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 FORMATE

    Chemical name                 Ethyl formate

    Empirical formula             C3H6O2

    Structural formula            HCOOC2H5

    Molecular weight              74.08

    Definition                    Ethyl formate contains not less than 93
                                  per cent. C3H6O2.

    Description                   Ethyl formate is a colourless flammable
                                  liquid having a characteristic odour.

    Biological Data

    Biochemical aspects

         This ester is absorbed through the lungs and from the
    gastrointestinal tract, and to a small extent through the intact skin.
    It probably metabolizes to ethyl alcohol and formic acid (Browning,
    1965).

    Acute toxicity

                                                                       

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

    Rat             oral       1850              Jenner et al., 1964

    Guinea-pig      oral       1110              Jenner et al., 1964

    Rabbit          dermal     20 ml             Smyth et al., 1954
                                                                       

    When rats were fed 28-115 mg daily for 9 days their weight gain was
    retarded (Shillinger, 1950).

    Short-term studies

         Rat. A 12-week feeding study on 15 males and 5 females using
    mixed ethyl esters showed no adverse effect at 79.4 mg/kg
    body-weight/day. Groups of 10 male and 10 female rats in another study
    were fed 0, 0.1, 0.25 and 1.0 per cent. ester in their diet for 17
    weeks. No adverse effects were seen on body-weight gain, organ weights
    and histology of major organs (Hagen et al., 1967).

         Rabbit. Feeding animals 6.8 mg daily for 3 months produced
    approximately 50 per cent. fall in body-weight, some disturbance in
    carbohydrate metabolism as evidenced by high fasting blood sugar level
    and longer hyperglycaemic period, and proteinuria with histological
    evidence of chronic nephritis (Shillinger, 1950.

    Long-term studies

         None available.

    Comments

         Despite the scanty animal data it is possible to evaluate this
    compound on the basis of its likely metabolic fate and the available
    short-term studies. Biochemical studies are needed.

    EVALUATION

    Level causing no toxicological effect

         Rat. 1 per cent. (= 10 000 ppm) in the diet, equivalent to 500
    mg/kg body-wieght/day.

    Estimate of acceptable daily intake for man

                                            mg/kg body-weight1

              Conditional acceptance               0-5

    Further work required

         Long-term toxicity studies in animals and metabolism studies in
    man.

    REFERENCES

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

    Hagan, E. C.  Hansen, W. H.  Fitzhugh, O. G. & Jenner, P. M., Jones,
    W.I., Taylor, J. M., Long, E. L., Nelson, A. A. & Brouwer, J. B.
    (1967) Fd Cosmet. Toxicol., 5(2), 141

    Jenner, P. M.  Hagan, E. C., Taylor, J. M.  Cook, E. L. & Fitzhugh, O.
    G. (1964) Fd Cosmet. Toxicol., 2, 327


                   

    1 As total formic acid from all food additive sources.

    Oser, B.L. (1967) Unpublished report

    Shillinger, Y. J. (1950) Gig. i. San., 37

    Smyth, H. F. jr, Carpenter, C. P.)., Weil, C. S. & Pozzani, U. G.
    (1954) Arch. ind. Hlth, 10, 61

    

    See Also:
       Toxicological Abbreviations
       Ethyl formate (ICSC)
       Ethyl formate (WHO Food Additives Series 14)
       ETHYL FORMATE (JECFA Evaluation)