Toxicological evaluation of some food
    additives including anticaking agents,
    antimicrobials, antioxidants, emulsifiers
    and thickening agents


    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


    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.



         These substances have been evaluated for acceptable daily intake
    by the Joint FAO/WHO Expert Committee on Food Additives (See Annex 1,
    Ref. No. 7) in 1963.

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



         Food fats are in the main triglycerides. However, many of them
    have been shown to contain small amounts of diglycerides and
    monoglycerides. The amount present is commonly in the region of 1%.
    There is some evidence also that further amounts of these partial
    glycerides may be formed during the preparation of certain foods.
    Therefore, apart from any addition of these substances to food for
    technological purposes, they will always be present in the food as
    consumed (National Academy of Sciences, 1960).

         In the body, the triglycerides undergo digestion in the
    gastrointestinal lumen. They are broken down mainly by pancreatic
    lipase with the formation of mono- and diglycerides. Pancreatic lipase
    removes fatty acids from the 1 and 3 positions preferentially, so that
    1,2-diglycerides and 2-monoglycerides are the immediate products.
    Mono- and diglycerides are absorbed into the intestinal cells. In
    their passage through the intestinal mucosa they are largely converted
    back into triglycerides. These pass into the body as a fine emulsion
    and give rise to the milky appearance of the chyle and the blood
    plasma. Under certain circumstances, these fat particles can be broken
    down by another fat-splitting enzyme in the blood-stream. When this
    occurs, the formation of mono- and diglycerides can be demonstrated.
    It is not certain what part this enzyme plays in normal fat
    metabolism.  Transesterification and isomerizatlon can occur under
    biological conditions. Diglycerides are readily converted in
    appropriate tissues either to triglycerides or to mono-glycerides.
    Monoglycerides can form diglycerides and triglycerides, but they are
    not always easily broken down to fatty acids and glycerol, although
    intestinal enzymes that rapidly bring this about have been described.
    There is no evidence that the presence of monoglycerides or
    diglycerides of food fats has any deleterious effect on cells or

         The various fatty acids that may be present in preparations of
    di- and monoglycerides used as food additives are not necessarily
    absorbed and metabolized in the same way as those of the natural food
    fats and their nutritional significance may also differ. Thus,
    saturated long-chain fatty acids have a lower digestibility than
    unsaturated fatty acids if fed alone, or in large quantities, and
    administration of many polyunsaturated fatty acids causes depression
    of the blood cholesterol level whereas the ingestion of saturated
    fatty acids tends to increase it (Frazer, 1962).


    Acute toxicity

         Monoglycerides and diglycerides have no acute toxic effects at
    practicable dosage levels.

    Short-term studies


         Glyceryl monostearate was fed to groups of five male hamsters at
    a level of 5% and to 10 at a level of 15% of the diet for 22 to 28
    weeks. Weight gain was somewhat less in the 15% group, but in a second
    experiment was improved by the addition of agar. The livers were
    enlarged in this group but no significant histopathological changes
    were evident (Orten & Dajani, 1957).

    Long-term studies


         Glyceryl monostearate was fed at levels of 15% and 25% as the
    sole source of fat in the diet to groups of 10 male and 10 female rats
    over three generations. Studies carried out during the rapid growth
    period in each generation showed no adverse effect on weight gain.
    Reproductive performance and lactation were also normal. In another
    study, 25% of the glyceryl monostearate was fed to groups of 12 male
    and 12 female rats for up to two years. Weight gain and survival were
    normal. There was a significant increase in liver weight and some
    renal calcification (Ames et. al., 1951).

         A mixture of lauric acid glycerides (40% monolaurin, 45%
    dilaurin, 15% trilaurin) was fed to rats over a two-year period in a
    concentration of 25% of the diet of a nutritionally adequate
    laboratory chow. There was no histopathological evidence of toxicity
    attributable to the lauric glycerides (Fitzhugh et al., 1960).

         Glyceryl monostearate was fed to rats at a level of 14% of the
    diet (Briski, 1969).


         Mono- and diglycerides are consumed every day in any normal mixed
    diet and they are also formed from triglycerides during the digestion
    and absorption of every meal containing fat. No harmful effects have
    been specifically associated with mono- or diglycerides.


         The mono- and diglycerides most likely to cause unwanted effects
    are those containing long-chain saturated fatty acids, especially
    stearic acid. Such compounds have been investigated in long-term
    animal studies. (The increase in liver weight reported in these
    studies is commonly seen in animals receiving a high fat intake; it is
    not regarded as having any toxicological significance.) These studies
    provide useful additional information to the wide experience with
    glycerides which are a normal constituent of the human diet.


    Estimate of acceptable daily intake for man

         Not limited.*


    Ames, S. R. et al. (1951) J. Amer. Oil Chem. Soc., 28, 31

    Briski, B. (1969) Farm. Glas., 25, 143-155

    Fitzhugh, O. G., Schonboe, P. J. & Nelson, A. A. (1960)
         Toxicol. appl. Pharmacol., 2, 59

    Frazer, A. C. (1962) Chem. and Ind., p. 1438

    National Academy of Sciences (1960) The safety of mono- and
         diglycerides for use as intentional additives in food (N.A.S.)
         Publication No. 251)

    Orten. J. M, & Dajani, R. N. (1957) Food Res., 22, 529


    *    See relevant paragraph in the seventeenth report, pages 10-11.

    See Also:
       Toxicological Abbreviations