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.
CITRIC ACID AND ITS CALCIUM, POTASSIUM AND SODIUM SALTS
Explanation
These compounds have been evaluated for acceptable daily intake
by the Joint FAO/WHO Expert Committee on Food Additives (see Annex 1,
Refs Nos 6, 7 and 13) in 1961, 1963 and 1965.
Since the previous evaluation, additional data have become
available and are summarized and discussed in the following monograph.
The previously published monographs have been expanded and are
reproduced in their entirety below.
BIOLOGICAL DATA
BIOCHEMICAL ASPECTS
Citric acid is an intermediary substance in oxidative metabolism,
being engaged in the tricarboxylic acid cycle. Citric acid and
citrates occur in many foods and are normal metabolites in the body
(Gruber & Halbeisen, 1948).
Potassium and sodium citrate in doses of up to 4 g have been
extensively used in medical practice for many years without giving
rise to ill effects. The calcium salt probably behaves similarly in
the body. As food additives, therefore, all the citrates can be
considered together.
There is no reason to believe that the use of these citrates as
food additives constitutes a significant toxicological hazard to man.
TOXICOLOGICAL STUDIES
Acute toxicity
LD50
Animal Route (mg/kg bw) Reference
Mouse i.v. 42 Gruber & Halbeisen, 1948
(rapid injection)
Mouse i.p. 961 Gruber & Halbeisen, 1948
Rat i.p. 884 Gruber & Halbeisen, 1948
Short-term studies
Dog
A daily oral dose of 1380 mg/kg bw given to three dogs for 112 to
120 days produced no symptoms or evidence of renal damage (Krop &
Gold, 1945).
Long-term studies
Rat
Diets containing 1.2% of citric acid had no harmful effect on the
growth of two successive generations of rats over a period of 90
weeks. No detrimental effect could be observed on reproduction. No
significant change could be noted in the blood picture nor was there
any other pathological finding that could be attributed to the diet.
Loss of calcium or other fixed bases was not observed. The dental
attrition was found to be slightly more marked than in the control
groups (Bonting & Jansen, 1956).
OBSERVATIONS IN MAN
Ingestion of citric acid frequently or in large doses may cause
erosion of teeth and local irritation, apparently because of the low
pH: the effects also occur with lemon juice which contains about 7% of
citric acid and has a pH of less than three. A 1% solution has been
used as a cooling drink in fever. Potassium citrate has been used in
daily doses totalling up to 10 g as a mild diuretic, to render the
urine less acid and as a potassium supplement. Sodium citrate has also
been used in daily doses of up to 10 g to render the urine less acid
and as a mild diuretic (Martindale, 1972).
Comments:
In evaluating the acceptance of citric acid, emphasis is placed
on its well-established metabolic pathways. Toxicological studies on
animals supplement this information.
Citric acid and its calcium, potassium and sodium salts do not
constitute a significant toxicological hazard to man.
EVALUATION
Estimate of acceptable daily intake for man
Not limited.*
* See relevant paragraph in the seventeenth report (pp. 10-11).
REFERENCES
Bonting, S. L. & Jansen, B. C. (1956) Voeding, 17, 137
Gruber, C. M & Halbeisen, W. A. (1948) J. Pharmacol. exp. Ther., 94,
65
Krop, S. & Gold, H. (1945) J. Amer. pharm. Ass., sci. Ed., 34, 86
Martindale's Extra Pharmacopoeia, 26th Ed. (1972) The Pharmaceutical
Press, London