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.
ASCORBIC ACID AND ITS POTASSIUM AND SODIUM SALTS
Explanation
Ascorbic acid and sodium ascorbate were evaluated for acceptable
daily intake by the Joint FAO/WHO Expert Committee on Food Additives
(see Annex 1, Ref. No. 6) in 1961.
Since the previous evaluation, additional data have become
available and are summarized and discussed in the following monograph.
The previously published monograph has been expanded and is reproduced
in its entirety below.
BIOLOGICAL DATA
BIOCHEMICAL ASPECTS
Ascorbic acid is readily absorbed and metabolized. However, after
oral administration of large quantities only small amounts are
excreted in the urine, while there is a steady rise in the level of
ascorbic acid in the plasma. If the oral ingestion is continued for a
sufficient period, the plasma concentration rises to a maximum, after
which a rapid urinary excretion of a large part of the ingested
ascorbic acid occurs (Abt & Farmer, 1938).
Using 14C-labelled ascorbic acid, it was found that in the rat
after intraperitoneal injection of 1.5-5.9 mg approximately 19 to 29%
was converted to CO2 and only 0.4% was excreted as oxalate within 24
hours (Curtin & King, 1955).
TOXICOLOGICAL STUDIES
Acute toxicity
LD50
Animal Route (mg/kg bw) Reference
Mouse oral > 5 000 Demole, 1934
i.v. > 1 000
Rat oral > 5 000 Demole, 1934
i.v. > 1 000
Guinea-pig oral > 5 000 Demole, 1934
i.v. > 500
Short-term studies
Mouse
Mice given ascorbic acid orally, subcutaneously and intravenously
in daily doses of 500-1000 mg/kg bw for seven days, showed no
difference in appetite, weight gain and general behaviour from
controls receiving the same amount of the biologically inactive
galacturonic acid. Histological examination of various organs showed
no definite changes (Demole, 1934).
Guinea-pig
Guinea-pigs given ascorbic acid orally, subcutaneously and
intravenously in daily doses of 400-2500 mg/kg bw for six days, showed
no difference in appetite, weight gain and general behaviour from
controls receiving the same amounts of the biologically inactive
galacturonic acid. Histological examination of various organs showed
no definite changes (Demole, 1934).
Long-term studies
Rat
Four groups of 26 male and 26 female rats were given in their
diet for two years daily doses of 0, 1000, 1500 or 2000 mg/kg bw of
L-ascorbic acid. Haematological examinations, urine analyses, blood
enzyme activity, liver and renal function tests yielded results within
the normal range of values observed in the control group.
No macro- or micropathologically detectable toxic organic lesions
were observed which could be attributed to the daily ingestion of
large doses of L-ascorbic acid. Age-dependent degenerative processes
in organs, increasing predisposition of aging animals to intercurrent
diseases and the appearance of spontaneous tumours occurred at the
same rate in control animals and in those treated (Surber & Cerioli,
1971).
OBSERVATIONS IN MAN
One woman and three men were each given 1000 mg of ascorbic acid
a day for three months. The ascorbic acid levels in the serum and in
the white blood cells and the urinary excretion of this acid did not
shown any progressive changes. Further, no harmful effects were
observed in these four subjects during the three months (Lowry et al.,
1952).
After a daily dose of 5 mg/kg for three days a significant
increase in urinary volume was observed in 30 children (10 active
rheumatic, 10 convalescent rheumatic patients and 10 controls)
(Abbasy, 1937). This diuretic effect was confirmed in another study on
nine patients with heart failure, given 300 mg of ascorbic acid daily
(Evans, 1938).
Doses up to 6000 mg of ascorbic acid were given to 29 infants,
93 children of preschool and school age, and 20 adults for more than
1400 days. With the higher doses, toxic manifestations were observed
in five adults and four infants. The signs and symptoms in adults were
nausea, vomiting, diarrhoea, flushing of the face, headache, fatigue
and disturbed sleep. The main toxic reactions in the infants were skin
rashes (Widenbauer, 1936).
Comments:
Animal studies reveal that ascorbic acid is not toxic after a
single or repeated administrations of relatively large doses.
Studies in man indicate that ascorbic acid has a diuretic effect
at 5 mg/kg bw in children and adults and glycosuria was observed with
doses of 30-100 mg/kg. Daily doses, of the order of 200 mg/kg, have
been taken over periods of time for a therapeutic effect which has not
been unequivocably demonstrated. The recommended dietary allowances
range from 30-75 mg with a minimum of 5-10 mg/day. It is estimated
that the daily intake of ascorbic acid is between 30-100 mg from
natural sources.
EVALUATION
Estimate of acceptable daily intake for man
0-15 mg/kg bw
REFERENCES
Abbasy, M. A. (1937) Biochem. J., 31, 339
Abt, A. F. & Farmer, C. J. (1938) J. Amer. med. Ass., 111, 1555
Curtin, C. O' H. & King, C. G. (1955) J. biol. Chem., 216, 539
Demole, V. (1934) Biochem. J., 28, 770
Evans, W. (1938) Lancet, 1, 308
Lowry, O. H., Bessy, O. A. & Bunch, H. B. (1952) Proc. Soc. exp.
Biol., 80, 361
Surber, W. & Cerioli, A. (1971) A two-year toxicity study with
L-ascorbic acid on the rats. Unpublished report of the Battelle
Laboratories submitted by Hoffman-La Roche AG
Widenbauer, F. (1936) Klin. Wschr., 33, 1157