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.
ALGINIC ACID AND ITS AMMONIUM, CALCIUM, POTASSIUM AND SODIUM SALTS
Explanation
These substances have been evaluated for acceptable daily intake
by the Joint FAO/WHO Expert Committee on Food Additives (see Annex 1,
Ref. No. 7) in 1963.
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
Calcium balance experiments on six healthy adults taking 8 g of
sodium alginate daily for seven days failed to show any interference
with the absorption of calcium from a normal mixed diet (Millis &
Reed, 1947).
In 14 out of 15 humans receiving 1.5 g sodium alginate the
gastrointestinal of strontium was reduced by a factor of two. Calcium
absorption was hardly affected (Harrison et al., 1966).
From the clinical experiments reported (Feldman et al., 1952;
Gill & Duncan, 1952) it appears that alginic acid does not bind sodium
in man to any great extent.
C14-labelled alginates were fed as 10% of the diet to 10-week-
old rats that had been starved for 24 hours; and the subsequent
metabolism over a 17-hour period measured. 85-91% of the radioactivity
was recovered in the faeces. Recoveries of administered 14C in
urine (0.11-0.16%), respiratory CO2 (0.21-0.42%), and plasma
(0.002-0.007%), show that alginate absorption under these conditions
of feeding is extremely small (Humphreys & Triffitt, 1968).
The absorption and retention of 17Ca and 85Sr was compared for
four human volunteers on a normal diet with and without supplement of
sodium alginate. Alginate was given for seven days in amounts
approximately chemically equivalent to the dietary calcium. Alginate
decreased the retention of 85Sr and 17Ca by about 70% and 77%
respectively (Carr et al., 1968). In a limited trial with three human
volunteers, the absorption of 203pb was unchanged by alginate
supplement (Harrison et al., 1969).
The absorption of orally administered riboflavin-5'-phosphate by
healthy male subjects was increased significantly when the vitamin was
administered in 50 ml of 2% alginate solution rather than water alone
(Levy & Rao, 1972).
TOXICOLOGICAL STUDIES
Special studies on carcinogenicity
Mouse
Infant albino mice (ICR/HA) strain were injected subcutaneously
in the nape of the neck with suspensions of alginic acid (10 and
100 mg/ml) or solvent alone in volumes of 0.1, 0.1, 0.2 and 0.2 ml on
days 1, 7, 14 and 21 respectively after birth, and maintained on
normal diets for 49 to 53 weeks. The tumour frequency fell within
control ranges (Epstein et al., 1970).
Acute toxicity
LD50
Compound Animal Route (mg/kg bw) References
Alginic acid Rat i.p. 1 600 Thienes et al.,
1957
Sodium alginate Mouse i.v. less than 200 Solandt, 1941
Sodium alginate Rabbit i.v. approx. 100 Solandt, 1941
Sodium atginate Cat i.p. approx. 250 Chenoweth, 1948
Sodium alginate Rat oral > 5 000 Woodard Research
Corp., 1972
Sodium alginate Rat i.v. 1 000 Sokov, 1970
Calcium alginate Rat i.p. 1 407 Sokov, 1970
Calcium alginate Rat i.v. 64 Sokov, 1970
Subcutaneous and intramuscular injections of 0.1 ml of a 1%
dispersion of alginic acid were not followed by any injurious
reactions in mice or rats (Chenoweth, 1948).
Short-term studies
Rat
Groups of six rats were fed sodium alginate for 10 weeks at
levels of 5%, 10%, 20% and 30% in the diet. The mortality rate was
high in the 20% and 30% groups during the first two weeks, apparently
due to inanition. The weight gains of the 5% and 10% groups were
slightly decreased (Nilson & Wagner, 1951).
Potassium alginate at a level of 5% in the feed acted as a
laxative; calcium alginate 5% was without this effect (Thienes et al.,
1957).
Groups of five rats were fed 5%, 10% and 20% of alginic acid in
the diet for two months. Rats on the 20% diet showed a decreased rate
of weight gain. Those on the lower levels were unaffected (Thienes et
al., 1957).
Guinea-pig
Two groups of five adult male albino guinea-pigs were given 1%
sodium alginate in their drinking water for 10 weeks. A further four
groups of six animals were used for a seven-month study. No ill
effects were observed and no colonic ulceration occurred (Watt &
Marcus, 1972).
