The biological data on ethyl formate were reviewed at the
    eleventh meeting of the Joint FAO/WHO Expert Committee on Food
    Additives, specifications were prepared, and a conditional acceptable
    daily intake (ADI) of 0-5 mg/kg bw (as total formic acid from all food
    additive sources) was established (FAO/WHO, 1967; FAO/WHO, 1968).

         Since this previous review, new data have become available and
    are included in this summary.



         Ethyl formate is absorbed through the lungs, from the
    gastrointestinal tract, and to a small extent through the skin
    (Browning, 1967). This ester is hydrolysed into ethyl alcohol and
    formic acid with subsequent metabolism via well-known pathways,
    primarily to CO2 in the case of ethanol, while formic acid is reduced
    to biologically active methyl, or excreted as the free acid. (FEMA,
    1974; Williams, 1959).


    Special studies on carcinogenicity

         In a 24-week screening test, groups of 15 male and 15 female A/He
    mice received in the first eight weeks of the test period, a total
    dose of 2.4 or 12.0 g/kg bw of ethyl formate in 24 thrice-weekly i.p.
    injections. The higher dose had previously been calculated to be the
    maximum tolerated dose. There was no increase in the incidence of
    tumours of the lung, liver, kidney, spleen, thymus, intestine, or
    salivary or endocrine glands. Survival was not affected (Stoner et
    al., 1973).

    Special studies on pharmacological effects

         In rabbits the single oral Narcotic Dose (ND50) of 28 mmol/kg bw
    (approximately equivalent to 2070 mg/kg bw, the oral LD50 dose)
    produced stupor and loss of voluntary movements; higher doses caused a
    disappearance of corneal reflexes, nystagmus, dyspnoea and bradycardia
    (Munch, 1972).

    Acute toxicity

    Animal         Route     LD50             Reference
                             mg/kg bw

    Rat            Oral      1 850         Jenner et al., 1964

    Rat            Oral      4 290         Smyth et al., 1954

    Guinea-pig     Oral      1 110         Jenner et al., 1964

    Rabbit         Oral      2 070*        Munch, 1972

    Rabbit         Dermal    5 000         Opdyke, 1978

    Rabbit         Dermal    20 (ml/kg)    Smyth et al., 1954

    *    Approximately equivalent to 28 mmol/kg.

    Short-term studies


         The maximum tolerated dose (MTD) of ethyl formate, defined as the
    maximum single dose that all five mice tolerated after receiving six
    i.p. injections over a two-week period, was found to be 500 mg/kg bw
    (Stoner et al., 1973).


         Groups of 10 male and 10 female rats were maintained for 17 weeks
    on diets containing ethyl formate at levels of 0, 1000, 2500, and
    10 000 ppm (approximately equivalent to 0, 50, 150, and 500 mg/kg bw).
    No adverse effects were observed on body weight gain, organ weights,
    or histology of major organs (Hagan, 1967).

         Groups of 15 male and 15 female rats were fed for 12 weeks a diet
    containing a mixture of ethyl esters, including ethyl formate at a
    level equivalent to 79.4 mg/kg bw/day. No adverse effects were noted
    as judged from body weights, haematology, organ weights, gross
    examination and histopathology (Oser, 1967).


         Rabbits, receiving daily oral doses of 6.8 mg/kg bw over a period
    of three months, showed a 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

         In a study of 100-150 days' duration, six male (castrated) and
    six female pigs per dosage group were fed diets containing 0 (control)
    and 0.9% formic acid plus 0.4% propionic acid. Neither growth rate nor
    EFU of the experimental group were significantly different from the
    controls in either ad lib or restricted feeding (Perez-Aleman et
    al., 1971).

         Calcium formate fed at 0.2% of the diet produced no adverse
    effects when fed to rats over five generations over a three-year
    period. In a related study, 0.4% calcium formate was similarly
    negative (Malorny, 1969).


         Ethyl formate was evaluated on the basis of the short-term
    studies, its known metabolic fate, and toxicological data from formic
    acid and other formic acid esters. The Committee concluded that ethyl
    formate could be included in a group ADI for formic acid.


    Estimate of acceptable daily intake for man

    Group ADI for formic acid 0-3 mg/kg bw expressed as formic acid.


    Browning, E. (1965) Toxicity and metabolism of industrial solvents,
         Elsevier, London and New York

    FAO/WHO (1967) Toxicological evaluation of some flavouring
         substances and non-nutritive sweetening agents, FAO Nutrition
         Meetings Report, Series No. 44a; WHO/Food Add./68.33

    FAO/WHO (1968) Specifications for the identity and purity of food
         additives and their toxicological evaluation: some flavouring
         substances and non-nutritive sweetening agents. Eleventh Report
         of the Joint FAO/WHO Expert Committee on Food Additives. FAO
         Nutrition Meetings Report Series No. 44; Wld Hlth Org. techn.
         Rep. Ser. No. 383

    FEMA (1974) Scientific literature review of aliphatic primary
         alcohols, aldehydes, esters, and acids in flavor usage. Published
         by the National Information Services under Contract with the
         Food and Drug Administration

    Hagan, E. C. et al. (1967) Food flavourings and compounds of related
         structure. II. Subacute and chronic toxicity, Food Cosmet.
         Toxicol., 5, 141-157

    Jenner, P. M. et al. (1964) Food flavourings and compounds of related
         structure. I. Acute oral toxicity, Food Cosmet. Toxicol., 2,

    Malorny, G. (1969) Acute and chronic toxicity of formic acid and
         formates, Z. Ernaehrungswiss., 9 (4), 443-449

    Munch, J. C. (1972) Aliphatic alcohols and alky esters: narcotic and
         lethal potencies to tadpoles and to rabbits, Industrial
         Medicine, 41 (4), 31-33

    Opdyke, D. L. J. (1978) Fragrance raw materials monographs, Food
         Cosmet. Toxicol., 16, Suppl. 1

    Oser, B. L. (1967) Unpublished report

    Perez-Aleman, S. et al. (1971) Moist barley preserved with acid in
         the diet of the growing pig, Anim. Prod., 13 (2), 271-277

    Shillinger, Yu. I. (1950) Action of some synthetic substances on
         animal organisms, Gig. i. San., 3, 37-41 (In Russian)

    Smyth, H. F. et al. (1954) Range finding toxicity data. List V. Arch.
         Ind. Hyg. Occup. Med., 10, 61-68

    Stoner, G. D. et al. (1973) Test for carcinogenicity of food additives
         and chemotherapeutic agents by the pulmonary tumor response in
         strain A mice, Cancer Res., 33, 3069-3085

    Williams, R. T. (1959) Detoxication mechanisms, p. 50: the metabolism
         and detoxication of drugs, toxic substances and other organic

    See Also:
       Toxicological Abbreviations
       Ethyl formate (ICSC)
       Ethyl formate (FAO Nutrition Meetings Report Series 44a)
       ETHYL FORMATE (JECFA Evaluation)