term studies

    Rat. Groups of 10 male and 10 female rats were fed diets containing
    0 per cent., 1.3 per cent., 2.5 per cent., 5 per cent. and 10 per
    cent, stearyl citrate for six weeks, There was no demonstrable effect
    on growth (Deuel et al.,1951). In another experiment four groups, of
    19 male and female weanling rats each, were fed for 10 weeks on a diet
    containing unheated margarine, margarine heated continuously for eight
    hours to 205°C., 0.86 per cent. stearyl citrate in similarly treated

    margarine and 0.68 per cent. stearyl citrate potato chips fried in
    margarine with this additive. Growth rates were identical in all four
    groups (Deuel et al., 1951).

    Three groups of 14 - 15 weanling rats were kept for ten weeks an a
    diet containing 0 per cent., 1.9 per cent. and 9.5 per cent. stearyl
    citrate, mated when 13 weeks old and continued on the same diet
    throughout pregnancy and lactation. The second generation was weaned
    at three weeks and treated like the parent generation. Studies were
    continued to the weaning of the fifth generation. No deleterious
    effects on litter size, fertility, lactation and body-weight on growth
    of progeny were noted (Deuel et al., 1951).

    Rabbit. Groups of eight rabbits received diets containing 0 per
    cent., 2 per cent. and 10 per cent. stearyl citrate for six weeks.
    There was no demonstrable effect on growth except for one animal which
    lost weight during the early test when it failed to eat; this rabbit
    began to regain its weight during the last week of the test. A
    complete histopathological examination made on all eight rabbits of
    the control and 10 per cent. stearyl citrate group showed no
    pathological findings (Deuel et al., 1951).

    Dog. Two groups of four animals each were fed 0 per cent. and 3 per
    cent. stearyl citrate in the diet for 12 weeks. No difference in
    weight gain was noted between controls and treated animals at four,
    eight and 12 weeks. Haemoglobin levels at the end of the period were
    practically identical for the two groups. Histopathological
    examination of the livers and kidneys showed no pathological findings
    (Deuel et al., 1951).

    Long-term studies

    Rat. Groups of 10 male and 10 female rats were fed for two years on
    diets containing 0 per cent., 0.5 per cent., 2 per cent. and 10 per
    cent. stearyl citrate. From 55 per cent. to 65 per cent. survived in
    the test groups compared with 44 per cent, in the control group. No
    variations in weight gains were noted between test animals and
    controls. A complete histopathological examination was carried out in
    the animals which received 10 per cent. stearyl citrate. No specific
    pathological findings were seen; there were metastatic calcification
    and tumours not significantly different from the controls (Deuel et
    al., 1951).

    Comments

    Addition of this material to the diet reduces absorption of fat in the
    rat and to a lesser extent in the dog. The compound itself is poorly
    absorbed in the rat at levels above 0.5 per cent. of the diet and for
    this reason the lowest level tested in the long-term study evaluated
    has been selected as the basis of assessment. The short-term studies
    are inadequate as regards absence of organ function tests and failure
    to provide evidence on cumulation.

    EVALUATION

    Level causing no significant toxicological effect in the rat

    0.5 per cent. (= 5000 ppm) in the diet equivalent to 250 mg/kg
    body-weight per day.

    Estimate of acceptable daily intake for man

                                            mg/kg body-weight

    Temporary acceptance                         0 - 1.25

    Further work required by June 1972

    Adequate short-term studies in two species (one a non-rodent mammalian
    species); some of these studies should use combinations with hard
    fats. Emphasis should be placed on evaluation of kidney function.

    REFERENCES

    Calbert, C.E., Greenberg, S. M., Kryder, G. & Douel, H. J., Jr. (1951)
    Rood Res., 16, 294

    Deuel, H. J. Jr., Greenberg, S. M., Calbert, C. E., Baker, R. &
    Fisher, H. R.(1951) Food Res., 16, 258
    


    See Also:
       Toxicological Abbreviations
       Stearyl citrate (WHO Food Additives Series 5)
       STEARYL CITRATE (JECFA Evaluation)