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. 11) in 1965.

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



         Acetate enters naturally into the metabolism of the body. It is
    absorbed from the gastrointestinal tract and is completely utilized in
    oxidative metabolism or in anabolic syntheses. Isotope experiments
    have shown acetates to be utilized in the formation of glycogen,
    intermediates of carbohydrates and fatty acid synthesis as well as
    cholesterol synthesis. In addition it participates in the acetylation
    of amines and may be converted to alanine by transamination and thence
    incorporated into proteins of plasma, liver, kidney, gut mucosa,
    muscle and brain (Documenta, Geigy, 1970).


    Acute toxicity
    Animal    Route               (mg/kg bw)        References

    Mouse     Oral
              (free acid)         4 960             Woodard et al., 1941

    Rat       Oral
              (free acid)         3 310             Woodard et al., 1941
              (sod. acetate)      3 530             Smyth, 1951

    Rabbit    Rectal              1 200
              (free acid)         (LD, 1 hour)      Dreyfus, 1920
              s.c.                1 200
              (free acid)         (LD, 48 hours)    Dreyfus, 1920
              Oral                1 200
              (free acid)         (LD, 6 days)      Dreyfus, 1920

         Toxic effects of acetic acid are due not only to its irritant
    properties but also to its effect on the central nervous system and
    kidneys. Large oral doses cause narcotic CNS depression and death in
    rats and mice (Woodard et al., 1941).

         The immediate toxic effects of glacial acetic acid are due to its
    corrosive acid action and to dehydration of tissues with which it
    comes into contact. Ingestion results in severe pain and the formation
    of white plaques and ulcers of mucosal surfaces, and may be followed
    by haematemesis (Martindale, 1972).

    Short-term studies


         Groups of three to six rats were given 0.01, 0.1, 0.25 and 0.5%
    acetic acid in drinking-water for periods of from nine to 15 weeks.
    Fluid intake was the same in all groups; at the 0.5% level there was
    immediate progressive reduction in body weight gain, loss of appetite
    and fail in food consumption to 27%. Mortality rate was unaffected
    (Sollmann, 1921). In another experiment groups of three to four
    rats survived 14 days when given 1800 mg/kg bw per day free acid
    intragastrically or 4200-4800 mg/kg bw sodium acetate, but only three
    to five days on daily intragastric 2400 mg/kg bw free acid. Animals
    lost weight before death and showed blistered paws and reddened noses.
    No autopsies were done (Hemmingway & Sparrow, 1942). Intragastric
    intubation of 3 ml of 10% solution acetic acid to rats for 90 days
    produced a drop in haemoglobin concentration and erythrocyte count
    (Wysokinska, 1952).


         Four groups of two young pigs were fed daily diets containing 0,
    240, 720, 960 and 1200 mg/kg bw per day for successive 30-day periods
    to a total of 150 days. There were no significant differences in
    growth rate, weight gain, early morning urinary ammonia and terminal
    blood pH between controls and test groups. No autopsies were done
    (Lamb & Evvard, 1919).

    Long-term studies

         No animal studies are available.

         About 1 g/day of acetic acid present in vinegar and other items
    of food and drink has been consumed by man for centuries apparently
    without causing any adverse effects. However, continued ingestion of
    large doses has been regarded as a contributory factor in the
    development of Laennec type of liver cirrhosis (Singer, 1936).


         In evaluating the acceptance of acetic acid, emphasis is placed
    on its established metabolic pathways and its consumption by man as a
    normal constituent of the diet.


    Estimate of acceptable daily intake for man

         Not limited.*


    Documenta, Geigy, ]970, 7th ed. (J. R. Geigy S.A., Basle)

    Dreyfus, L. (1920) Compt. rend. soc. biol., 83, 136

    Hemmingway, A. & Sparrow, A. (1942) Proc. Soc. exper. Biol. Med., 51,

    Lamb, A. R. & Evvard, M. J. (1919) J. Biol. Chem., 37, 317

    Martindale's Extra Pharmacopoeia, 1972, 26th ed. (The Pharmaceutical
         Press, London)

    Singer, L. (1936) Munch. med. Wschr., 83, 1288

    Sollmann, T. (1921) J. Pharm. Exp. Therap., 16, 463

    Woodard, G. et al. (1941) J. Ind. Hyg. Toxic., 23, 78

    Wysokinska, Z. (1952) Roczniki Panstwowego Zakladu Hig., 3, 273


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

    See Also:
       Toxicological Abbreviations