Toxicological evaluation of some food
    additives including anticaking agents,
    antimicrobials, antioxidants, emulsifiers
    and thickening agents


    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


    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.



         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.



         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).


    Special studies on carcinogenicity


         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

    Compound           Animal  Route    (mg/kg bw)       References

    Alginic acid       Rat     i.p.            1 600     Thienes et al.,

    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


         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.,

         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).


         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).


         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


         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).


         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).


         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.


    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.


    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

    Nilson, H. W. & Wagner, J. A. (1951) Proc. Soc. exp. Biol. (N.Y.). 76,

    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

    Woodard Research Corp. (1972) Unpublished report submitted to Kelco

    See Also:
       Toxicological Abbreviations
       Alginic acid and its ammonium, calcium, potassium and sodium salts (WHO Food Additives Series 30)