FAO Nutrition Meetings Report Series 
    No. 46A WHO/FOOD ADD/70.36

    The content of this document is the result of the deliberations of the
    Joint FAO/WHO Expert Committee on Food Additives which met in Rome,
    27 May - 4 June 19691

    Food and Agriculture Organization of the United Nations

    World Health Organization

    1 Thirteenth report of the Joint FAO/WHO Expert Committee on Food
    Additives, FAO Nutrition Meetings Report Series, in press;
    Wld Hlth Org. techn.  Rep. Ser., in press.


    This material contains sulfated galactose units.

    Biological Data

    Biochemical aspects

    Rats excrete carrageenan quantitatively in the faeces if administered
    in the diet at levels of 2-20 per cent. and it therefore has no direct
    nutritive value (Hawkins & Yaphe, 1965). Oral administration of
    undegraded carrageenan to guinea-pigs up to 158 mg causes no
    detectable excretion in the urine. However, if given intraduodenally
    to guinea-pigs with ligated pylorus, it exerts an antigastric effect.
    Hence, absorption is still a possibility although its molecular size
    is very large (Anderson & Soman, 1966). Groups of six rats were fed
    diets containing 17.4 or 34.8 per cent. carrageenan for three weeks.
    Weight gain was significantly reduced especially at higher levels.
    Food efficiency showed interference with utilization of other
    nutrients in the diet. Only 10-15 per cent. appeared digestible as
    estimated from faecal examination (Carey, 1958). Using nine groups of
    three, four or five guinea-pigs it was noted that single intravenous
    injections of degraded carrageenan leads to a dose-related increase in
    urinary polysaccharides. Oral or intraduodenal administration of
    degraded carrageenan gave detectable residues in the urine and had an
    antigastric activity in guinea-pigs with ligated pylorus. However the
    amounts absorbed are very small and some additional protective
    mechanism may be involved (Anderson & Soman, 1966). Carrageenan
    inhibits pepsin action by binding the substrate (Anderson & Watt,
    1959; Piper & Fenton, 1961; and Houck & Bhayana, 1960). Interference
    with pepsin activity depends on concentration of carrageenan and
    protein. It occurs only over a narrow range (Márquez & Garcia, 1960;
    Vaughan et al., 1961; and Vaughan et al., 1962). At a level of five
    per cent. in the diet of rats carrageenan had no effect on utilization
    of casein, soybean protein, or of other proteins of variable quality
    (Friedman & Douglass, 1960).

    No difference in protein economy of the growing rat was observed with
    a diet of 0.5-5 per cent. carrageenan and either a high quality
    protein (casein) or a low quality vegetable protein (USFDA, 1969).

    Subcutaneous injected carrageenan stimulates the biosynthesis of
    collagen and the formation of connective tissue (Robertson & Schwartz,
    1953; and Jackson, 1956). Three per cent. carrageenan in the diet has
    been reported to reduce the plasma cholesterol level in chicks by 50
    per cent. (Riccardi & Fahrenbach, 1965). Carrageenan acts as an
    antithrombic in both human and dog blood plasma (Hawkins & Leonhard,
    1962). The presence of carrageenan in infant feeds does not affect the
    availability of any added iron (Gorten et al., 1963; Gorten & Cross,
    1964; Owen & Fomon, 1963; Fomon et al., 1961).

    A seven-month infant feeding study of the nutritional value of Formil
    an infant formula containing carrageenan (concentration not stated),
    showed normal results in feeding pattern, growth, bowel function; and
    serum calcium, phosphorus and cholesterol levels (Marine Colloids,
    Inc., 1969).

    Acute toxicity

    Intravenous injection of undegraded carrageenan is very toxic to
    rabbits (Anderson & Duncan, 1961).

    Intravenous injection of 50 mg killed rabbits within 48 h. These
    animals showed total obstruction of the glomerular capillaries by a
    fibrinoid-like substance, and extensive tubular neurosis. Rabbits
    survived 10 mg intravenously, but showed histopathologic changes in
    the kidney. Similar results were obtained in rats and guinea-pigs.
    Guinea-pigs survived intravenous injection of 5-10 mg/kg (Morard et
    al., 1964). Intravenous carrageenan in doses of 1 mg/kg kills
    guinea-pigs within 30 mins (Anderson & Soman, 1966). The injection of
    lambda-carrageenan induced collagenous growth in the rabbit cornea
    (Dass & McCandless). A single injection of 5 ml of a one per cent.
    carrageenan solution produced sarcomata in female rats and fibrous
    degeneration of mammillary gland epithelium with hyaline thickening of
    capillary walls (Cater, 1961).

    Short-term studies

    Rat. Groups of six male rats were fed for a 10-week period 0, 5, 10
    and 20 per cent. of a refined preparation. The animals grew well
    except at the highest test level which showed a 50 per cent. mortality
    (Nilson & Schaller, 1941). In similar feeding experiments using 10
    rats there was some growth retardation, decreased food intake and
    reduced urinary nitrogen excretion at dietary levels over 10 per cent.
    (Hawkins & Yaphe, 1965).

