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 ethanoate
Empirical formula C4H8O2
Structural formula CH3COOC2H5
Molecular weight 88.11
Definition Ethyl acetate contains not less than 97
per cent. C4H8O2.
Description Ethyl acetate is a transparent,
colourless liquid, with a fragrant,
refreshing, slightly acetone odour and
an acetous, burning taste.
This ester is probably absorbed with ease from the
gastrointestinal tract and is soluble in plasma. It is hydrolysed by
liver and plasma esterases and pancreatic lipase to ethyl alcohol and
acetate (Oppenheimer, 1925; Fassett. 1963; Zipf, 1928; Nishida, 1957).
The ethyl alcohol is partly excreted in the expired air and urine, the
rest is metabolized, the acetate fraction becoming incorporated in the
body pool (Fassett, 1963).
Animal Route LD50 Referenes
Rat oral 5620 Smyth, unpublished
Guinea-pig s.c. 4000(LD) Flury & Wirth, 1934
Cat s.c. 3000 Flury & Wirth, 1934
Doses of 13-115 mg fed daily to rats for 5-9 days produced fatty
infiltration of the liver (Shillinger, 1950).
Ethyl acetate was injected into the yolk sac of fertile White
Leghorn eggs prior to incubation to study any toxic or teratogenic
effect of this substance. Ethyl acetate was used undiluted, and 0.05
or 0.10 ml per egg was injected. The hatchability was 35 per cent. and
15 per cent., respectively.
In a second experiment 9, 22.5, 45 and 90 mg per egg of ethyl
acetate were injected into the yolk sac of fresh fertile chicken eggs.
The hatchabilities were, respectively: 85, 50, 35 and 15 per cent.
(McLaughlin et al, 1963; 1964.
Although this compound has irritant properties when inhaled, it
is readily metabolized after oral administration. Despite the absence
of toxicological studies, this compound is evaluated on the basis of
its known metabolic fate. Further studies on the hydrolysis of this
compound in the gastrointestinal tract are desirable.
Estimate of acceptable daily intake for man
Unconditional acceptance 0-25
Browning, E. (1965) Toxicity of Industrial Solvents, Elsevier, London
& New York
Fassett, D. W. (1963) In: Patty, F. A., Industrial Hygiene and
Toxicology, Second Edition, Interscience, New York & London
McLaughlin, J. jr, Marliac, J. P. Verrett, M. J., Mutchler, M. K. &
Fitzhugh, O. G. (1963) Toxicol. appl. Pharmacol., 5, 760
McLaughlin, J. jr, Marliac, J. P., Verrett. M. J., Mutchler, M. K. &
Fitzhugh, O. G. (1964) Amer. Ind. Hyg. Ass. Journ., 25, 282
Nishida, M. (1957) Yakugaku Zasshi, 77, 1141
Oppenheimer, C. (1925) Die Fermente und ihre Wirkungen, Leipzig, p.
Shillinger, J. I. (1950) Gig. i. San., 3, 37
Smyth, H. F., jr, Unpublished report
Zipf, K. (1928) Arch. f. exper. Path. Pharm., 128, 121