Dog
Groups each of six beagle dogs (equally divided by sex), were
maintained on diets containing 0, 5 or 15% sodium alginate for one
year. Weight gain, behaviour, appearance, periodic blood values,
terminal urinalysis, blood urea nitrogen, blood glucose and serum
alkaline phosphase were within normal limits. Gross autopsy and
histopathologic examination of tissues revealed no compound-related
effects (Woodard Research Corp., 1959).
Long-form studies
Rat
Two groups of 10 male albino rats were fed two different
commercial preparations of sodium alginate at the 5% level over their
life span (maximum 128 weeks). Data on longevity, maximum weight and
food and water consumption indicate no adverse effect. Gross necropsy
studies revealed no abnormalities. Histopathological examination was
not carried out (Nilson & Wagner, 1951).
Groups each of 40 rats (equally divided by sex) were maintained
on diets containing 0 or 5% sodium alginate for a period of two years.
During this period approximately half the rats were bred once to
produce an F1 generation, which was subsequently bred to produce an
F2 generation. There were no significant differences in growth rate
of test groups and controls, for both the parent group over the two-
year period, as well as the progeny (F1 and F2). Reproduction was
normal. Haematologic values of the Parent group, as well as that of
the F2 offsprings were normal. Gross and microscopic study of various
tissues and organs of the parent groups at two years, and the F1 and
F2 groups at the conclusion of the rapid growth period was normal
(Morgan et al., undated).
OBSERVATIONS IN MAN
Six healthy adults were given 8 g of sodium alginate daily for
seven days without untoward effects (Millis & Reed, 1947).
Three patients whose clinical condition warranted sodium
restriction were given oral doses of 15 g of alginic acid three times
daily for seven days. A slightly increased faecal sodium and potassium
excretion was noted, but no changes in plasma electrolyte
concentration (Feldman et al., 1952).
Six patients with essential hypertension were given daily doses
of 45 g of alginic acid containing 10% of potassium alginate for five
to nine weeks and three patients in an oedematous state were given the
same dosage for about a week. It was well tolerated and produced no
gastrointestinal disturbance (Gill & Duncan, 1952).
Comments:
It seems reasonable to consider alginic acid and the four salts
of alginic acid together. Additional data are available to show that
the alginates per se are poorly absorbed.
EVALUATION
Level causing no toxicological effect
Rat: 50 000 ppm (5%) in the diet equivalent to 2500 mg/kg bw.
Estimate of acceptable daily intake for man
0-25* mg/kg bw.
* Calculated on alginic acid.
REFERENCES
Carr, T. E. F. et al. (1968) Int. J. Radial. Biol., 14, 225
Chenoweth, M. B. (1948) Ann. Surg., 127, 1173
Epstein, S. S. et al. (1970) Tox. & Appl. Pharm., 16, 321
Feldman, H. S. et al. (1952) Proc. Soc. exp. Biol. (N.Y.), 79, 439
Gill, R. J. & Duncan, G. G. (1952) Amer. J. med. Sci., 224, 569
Harrison, G. E. et al. (1969) Nature, 224, 1115
Harrison, J., McNeill, K. G. & Janiga, A. (1966) Can. med. Ass. J.,
95, 532
Humphreys, E. R. & Triffitt, J. T. (1968) Nature, 219, 1172
Levy, G. & Rao, K. (1972) J. Pharm. Sci., 61, 279
Millis, J. & Reed, F. B. (1947) Biochem. J., 41, 273
Morgan, C. F., Faber, J. E., jr & Dardin, V. J. (undated) Georgetown
University Medical School, Washington, D. C., 113 pp (Unpublished
report)
Nilson, H. W. & Wagner, J. A. (1951) Proc. Soc. exp. Biol. (N.Y.). 76,
630
Solandt, O. M. (1941) Quart. J. exp. Physiol., 31, 25
Sokov, L. A. (1970) Radioaktivnye Izotopy Vo Vneshnei Srede i
Organizine. Atomizdat, Moscow 247
Thienes, C. H. et al. (1957) Arch. int. Pharmacodyn., 111, 167
Watt, J. & Marcus, R. (1971) Proc. Nutr. Soc., 30, 81A
Woodard Research Corp. (1959) Unpublished report submitted to Kelco
Co.
Woodard Research Corp. (1972) Unpublished report submitted to Kelco
Co.