    Guinea-pig. Fifty male guinea-pigs were injected daily for 1-41 days
    with 0.25 mg histamin/100 g body weight in order to induce gastric
    ulceration. Fifty per cent. carrageenan in the diet did not accentuate
    the mucosal lesions (Holzmann & Schott, 1963).

    Man. In a nutritional study of tocopherol requirements an infant
    formula (Similac) containing carrageenan was fed as the basic diet for
    six months to 44 healthy premature infants (Goldbloom, 1963).

    Long-term studies

    Mouse. Groups of five male and five female mice of two strains were
    maintained over their life span on diets containing 0, 1 per cent., 5
    per cent., 15 per cent. and 25 per cent. carrageenan without apparent
    ill-effects on growth, survival, gross and histopathology of the
    gastro-intestinal tract, liver and kidneys (Nilson & Wagner, 1959).

    Rat. Groups of five male and five female rats of two strains were
    fed 0, 1 per cent., 5 per cent., 15 per cent. and 25 per cent.
    carrageenan for their life span. Food consumption increased in
    proportion to the increased carrageenan content. No effect was noted
    on mortality. At the 25 per cent. level there was evidence of hepatic
    cirrhosis but all other levels showed no histopathological
    abnormalities of the intestinal tract, liver, kidneys. (Nilson &
    Wagner, 1959).


    These closely related polysaccharides are very little absorbed when
    ingested by several animal species. The available short- and long-term
    studies support the safety of these materials despite the small
    numbers of animals employed. Carrageenan has a long history of human
    use without known ill-effect.


    Level causing no toxicological effect in the rat

    10 per cent. (= 100 000 ppm) in the diet equivalent to 5000 mg/kg body

    Estimate of acceptable daily intake for man

                                            mg/kg body weight

    Unconditional acceptance                       0-501


    Anderson, W. & Watt, J. (1959) J. Pharm. (Lond.), 11, 318

    Anderson, W. & Duncan, J. G. C. (1965) J. Pharm. (Lond.), 17, 647

    Anderson, W. & Soman, P. D. (1966) J. Pharm. (Lond.), 18, 827

    Carey P. L. (1958) Thesis submitted to Purdue University

    Cater, D. B. (1961) Brit. J. Cancer, 15, 607

    Dass. B. & McCandless, E. L. (1966) Fed. Proc., 25, 706

    Fomon, S. J., Owen, G. M. & Thomas, L. N. (1961) Amer. J. Dis.
    Child., 108, 601


    1 As carrageenan or furcellaran or the sum of both.

    Friedman, L. & Douglass, C. D. (1960) Unpublished summary report
    submitted by Marine Colloids Inc.

    Goldbloom, R. B. (1963) Pediatrics, 32, 36

    Gorten, M. K., Hepner, R. & Workman, J. B. (1963) J. Pediat., 63,

    Gorten, M. K. & Cross, E. R. (1964) J. Pediat., 64, 509

    Hawkins, W. W. & Leonhard, V. G. (1962) J. Lab. clin. Med., 60, 641

    Hawkins, W. W. & Yaphe, W. (1965) Canad. J. Biochem., 43, 479

    Holzmann, H. & Schott, H. J. (1963) Naturwissenschaften, 50, 502

    Houck, J. C. & Bhayana, J. L. (1960) Gastroenterology, 39, 196

    Jackson, D. S. (1956) Biochem. J., 62, 250

    Marine Colloids Inc. (1969) Unpublished report

    Márquez, V. M. & Garcia, R. G. (1960) Rev. Fac. Pharmac.
    (Venezuela), 3, 237

    Morard, J. C. et al. (1964) Nature, 202, 401

    Nilson, H. W. & Schaller, J. W. (1941) Food Res., 6, 461

    Nilson, H. W. & Wagner, J. A. (1959)  Food-Res., 24, 235

    Owen, G. M. & Fomon, S. J. (1963) Midwest Soc. Pediat. Res., 63, 490

    Piper, D. W. & Fenton, B. (1961) Gastroenterology, 40, 638

    Riccardi, B. A. & Fahrenbach, M. J. (1965) Fed. Proc., 24, 263

    Robertson, W. B. van & Schwartz, B. (1953) J. biol. Chem., 201, 689

    United States Food and Drug Administration (1969) Unpublished summary

    Vaughan, O. W., Rezabek, H. & Filer, L. J. (1961) Fed. Proc., 20,

    Vaughan. O. W., Filer, L. J. jr & Churella, H. (1962) Agric. Fd
    Chem., 10, 517

    See Also:
       Toxicological Abbreviations
       Carrageenan and Furcellaran (WHO Food Additives Series 5)
       Carrageenan and furcellaran (WHO Food Additives Series 19)