FAO Nutrition Meetings
Resort Series No. 44A
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
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.
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,
Animal Route LD50 References
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).
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.
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.
Level causing no toxicological effect
Rat. 1 per cent. (= 10 000 ppm) in the diet, equivalent to 500
Estimate of acceptable daily intake for man
Conditional acceptance 0-5
Further work required
Long-term toxicity studies in animals and metabolism studies in
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