FAO Nutrition Meetings
    Resort Series No. 44A
    WHO/Food Add./68.33




    TOXICOLOGICAL EVALUATION OF SOME
    FLAVOURING SUBSTANCES AND
    NON-NUTRITIVE SWEETENING AGENTS





    Geneva, 21-28 August 1967



    The Eleventh Report of the Joint FAO/WHO Expert Committee on Food
    Additives is published as FAO Nutrition Meetings Report Series,
    1967, No. 44; Wld Hlth Org. techn. Rep. Ser., 1968, 383. This
    Report contains general considerations, including the principles
    adopted for the evaluation, and a summary of the results of the
    evaluations of a number of food additives. Additional information,
    such as biological data and a toxicological evaluation, considered at
    that meeting, is to be found in this document.


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


    ETHYL ACETATE

    Chemical name                 Ethyl ethanoate

    Empirical formula             C4H8O2

    Structural formula            CH3COOC2H5

    Molecular weight              88.11

    Definition                    Ethyl acetate contains not less than 97
                                  per cent. C4H8O2.

    Description                   Ethyl acetate is a transparent,
                                  colourless liquid, with a fragrant,
                                  refreshing, slightly acetone odour and
                                  an acetous, burning taste.

    Biological Data

    Biochemical aspects

         This ester is probably absorbed with ease from the
    gastrointestinal tract and is soluble in plasma. It is hydrolysed by
    liver and plasma esterases and pancreatic lipase to ethyl alcohol and
    acetate (Oppenheimer, 1925; Fassett. 1963; Zipf, 1928; Nishida, 1957).
    The ethyl alcohol is partly excreted in the expired air and urine, the
    rest is metabolized, the acetate fraction becoming incorporated in the
    body pool (Fassett, 1963).

    Acute toxicity

                                                                       

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

    Rat             oral        5620              Smyth, unpublished

    Guinea-pig      s.c.        4000(LD)          Flury & Wirth, 1934

    Cat             s.c.        3000              Flury & Wirth, 1934
                                                                       

         Doses of 13-115 mg fed daily to rats for 5-9 days produced fatty
    infiltration of the liver (Shillinger, 1950).

    Short-term studies

         None available.

    Long-term studies

         None available.

    Special studies

         Ethyl acetate was injected into the yolk sac of fertile White
    Leghorn eggs prior to incubation to study any toxic or teratogenic
    effect of this substance. Ethyl acetate was used undiluted, and 0.05
    or 0.10 ml per egg was injected. The hatchability was 35 per cent. and
    15 per cent., respectively.

         In a second experiment 9, 22.5, 45 and 90 mg per egg of ethyl
    acetate were injected into the yolk sac of fresh fertile chicken eggs.
    The hatchabilities were, respectively: 85, 50, 35 and 15 per cent.
    (McLaughlin et al, 1963; 1964.

    Comments

         Although this compound has irritant properties when inhaled, it
    is readily metabolized after oral administration. Despite the absence
    of toxicological studies, this compound is evaluated on the basis of
    its known metabolic fate. Further studies on the hydrolysis of this
    compound in the gastrointestinal tract are desirable.

    EVALUATION

    Estimate of acceptable daily intake for man

                                       mg/kg body-weight

       Unconditional acceptance              0-25

    REFERENCES

    Browning, E. (1965) Toxicity of Industrial Solvents, Elsevier, London
    & New York

    Fassett, D. W. (1963) In: Patty, F. A., Industrial Hygiene and
    Toxicology, Second Edition, Interscience, New York & London

    McLaughlin, J. jr, Marliac, J. P. Verrett, M. J., Mutchler, M. K. &
    Fitzhugh, O. G. (1963) Toxicol. appl. Pharmacol., 5, 760

    McLaughlin, J. jr, Marliac,  J. P., Verrett. M. J., Mutchler, M. K. &
    Fitzhugh, O. G. (1964) Amer. Ind. Hyg. Ass. Journ., 25, 282

    Nishida, M. (1957) Yakugaku Zasshi, 77, 1141

    Oppenheimer, C. (1925) Die Fermente und ihre Wirkungen, Leipzig, p.
    232

    Shillinger, J. I. (1950) Gig. i. San., 3, 37

    Smyth, H. F., jr, Unpublished report

    Zipf, K. (1928) Arch. f. exper. Path. Pharm., 128, 121
    

    See Also:
       Toxicological Abbreviations
       Ethyl acetate (ICSC)
       ETHYL ACETATE (JECFA Evaluation)