Toxicological evaluation of some food
additives including anticaking agents,
antimicrobials, antioxidants, emulsifiers
and thickening agents
WHO FOOD ADDITIVES SERIES NO. 5
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
Geneva
1974
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
Explanation
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.
BIOLOGICAL DATA
BIOCHEMICAL ASPECTS
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.
TOXICOLOGICAL STUDIES
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
Dog
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.
OBSERVATIONS IN MAN
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).
Comments:
An evaluation may be made on the basis of the available
biochemical studies on man and on the knowledge of its role in normal
metabolism.
EVALUATION
Estimate of acceptable daily intake for man
0-3 mg/kg bw.
REFERENCES
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)