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    FAO Nutrition Meetings
    Report Series No. 40A,B,C
    WHO/Food Add./67.29




    TOXICOLOGICAL EVALUATION OF SOME
    ANTIMICROBIALS, ANTIOXIDANTS, EMULSIFIERS,
    STABILIZERS, FLOUR-TREATMENT AGENTS, ACIDS AND BASES





    The content of this document is the result of the deliberations of the
    Joint FAO/WHO Expert Committee on Food Additives which met at Rome,
    13-20 December, 19651 Geneva, 11-18 October, 19662




                   

    1 Ninth Report of the Joint FAO/WHO Expert Committee on Food
    Additives, FAO Nutrition Meetings Report Series, 1966 No. 40; 
    Wld Hlth Org. techn. Rep. Ser., 1966, 339

    2 Tenth Report of the Joint FAO/WHO Expert Committee on Food
    Additives, FAO Nutrition Meetings Report Series, 1967, in press; 


    Food and Agriculture Organization of the United Nations
    World Health Organization
    1967


    ACETIC ACID, GLACIAL

    Chemical name                 Acetic acid

    Empirical formula             C2H4O2

    Structural formula            CH3COOH

    Molecular weight              60.05

    Definition                    Glacial acetic acid contains not less 
                                  than 99.0 per cent. C2H4O2.

    Description                   A colourless liquid or crystalline
                                  solid, having a pungent characteristic
                                  odour and, when well diluted with water,
                                  an acid taste.

    Uses                          As acidifier, flavouring agent, for the
                                  prevention of rope in baking and as a
                                  solvent.

    Biological Data

    Biochemical aspects

         Acetate enters naturally into the metabolism of the body. It is
    absorbed from the gastrointestinal tract and through the lungs and
    almost completely oxidized by tissues. The metabolic pathways are
    reasonably well-known and involve the formation of ketone bodies.
    Isotope experiments have shown the various C atoms 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 formation of proteins of
    plasma, liver, kidney, gut mucosa, muscle and brain (von Oettingen,
    1960).

    Acute toxicity

                                                                       

    Animal     Route              LD50)               References
                                  (mg/kg 
                                  body-weight)
                                                                       

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

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

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

         Toxic effects of acetic acid are due to its irritant properties
    as well as its effect on the central nervous system and kidneys. Large
    oral doses causes narcotic C.N.S. depression and death in rats and
    mice (Woodard et al., 1941).

    Short-term studies

         Rat. Groups of 3-6 rats were given 0.01, 0.1, 0.25 and 0.5 per
    cent. acetic acid in drinking water for periods of from 9-15 weeks.
    fluid intake was the same in all groups; at the 0.5 per cent. level
    there was immediate progressive reduction in body-weight gain, loss of
    appetite and fall in food consumption to 27 per cent. Mortality rate
    was unaffected (Sollmann, 1921). In another experiment groups of 3-4
    rats survived 14 days when given 1800 mg/kg body-weight/day free acid
    intragastrically or 4200-4800 mg/kg body-weight sodium acetate, but
    only 3-5 days on daily intragastric 2400. mg/kg body-weight 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 per cent. solution acetic acid
    to rats for 90 days produced a drop in haemoglobin concentration and
    erythrocyte count (Wysokinska, 1952).

         Swine. Four groups of 2 young pigs were fed daily diets
    containing 0, 240, 720, 960 and 1200 mg/kg body-weight/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).

    Comments

         Acetic acid has a sufficiently acid taste to limit the amount
    used in foods. Human studies determining the maximum metabolic load of
    acetate are not available. In evaluating the acceptance of acetic
    acid, emphasis is placed on its established metabolic pathways and its
    normal consumption by man.

    Evaluation

         For purposes of evaluation all sources of acetate used as food
    additives should be considered together. Since acetic acid has a
    sufficiently acid taste to limit the amount used in foods, it is not
    necessary to indicate acceptable daily intakes for man.

    REFERENCES

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

    Hemmingway, A. & Sparrow, A. (1942) Proc. Soc. exper. Biol. Med.,
    51,   44

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

    von Oettingen, W. F. (1960) Arch. Ind. Health, 21, 28

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

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

    Woodard, G., Lange, S. W., Nelson, K. W. & Calvery, H. O. (1941)
    J. Ind. Hyg. Toxic., 23, 78

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


    See Also:
       Toxicological Abbreviations
       Acetic acid (ICSC)
       ACETIC ACID (JECFA Evaluation)