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.



         Formic acid has been evaluated for acceptable daily intake by the
    Joint FAO/WHO Expert Committee on Food Additives (see Annex 1, Refs
    No. 6 and No. 9) in 1961 and 1964. The previously published monographs
    are reproduced in their entirety below.



         Formate is an intermediate in normal metabolism. It takes part in
    the metabolism of one-carbon compounds and its carbon may appear in
    methyl groups undergoing transmethylation. It is eventually oxidized
    to carbon dioxide (Williams, 1959). When formate is administered it
    could also be expected to enter one-carbon metabolism. However, there
    is a species difference in the extent of this metabolism, for in
    rabbits no administered formate is excreted, whereas in dogs about
    half the administered formate is excreted unchanged in the urine
    (Croner & Seligmann, 1907). Its metabolism in human beings is probably
    somewhere between that in dogs and that in rabbits, judging from the
    relative amounts of formate excreted by man, dogs and rabbits
    receiving methanol (Lund, 1948a; Lund, 1948b).

         Formic acid (or formate) is apparently more toxic than other
    fatty acids, possibly owing to its enzyme-inhibiting activity (Bleyer
    et al., 1933). However, no cumulative toxic effects are known.


    Special studies

         No data are available.

    Acute toxicity

         Exact LD50 values are not available. In dogs, sodium formate in
    oral doses of 4000 mg/kg and i.v. doses of 3000 mg/kg bw produced
    toxic effects such as methaemoglobinaemia and heart congestion (Fleig,
    1907). About 50 mg/kg in 10% aqueous solution given orally to dogs or
    6 mg/kg given s.c. to rabbits produced methaemoglobinaemia which
    lasted about 10 days (Croner & Seligmann, 1907). This slow
    disappearance may be due to the inhibition of catalase by formic acid
    (Lück, 1957). 4.6 mg/kg i.v. given to six dogs produced no ill effect
    and 13.8 mg/kg only slight hypertension (Erra, 1958).

    Short-term studies


         0.5 g of formic acid daily in the food has been tolerated by dogs
    without effect (Dick, 1909).

    Long-term studies

         No data are available.


         2-4 g of sodium formate daily did not produce toxic
    manifestations in human subjects, even if they were suffering from
    kidney disease. It has been stated that a daily intake of 2-4 g for
    therapeutic purposes could be tolerated for months without untoward
    effects (Rost, 1917).


         An evaluation may be made on the basis of the available
    biochemical studies on man and on the knowledge of its role in normal


    Estimate of acceptable daily intake for man

         0-3 mg/kg bw.


    Bleyer, B., Diemair, W. & Leonhard, K. (1933) Arch. Pharm. (Weinheim),
         271, 539

    Croner, F. & Seligmann, E. (1907) Z. Hyg. Infekt.-Kr., 56, 387

    Dick (1909) Hygienische Rundschan, 14, 313

    Erra, U. (1958) Fol. med. (Napoli), 41, 366

    Fleig, C. (1907) Arch. int. Pharmacodyn., 17, 147

    Lück, H. (1957) Biochem. Z., 328, 411

    Lund, A. (1948a) Acta pharmacol. (Kbh.), 4, 99

    Lund, A. (1948b) Acta pharmacol. (Kbh.), 4, 108

    Rost, E. (1917) Arb. Reichsgesundh.-Amte, 50, 405

    Williams, R. T. (1959) Detoxication mechanisms, London, Chapman & Hall

    See Also:
       Toxicological Abbreviations
       Formic acid (ICSC)
       Formic acid (FAO Nutrition Meetings Report Series 38a)
       FORMIC ACID (JECFA Evaluation)